ObjectiveTo analyze the pharmacodynamic activity of Bupleuri Radix processed with Trionyx sinensis blood in the treatment of Yin deficiency and study the spectrum-effect relationship of this medicine. MethodsHigh performance liquid chromatography was employed to establish the fingerprints of 15 batches of Bupleuri Radix processed with Trionyx sinensis blood， and the similarity was evaluated according to the SOP of Similarity Evaluation System of Chromatographic Fingerprint of TCM （version 2012）. A mouse model of Yin deficiency induced by thyroxine was established. The relationship between the active components and the effect on Yin deficiency was explored by grey correlation analysis and partial least squares method based on the changes in the serum levels of triiodothyronine （T3）， thyroxine （T4）， cyclic adenosine phosphate （cAMP）， and cyclic guanosine phosphate （cGMP）. The components screened out based on the spectrum-effect relationship were used for retrieval of the targets from the Traditional Chinese Medicine Systems Pharmacology and Analysis Database （TCMSP）， The Encyclopedia of Traditional Chinese Medicine （ETCM）， and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP）. Furthermore， the Online Mendelian Inheritance in Man （OMIM）， GeneCards， TTD， DisGeNET， and Drugbank were employed to establish the active component-target against Yin deficiency network of Bupleuri Radix processed with Trionyx sinensis blood. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were carried out for the core targets. Real-time PCR was conducted to verify the predicted key pathways and mechanisms. ResultsThe fingerprints of the 15 batches of Bupleuri Radix processed with Trionyx sinensis blood showed the similarities of 0.976-0.999 with the control fingerprint. Compared with the model group， the drug administration group showed elevated levels of T3 and T4 and lowered levels of cAMP， cGMP and cAMP/cGMP. The results of grey correlation analysis showed that active components in terms of the correlations followed the trend of saikosaponin B₁ > saikosaponin B₂ > saikosaponin C > saikosaponin D > saikosaponin A. The partial least squares analysis showed that saikosaponins A， D， B₁， and B₂ had higher VIP values. Network pharmacology predicted a total of 30 common targets， which were enriched in 276 GO terns and 115 KEGG pathways. The results of Real-time PCR showed that the model group had lower mRNA levels of Caspase-9， kinase insert domain receptor （KDR）， and mammalian target of rapamycin （mTOR） and higher mRNA level of mouse double minute 2 homolog （MDM2） than the blank group and the drug administration group. ConclusionBupleuri Radix processed with Trionyx sinensis blood has therapeutic effect on Yin deficiency syndrome， which provides a new idea for studying Bupleuri Radix processed with Trionyx sinensis blood.

The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.

ObjectiveThis study aims to explore the mechanism of action of Huangqi Guizhi Wuwutang in treating rheumatoid arthritis （RA）-associated sarcopenia by regulating autophagy and improving skeletal muscle homeostasis based on network pharmacology，bioinformatics，machine learning，and animal experiments. MethodsActive ingredients and targets of Huangqi Guizhi Wuwutang were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP），PubChem，and SwissTargetPrediction databases. RA-related datasets were retrieved from the GEO database，and differential genes were screened. Sarcopenia-related targets were searched through GeneCards and the Comparative Toxicology Database （CTD），and autophagy-related gene sets were downloaded from the Human Autophagy Database （HADb）. Their intersection was analyzed to identify autophagy-related therapeutic targets，followed by enrichment analysis. A protein-protein interaction （PPI） network was constructed using the STRING database，and key targets were selected using multiple methods. Machine learning was applied to predict models based on the expression profiles of intersecting targets，and nomogram models were constructed based on key targets. Molecular docking of the top four active ingredients with key targets was performed using AutoDockVina. A collagen-induced arthritis （CIA） rat model was established using bovine type Ⅱ collagen，with SD rats divided into groups including a blank group，a model group，and low-，medium-，and high-dose groups of Huangqi Guizhi Wuwutang （2.44，4.88，and 9.76 g·kg^-1） and administered for five consecutive weeks. Joint scores and gastrocnemius muscle mass were recorded and analyzed after modeling. Hematoxylin and eosin （HE） staining and Masson's staining were used to observe pathological changes in muscle tissue. Immunofluorescence staining was applied to observe the protein expression levels of myosin heavy chain （MYHC） and insulin-like growth factor-1 （IGF-1） in skeletal muscle. Western blot was used to detect the protein expression levels of autophagy-related proteins ATG5，Beclin1，LC3B，muscle-specific proteins （MuRF1），MaFbx，and MYHC. Real-time quantitative reverse transcription PCR （Real-time PCR） was performed to measure the mRNA expression levels of ATG5，Beclin1，LC3B，MuRF1，MaFbx，and MYHC in muscle tissue. ResultsNetwork pharmacology revealed that Huangqi Guizhi Wuwutang shared 25 common targets with autophagy genes related to RA-associated sarcopenia. The PPI network and machine learning identified six key targets，which were primarily involved in autophagy and inflammatory pathways. Animal experiments showed that compared to the blank group，the model group had significantly higher joint scores （P<0.01） and lower gastrocnemius muscle index （P<0.01）. HE staining indicated a significant reduction in the cross-sectional area of gastrocnemius muscle fibers，with notable inflammatory cell infiltration and muscle atrophy in the model group. Masson's staining revealed obvious collagen fiber proliferation and deposition，with significant muscle fibrosis in the model group. The protein and mRNA expression levels of ATG5，Beclin1，LC3B，MuRF1，and MaFbx were significantly increased （P<0.01），while the protein expression of MYHC and IGF1 was significantly downregulated （P<0.01）. Compared with the model group，the high-dose group of Huangqi Guizhi Wuwutang showed significantly reduced protein and mRNA expression levels of ATG5，Beclin1，LC3B，MuRF1，and MaFbx （P<0.01） and increased protein expression levels of MYHC and IGF1 （P<0.01）. The cross-sectional area of muscle fibers increased，and the muscle cell morphology approached normal. Moreover，pathological abnormalities in the gastrocnemius muscle were significantly improved，with reduced collagen fiber proliferation （P<0.01）. ConclusionHuangqi Guizhi Wuwutang can mediate autophagy by regulating the expression of ATG5，Beclin1，LC3B，and IGF1，thereby reducing skeletal muscle catabolism and improving skeletal muscle homeostasis，which contributes to the treatment of RA-associated sarcopenia. The findings provide insight into the mechanisms underlying the effects of Huangqi Guizhi Wuwutang in the treatment of RA-related sarcopenia and offer a reference for its enhanced clinical application.

