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Soybean meal is rich in soybean isoflavones, which exhibit antioxidant, anti-inflammatory, antiviral and anticancer functions in humans and animals. This study was conducted to investigate the effects of soybean isoflavones on the growth performance, intestinal morphology and antioxidative properties in pigs. A total of 72 weaned piglets (7.45 ± 0.13 kg; 36 males and 36 females) were allocated into three treatments and fed corn-soybean meal (C-SBM), corn-soy protein concentrate (C-SPC) or C-SPC supplemented with equal levels of the isoflavones found in the C-SBM diet (C-SPC + ISF) for a 72-day trial. Each treatment had six replicates and four piglets per replicate, half male and half female. On day 42, one male pig from each replicate was selected and euthanized to collect intestinal samples. The results showed that compared to pigs fed the C-SPC diet, pigs fed the C-SBM and C-SPC + ISF diets had higher BW on day 72 (P < 0.05); pigs fed the C-SBM diet had significantly higher average daily gain (ADG) during days 14 to 28 (P < 0.05), with C-SPC + ISF being intermediate; pigs fed the C-SBM diet tended to have higher ADG during days 42 to 72 (P = 0.063), while pigs fed the C-SPC + ISF diet had significantly higher ADG during days 42 to 72 (P < 0.05). Moreover, compared to pigs fed the C-SPC diet, pigs fed the C-SBM diet tended to have greater villus height (P = 0.092), while pigs fed the C-SPC + ISF diet had significantly greater villus height (P < 0.05); pigs fed the C-SBM and C-SPC + ISF diets had significantly increased villus height-to-crypt depth ratio (P < 0.05). Compared with the C-SPC diet, dietary C-SPC + ISF tended to increase plasma superoxide dismutase activity on days 28 (P = 0.085) and 42 (P = 0.075) and reduce plasma malondialdehyde (MDA) content on day 42 (P = 0.089), as well as significantly decreased jejunal mucosa MDA content on day 42 (P < 0.05). However, no significant difference in the expression of tight junction genes among the three groups was found (P > 0.05). In conclusion, our results suggest that a long-term exposure to soybean isoflavones enhances the growth performance, protects the intestinal morphology and improves the antioxidative properties in pigs.
The catechol-O-methyltransferase (COMT) gene is related to dopamine degradation and has been suggested to be involved in the pathogenesis of major depressive disorder (MDD). However, how this gene affects brain function properties in MDD is still unclear.
Methods:
Fifty patients with MDD and 35 cognitively normal participants underwent a resting-state functional magnetic resonance imaging scan. A voxelwise and data-drive global functional connectivity density (gFCD) analysis was used to investigate the main effects and the interactions of disease states and COMT rs4680 gene polymorphism on brain function.
Results:
We found significant group differences of the gFCD in bilateral fusiform area (FFA), post-central and pre-central cortex, left superior temporal gyrus (STG), rectal and superior temporal gyrus and right ventrolateral prefrontal cortex (vlPFC); abnormal gFCDs in left STG were positively correlated with severity of depression in MDD group. Significant disease × COMT interaction effects were found in the bilateral calcarine gyrus, right vlPFC, hippocampus and thalamus, and left SFG and FFA. Further post-hoc tests showed a nonlinear modulation effect of COMT on gFCD in the development of MDD. Interestingly, an inverted U-shaped modulation was found in the prefrontal cortex (control system) but U-shaped modulations were found in the hippocampus, thalamus and occipital cortex (processing system).
Conclusion:
Our study demonstrated nonlinear modulation of the interaction between COMT and depression on brain function. These findings expand our understanding of the COMT effect underlying the pathophysiology of MDD.
The potential pattern of regional cerebral blood flow (rCBF) in major depressive disorder (MDD) underlies different response to antidepressants medication remain unclear. This study aimed to investigate the differences of rCBF between patients with different treatment response.
Methods
Eighty MDD patients [(44 treatment-responsive depression (RD) and 36 non-responding depression (NRD)] and 42 healthy controls (HC) underwent pulsed arterial spin labeling (PASL) scans in magnetic resonance imaging and clinical estimates. The exact rCBF values of each groups were obtained via quantification evaluation.
