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The plant Camellia fascicularis, belonging to family Theaceae, has high ornamental and medicinal value, and rare gene resources for genetic improvement of Camellia crops, but is currently threatened with extinction because of the unique and extremely small wild populations. Molecular markers have clarified the wild plant species’ genetic diversity structure, new gene resources and relationship with crops. This will be beneficial for conservation of these valuable crop-related wild species and crop improvement. In this study, we identified 95,979 microsatellite loci from 155,011 transcriptome unigenes, and developed 14 polymorphic expressed sequence tag-derived simple sequence repeat (EST-SSR) microsatellite markers for C. fascicularis. The number of alleles (Na) per locus was 2–8 with a mean of 4.86. The genetic diversity of 40 individuals from four natural populations of C. fascicularis was analysed using these polymorphic markers. The number of alleles (Na) for EST-SSR ranged from 2 to 5, with the expected heterozygosities (He) and observed heterozygosities (Ho) in all loci ranging from 0.183 to 0.683, and from 0.201 to 0.700, respectively, implying a rich genetic variation present in wild C. fascicularis populations. Moreover, the phylogenetic analysis among four populations, using the 14 EST-SSR markers developed in this study, grouped 40 individuals into three groups, which coincide with their geographic distribution. These results showed that 14 EST-SSR markers are available for the analysis of genetic variation in C. fascicularis populations and genetic improvement of new Camellias cultivars by interspecific hybridization, and are beneficial for conservation of the endangered species.
Single-particle cryo-electron microscopy (cryo-EM) is a powerful imaging modality capable of visualizing proteins and macromolecular complexes at near-atomic resolution. The low electron-doses used to prevent radiation damage to the biological samples, however, result in images where the power of the noise is 100 times greater than the power of the signal. To overcome these low signal-to-noise ratios (SNRs), hundreds of thousands of particle projections are averaged to determine the three-dimensional structure of the molecule of interest. The sampling requirements of high-resolution imaging impose limitations on the pixel sizes that can be used for acquisition, limiting the size of the field of view and requiring data collection sessions of several days to accumulate sufficient numbers of particles. Meanwhile, recent image super-resolution (SR) techniques based on neural networks have shown state-of-the-art performance on natural images. Building on these advances, here, we present a multiple-image SR algorithm based on deep internal learning designed specifically to work under low-SNR conditions. Our approach leverages the internal image statistics of cryo-EM movies and does not require training on ground-truth data. When applied to single-particle datasets of apoferritin and T20S proteasome, we show that the resolution of the 3D structure obtained from SR micrographs can surpass the limits imposed by the imaging system. Our results indicate that the combination of low magnification imaging with in silico image SR has the potential to accelerate cryo-EM data collection by virtue of including more particles in each exposure and doing so without sacrificing resolution.
This paper presents a multi-band rectangular slot antenna, which can be used in Beidou navigation system, 4G, WLAN and 5G system. The proposed antenna adopts a single feeding line, generating circular polarization for satellite navigation, and linear polarization for mobile communication systems. The proposed antenna consists of three c-type resonators and three rectangular loop slots. A c-type resonator and a rectangular loop slot work together to produce a usable frequency band. Multiple frequency bands can be generated by increasing the number of c-type resonator and rectangular loop slots. It is found that the c-type resonator changes the current distribution on the antenna surface, making the axial ratio less than 3 dB in the low frequency bands. Eventually, five operation frequency bands are realized. Experimentally, it is verified that the impedance bandwidths of each frequency band are 11.8% (1.12–1.26 GHz), 15.4% (1.5–1.75 GHz), 11.9% (2.36–2.66 GHz), 19.7% (3.15–3.84 GHz) and 2.6% (4.47–4.59 GHz), respectively. The measured 3 dB axial ratio bandwidths are 20 MHz at 1.2 and 1.56 GHz, fully covering BDS B1 and B2 bands. The measured gains are 3, 3.59, 4.07, 4.2 and 4.35 dBi, respectively.
