Sleep is an instinctive behavior alternating awakening state, sleep entails many active processes occurring at the cellular, circuit and organismal levels. The function of sleep is to restore cellular energy, enhance immunity, promote growth and development, consolidate learning and memory to ensure normal life activities. However, with the increasing of social pressure involved in work and life, the incidence of sleep disorders (SD) is increasing year by year. In the short term, sleep disorders lead to impaired memory and attention; in the longer term, it produces neurological dysfunction or even death. There are many ways to directly or indirectly contribute to sleep disorder and keep the hormones, including pharmacological alternative treatments, light therapy and stimulus control therapy. Exercise is also an effective and healthy therapeutic strategy for improving sleep. The intensities, time periods, and different types of exercise have different health benefits for sleep, which can be found through indicators such as sleep quality, sleep efficiency and total sleep time. So it is more and more important to analyze the mechanism and find effective regulation targets during sleep disorder through exercise. Dopamine (DA) is an important neurotransmitter in the nervous system, which not only participates in action initiation, movement regulation and emotion regulation, but also plays a key role in the steady-state remodeling of sleep-awakening state transition. Appreciable evidence shows that sleep disorder on humans and rodents evokes anomalies in the dopaminergic signaling, which are also implicated in the development of psychiatric illnesses such as schizophrenia or substance abuse. Experiments have shown that DA in different neural pathways plays different regulatory roles in sleep behavior, we found that increasing evidence from rodent studies revealed a role for ventral tegmental area DA neurons in regulating sleep-wake patterns. DA signal transduction and neurotransmitter release patterns have complex interactions with behavioral regulation. In addition, experiments have shown that exercise causes changes in DA homeostasis in the brain, which may regulate sleep through different mechanisms, including cAMP response element binding protein signal transduction, changes in the circadian rhythm of biological clock genes, and interactions with endogenous substances such as adenosine, which affect neuronal structure and play a neuroprotective role. This review aims to introduce the regulatory effects of exercise on sleep disorder, especially the regulatory mechanism of DA in this process. The analysis of intracerebral DA signals also requires support from neurophysiological and chemical techniques. Our laboratory has established and developed an in vivo brain neurochemical analysis platform, which provides support for future research on the regulation of sleep-wake cycles by movement. We hope it can provide theoretical reference for the formulation of exercise prescription for clinical sleep disorder and give some advice to the combined intervention of drugs and exercise.

Purpose To explore the clinical and pathological features,differential diagnosis,treatment methods and prognosis of urachal adenocarcinoma.Methods Nineteen cases of urachal adenocarcinoma were collected and an-alyzed by combining clinical symptoms,auxiliary examinations,histology,immunohistochemical,and genetic testing and 11 cases of bladder adenocarcinomas.Results Among the 19 patients(15 males,4 females;age range:33-75 years,mean:55 years),tumors were located at the dome or anterior wall of the bladder.Histological subtypes includ-ed mucinous adenocarcinoma(6 cases),adenocarcinoma not otherwise specified(4 cases),enteric-type adenocarci-noma(6 cases),adenocarcinoma with focal mucinous differentiation(1 case),adenocarcinoma with signet-ring cell carcinoma(1 case),and metastatic urachal adenocarcinoma(1 case).Immunophenotypic analysis revealed membra-nous positivity for β-catenin,diffuse positivity for CK34βE 12,MUC-2,and CK20,focal CK7 positivity in some cases,and