Results
Compared to NRD, the RD patients showed decreased rCBF values in frontal sensorimotor network (i.e. left paracentral lobule, left medial frontal gyrus, right superior frontal gyrus and right middle frontal gyrus), and further receiver operating curve (ROC) analyses demonstrated that the altered rCBF in these four regions exhibited outstanding performance on distinguishing NRD from RD. The NRD also exhibited reduced rCBF in bilateral cerebellum posterior lobe and right middle occipital gyrus and elevated rCBF in right postcentral gyrus and right middle frontal gyrus as compared to HC.
Conclusions
The decreased rCBF in frontal sensorimotor network appeared to be distinct characteristics for NRD, and might be severed as promising neuroimaging markers to differentiate depressed patients with weak early response to antidepressant medication. These findings expand our understanding of neural substrate underlying the antidepressant efficacy.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The intuitive association between cognitive dysfunction in late onset depression (LOD) and the aberrant functional activity in the brain's default-mode network (DMN) has prompted interest in exploring the role of the DMN in LOD. The altered pattern of resting state voxel-mirrored homotopic connectivity (VMHC) in cognitive processes is not yet well understood in LOD.
Methods
The study was designed to examine the implicit coupling between the alteration of interhemispheric functional coordination and cognitive impairment in LOD. Thirty-one LOD patients and 37 matched healthy controls (HC) underwent neuropsychological tests and functional magnetic resonance imaging (fMRI) in this study.
Results
Compared to HC group, attenuated VMHC in superior frontal gyrus, superior temporal gyrus, posterior cerebellar lobe, postcentral and precentral gyrus was observed in LOD. Neuro-behavioral relevancy approach revealed that the imbalanced interhemispheric functional coordination in bilateral cerebellum was positively correlated with the performance of trail making test in LOD (r = 0.367, P = 0.040).
Conclusion
Altered linkage pattern of intrinsic homotopic connectivity and cognition was firstly investigated in LOD, and it would provide a novel clue to reveal the neural substrates underlying the cognitive dysfunction in LOD.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Psychomotor retardation (PMR) in depression is analogous to the hypokinesia in Parkinson's disease, which is associated with the unbalanced direct and indirect pathways of cortico-basal ganglia-thalamo-cortical (CBTC) circuitry. This study hypothesized PMR in major depressive disorder (MDD) should be associated with the hyperactivity of CBTC indirect pathways.
Objectives
To substantiate the hypothesis that the PMR symptom of MDD might attribute to the hyperactivity of the ortico-basal ganglia-thalamo-cortical indirect pathway which could inhibit psychomotor performance.
Methods
We investigated the intrinsic stiato-subthalamic nucleus (STN)-thalamic functional connectivity (FC), three pivotal hubs of the indirect pathway, in 30 MDD patients with PMR (PMR group) and well matched 30 patients without PMR (NPMR group) at baseline, and 11 patients of each group at follow-up who remitted after antidepressant treatment.
Results
The results showed increased STN-striatum FC of PMR group at baseline and no more discrepancy at follow-up, and significant correlation between PMR severity and thalamo-STN FC.
Conclusions
Our findings suggested the increased STN- striatum FC should be considered as a state biomarker to distinguish MDD patients with PMR from patients without PMR at acute period, and thalamo-STN FC could be identified as the predictor of the PMR severity for MDD patients.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Emerging evidences indicate that the alteration of interhemispheric functional coordination may be involved in the pathogenesis of major depressive disorder (MDD). In present study, we aim to explore the potential marker by using the voxel-mirrored homotopic connectivity (VMHC) approach, which may be contributing to predict the clinical prognosis in MDD.
Methods
Eighty-two MDD patients and 50 normal control (NC) subjects participated in this study. We divided the MDD group into unremitted and remitted group according to the reduction rate of Hamilton Rating Scale for Depression (HAMD) within 2 weeks.
