Objective:The aim of this study was to analyze the registration status of osteoporosis drug clinical trials in China, providing a reference for the research and development of therapeutic drugs for osteoporosis.Methods:Using the Drug Clinical Trial Registration and Information Publication Platform on the website of the State Drug Administration as the search platform, we retrieved the information on the public announcement of drug clinical trials with osteoporosis as an indication, and the search period was limited from 2013 to February 2025.Researchers extracted the key information and performed statistics.Results:A total of 182 registered osteoporosis drug clinical trial projects were collected.The main target indications were predominantly osteoporosis in postmenopausal women, and there were relatively few trials targeting the elderly subjects.56.0%(102/182)of the registered trials were bioequivalence studies, and 21.4%(39/182)were phase I clinical studies.Conclusions:The number of registered trials and the research and development process of domestic osteoporosis drug clinical trials in China have shown a stable trend in general, and the types of trials are mainly concentrated in bioequivalence studies and early clinical studies.In order to further meet the medication needs of domestic patients, China still needs to increase the research and development efforts of innovative osteoporosis drugs.

Objective:The aim of this study was to analyze the registration status of osteoporosis drug clinical trials in China, providing a reference for the research and development of therapeutic drugs for osteoporosis.Methods:Using the Drug Clinical Trial Registration and Information Publication Platform on the website of the State Drug Administration as the search platform, we retrieved the information on the public announcement of drug clinical trials with osteoporosis as an indication, and the search period was limited from 2013 to February 2025.Researchers extracted the key information and performed statistics.Results:A total of 182 registered osteoporosis drug clinical trial projects were collected.The main target indications were predominantly osteoporosis in postmenopausal women, and there were relatively few trials targeting the elderly subjects.56.0%(102/182)of the registered trials were bioequivalence studies, and 21.4%(39/182)were phase I clinical studies.Conclusions:The number of registered trials and the research and development process of domestic osteoporosis drug clinical trials in China have shown a stable trend in general, and the types of trials are mainly concentrated in bioequivalence studies and early clinical studies.In order to further meet the medication needs of domestic patients, China still needs to increase the research and development efforts of innovative osteoporosis drugs.

Objective:To analyze the clinical phenotypes and genotypes of fetal Zellweger spectrum disorders (ZSD).Methods:A retrospective analysis was conducted on the clinical data of three fetuses diagnosed with ZSD and their parents, who underwent family genetic testing at the Prenatal Diagnosis Center of the Third Affiliated Hospital of Zhengzhou University (Maternal and Child Health Hospital of Henan Province) from June 2020 to December 2021. The prenatal phenotypic and genotypic characteristics were summarized in combination with previous literature. Descriptive statistical analysis was used for the data.Results:The mothers of the three fetuses were all primiparous, aged 32, 29, and 33 years, respectively. The gestational weeks at the first detection of fetal abnormalities were 23 weeks and 2 days, 24 weeks, and 33 weeks and 3 days, respectively. Case 1 only showed increased nuchal translucency, while Case 2 and 3 showed brain structural abnormalities. Chromosomal microarray analysis of the three cases did not detect any pathogenic or potentially pathogenic copy number variations. However, heterozygous deletions of unknown significance at 6q13q15 and 7q21.13q22.1 were detected in Case 1. All three fetuses were found to have pathogenic PEX1 variants, which were inherited from their parents. A novel heterozygous variant c.1 246_1247del detected in Case 3 was not previously reported in China. All three families chose to terminate the pregnancies. The mother in family 2 conceived naturally six months later, and an early pregnancy test revealed a pathogenic heterozygous variant c.892_895dup (p.N299Ifs*2) in the PEX1 gene, leading to a diagnosis of being a carrier of the pathogenic PEX1 variant. She continued the pregnancy to full term, and the newborn was followed up with good health. The remaining two families did not have any further pregnancies. Conclusions:PEX1 gene variants may predominantly characterize the mutation spectrum of ZSD. When prenatal examinations reveal fetal craniofacial malformations, brain structural abnormalities, increased nuchal translucency, or high echogenicity of the liver and kidneys, heightened vigilance and comprehensive genetic testing are warranted to reduce birth defects.