rare GATA-3 positivity.Mutations in p53 were observed,while KRAS,NRAS,BRAF,and PIK3CA mutations were absent.In colorectal adenocarcinomas,CK34βE12 positivity was 40％,nuclear β-catenin positivity was 48％,and MUC-2 expression was approximately 50％.In bladder adenocarcinomas,GATA-3 and MUC-2 positivity rates were 45％and 63.6％,respectively.Conclusion Distinguishing urachal adenocarcinoma from colorectal and primary bladder adenocarcinomas remains challenging.Urachal adenocarcinoma should be suspected in patients with anterior bladder wall or dome lesions,gross hematuria,or mucinuria.No definitive diagnostic markers currently exist for ura-chal adenocarcinoma.Immunophenotypic features such as membranous β-catenin,MUC-2,and CK7 positivity may fa-vor urachal adenocarcinoma over colorectal adenocarcinoma.Additional markers(e.g.,GATA-3,CK20,CK34βE12)aid in differential diagnosis,though individual markers lack specificity.Comprehensive evaluation integrating clinical presentation,imaging,and clinicopathological features is essential for accurate diagnosis.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

Objective:To investigate the effects of dagliprazin combined with olmesartan ester on the expression of Plin and miR-26a in renal tissues of diabetic nephropathy rats.Methods:Sixty male SD rats were selected and fed adaptively for 1 week, then fed high-fat and high-sugar diet for 2 months, and then injected streptozotocin (STZ) 30 mg/kg for modeling. They were given 10 mg/kg daaglizin intragastric administration as daglizin group, 10 mg/kg olmesartan ester intragastric administration as olmesartan ester group, 5 mg/kg daaglizin and 5 mg/kg olmesartan ester intragastric administration as daglizin and olmesartan ester combination group, respectively. Twenty rats were given 10 mg/kg normal saline intragastric administration as normal control group. After 3 months, the serum samples of rats were taken to detect the levels of fasting blood glucose, blood creatinine, urea nitrogen, 24h urinary microalbumin and other renal function indicators and the levels of C-reactive protein (CRP), tumor necrosis factor (TNF-α), cell surface specific marker antigen (ED-1) and other inflammatory responses. Then the rats were killed and their kidney tissues were taken. The protein and gene expression of vascular endothelial growth factor (VEGF), perilipin (Plin), Nephlrin, miR-26a were detected by Western blot and real-time fluorescence quantitative PCR.Results:The levels of fasting blood glucose, urea nitrogen, creatinine and 24h urinary microalbumin in dagliprazin group, olmesartan ester group and combined group were higher than those in normal control group ( P<0.05), while the levels of fasting blood glucose, urea nitrogen, creatinine and 24h urinary microalbumin in combined group were lower than those in dagliprazin group and olmesartan ester group ( P<0.05). The difference between groups was statistically significant ( P<0.05). The levels of serum CRP, TNF-αand ED-1 in dagliprazin group, olmesartan ester group and combined group were higher than those in normal control group ( P<0.05), while the levels of CRP, TNF-αand ED-1 in combined group were lower than those in dagliprazin group and olmesartan ester group ( P<0.05), and the differences between groups were statistically significant ( P<0.05). The expression of serum VEGF, Plin and Nephlrin protein in dagliprazin group, olmesartan ester group and combined group were lower than those in normal control group ( P<0.05), while the protein and gene of Plin and Nephlrin in combined group were lower than those in dagliprazin group and olmesartan ester group. The mRNA and protein expressions of miR-26a and VEGF were higher than those of Daglipzin group and olmesartan ester group ( P<0.05), and the differences between groups were statistically significant ( P<0.05) . Conclusion:Dagliprazin combined with olmesartan ester can reduce kidney injury and delay the progression of diabetic nephropathy by regulating the expression of Plin and miR-26a protein and gene in renal tissue of diabetic nephropathy rats.