Results
The study detected significantly decreased VMHC in bilateral precuneus (pCu), inferior temporal gyrus (ITG) and increased VMHC in middle frontal gyrus (MFG) and caudate nucleus when compared remitted depression (RD) group to unremitted depression (URD) group. Meanwhile, when compared with NC group, the URD group presented reduced VMHC in bilateral cerebellum anterior lobe, thalamus and postcentral gyrus. Furthermore, the VHMC in media frontal gyrus, postcentral gyrus and precentral gyrus were significantly decreased in RD group. Correlation analysis suggested that reduced VMHC in bilateral pCu was negatively correlated with the baseline HAMD score of URD (r = −0.325, P = 0.041). Receiver operating characteristic (ROC) curve indicated that three regional VMHC changes could identify depressed patient with poorer treatment response: ITG [area under curve (AUC) = 0.699, P = 0.002, 95% CI = 0.586–0.812], MFG (AUC = 0.692, P = 0.003, 95% CI = 0.580–0.805), pCu (AUC = 0.714, P = 0.001, 95% CI = 0.603–0.825).
Conclusion
The current study combined with previous evidence indicates that the subdued intrinsic interhemispheric functional connectivity might represents a novel neural trait involved in the pathophysiology of MDD.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Several lines of evidence implicate dopamine is involved in the psychomotor retardation (PMR) in major depressive disorder (MDD). Besides, abnormal cerebral blood flow (CBF) of PMR was also found in the cortico-basal ganglia-thalamo-cortical (CBTC) circuitry. We hypothesize that the polymorphisms of the dopaminergic pathway should be associated the abnormal CBF in the CBTC circuitry.
Objective
To investigate the association of the polymorphisms throughout the dopaminergic pathway with the cerebral blood flow (CBF) of PMR in MDD.
Methods
The blood sample of 63 patients (23 PMR, 40 NPMR) were collected for genotyping the dopaminergic polymorphisms (92 SNPs from10 genes). After quality controlling, 15 SNPs in 8 candidate genes were entered into the mass univariate modeling analysis. For the statistical analysis, patients with unqualified fMRI image and unmatched demographic data were ruled out. Consequently 56 patients (23 PMR, 33 NPMR) were taken into the statistical analysis.
Results
Genotype-by PMR associations with the CBF differences predominately distributed in bilateral prefrontal cortex (PFC), temporal cortex, and striatum, the left thalamus, the right primary motor cortex, insular cortex, fusiform gyri, and lingual gyri. There were significant negative correlation between the CBF of the PFC and the PMR severity. However, the CBF of the striatum and the thalamus were positively correlated with the PMR severity.
Conclusions
The polymorphisms of dopaminergic pathway are associated with not only CSTC circuitry, but also some other brain regions involving in cognition and emotion controlling. While the increased CBF of PFC might suppress PMR, the increased CBF of striatum and thalamus adversely aggravate PMR.
The small intestine is an important digestive organ and plays a vital role in the life of a pig. We tested the hypothesis that the length of the small intestine is related to growth performance and intestinal functions of piglets. A total of 60 piglets (Duroc × Landrace × Yorkshire), weaned at day 21, were fed an identical diet during a 28-day trial. At the end of the study, all piglets were sacrificed, dissected and grouped according to small intestine lengths (SILs), either short small intestine (SSI), middle small intestine (MSI) or long small intestine (LSI), respectively. Positive relationships between SIL and BW, average daily gain (ADG), average daily feed intake (ADFI) and gain-to-feed ratios (G : F) were observed. Final BW, ADG, ADFI and G : F significantly increased (P < 0.05) in MSI and LSI piglets compared with SSI piglets. Short small intestine and MSI had greater jejunal mucosa sucrase and alkaline phosphatase activities (P < 0.05) than LSI piglets. The mRNA level of solute carrier family 2 member 2 (Slc2a2) in the jejunal mucosa of SSI piglets was the greatest. The MSI piglets had a greater (P < 0.05) ileal villus height than other piglets and greater (P < 0.05) villus height-to-crypt depth ratios than LSI piglets. However, the LSI piglets had a greater (P < 0.05) ileal crypt depth than SSI piglets. No significant differences in duodenal, jejunal, caecal and colonic morphologies were detected among the groups. Moreover, luminal acetate, propionate, butyrate and total short-chain fatty acid contents were greater (P < 0.05) in SSI and MSI piglets than those in LSI piglets. In addition, there was greater serum glucose concentration in MSI piglets than other piglets. Serum albumin concentration in SSI piglets was the lowest. In conclusion, these results indicate that SIL was significantly positively associated with growth performance, and in terms of intestinal morphology and mucosal digestive enzyme activity, the piglets with a medium length of small intestine have better digestion and absorption properties.
