BACKGROUND:Hypoxic exercise can promote the degradation of body fat,and changes in the external environment can affect the circadian rhythm of animals,but the mechanisms by which changes in circadian rhythm regulate adipose tissue browning and fat degradation are unclear. OBJECTIVE:To elucidate the mechanism of clock gene regulation on epididymal adipose tissue Browning in obese rats undergoing hypoxia exercise. METHODS:Forty obese rats were randomly selected and divided into four groups(n=10 per group):normoxic sedentary group,hypoxic sedentary group,normoxic exercise group,and hypoxic exercise group for 4 weeks of intervention.The rats in the sedentary groups were not intervened,while those in the hypoxic groups lived in a hypoxic chamber with an oxygen concentration of 13.6%for the whole day.In the exercise groups,adaptive training was performed in the 1st week,and the speed and length of training remained unchanged for the last 3 weeks.The body mass,body length and perirenal fat mass of obese rats were measured.Serum levels of triacylglycerol,total cholesterol,low-density lipoprotein cholesterol,and high-density lipoprotein cholesterol in obese rats were detected by a biochemical assay kit.Liver fat content was observed by oil red O staining.Hematoxylin-eosin staining was used to evaluate the browning of epididymal adipose tissue of rats in different groups.RNA sequencing combined with bioinformatics analysis was used to analyze transcriptome changes in adipose tissue.The mRNA expressions of PGC-1α,Beclin 1,KLF 2 and Perilipin 1 in epididymal adipose tissue were detected by RT-PCR. RESULTS AND CONCLUSION:Hypoxic exercise intervention significantly decreased body mass,body fat percentage,Lee's index,serum triacylglycerol,total cholesterol,and low-density lipoprotein cholesterol levels(P＜0.01),and significantly increased high-density lipoprotein cholesterol level(P＜0.01).Oil red O staining and hematoxylin-eosin staining results showed that hypoxic exercise was more effective in promoting fat mobilization in liver tissue and promoting the browning of parepididymal adipose tissue compared with normoxic sedentary group,hypoxic sedentary group,and normoxic exercise group.RNA-seq results showed that hypoxic exercise significantly upregulated the expression of clock genes Dbp,Nr1d1,Sik1 and adipose tissue browning gene Ppargc1a(PGC-1α)and downregulated the expression of Arntl(Bmal1),accompanied by the enhanced expression of genes related to substance metabolism.qRT-PCR indicated that hypoxic exercise significantly increased the mRNA expression levels of PGC-1α and Perilipin1(P＜0.01).Therefore,these findings indicate that clock genes play an important role in promoting adipose tissue browning during hypoxic exercise.

Objective:To analyze the changes in service efficiency and cost structure before and after implementing multidisci-plinary treatment in the GD19(appendectomy with perforation,suppuration,gangrene,etc.)and GD29(appendectomy)groups of pedi-atric specialty medical institutions.Methods:The case data of GD19 and GD29 groups of medical insurance patients in sample hospi-tals in Beijing from 2021 to 2022 were collected.Mann Whitney U test was used to analyze the changes of medical expenses and effi-ciency indicators,and intermittent time series model was established to analyze the change trend.Results:Compared to 2021,the av-erage hospitalization expenses of GD19 group in 2022 decreased by 2 462.00 yuan year-on-year,and that of GD29 group decreased by 2 042.60 yuan year-on-year(P＜0.05).Among them,the cost of medicines,consumables,examinations and tests and treatment have all decreased.In the month when the management measures were implemented,the average consumption cost of GD19 group de-creased by 920.00 yuan(P＜0.05),and the average consumption cost of GD29 group decreased by 632.50 yuan.The average length of stay in GD29 group decreased from 3.74 days to 2.78 days(P＜0.05).Conclusion:After the implementation of management mea-sures,the cost of drug consumables in GD19 group and GD29 group was controlled,the cost level was reduced,and the operation effi-ciency was improved.It is suggested to adhere to the management measures of selection of key DRG groups and multidisciplinary con-sultation,mobilize the management enthusiasm of clinical departments,and strengthen the demonstration and optimization of pediatric DRG grouping and payment scheme.