Objective:To analyze the clinical phenotypes and genotypes of fetal Zellweger spectrum disorders (ZSD).Methods:A retrospective analysis was conducted on the clinical data of three fetuses diagnosed with ZSD and their parents, who underwent family genetic testing at the Prenatal Diagnosis Center of the Third Affiliated Hospital of Zhengzhou University (Maternal and Child Health Hospital of Henan Province) from June 2020 to December 2021. The prenatal phenotypic and genotypic characteristics were summarized in combination with previous literature. Descriptive statistical analysis was used for the data.Results:The mothers of the three fetuses were all primiparous, aged 32, 29, and 33 years, respectively. The gestational weeks at the first detection of fetal abnormalities were 23 weeks and 2 days, 24 weeks, and 33 weeks and 3 days, respectively. Case 1 only showed increased nuchal translucency, while Case 2 and 3 showed brain structural abnormalities. Chromosomal microarray analysis of the three cases did not detect any pathogenic or potentially pathogenic copy number variations. However, heterozygous deletions of unknown significance at 6q13q15 and 7q21.13q22.1 were detected in Case 1. All three fetuses were found to have pathogenic PEX1 variants, which were inherited from their parents. A novel heterozygous variant c.1 246_1247del detected in Case 3 was not previously reported in China. All three families chose to terminate the pregnancies. The mother in family 2 conceived naturally six months later, and an early pregnancy test revealed a pathogenic heterozygous variant c.892_895dup (p.N299Ifs*2) in the PEX1 gene, leading to a diagnosis of being a carrier of the pathogenic PEX1 variant. She continued the pregnancy to full term, and the newborn was followed up with good health. The remaining two families did not have any further pregnancies. Conclusions:PEX1 gene variants may predominantly characterize the mutation spectrum of ZSD. When prenatal examinations reveal fetal craniofacial malformations, brain structural abnormalities, increased nuchal translucency, or high echogenicity of the liver and kidneys, heightened vigilance and comprehensive genetic testing are warranted to reduce birth defects.

ObjectiveThis study aimed to predict the pharmacodynamic material basis and core targets of Bailing capsules in the treatment of chronic obstructive pulmonary disease （COPD） based on network pharmacology and molecular docking， which were further verified by cell experiments to explore the mechanism. MethodThe main active ingredients and related targets of Bailing capsules were screened in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and SwissTargetPrediction. The main COPD targets were searched from GeneCards， DrugBank， Online Mendelian Inheritance in Man （OMIM） and Therapeutic Target Database （TTD）. The protein-protein interaction （PPI） network was constructed by STRING and Cytoscape 3.6.1. Gene Ontology （GO） function annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed by the Database for Annotation， Visualization and Integrated Discovery （DAVID）. Molecular docking verification was carried out using AutoDock Vina. The cell viability was detected by 3-（4，5-dimethylthiazol-2-yl）-5-（3-carboxymethoxyphenyl）-2-（4-sulfophenyl）-2H-tetrazolium （MTS） assay， and the mRNA level of the targets was detected by real-time polymerase chain reaction （Real-time PCR）. ResultA total of 11 active ingredients of Bailing capsules such as cerevisterol， 270 related drug targets， and 1 020 COPD target proteins were obtained， with 74 intersection targets. The visualization analysis of the PPI network showed that the core targets of Bailing capsules in the treatment of COPD were tumor protein P53 （TP53）， catenin beta 1 （CTNNB1）， tumor necrosis factor （TNF）， interleukin-6 （IL-6） and insulin （INS）. Further， 20 signaling pathways were screened by KEGG enrichment analysis as the main pathways for Bailing capsules to treat COPD， involving phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， cyclic adenosine monophosphate （cAMP）， forkhead box O （FoxO）， TNF， and hypoxia inducible factor-1 （HIF-1） signaling pathways. Molecular docking validation demonstrated that four active ingredients had stable binding to IL-6， with the lowest energy. Bailing capsules could reduce the mRNA level of IL-6 in RAW264.7 cells induced by lipopolysaccharide （LPS） （P<0.01） compared with the control group. ConclusionThe pharmacological mechanism of Bailing capsules in the treatment of COPD might be that its main active ingredients improved the inflammatory response by acting on TP53， CTNNB1， TNF， IL-6 and other targets and regulating PI3K/Akt， cAMP and other signaling pathways， thereby ameliorating COPD symptoms. This study provided experimental basis for subsequent in-depth research， and provided a diagnosis and treatment direction for disease-related clinical treatment.