This research communication investigated the role and the underlying mechanism of sn-1-acylglycerol-3-phosphate O-acyltransferase 6 (AGPAT6) in acetate-induced mTORC1 signaling activation and milk fat synthesis in dairy cow mammary epithelial cells. The data showed AGPAT6 knockdown significantly decreased acetate-induced phosphorylation of mTORC1 signaling molecules and intracellular triacylglycerol (TAG) content, whereas this inhibition effect was reversed after the addition of 16:0,18:1 phosphatidic acid (PA), suggesting that AGPAT6 could generate PA in response to acetate simulation, that in turn activates mTORC1 signaling. PPARγ is the upstream regulator of AGPAT6 upon acetate stimulation. Luciferase assay with clones containing various deletions and mutation in AGPAT6 promoter showed that there is a RXRα binding sequence located at −96 bp of AGPAT6 promoter. Acetate stimulation significantly increased the interaction between PPARγ and AGPAT6 via this RXRα binding site. Taken together, our data indicated that AGPAT6 could activate mTORC1 signaling by producing PA during acetate-induced milk fat synthesis, and PPARγ acts as a transcription factor to mediate the effect of acetate on AGPAT6 via RXRα.
Whether starchy and non-starchy vegetables have distinct impacts on health remains unknown. We prospectively investigated the intake of starchy and non-starchy vegetables in relation to mortality risk in a nationwide cohort. Diet was assessed using 24-h dietary recalls. Deaths were identified via the record linkage to the National Death Index. Hazard ratios (HR) and 95 % CI were calculated using Cox regression. During a median follow-up of 7·8 years, 4904 deaths were documented among 40 074 participants aged 18 years or older. Compared to those with no consumption, participants with daily consumption of ≥ 1 serving of non-starchy vegetables had a lower risk of mortality (HR = 0·76, 95 % CI 0·66, 0·88, Ptrend = 0·001). Dark-green and deep-yellow vegetables (HR = 0·79, 95 % CI 0·63, 0·99, Ptrend = 0·023) and other non-starchy vegetables (HR = 0·80, 95 % CI 0·70, 0·92, Ptrend = 0·004) showed similar results. Total starchy vegetable intake exhibited a marginally weak inverse association with mortality risk (HR = 0·89, 95 % CI 0·80, 1·00, Ptrend = 0·048), while potatoes showed a null association (HR = 0·93, 95 % CI 0·82, 1·06, Ptrend = 0·186). Restricted cubic spline analysis suggested a linear dose–response relationship between vegetable intake and death risk, with a plateau at over 300 and 200 g/d for total and non-starchy vegetables, respectively. Compared with starchy vegetables, non-starchy vegetables might be more beneficial to health, although both showed a protective association with mortality risk. The risk reduction in mortality plateaued at approximately 200 g/d for non-starchy vegetables and 300 g/d for total vegetables.
Benzodiazepine receptor agonists (BZRAs) are commonly used clinically and data on their hazardous use from large populations of psychiatric patients is limited.
Aims
To assess the current status of hazardous BZRA use and related factors in Chinese out-patient psychiatric settings.
Method
The study included out-patients with at least one BZRA prescription from five psychiatric settings in east, central and west China in 2018. Demographic and prescription information were extracted from the electronic prescription database. We defined the co-occurrence of overdose and long-term use as hazardous use, and patients whose recorded diagnoses did not meet any indications approved by the Chinese Food and Drug Administration as over-indication users. Additionally, 200 hazardous users were randomly selected for follow-up interview to confirm the actual situation.
Results
Among 720 054 out-patients, 164 450 (22.8%) had at least one BZRA prescription; 55.9% of patients were prescribed over-indication and 3% were defined as hazardous users. Multilevel multivariate regression analysis with hospital as a random effect showed that factors associated with hazardous use were older age (18–64 years: β = 0.018; 95% CI 0.013–0.023; >65 years: β = 0.015; 95% CI 0.010–0.021), male (β = 0.005, 95% CI 0.003–0.007), over-indication (β = 0.013, 95% CI 0.012–0.015), more out-patient visits (β = 0.006, 95% CI 0.006–0.006) and more visits to different doctors (β = 0.007, 95% CI 0.007–0.008); 98.5% of hazardous users (197/200) could not be contacted.
Conclusions
BZRAs are commonly used and there is a relatively large proportion of over-indication users among Chinese psychiatric out-patients. However, only a small proportion of hazardous users were detected. The study highlights how to use prescription data to support improvements in clinical practice.
The relationship of a diet low in fibre with mortality has not been evaluated. This study aims to assess the burden of non-communicable chronic diseases (NCD) attributable to a diet low in fibre globally from 1990 to 2019.