Objective: To explore the association between physical activity and sleep quality among middle school students, so as to provide reference for adolescent sleep improvement. Methods: From September to December 2023, 5 713 middle school students aged 13-18 years were selected from Shanghai, Suzhou, Taiyuan, Wuyuan, Xingyi and Urumqi by stratified cluster random sampling method. Pittsburgh Sleep Quality Index (PSQI) and Evaluation of Physical Activity Levels of Children and Adolescents Aged 7-18 Years were used to investigate and evaluate sleep quality and physical activity. Comparisons between groups were made using the t-test, Mann-Whitney U-test, and associations between physical activity and sleep quality of middle school students were analyzed using Spearman correlation and linear regression methods. Results: The total PSQI scores were 4.0(2.0,6.0) and 5.0 (3.0,6.0) for boys and girls, respectively, with significant sex difference ( Z =-10.90, P <0.01); light physical activity(LPA) and moderate to vigorous physical activity(MVPA) of boys were 18.57 (2.86, 42.86) and 68.57 (35.71, 119.18)min, and girls were 14.29 (0.00, 30.00) and 55.71 (31.43, 92.86)min respectively, and the differences were statistically significant ( Z =3.65, -8.65 , P <0.01). The results of Spearman correlation regression showed that adolescents MVPA was negatively correlated with the total PSQI score ( r =-0.04, P <0.01). After controlling for variables such as mental health, nutritional status and maximum oxygen uptake, the results of linear regression analysis showed that PSQI total score negatively predicted MVPA among middle school students ( B =-4.76, 95% CI =-7.16 to -2.36, P <0.05). Conclusion The longer the duration of physical activity among middle school students, the better the quality of sleep.

Humans ; Consanguinity ; Exome Sequencing ; Mutation/genetics* ; Sequence Analysis, DNA ; Ciliary Motility Disorders ; Axonemal Dyneins/genetics*

Objective To explore the eradication rate of human papillomavirus(HPV)and gestational outcome of patients with high-grade squamous intraepithelial disease of the cervix(HSIL)after loop electrosurgical excision procedure(LEEP)by transvaginal dissection of the vesicorectal form the cervix.Methods A total of 53 patients treated with LEEP by transvaginal dissection of the vesicorectal form the cervix in Obstetrics and Gynecology Hospital,Fudan University from Jan to Dec,2019 were investigated.Clinical information of cervical cytological examination,HPV test and cervical biopsy under colposcopy were followed up for 6,12 and 24 months post-LEEP were collected.HPV infection in these 53 patients were compared before and after LEEP surgery.The rate of successful fertility of the cohort,the HPV conversion rate of patients with hysterectomy and LEEP done were compared.The association between the pathological type and positive surgical margin and the association between HPV infection type and positive surgical margin were analyzed.Results HPV infection rate of was 94.3%(50/53)and the proportion of HPV16 and/or 18 infection was 75.5%(40/53).Mono-HPV infection rate(69.8%,37/53)was significantly higher than mixed HPV infection rate(22.7%,13/53).Thirty-eight patients(71.7%)were found with positive surgical margin in previous LEEP operation.Fifteen patients had recurrence(28.3%)and 40 patients(75.5%)successfully delivered baby after surgery.Postoperative pathology was mainly HSIL,accounting for 66%(30/53),and 28.3%patients(15/53)had no pathological change.Forty cases had satisfying fertility-conservative operation outcome with negative surgical margin,and 38 patients eradicated HPV infection after LEEP,which took up 95%of patients with satisfying fertility-conservative operation.There was no significant difference of positive resection margin rate in between groups of HPV16/18 infection and other types.Five cases had successful delivery(12.5%,5/40)with 1 case of vaginal delivery and 4 cases of cesarean section.Among these 5 cases,3 cases undertook preventive cervical cerclage,with 1 case of vaginal delivery and 2 cases of cesarean sections.Conclusion HPV eradication rate and surgical outcome could be significantly improved by LEEP with transvaginal dissection of the vesicorectal from the cervix,which satisfied the fertility preservation of females at reproductive age.