Small intestinal epithelium homeostasis involves four principal cell types: enterocytes, goblet, enteroendocrine and Paneth cells. Epidermal growth factor (EGF) has been shown to affect enterocyte differentiation. This study determined the effect of dietary EGF on goblet, enteroendocrine and Paneth cell differentiation in piglet small intestine and potential mechanisms. Forty-two weaned piglets were used in a 2 × 3 factorial design; the major factors were time post-weaning (days 7 and 14) and dietary treatment (0, 200 or 400 µg/kg EGF supplementation). The numbers of goblet and enteroendocrine cells were generally greater with the increase in time post-weaning. Moreover, the supplementation of 200 µg/kg EGF increased (P < 0.01) the number of goblet and enteroendocrine cells in villus and crypt of the piglet small intestine as compared with the control. Dietary supplementation with 200 µg/kg EGF enhanced (P < 0.05) abundances of differentiation-related genes atonal homologue 1, mucin 2 and intestinal trefoil factor 3 messenger RNA (mRNA) as compared with the control. Piglets fed 200 or 400 µg/kg EGF diet had increased (P < 0.05) abundances of growth factor-independent 1, SAM pointed domain containing ETS transcription factor and pancreatic and duodenal homeobox 1 mRNA, but decreased the abundance (P < 0.01) of E74 like ETS transcription factor 3 mRNA as compared with the control. Animals receiving 400 µg/kg EGF diets had enhanced (P < 0.05) abundances of neurogenin3 and SRY-box containing gene 9 mRNA as compared with the control. The mRNA abundance and protein expression of lysozyme, a marker of Paneth cell, were also increased (P < 0.05) in those animals. As compared with the control, dietary supplementation with 200 µg/kg EGF increased the abundance of EGF receptor mRNA and the ratio of non-phospho(p)-β-catenin/β-catenin (P < 0.05) in villus epithelial cells at days 7 and 14. This ratio in crypt epithelial cells was higher (P < 0.05) on the both 200 and 400 µg/kg EGF groups during the same period. Our results demonstrated that dietary EGF stimulated goblet, enteroendocrine and Paneth cell differentiation in piglets during the post-weaning period, partly through EGFR and Wnt/β-catenin signalling.
Consumption of sugar-sweetened beverages (SSB) by infants and young children are less explored in Asian populations. The Growing Up in Singapore Towards healthy Outcomes cohort study examined associations between SSB intake at 18 months and 5 years of age, with adiposity measures at 6 years of age. We studied Singaporean infants/children with SSB intake assessed by FFQ at 18 months of age (n 555) and 5 years of age (n 767). The median for SSB intakes is 28 (interquartile range 5·5–98) ml at 18 months of age and 111 (interquartile range 57–198) ml at 5 years of age. Association between SSB intake (100 ml/d increments and tertile categories) and adiposity measures (BMI standard deviation scores (sd units), sum of skinfolds (SSF)) and overweight/obesity status were examined using multivariable linear and Poisson regression models, respectively. After adjusting for confounders and additionally for energy intake, SSB intake at age 18 months were not significantly associated with later adiposity measures and overweight/obesity outcomes. In contrast, at age 5 years, SSB intake when modelled as 100 ml/d increments were associated with higher BMI by 0·09 (95 % CI 0·02, 0·16) sd units, higher SSF thickness by 0·68 (95 % CI 0·06, 1·44) mm and increased risk of overweight/obesity by 1·2 (95 % CI 1·07, 1·23) times at age 6 years. Trends were consistent with SSB intake modelled as categorical tertiles. In summary, SSB intake in young childhood is associated with higher risks of adiposity and overweight/obesity. Public health policies working to reduce SSB consumption need to focus on prevention programmes targeted at young children.
The gut is composed of a single layer of intestinal epithelial cells and plays important roles in the digestion and absorption of nutrients, immune and barrier functions and amino acid metabolism. Weaning stress impairs piglet intestinal epithelium structural and functional integrities, which results in reduced feed intake, growth rates and increased morbidity and mortality. Several measures are needed to maintain swine gut development and growth performance after weaning stress. A large body of evidence indicates that, in weaning piglets, glutamine, a functional amino acid, may improve growth performance and intestinal morphology, reduce oxidative damage, stimulate enterocyte proliferation, modulate cell survival and death and enhance intestinal paracellular permeability. This review focuses on the effects of glutamine on intestinal health in piglets. The aim is to provide evidentiary support for using glutamine as a feed additive to alleviate weaning stress.