Background Papillary thyroid cancer is the result of a variety of pathogenic factors. The prevalence of papillary thyroid cancer varies greatly in different regions, and the disease is more harmful to women. Objective This study aims to explore the relationship between reproductive factors and papillary thyroid cancer, and to provide basic data for prevention and control of the disease. Methods A 1∶1 age (±3 years) matched case-control study was conducted in 331 pairs of newly confirmed papillary thyroid cancer cases and controls from two hospitals in Shanghai from November 2012 to December 2013. Comparisons were made in the history of menstruation, pregnancy, gynecological and breast diseases, and other variables between the two groups. Results The results of univariate analysis indicated that the proportions of education below bachelor degree, married, and mainly manual workers in the case group were significantly higher than those in the control group (P<0.05); the proportion of those with a family history of thyroid diseases in the case group was significantly higher than that in the control group (P<0.05); the proportions of the cases with irregular menstruation (77.34%), a history of using oral contraceptive or hormone drugs (24.77%), a history of benign gynecological diseases (31.72%), and a history of gynecological surgery (9.67%) were significantly higher than the proportions in the control group (P<0.05). After adjusting potential confounding factors such as history of CT examination, age, kinds of family salt, total iodine intake every day, education level, occupation, marital status, body mass index, and family history of thyroid diseases, the results of multiple logistic regression analysis showed that irregular menstruation (OR=1.767, 95%CI: 1.122-2.782; P=0.014), surgical menopause (OR=12.787, 95%CI: 3.202-51.057; P<0.001), pregnancy >1 time (OR =2.490, 95%CI: 1.196-5.184; P=0.015), and the history of using oral contraceptive or hormone drugs (OR=2.389, 95%CI: 1.338-4.268; P=0.003) were the risk factors of papillary thyroid cancer. Conclusion Irregular menstruation, surgical menopause, history of pregnancy, and history of using oral contraceptive or hormone drugs might be the risk factors of papillary thyroid cancer. To reduce the incidence of papillary thyroid cancer, strengthened health education and rational use of contraceptives are recommended.

Background Both domestic and foreign studies on the diet quality of patients with thyroid nodules are rare at present, and the relationship between thyroid nodules and diet quality is still unclear. Objective This study aims to evaluate the diet quality of thyroid nodules with the China Healthy Diet Index (CHDI) and to explore the relationship between diet quality and thyroid nodules. Methods We conducted a hospital-based case-control study in which 387 patients with thyroid nodules were matched individually (1∶1) by gender and age (±3 years) to the controls who ordered a routine physical examine and with negative thyroid nodules reported by B-ultrasound in the same hospital. A structured questionnaire was applied to collect data on general characteristics and diet. CHDI was employed to evaluate the diet quality of the two groups. CHDI is based on the Dietary Guidelines for Chinese Residents and the recommended food intake in the balanced diet pagoda, combined with the dietary nutritional status of Chinese population. The index contains 13 scoring components, and the highest total score is 100, with a higher score representing better dietary quality. CHDI scores < 60, 60-<80, and ≥80 are recognized as unqualified, qualified, and good diet quality, respectively. Results The scores of the thyroid nodule cases were lower than the scores of the controls in total vegetables, dark vegetables, fruits, and fish/shrimps (all Ps<0.05). The nonparametric test results found that there were significant differences in the distributions of scores in total vegetables, dark vegetables, fruits, soybeans, and fish/shrimps between the case and the control groups (all Ps<0.05). The percentages reaching the full scores in food variety, meat and eggs, and empty calories in both groups exceeded 60%, while the percentages reaching the full scores in whole grains/beans/tubers, dairy, soybeans, and sodium were lower than 30% in the two groups. The median CHDI scores of the thyroid nodule cases and the controls were 69.1 and 72.9, respectively; the cases' CHDI score was lower than the controls' (P<0.05). The proportions of unqualified diet in the case and the control groups accounted for 23.0% and 13.7% respectively (P=0.001). After being adjusted for education level, marital status, occupation, monthly household income per capita, body mass index, hypertension/diabetes, energy, and iodine intake, the results of logistic regression analysis showed that the risk for thyroid nodules was negatively associated with CHDI score (CHDI qualified group vs. CHDI unqualified group, OR=0.484, 95%CI: 0.291-0.804; CHDI good dietary quality group vs. CHDI unqualified group, OR=0.414, 95%CI: 0.230−0.746). Conclusion The diet quality of patients with thyroid nodules is lower than that of the control group, as the former reported lower consumptions of total vegetables, dark vegetables, fruits, and fish/shrimps. Those who have good or qualified diet quality show a reduced risk of thyroid nodules than those with unqualified dietary quality.