OBJECTIVE To evaluate the effectiveness and safety of Panlongqi tablets in the treatment of fractures based on real-world research. METHODS From September 2021 to September 2023， fracture patients admitted to 33 medical institutions were collected retrospectively. Patients who received conventional treatment were divided into control group （n＝3 750）， and patients who received combination of Panlongqi tablets on the basis of conventional treatment were divided into observation group （n＝ 3 706）. Self-reported indicators of patients were collected through telephone follow-up at 0， 4， 7 and 14 days after treatment. The improvement values of pain score， swelling score and health utility value， as well as effective rate and adverse drug reactions were compared between 2 groups. The propensity matching score （PSM） method was adopted to perform baseline matching on patient’s age， gender， fracture site， fracture severity， surgical type， type of hospital， and other indicators. Statistical analysis was performed on each therapeutic effect indicator. RESULTS After PSM， a total of 6 425 patients were included， of which 3 055 were in the observation group and 3 370 were in the control group. After 14 days of treatment， the observation group showed significant improvement in pain score （4.768 vs. 4.353）， swelling fangshiyuan2008@126.com grading score （2.979 vs. 2.391）， and life quality utility value （0.430 vs. 0.363）， as well as effective rate （87.20% vs.75.99%） compared to the control group （P＜0.05）. The results of subgroup analyses conducted by gender， age， hospital type， and fracture site were consistent with the aforementioned results. In terms of safety， the observation group had no serious adverse reactions， with a total of 29 cases of mild adverse reactions such as dizziness， stomach pain， and allergies， with an incidence rate of 0.78%. CONCLUSIONS Panlongqi tablets combined with conventional treatment are significantly better than conventional treatment in improving pain， swelling， quality of life， and effective rate in patients with fractures， and have good safety.

Objective To evaluate the effects of high-fat diet on the pharmacokinetics of metronidazole in Chinese healthy adult subjects.Methods This program is designed according to a single-center,randomized,open,single-dose trial.Forty-seven healthy subjects were assigned to receive single dose of metronidazole tablets 200 mg in either fasting and high-fat diet state,and blood samples were taken at different time points,respectively.The concentrations of metronidazole in plasma were determined by high performance liquid chromatography-mass spectromentry.Results The main pharmacokinetic parameters of metronidazole in fasting state and high-fat diet state were as follows:Cmax were(4 799.13±1 195.32)and(4 044.17±773.98)ng·mL-1;tmax were 1.00 and 2.25 h;t1/2 were(9.11±1.73)and(9.37±1.79)h;AUC0_t were(5.59±1.19)x 104 and(5.51±1.18)x 104 ng·mL-1·h;AUC0_∞ were(5.79±1.33)x 104 and(5.74±1.32)× 104 ng·mL-1·h.Compared to the fasting state,the tmaxof the drug taken after a high fat diet was delayed by 1.25 h(P＜0.01),Cmax,AUC0_t,AUC0-∞ were less or decreased in different degrees,but the effects were small(all P＞0.05).Conclusion High-fat diet has little effects on the pharmacokinetic parameters of metronidazole,which does not significantly change the degree of drug absorption,but can significantly delay the time to peak.

Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(＜65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P＞0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.

Spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disease with a carrier frequency of 1/60 ~ 1/40, is characterized by severe clinical symptoms, high mortality rate, and expensive treatment costs. Carrier screening is of paramount importance to detect high-risk couples, and therefore to reduce the occurrence of SMA. In China, SMA carrier screening has become widespread, though there is still a lack of genetic counseling expertise. This article has focused on the current challenges for SMA carrier screening, including the screening methods, target population, screening procedures, and pre-/post-testing counseling. The aim is to standardize its application and counseling in the clinical practice.