Feeding ruminants a high-grain (HG) diet is a widely used strategy to improve milk yield and cost efficiency. However, it may cause certain metabolic disorders. At present, information about the effects of HG diets on the systemic metabolic profile of goats and the correlation of such diets with rumen bacteria is limited. In the present study, goats were randomly divided into two groups: one was fed the hay diet (hay; n = 5), while the other was fed HG diets (HG; n = 5). On day 50, samples of rumen contents, peripheral blood serum and liver tissues were collected to determine the metabolic profiles in the rumen fluid, liver and serum and the microbial composition in rumen. The results revealed that HG diets reduced (P < 0.05) the community richness and diversity of rumen microbiota, with an increase in the Chao 1 and Shannon index and a decrease in the Simpson index. HG diets also altered the composition of rumen microbiota, with 30 genera affected (P < 0.05). Data on the metabolome showed that the metabolites in the rumen fluid, liver and serum were affected (variable importance projection > 1, P <0.05) by dietary treatment, with 47, 10 and 27 metabolites identified as differentially metabolites. Pathway analysis showed that the common metabolites in the shared key pathway (aminoacyl-transfer RNA biosynthesis) in the rumen fluid, liver and serum were glycine, lysine and valine. These findings suggested that HG diets changed the composition of the rumen microbiota and metabolites in the rumen fluid, liver and serum, mainly involved in amino acid metabolism. Our findings provide new insights into the understanding of diet-related systemic metabolism and the effects of HG diets on the overall health of goats.
A new generation of high power laser facilities will provide laser pulses with extremely high powers of 10 petawatt (PW) and even 100 PW, capable of reaching intensities of
$10^{23}~\text{W}/\text{cm}^{2}$
in the laser focus. These ultra-high intensities are nevertheless lower than the Schwinger intensity
$I_{S}=2.3\times 10^{29}~\text{W}/\text{cm}^{2}$
at which the theory of quantum electrodynamics (QED) predicts that a large part of the energy of the laser photons will be transformed to hard Gamma-ray photons and even to matter, via electron–positron pair production. To enable the investigation of this physics at the intensities achievable with the next generation of high power laser facilities, an approach involving the interaction of two colliding PW laser pulses is being adopted. Theoretical simulations predict strong QED effects with colliding laser pulses of
${\geqslant}10~\text{PW}$
focused to intensities
${\geqslant}10^{22}~\text{W}/\text{cm}^{2}$
.
Nitrogen (N) application and irrigation to winter wheat may decrease leaf temperature and enhance photosynthesis: as a result, more photosynthates will be allocated to the grains, resulting in higher grain yields. To investigate this hypothesis, a 2-year field study was conducted with three levels of N fertilizer application (no fertilizer, N0; 240 kg N/ha, N1; 360 kg N/ha, N2) and two different water regimes (rainfed with no irrigation, R; irrigation at the over-wintering, stem elongation and grain filling stages, W). The results show that both N application and supplemental irrigation significantly increased grain yield with increases in both grain number/m2 and the 1000-grain weight, viz., WN2>WN1>WN0>RN2>RN1>RN0. In addition, application of N under both water regimes significantly increased flag leaf area, above-ground biomass and single stem productivity and decreased leaf temperature, which led to an increase in net photosynthesis rates and ribulose bisphosphate (RuBP) carboxylase activity. Moreover, analysis of the chlorophyll α fluorescence transient showed that N fertilizer application and supplemental irrigation significantly increased electron donor and acceptor performance of the photosystem II reaction centre.