Design:
All data were from the Global Burden of Disease (GBD) Study 2019, in which the mortality, disability-adjusted life-years (DALY) and years lived with disability (YLD) were estimated with Bayesian geospatial regression using data at global, regional and country level acquired from an extensively systematic review.
Setting:
All data sourced from the GBD Study 2019.
Participants:
All age groups for both sexes.
Results:
The age-standardised mortality rates (ASMR) declined in most GBD regions; however, in Southern sub-Saharan Africa, the ASMR increased from 4·07 (95 % uncertainty interval (UI) (2·08, 6·34)) to 4·60 (95 % UI (2·59, 6·90)), and in Central sub-Saharan Africa, the ASMR increased from 7·46 (95 % UI (3·64, 11·90)) to 9·34 (95 % UI (4·69, 15·25)). Uptrends were observed in the age-standardised YLD rates attributable to a diet low in fibre in a number of GBD regions. The burden caused by diabetes mellitus increased in Central Asia, Southern sub-Saharan Africa and Eastern Europe.
Conclusions:
The burdens of disease attributable to a diet low in fibre in Southern sub-Saharan Africa and Central sub-Saharan Africa and the age-standardised YLD rates in a number of GBD regions increased from 1990 to 2019. Therefore, greater efforts are needed to reduce the disease burden caused by a diet low in fibre.
Let Q be a quiver of type
$\tilde {A}_n$
. Let
$\alpha =\alpha _1+\alpha _2+\cdots +\alpha _s$
be the canonical decomposition. For the polynomials
$M_Q(\alpha ,q)$
that count the number of isoclasses of representations of Q over
${\mathbb F}_q$
with dimension vector
$\alpha $
, we obtain a precise relation between the degree of
$M_Q(\alpha ,q)$
and that of
$\prod _{i=1}^{s} M_Q(\alpha _i,q)$
for an arbitrary dimension vector
$\alpha $
.
The association between dietary Cu intake and mortality risk remains uncertain. We aimed to investigate the relationship of dietary Cu intake with all-cause mortality among Chinese adults. A total of 17 310 participants from the China Health and Nutrition Survey, a national ongoing open cohort of Chinese participants, were included in the analysis. Dietary intake was measured by three consecutive 24-h dietary recalls in combination with a weighing inventory over the same 3 d. The average intakes of the 3-d dietary macronutrients and micronutrients were calculated. The study outcome was all-cause mortality. During a median follow-up of 9·0 years, 1324 (7·6 %) participants died. After adjusting for sex, age, BMI, ever alcohol drinking, ever smoking, education levels, occupations, urban or rural residents, systolic blood pressure, diastolic blood pressure and the intakes of fat, protein and carbohydrate, the association between dietary Cu intake and all-cause mortality followed a J-shape (Pfor nonlinearity = 0·047). When dietary Cu intake was assessed as quartiles, compared with those in the first quartile (<1·60 mg/d), the adjusted hazard ratios for all-cause mortality were 0·87 (95 % CI (0·71, 1·07)), 0·98 (95 % CI (0·79, 1·21)) and 1·49 (95 % CI (1·19, 1·86)), respectively, in participants in the second (1·60–<1·83 mg/d), third (1·83–<2·09 mg/d) and fourth (≥2·09 mg/d) quartiles. A series of subgroup analyses and sensitivity analyses showed similar results. Overall, our findings emphasised the importance of maintaining optimal dietary Cu intake levels for prevention of premature death.
The sequential occurrence of three layers of smooth muscle layers (SML) in human embryos and fetus is not known. Here, we investigated the process of gut SML development in human embryos and fetuses and compared the morphology of SML in fetuses and neonates. The H&E, Masson trichrome staining, and Immunohistochemistry were conducted on 6–12 gestation week human embryos and fetuses and on normal neonatal intestine. We showed that no lumen was seen in 6–7th gestation week embryonic gut, neither gut wall nor SML was developed in this period. In 8–9th gestation week embryonic and fetal gut, primitive inner circular SML (IC-SML) was identified in a narrow and discontinuous gut lumen with some vacuoles. In 10th gestation week fetal gut, the outer longitudinal SML (OL-SML) in gut wall was clearly identifiable, both the inner and outer SML expressed α-SMA. In 11–12th gestation week fetal gut, in addition to the IC-SML and OL-SML, the muscularis mucosae started to develop as revealed by α-SMA immune-reactivity beneath the developing mucosal epithelial layer. Comparing with the gut of fetuses of 11–12th week of gestation, the muscularis mucosae, IC-SML, and OL-SML of neonatal intestine displayed different morphology, including branching into glands of lamina propria in mucosa and increased thickness. In conclusions, in the human developing gut between week-8 to week-12 of gestation, the IC-SML develops and forms at week-8, followed by the formation of OL-SML at week-10, and the muscularis mucosae develops and forms last at week-12.