Objective To construct and validate a predictive model for gastric precancerous le-sions based on urea breath test,serum pepsinogen(PG)and gastrin-17(G-17).Methods Partici-pants who underwent endoscopic screening for upper gastrointestinal tumors were retrospectively en-rolled as study subjects.Using random function,all participants were divided into training cohort of 2,788 cases(comprising 1,290 cases in precancerous lesion group and 1,498 cases in control group)and validation cohort of 1,194 cases(comprising 581 cases in precancerous lesion group and 613 cases in control group)at a ratio of 7 to 3.A simple model was established based on urea breath test,PG and G-17.Clinical data between the precancerous lesion group and the control group in the training cohort were compared.A predictive model for gastric precancerous lesions was constructed u-sing multifactorial Logistic regression analysis,and a scoring model for gastric precancerous lesions(the complete model)was developed based on this predictive model.The complete model,the simple model,the new ABC method,and the Li's score were all included in the validation cohort to compare the predictive performance of the four models.Results Multifactorial Logistic regression analysis indicated that male,smoking,positive Helicobacter pylori(Hp)infection,PG Ⅱ ≥10.19 μg/L,the ratio of PG Ⅰ to PG Ⅱ(PGR)≤11.87,and G-17 ≥3.82 pmol/L were independent risk factors for gastric precancerous lesions(P＜0.05).A predictive model for gastric precancerous lesions was constructed based on these risk factors,and the complete model was established based on the predic-tive model.The total score ranged from 0 to 12(with 6 to 12 indicating a high-risk population for gastric precancerous lesions and 0 to 5 indicating a low-risk population).When the complete model,the simple model,the new ABC method,and the Li's score were included in the validation cohort for comparison,the predictive values of the complete model and the simple model were similar.Both models demonstrated higher sensitivity,specificity,positive predictive value,negative predictive value,and accuracy compared to the new ABC method and the Li's score.Furthermore,the diag-nostic value of the simple model in the high-sensitivity region was slightly superior to that of the com-plete model.Conclusion The simple model constructed based on the urea breath test,PG and G-17 exhibits favorable predictive efficacy,calibration,and clinical utility,and is of positive signifi-cance for the early identification of patients with gastric precancerous lesions.

Objective To observe the value of portal venous phase CT radiomics model based on machine learning(ML)for predicting postoperative complications of hepatic alveolar echinococcosis(HAE).Methods Totally 265 HAE patients were retrospectively enrolled and randomly divided into training set(n=185,including 106 cases with postoperative complications)and validation set(n=80,including 40 cases with postoperative complications)at a ratio of 7∶3.Based on portal venous phase CT images,HAE lesions were segmented,and radiomics features were extracted and screened.Totally 5 ML algorithms were used to construct models,and their performance for predicting postoperative complications were compared.Results Among 5 ML radiomics models,support vector machine(SVM)model had the best overall performance for predicting postoperative complications of HAE in both training and validation sets.DeLong test showed that in training set,the area under the curve(AUC)of SVM model was significantly higher than that of logistic regression(LR),K-nearest neighbor(KNN)and multilayer perceptron(MLP)models(all P＜0.001),while in validation set,the AUC of SVM model was significantly higher than that of adaptive boosting(AdaBoost)model(P=0.007).Decision curve analysis indicated that SVM model had the highest clinical net benefit.Conclusion Portal venous phase CT radiomics model based on ML algorithms,especially SVM algorithm,could effectively predict postoperative complications of HAE.