Objective:To observe the long-term efficacy and complication rate of fecal microbiota transplantation (FMT) and the effects of different ways of transplantation and treatment courses on the efficacy of FMT.Methods:From April 2012 to April 2020, the data of 3 932 patients (804 cases of Nanjing General Hospital of Nanjing Military Command and 3 128 cases of Tenth People′s Hospital of Tongji University) who voluntarily received FMT treatment were prospectively collected. After the first course of transplantation, the follow-up rate and efficacy and complications in 5 years were observed at the 1st, 12th, 24th, 36th, 48th and 60th month. According to the different ways of the first transplantation, 3 932 patients were divided into nasointestinal tube group (2 604 cases), capsule group (873 cases), colonoscopy group (268 cases) and enema group (187 cases). One month after transplantation, the effective rate and complication were observed. At the same time, the 1 813 patients with FMT less than four courses were divided into 1 treatment course group (369 cases), 2 treatment courses group (568 cases), 3 treatment courses group (497 cases) and 4 treatment courses group (379 cases). The effective rates of patients in four groups with different treatment courses were observed 6 months after finishing the treatment. Chi square test was used for statistical analysis.Results:Among 3 932 patients, the follow-up rates at 1st, 12th, 24th, 36th, 48th and 60th month after the first course of FMT were 93.67%(3 683/3 932), 82.30%(2 307/2 803), 82.17%(1 825/2 221), 62.41%(978/1 567), 59.85%(559/934) and 60.84%(289/475), respectively. The total effective rates at 1st, 12th, 24th, 36th, 48th and 60th month were 67.23%(2 476/3 683), 64.20%(1 481/2 307), 59.29%(1 082/1 825), 59.71%(584/978), 55.81%(312/559) and 59.17%(171/289), respectively. During FMT period, the total incidence of different complications was 34.49%(1 356/3 932). During follow-up period, the total rate of complication was 4.22%(166/3 932). There were no serious adverse events such as gastrointestinal perforation, multi-drug resistant bacterial infection, organ failure and death. One month after FMT, the effective rates of nasojejunal tube group, capsule group, colonoscopy group, and enema group were 67.18%(1 668/2 483), 68.63%(549/800), 67.23%(158/235), 61.21%(101/165), respectively. There was no significant difference among the four groups ( P>0.05). The effective rates of patients with chronic constipation in nasal jejunal tube group, capsule group and colonoscopy group were all higher than that of enema group (67.82%, 1 043/1 538; 67.98%, 138/203 and 62.96%, 17/27 vs. 26.67%, 8/30), and the differences were statistically significant ( χ2=22.55, 19.07 and 7.60, all P<0.01). During the period of FMT, the total incidence of complications of nasojejunal tube group, capsule group, colonoscopy group and enema group were 35.22%(917/2 604), 30.24%(264/873), 42.54%(114/268) and 32.62%(61/187), respectively. The difference was statistically significant among four groups ( χ2 =18.84, P<0.01). Among nasojejunal tube group, capsule group, colonoscopy group and enema group, there were significant differences in the incidence of diarrhea (4.49%, 117/2 604; 4.58%, 40/873; 7.83%, 21/268 and 5.35%, 10/187, respectively), throat pain (5.30%, 138/2 604; 0.69%, 6/873; 2.99%, 8/268 and 1.07%, 2/187, respectively), gastrointestinal bleeding (0; 0; 1.87%, 5/268 and 0.53%, 1/187, respectively) and enterogenous infection (0; 0; 1.49%, 4/268 and 0.53%, 1/187, respectively) ( χ2 =8.24, 39.24, 63.13 and 49.68, all P<0.05). At the 6th month after treatment, the effective rates of 1 treatment course group, 2 treatment courses group, 3 treatment courses group and 4 treatment courses group were 63.94%(211/330), 61.93%(301/486), 65.75%(286/435) and 72.54%(251/346), respectively. There were statistically significant differences among groups with different treatment courses ( χ2 =10.70, P =0.01). The effective rate of the four treatment courses group was significantly higher than those of the one treatment course group, two treatment courses group and three treatment courses group, and the differences were statistically significant ( χ2=5.78, 10.18 and 4.14, all P<0.05). The effective rates of in chronic constipation and autism in 4 treatment courses group were significantly higher than those in 1 treatment course group and 2 treatment courses group (72.73%(136/187) vs.55.47%(71/128) and 58.71%(155/264), 72.73%(40/55) vs.6/15 and 47.83%(11/23)), the effective rate of autism in 3 treatment courses group was higher than that in 1 treatment course group (69.05%(29/42) vs. 6/15), and the differences were statistically significant ( χ2=10.05, 9.39, 5.60, 4.44 and 3.94, all P<0.05). Conclusions:The long-time efficacy of FMT is definite in the treatment of intestinal flora derangement related intestinal diseases and extraintestinal diseases complicated with intestinal disfunction and there are no serious adverse events. The efficacy of FMT is related to the way of transplantation and treatment. The incidence of complications of FMT is related to the way of transplantation. Different ways of transplantation and treatment courses should be formulated for different diseases.