When a charge neutral drop impacts on a flat solid substrate, a small air bubble is always trapped underneath due to the lubrication pressure coming from the viscous stress in the squeezed air film. Herein we find experimentally and numerically that the process of the air entrapment and the initial contact state of the drop with the substrate can be profoundly altered via an external electric field. In an electric field, the induced electric stresses at the bottom of the drop increase drastically right before the drop contacts the substrate, which acts against the lubrication pressure, resulting in reduced initial contact radius and air bubble size. When the external electric field reaches a critical value, the electrical stress accelerates the flow near the bottom of the drop and generates a conical tip quickly instead of a dimple, resulting in a centre contact and eliminating the air bubble entrapment. Based on the dipole mirror charge model, we find the dimensionless strength of critical electric field scales with the square root of capillary number based on the air viscosity. This scaling law of the critical electric field for eliminating the air bubble entrapment is verified experimentally and numerically. This work may offer a new way to mitigate defects caused by air bubble entrapment for inkjet printing and droplet-based additive manufacturing.
The study was to evaluate the reproducibility and validity of the FFQ for residents of northeast China. A total of 131 participants completed two FFQ (FFQ1 and FFQ2) within a 3-month period, 125 participants completed 8-d weighed diet records (WDR) and 112 participants completed blood biomarker testing. Reproducibility was measured by comparing nutrient and food intake between FFQ1 and FFQ2. The validity of the FFQ was assessed by WDR and the triad method. The Spearman correlation coefficients (SCC) and intraclass correlation coefficients (ICC) for reproducibility ranged from 0·41 to 0·69 (median = 0·53) and from 0·18 to 0·68 (median = 0·53) for energy and nutrients and from 0·37 to 0·73 (median = 0·59) and from 0·33 to 0·86 (median = 0·60) for food groups, respectively. The classifications of same or adjacent quartiles ranged from 73·64 to 93·80 % for both FFQ. The crude SCC between the FFQ and WDR ranged from 0·27 to 0·55 (median = 0·46) for the energy and nutrients and from 0·26 to 0·70 (median = 0·52) for food groups, and classifications of the same or adjacent quartiles ranged from 65·32 to 86·29 %. The triad method indicated that validation coefficients for the FFQ were above 0·3 for most nutrients, which indicated a moderate or high level of validity. The FFQ that was developed for residents of northeast China for the Northeast Cohort Study of China is reliable and valid for assessing the intake of most foods and nutrients.
This paper presents a new method to reveal the relation between the surface deformation and near-field amplitude of a reflector antenna based on complex geometrical optics, which could be used as an efficient way to estimate the antenna surface verified by simulation results. The measurement process based on this method is envisaged to be realized by a single scanning of the near-field amplitude which would overcome many limitations of radio holography and phase retrieval methods such as the frequency and elevation. The largest source of error in the original deformation-amplitude equation (DAE) has been corrected by considering the Gaussian feed as a complex point source. To track the ray trajectory so that the improved DAE could be solved, an iteration method including a golden section search algorithm is designed to make the solution converge. By solving the modified DAE, simulation result shows that a more accurate solution could be obtained, and the antenna surface could be recovered to a root mean square error of under 30 microns.