Objective:To formulate the audit standards of Chinese patent medicine prescriptions, and provide reference for rational prescriptions of Chinese patent medicine.Methods:A three-level evidence system for prescription review of Chinese patent medicine was established according to the national regulatory documents, drug labels, relevant guidelines, and expert consensuses. The catalog of Chinese patent medicines in Army Medical Center of the People′s Liberation Army was integrated and classified, preliminary review criteria including indications, drug selection, usage and dosage, and combination drugs was established and submitted to clinical experts of traditional Chinese medicine for review and revision, and finally the prescription review standard was confirmed.Results:The Chinese patent medicine catalog of the Medical Center contained 218 drugs, which were divided into 23 kinds according to efficacy and 17 kinds according to dosage forms. The prescription review standards of Chinese patent medicine were as follows. (1) Indications: both traditional Chinese medicine and Western medicine diagnosis were required. (2) Drug selection: 37 kinds of Chinese patent medicines were marked as forbidden for pregnant women in the labels, and 16 kinds were not marked but contained forbidden ingredients; 4 kinds were marked with caution for patients with liver dysfunction, and 24 kinds were not marked but contained ingredients with caution; 2 kinds of Chinese patent medicines were marked with caution for patients with renal insufficiency, and 9 kinds were not marked but contained ingredients with caution. (3) Usage and dosage: the usage and dosage rules of Chinese patent medicines for children, the elderly and patients with liver and kidney dysfunction were formulated. (4) Combined medication: 5 and 21 kinds of Chinese patent medicines were marked as "highly toxic" and "toxic" in the labels, respectively, 11 kinds of Chinese patent medicines contained incompatible ingredients of "Shibafan" (eighteen antagonisms) and "Shijiuwei (nineteen incompatibilities), and a new review scale for repeated use of Chinese patent medicine was developed.Conclusions:Based on the existing evidence-based medicine, the evidence system of prescription review of Chinese patent medicine is established, the prescription review standards of Chinese patent medicine prescription based on the pharmaceutical interaction mode is formulated and constructed.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

Objective:To investigate the effects of dagliprazin combined with olmesartan ester on the expression of Plin and miR-26a in renal tissues of diabetic nephropathy rats.Methods:Sixty male SD rats were selected and fed adaptively for 1 week, then fed high-fat and high-sugar diet for 2 months, and then injected streptozotocin (STZ) 30 mg/kg for modeling. They were given 10 mg/kg daaglizin intragastric administration as daglizin group, 10 mg/kg olmesartan ester intragastric administration as olmesartan ester group, 5 mg/kg daaglizin and 5 mg/kg olmesartan ester intragastric administration as daglizin and olmesartan ester combination group, respectively. Twenty rats were given 10 mg/kg normal saline intragastric administration as normal control group. After 3 months, the serum samples of rats were taken to detect the levels of fasting blood glucose, blood creatinine, urea nitrogen, 24h urinary microalbumin and other renal function indicators and the levels of C-reactive protein (CRP), tumor necrosis factor (TNF-α), cell surface specific marker antigen (ED-1) and other inflammatory responses. Then the rats were killed and their kidney tissues were taken. The protein and gene expression of vascular endothelial growth factor (VEGF), perilipin (Plin), Nephlrin, miR-26a were detected by Western blot and real-time fluorescence quantitative PCR.Results:The levels of fasting blood glucose, urea nitrogen, creatinine and 24h urinary microalbumin in dagliprazin group, olmesartan ester group and combined group were higher than those in normal control group ( P<0.05), while the levels of fasting blood glucose, urea nitrogen, creatinine and 24h urinary microalbumin in combined group were lower than those in dagliprazin group and olmesartan ester group ( P<0.05). The difference between groups was statistically significant ( P<0.05). The levels of serum CRP, TNF-αand ED-1 in dagliprazin group, olmesartan ester group and combined group were higher than those in normal control group ( P<0.05), while the levels of CRP, TNF-αand ED-1 in combined group were lower than those in dagliprazin group and olmesartan ester group ( P<0.05), and the differences between groups were statistically significant ( P<0.05). The expression of serum VEGF, Plin and Nephlrin protein in dagliprazin group, olmesartan ester group and combined group were lower than those in normal control group ( P<0.05), while the protein and gene of Plin and Nephlrin in combined group were lower than those in dagliprazin group and olmesartan ester group. The mRNA and protein expressions of miR-26a and VEGF were higher than those of Daglipzin group and olmesartan ester group ( P<0.05), and the differences between groups were statistically significant ( P<0.05) . Conclusion:Dagliprazin combined with olmesartan ester can reduce kidney injury and delay the progression of diabetic nephropathy by regulating the expression of Plin and miR-26a protein and gene in renal tissue of diabetic nephropathy rats.