Iron-deficiency anemia is a public health concern that frequently occurs in pregnant mammals and neonatal offspring. Ferrous N-carbamylglycinate chelate (Fe-CGly) is a newly designed iron fortifier with proven effects in iron-deficient rats and weanling piglets. However, the effects of this new compound on pregnant mammals are unknown. Therefore, this experiment was conducted to evaluate the effects of Fe-CGly on sow reproductive performance and iron status of both sows and neonatal piglets. A total of 40 large-white sows after second parity were randomly assigned to two groups (n=20). They were receiving a diet including 80 mg Fe/kg as FeSO4 or Fe-CGly, respectively, from day 85 of gestation to parturition. The serum (day 110 of pregnancy) and placentas of sows were sampled. Litter size, mean weight of live born piglets, birth (live) litter weight, number of live born piglets, and the number of still-born piglets, mummies, and weak-born piglets were recorded. Once delivered, eight litters were randomly selected from the 20 litters per treatment, and one new-born male piglet (1.503±0.142 kg) from each selected litter was slaughtered within 3 h after birth from the selected litters, without colostrum ingestion. The serum, longissimus muscle, liver and kidneys of the piglets were collected. The iron status of the serum samples and the messenger RNA level of iron-related genes in the placenta, liver and kidney were analyzed. The results showed that litter weight of live born piglets was higher (P=0.030) in the Fe-CGly group (19.86 kg) than in the FeSO4 group (17.34 kg). Fe-CGly significantly increased placental iron concentration (P<0.05) of sows. It also significantly increased iron saturation and reduced the total iron-binding capacity of piglets (P<0.05) at birth. However, the results revealed that supplementation of Fe-CGly in sows reduced liver and kidney iron concentration of neonatal piglets (P<0.05), indicating decreased iron storage. In addition, the concentration of iron in the colostrum was not significantly changed. Therefore, the present results suggested that replacement of maternal FeSO4 supplement with Fe-CGly in the late-gestating period for sows could improve litter birth weight, probably via enhanced iron transportation in the placenta.
Fruit flies in the genus Bactrocera are global, economically important pests of agricultural food crops. However, basic life history information about these pests, which is vital for designing more effective control methods, is currently lacking. Artificial diets can be used as a suitable replacement for natural host plants for rearing fruit flies under laboratory conditions, and this study reports on the two-sex life-table parameters of four Bactrocera species (Bactrocera correcta, Bactrocera dorsalis, Bactrocera cucurbitae, and Bactrocera tau) reared on a semi-artificial diet comprising corn flour, banana, sodium benzoate, yeast, sucrose, winding paper, hydrochloric acid and water. The results indicated that the larval development period of B. correcta (6.81 ± 0.65 days) was significantly longer than those of the other species. The fecundity of B. dorsalis (593.60 eggs female−1) was highest among the four species. There were no differences in intrinsic rate of increase (r) and finite rate of increase (λ) among the four species. The gross reproductive rate (GRR) and net reproductive rate (R0) of B. dorsalis were higher than those of the other species, and the mean generation time (T) of B. cucurbitae (42.08 ± 1.21 h) was longer than that of the other species. We conclude that the semi-artificial diet was most suitable for rearing B. dorsalis, due to its shorter development time and higher fecundity. These results will be useful for future studies of fruit fly management.
Retreatment of tuberculosis (TB) often fails in China, yet the risk factors associated with the failure remain unclear. To identify risk factors for the treatment failure of retreated pulmonary tuberculosis (PTB) patients, we analyzed the data of 395 retreated PTB patients who received retreatment between July 2009 and July 2011 in China. PTB patients were categorized into ‘success’ and ‘failure’ groups by their treatment outcome. Univariable and multivariable logistic regression were used to evaluate the association between treatment outcome and socio-demographic as well as clinical factors. We also created an optimized risk score model to evaluate the predictive values of these risk factors on treatment failure. Of 395 patients, 99 (25·1%) were diagnosed as retreatment failure. Our results showed that risk factors associated with treatment failure included drug resistance, low education level, low body mass index (<18·5), long duration of previous treatment (>6 months), standard treatment regimen, retreatment type, positive culture result after 2 months of treatment, and the place where the first medicine was taken. An Optimized Framingham risk model was then used to calculate the risk scores of these factors. Place where first medicine was taken (temporary living places) received a score of 6, which was highest among all the factors. The predicted probability of treatment failure increases as risk score increases. Ten out of 359 patients had a risk score >9, which corresponded to an estimated probability of treatment failure >70%. In conclusion, we have identified multiple clinical and socio-demographic factors that are associated with treatment failure of retreated PTB patients. We also created an optimized risk score model that was effective in predicting the retreatment failure. These results provide novel insights for the prognosis and improvement of treatment for retreated PTB patients.