Obesity contributes to reduced fertility, infertility and adverse maternal and infant outcomes through multiple mechanisms. Individuals with obesity encounter numerous impediments during fertility treatments and subsequent pregnancy, leading to intensified physical, psychological, and socio-economic burdens. Given the recent progress in research and the expansion of treatment modalities, there is an imperative need to refine the diagnostic and therapeutic frameworks for obese patients with infertility through a multidisciplinary approach. The Reproductive Medicine Specialized Committee of the Chinese Medical Doctor Association (CMDA) has established a multidisciplinary team of experts to develop an evidence-based guideline. This guideline's development will adhere to both national and international standards for guideline development and reporting. This proposal mainly describes the significance and purpose of guideline development, the method of evidence retrieval and quality assessment, the process of guideline development, and the plan for publication, implementation and dissemination of the guideline.

Obesity contributes to reduced fertility, infertility and adverse maternal and infant outcomes through multiple mechanisms. Individuals with obesity encounter numerous impediments during fertility treatments and subsequent pregnancy, leading to intensified physical, psychological, and socio-economic burdens. Given the recent progress in research and the expansion of treatment modalities, there is an imperative need to refine the diagnostic and therapeutic frameworks for obese patients with infertility through a multidisciplinary approach. The Reproductive Medicine Specialized Committee of the Chinese Medical Doctor Association (CMDA) has established a multidisciplinary team of experts to develop an evidence-based guideline. This guideline's development will adhere to both national and international standards for guideline development and reporting. This proposal mainly describes the significance and purpose of guideline development, the method of evidence retrieval and quality assessment, the process of guideline development, and the plan for publication, implementation and dissemination of the guideline.

Objective:To evaluate the efficacy and safety of domestic recombinant human follicle-stimulating hormone (rhFSH) in assisted reproductive technology (ART) of controlled ovarian hyperstimulation (COH).Methods:In a multicenter, randomized, double-blind, positive, parallel controlled non-inferiority clinical trial, the infertile women with normal ovarian reserve who received ART-COH in six reproductive medical centers from July 2017 to June 2019 were randomly divided into two groups: experimental group (domestic rhFSH, n=134) and control group (imported rhFSH, n=133). Eight subjects were excluded due to various reasons during the experimental process, 7 in experimental group and 1 in control group. At last, 127 subjects in experimental group and 132 subjects in control group complete the experiment following the research protocol. The total number of oocytes, usage of FSH, fertilization rate of oocytes, the number of high-quality embryos, clinical pregnancy rate, live birth rate, neonatal characteristics and the incidence of adverse reactions were compared between the two groups during the cycle of COH. Results:During the initiation cycle of ovulation induction therapy, the total number of oocytes obtained in experimental group and control group were 13.0±5.8 and 12.9±5.7, respectively, with no statistically significant difference ( P>0.05). Among the 82 intracytoplasmic sperm injection (ICSI) patients, the number of M II oocytes obtained in experimental group (39 cases) was markedly higher than that in control group (43 cases) (9.9±3.9 vs. 7.5±3.0, P=0.003). The fertilization rate of oocytes in experimental group was obviously higher than that in control group [63.82% (1048/1642) vs. 56.19% (958/1705), P<0.001]. There were no significant differences of stimulated duration and dosage of rhFSH, number of high-quality embryos, clinical pregnancy rate, preterm rate, live birth rate, incidence of neonatal abnormalities, neonatal weight or Apgar score between the two groups (all P>0.05). The incidence of ovarian hyperstimulation syndrome and other adverse reactions in treatment period were not significantly different between the two groups (all P>0.05), which were known adverse reaction occurred in the imported rhFSH. Conclusion:The efficacy and safety of domestic rhFSH were the same as that of imported rhFSH in infertile patients with normal ovarian reserve under the same ovarian stimulation regimen.