Objective:To analyze the compatibility of prescriptions for infertility (female) in the Dictionary of Traditional Chinese Medicine Prescriptions. Methods:The prescriptions for infertility (female) in the Dictionary of Traditional Chinese Medicine Prescriptions were collected and analyzed by association rules analysis, mutual information method, complex system entropy clustering and unsupervised entropy hierarchical clustering with the Traditional Chinese Medicine Inheritance Support System (v2.5). Results:A total of 302 prescriptions were collected for the treatment of infertility (female), involving 352 kinds of traditional Chinese medicine, with warm nature as the main property and sweet taste as the main flavor, followed by pungent and bitter flavor, mainly belonging to liver, spleen, kidney and heart meridian. Thirty seven prescriptions were used more than 30 times, and the top ten were Angelicae sinensis radix, Chuanxiong rhizoma, Poria, Rehmanniae radix praeparata, Paeoniae radix alba, Ginseng radix et rhizoma, Cyperi rhizoma, Atractylodis macrocephalae rhizoma, Cinnamomi cortex and Rehmanniae radix. There were 40 common drug combinations for 60 times, the top four including Angelicae sinensis radix- Chuanxiong rhizoma, Angelicae sinensis radix- Paeoniae radix alba, Rehmanniae radix praeparata- Angelicae sinensis radix and Chuanxiong rhizoma-Paeoniae radix alba. Thirteen core combinations of 3-5 herbs were obtained by complex system entropy clustering, and 13 new prescriptions were formed by further clustering. Conclusions:According to the Dictionary of Traditional Chinese Medicine Prescriptions, prescriptions for infertility (female) are mainly used to regulate qi and blood, nourish the five zang organs, and properly matching with those for regulating qi to open depression, drying dampness to dissipate phlegm, and warming meridians to dredge stagnation.

Monoclonal antibodies (mAbs) are widely used in many fields due to their high specificity and ability to recognize a broad range of antigens. IL-17A can induce a rapid inflammatory response both alone and synergistically with other proinflammatory cytokines. Accumulating evidence suggests that therapeutic intervention of IL-17A signaling offers an attractive treatment option for autoimmune diseases and cancer. Here, we present a combinatorial approach for optimizing the affinity and thermostability of a novel anti-hIL-17A antibody. From a large naïve phage-displayed library, we isolated the anti-IL-17A mAb 7H9 that can neutralize the effects of recombinant human IL-17A. However, the modest neutralization potency and poor thermostability limit its therapeutic applications. affinity optimization was then used to generate 8D3 by using yeast-displayed random mutagenesis libraries. This resulted in four key amino acid changes and provided an approximately 15-fold potency increase in a cell-based neutralization assay. Complementarity-determining regions (CDRs) of 8D3 were further grafted onto the stable framework of the huFv 4D5 to improve thermostability. The resulting hybrid antibody 9NT/S has superior stabilization and affinities beyond its original antibody. Human fibrosarcoma cell-based assays and analyses in mice indicated that the anti-IL-17A antibody 9NT/S efficiently inhibited the secretion of IL-17A-induced proinflammatory cytokines. Therefore, this lead anti-IL-17A mAb might be used as a potential best-in-class candidate for treating IL-17A related diseases.