Acoustic emission of a NACA 0012 aerofoil is investigated over a range of free-stream velocities. Acoustic spectra show a dominant tone and two sets of weaker side tones characterised by different frequency intervals. The frequency of the dominant tones in the acoustic spectra varies with velocity in a ladder-type structure. With increasing Reynolds number, the spectrum becomes progressively more broadband in nature. Through synchronised particle image velocimetry and acoustic measurements, the aeroacoustic noise generation mechanisms, resulting in different spectral characteristics and modulation types, are further investigated. A separation bubble and related significant velocity fluctuations are observed on the pressure side. Pressure side velocity spectra show characteristics similar to the acoustic ones, whereas velocity spectra on the suction side feature broadband characteristics. These findings confirm that noise emission is dominated by pressure side events for the Reynolds number range of this study, i.e. $2 \times 10^{5}$–$7 \times 10^{5}$. As the acoustic emission is defined by coherent flow structures, the proper orthogonal decomposition method is adopted to facilitate the understanding of the relation between the complex flow field and acoustic emission. Side tones in the acoustic spectra are attributed to two different modulation mechanisms in the aeroacoustic source region near the trailing edge. By aligning the sound pressure time history and the time coefficients of the dominant modes, the primary modulation of the dominant tone is found to be related to the amplitude modulation of the high-frequency velocity fluctuations associated with the acoustic feedback loop. A secondary modulation is attributed to periodic variation of the separation bubble and, therefore, variation in the roll-up of the shear layer, which results in a modulation of the amplitude of the velocity fluctuations associated with the convecting vortices at the trailing edge.
This study is performed to figure out how the presence of diabetes affects the infection, progression and prognosis of 2019 novel coronavirus disease (COVID-19), and the effective therapy that can treat the diabetes-complicated patients with COVID-19. A multicentre study was performed in four hospitals. COVID-19 patients with diabetes mellitus (DM) or hyperglycaemia were compared with those without these conditions and matched by propensity score matching for their clinical progress and outcome. Totally, 2444 confirmed COVID-19 patients were recruited, from whom 336 had DM. Compared to 1344 non-DM patients with age and sex matched, DM-COVID-19 patients had significantly higher rates of intensive care unit entrance (12.43% vs. 6.58%, P = 0.014), kidney failure (9.20% vs. 4.05%, P = 0.027) and mortality (25.00% vs. 18.15%, P < 0.001). Age and sex-stratified comparison revealed increased susceptibility to COVID-19 only from females with DM. For either non-DM or DM group, hyperglycaemia was associated with adverse outcomes, featured by higher rates of severe pneumonia and mortality, in comparison with non-hyperglycaemia. This was accompanied by significantly altered laboratory indicators including lymphocyte and neutrophil percentage, C-reactive protein and urea nitrogen level, all with correlation coefficients >0.35. Both diabetes and hyperglycaemia were independently associated with adverse prognosis of COVID-19, with hazard ratios of 10.41 and 3.58, respectively.
Sleep disturbance is an important factor in the pathophysiology and progression of psychiatric disorders, but whether it is a cause, or a downstream effect is still not clear.
Methods
To investigate causal relationships between three sleep-associated traits and seven psychiatric diseases, we used genetic variants related to insomnia, chronotype and sleep duration to perform a two-sample bidirectional Mendelian randomisation analysis. Summary-level data on psychiatric disorders were extracted from the Psychiatric Genomics Consortium. Effect estimates were obtained by using the inverse-variance-weighted (IVW), weights modified IVW, weighted-median methods, MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO) test and Robust Adjusted Profile Score (RAPS).
Results
The causal odds ratio (OR) estimate of genetically determined insomnia was 1.33 (95% confidence interval (CI) 1.22–1.45; p = 5.03 × 10−11) for attention-deficit/hyperactivity disorder (ADHD), 1.31 (95% CI 1.25–1.37; p = 6.88 × 10−31) for major depressive disorder (MDD) and 1.32 (95% CI 1.23–1.40; p = 1.42 × 10−16) for post-traumatic stress disorder (PTSD). There were suggestive inverse associations of morningness chronotype with risk of MDD and schizophrenia (SCZ). Genetically predicted sleep duration was also nominally associated with the risk of bipolar disorder (BD). Conversely, PTSD and MDD were associated with an increased risk of insomnia (OR = 1.06, 95% CI 1.03–1.10, p = 7.85 × 10−4 for PTSD; OR = 1.37, 95% CI 1.14–1.64; p = 0.001 for MDD). A suggestive inverse association of ADHD and MDD with sleep duration was also observed.
Conclusions
Our findings provide evidence of potential causal relationships between sleep disturbance and psychiatric disorders. This suggests that abnormal sleep patterns may serve as markers for psychiatric disorders and offer opportunities for prevention and management in psychiatric disorders.