Objective:To evaluate the efficacy and safety of domestic recombinant human follicle-stimulating hormone (rhFSH) in assisted reproductive technology (ART) of controlled ovarian hyperstimulation (COH).Methods:In a multicenter, randomized, double-blind, positive, parallel controlled non-inferiority clinical trial, the infertile women with normal ovarian reserve who received ART-COH in six reproductive medical centers from July 2017 to June 2019 were randomly divided into two groups: experimental group (domestic rhFSH, n=134) and control group (imported rhFSH, n=133). Eight subjects were excluded due to various reasons during the experimental process, 7 in experimental group and 1 in control group. At last, 127 subjects in experimental group and 132 subjects in control group complete the experiment following the research protocol. The total number of oocytes, usage of FSH, fertilization rate of oocytes, the number of high-quality embryos, clinical pregnancy rate, live birth rate, neonatal characteristics and the incidence of adverse reactions were compared between the two groups during the cycle of COH. Results:During the initiation cycle of ovulation induction therapy, the total number of oocytes obtained in experimental group and control group were 13.0±5.8 and 12.9±5.7, respectively, with no statistically significant difference ( P>0.05). Among the 82 intracytoplasmic sperm injection (ICSI) patients, the number of M II oocytes obtained in experimental group (39 cases) was markedly higher than that in control group (43 cases) (9.9±3.9 vs. 7.5±3.0, P=0.003). The fertilization rate of oocytes in experimental group was obviously higher than that in control group [63.82% (1048/1642) vs. 56.19% (958/1705), P<0.001]. There were no significant differences of stimulated duration and dosage of rhFSH, number of high-quality embryos, clinical pregnancy rate, preterm rate, live birth rate, incidence of neonatal abnormalities, neonatal weight or Apgar score between the two groups (all P>0.05). The incidence of ovarian hyperstimulation syndrome and other adverse reactions in treatment period were not significantly different between the two groups (all P>0.05), which were known adverse reaction occurred in the imported rhFSH. Conclusion:The efficacy and safety of domestic rhFSH were the same as that of imported rhFSH in infertile patients with normal ovarian reserve under the same ovarian stimulation regimen.

OBJECTIVE: To screen new serum metabolic biomarkers for different drug resistance profiles of pulmonary tuberculosis (TB) and explore their mechanisms and functions. METHODS: We collected serum samples from TB patients with drug sensitivity (DS), monoresistance to isoniazid (MR-INH), monoresistance to rifampin (MR-RFP), multidrug resistance (MDR), and polyresistance (PR). The metabolites in the serum samples were extracted by oscillatory and deproteinization for LC-MS/MS analysis, and the results were normalized by Pareto-scaling method and analyzed using Metaboanalyst 4.0 software to identify the differential metabolites. The differential metabolites were characterized by function enrichment and co-expression analysis to explore their function and possible pathological mechanisms. RESULTS: Compared with the DS group, 286 abnormally expressed metabolites were identified in MR-INH group, 362 in MR-RPF group, 277 in MDR group and 1208 in PR group by LC-MS/MS analysis. Acetylagmatine ( < 0.05), aminopentol ( < 0.05), and tetracosanyl oleate ( < 0.05) in MR-INH group; Ala His Pro Thr ( < 0.001) and glycinoprenol-9 ( < 0.05) in MR-RFP group; trimethylamine ( < 0.05), penaresidin A ( < 0.05), and verazine ( < 0.05) in MDR group; and PIP (18:1(11Z)/ 18:3(6Z, 9Z, 12Z)) ( < 0.001), Pro Arg Trp Tyr ( < 0.001), N-methyldioctylamine ( < 0.001), and phytolaccoside E ( < 0.05) in PR group all showed significant differential expressions. Significant differential expressions of phthalic acid mono-2-ethylhexyl ester ( < 0.05) and eicosanoyl-EA ( < 0.05) were found in all the drug resistant groups as compared with DS group. CONCLUSIONS Acetylagmatine, aminopentol, tetracosanyl oleate, Ala His Pro Thr, glycinoprenol-9, trimethylamine, penaresidin A, verazine, PIP(18:1(11Z)/18:3(6Z, 9Z, 12Z)), Pro Arg Trp Tyr, N-methyldioctylamine, phytolaccoside E, phthalic acid mono-2-ethylhexyl ester, and eicosanoyl-EA are potentially new biomarkers that indicate monoresistance, multi-drug resistance and polyresistance of Mycobacterium tuberculosis. The combined use of these biomarkers potentially allows for assessment of drug resistance in TB and enhances the diagnostic sensitivity and specificity.
Biomarkers ; Chromatography, Liquid ; Humans ; Tandem Mass Spectrometry ; Tuberculosis, Multidrug-Resistant ; Tuberculosis, Pulmonary

Objective To research the performance of direct settlement for allopatry medical insurance at a tertiary specialized children′s hospital in Beijing, and to analyze the basics of these inpatients and the structural characteristics of their diseases, for basis and suggestions for improving the policy of direct settlement of allopatry medical insurance. Methods A statistical description of direct settlement data was made for allopatry medical insurance at this hospital from August 2017 to July 2018, to study the age, hometown, attribute, distribution of inpatient departments and disease distribution of these children. Results The patients mainly came upon referrals, preschool children in most cases. The average daily hospitalization cost of the disease was high relatively, and the number of hospitalizations was high as well. Compared with children inpatients in Beijing, these patients tend to come for surgical treatment for malignant tumors and congenital diseases.Conclusions The allopatry direct settlement of children′s medical insurance settlement is found mostly with diseases those are complicated and severe. The management of such settlement can be improved by cooperating with their local institutions in advance, data checking in the course, simplifying the formalities for special diseases, and the differential reimbursement ratio for these patients.

Existing arrhythmia classification methods usually use manual selection of electrocardiogram (ECG) signal features, so that the feature selection is subjective, and the feature extraction is complex, leaving the classification accuracy usually affected. Based on this situation, a new method of arrhythmia automatic classification based on discriminative deep belief networks (DDBNs) is proposed. The morphological features of heart beat signals are automatically extracted from the constructed generative restricted Boltzmann machine (GRBM), then the discriminative restricted Boltzmann machine (DRBM) with feature learning and classification ability is introduced, and arrhythmia classification is performed according to the extracted morphological features and RR interval features. In order to further improve the classification performance of DDBNs, DDBNs are converted to deep neural network (DNN) using the Softmax regression layer for supervised classification in this paper, and the network is fine-tuned by backpropagation. Finally, the Massachusetts Institute of Technology and Beth Israel Hospital Arrhythmia Database (MIT-BIH AR) is used for experimental verification. For training sets and test sets with consistent data sources, the overall classification accuracy of the method is up to 99.84% ± 0.04%. For training sets and test sets with inconsistent data sources, a small number of training sets are extended by the active learning (AL) method, and the overall classification accuracy of the method is up to 99.31% ± 0.23%. The experimental results show the effectiveness of the method in arrhythmia automatic feature extraction and classification. It provides a new solution for the automatic extraction of ECG signal features and classification for deep learning.
Arrhythmias, Cardiac ; classification ; Databases, Factual ; Electrocardiography ; Heart Rate ; Humans ; Neural Networks (Computer)

Objective To investigate the efficacy and safety of intravesical instillation with Sufuning (SFN) lotion for prevention of postoperative recurrence of bladder cancer. Methods A total of 240 bladder cancer patients who were diagnosed as bladder cancer and accepted trans-urethral resection of bladder tumor from January 2010 to June 2016 in Shanxi Provincial Cancer Hospital were randomly divided into the experimental group (120 cases) and the control group (120 cases) according to the envelope method. The patients in the experimental group were treated with SFN lotion for immediate intravesical instillation(250 mg for once), and the patients in the control group were treated with pirarubicin (THP) for immediate intravesical instillation (30 mg for once). The patients of two groups were treated with intravesical chemotherapy once a week for 8 times, and the chemotherapy was performed once a month for 1 year. The recurrence rate, progression-free survival (PFS) rate, overall survival (OS) rate and recent side effects were compared between the two groups. Results The patients were followed up for 6 to 60 months. The median follow-up time was 36.5 months.In the experimental group,6 patients were lost and 8 patients were lost in the control group.The experimental group, the total recurrence rate was 26.3 % (30/114). The control group, the overall recurrence rate was 25.0 % (28/112) (χ2= 0.142, P = 0.781). Five years of PFS rate in the experimental group and the control group was 73.7 % (84/114) and 75.0 % (84/112) respectively, and there was no significant difference between the two groups (χ2= 2.011, P= 0.615). Five years of OS rate in the experimental group and the control group was 95.6 % and 92.9 % respectively, and there was no significant difference between the two groups (χ 2= 1.611, P= 0.425). The major side effects included chemical cystitis and hematuria. The incidence of chemical cystitis and hematuria in the experimental group was significantly lower than that in the control group(χ2=5.991,P=0.018;χ2=4.925,P=0.036).There was a statistically significant difference of the hematological side effects (blood routine changes) between the two groups (χ 2= 4.891, P= 0.032). Conclusion It is safe and effective for intravesical instillation of SFN lotion to prevent the recurrence of bladder cancer.