There is a lack of evidence related to the prevalence of mental health symptoms as well as their heterogeneities during the coronavirus disease 2019 (COVID-19) pandemic in Latin America, a large area spanning the equator. The current study aims to provide meta-analytical evidence on mental health symptoms during COVID-19 among frontline healthcare workers, general healthcare workers, the general population and university students in Latin America.
Methods
Bibliographical databases, such as PubMed, Embase, Web of Science, PsycINFO and medRxiv, were systematically searched to identify pertinent studies up to August 13, 2021. Two coders performed the screening using predefined eligibility criteria. Studies were assigned quality scores using the Mixed Methods Appraisal Tool. The double data extraction method was used to minimise data entry errors.
Results
A total of 62 studies with 196 950 participants in Latin America were identified. The pooled prevalence of anxiety, depression, distress and insomnia was 35%, 35%, 32% and 35%, respectively. There was a higher prevalence of mental health symptoms in South America compared to Central America (36% v. 28%, p < 0.001), in countries speaking Portuguese (40%) v. Spanish (30%). The pooled prevalence of mental health symptoms in the general population, general healthcare workers, frontline healthcare workers and students in Latin America was 37%, 34%, 33% and 45%, respectively.
Conclusions
The high yet heterogenous level of prevalence of mental health symptoms emphasises the need for appropriate identification of psychological interventions in Latin America.
Gut microbiome and dietary patterns have been suggested to be associated with depression/anxiety. However, limited effort has been made to explore the effects of possible interactions between diet and microbiome on the risks of depression and anxiety.
Methods
Using the latest genome-wide association studies findings in gut microbiome and dietary habits, polygenic risk scores (PRSs) analysis of gut microbiome and dietary habits was conducted in the UK Biobank cohort. Logistic/linear regression models were applied for evaluating the associations for gut microbiome-PRS, dietary habits-PRS, and their interactions with depression/anxiety status and Patient Health Questionnaire (PHQ-9)/Generalized Anxiety Disorder-7 (GAD-7) score by R software.
Results
We observed 51 common diet–gut microbiome interactions shared by both PHQ score and depression status, such as overall beef intake × genus Sporobacter [hurdle binary (HB)] (PPHQ = 7.88 × 10−4, Pdepression status = 5.86 × 10−4); carbohydrate × genus Lactococcus (HB) (PPHQ = 0.0295, Pdepression status = 0.0150). We detected 41 common diet–gut microbiome interactions shared by GAD score and anxiety status, such as sugar × genus Parasutterella (rank normal transformed) (PGAD = 5.15 × 10−3, Panxiety status = 0.0347); tablespoons of raw vegetables per day × family Coriobacteriaceae (HB) (PGAD = 6.02 × 10−4, Panxiety status = 0.0345). Some common significant interactions shared by depression and anxiety were identified, such as overall beef intake × genus Sporobacter (HB).
Conclusions
Our study results expanded our understanding of how to comprehensively consider the relationships for dietary habits–gut microbiome interactions with depression and anxiety.
T long-term effects of cognitive therapy and behavior therapy (CTBT) for menopausal symptoms are unknown, and whether the effects are different between natural menopause and treatment-induced menopause are currently unclear. Therefore, we sought to conduct an accurate estimate of the efficacy of CTBT for menopausal symptoms.
Methods
We conducted searches of Cochrane Library, EMBASE, PsycINFO, PubMed, and Web of Science databases for studies from 1 January 1977 to 1 November 2021. Randomized controlled trials (RCTs) comparing intervention groups to control groups for menopausal symptoms were included. Hedge's g was used as the standardized between-group effect size with a random-effects model.
Results
We included 14 RCTs comprising 1618 patients with a mean sample size of 116. CTBT significantly outperformed control groups in terms of reducing hot flushes [g = 0.39, 95% confidence interval (CI) 0.23–0.55, I2 = 45], night sweats, depression (g = 0.50, 95% CI 0.34–0.66, I2 = 51), anxiety (g = 0.38, 95% CI 0.23–0.54, I2 = 49), fatigue, and quality of life. Egger's test indicated no publication bias.
Conclusions
CTBT is an effective psychological treatment for menopausal symptoms, with predominantly small to moderate effects. The efficacy is sustained long-term, although it declines somewhat over time. The efficacy was stronger for natural menopause symptoms, such as vasomotor symptoms, than for treatment-induced menopause symptoms. These findings provide support for treatment guidelines recommending CTBT as a treatment option for menopausal symptoms.