Objective To explore the pharmacokinetic characteristics of sufentanil in individuals with normal body mass index(BMI),overweight BMI,and different CYP3A4/5 enzyme genotypes.Methods The patients receiving laparoscopic surgery under general anesthesia in the First Affiliated Hospital of Army Medical University from November 2020 to September 2021 were prospectively recruited in this study.Before the operation,the oral swabs were collected from all the patients for genotyping using the human CYP3A4/5 gene kit.Based on the potential impact of combination of their polymorphisms on sufentanil metabolism and the proportion of different genotype combinations of CYP3A4/5 enzymes,the patients were divided into groups I(3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation),II(3A4 heterozygous mutation+3A5 heterozygous mutation),and III(3A4 wild type or 3A4 heterozygous mutation+3A5 wild type).According to their BMI,they were also assigned into a normal body weight group(18.5～24.0 kg/m2)and an overweight group(24～<28 kg/m2),and the differences in drug metabolism parameters were statistically analyze between the 2 groups.After routine general anesthesia induction(sufentanil 0.5 μg/kg),venous blood samples were collected to detect the changes in its concentration using high performance liquid chromatography-mass spectrometry(HPLC-MS).The pharmacokinetic data of sufentanil were calculated between the normal BMI group and overweight group in all participants and between the 2 body weight groups among those with different genotype combinations.Results Among the 90 participants completing the blood drug concentration test,8 patients had their blood samples contaminated(including 1 case with an anesthesia duration of<2 h),and 3 were excluded due to low weight or overweight.Eventually,79 participants were included in the pharmacokinetic analysis on the normal body weight group and the overweight group.Compared with the normal body weight group,the central compartment volume of distribution in the overweight group was significantly reduced(P<0.05),while no obvious differences were observed between the 2 groups in terms of peripheral compartment volume of distribution,total clearance rate,peripheral compartment clearance rate,distribution half-life,clearance half-life,and area under the blood concentration-time curve.In group Ⅰ(n=26),the overweight patients(n=13)had significantly reduced central compartment volume of distribution,peripheral compartment volume of distribution,and peripheral compartment clearance rate when compared with the normal body weight patients(n=13)(P<0.05),while no differences were observed in other pharmacokinetic parameters.In groups Ⅱ(n=25)and Ⅲ(n=28),the overweight patients and normal body weight patients had no statistical differences in all pharmacokinetic parameters.Conclusion Among the patients with the same genotype combination of CYP3A4/5 mutations,there was no difference in the metabolism of sufentanil between the overweight and normal weight patients.Additionally,in the population of 3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation,the overweight patients have smaller peripheral distribution range of sufentanil,and weakened metabolic process.

Objective To explore whether creatine therapy regulates neuronal ferroptosis by inhibiting the activation of STAT1 signaling pathway associated with suppressor of cytokine signaling 1(SOCS1)in Alzheimer's disease.Methods Immunohistochemical staining and counting of positive results using paraffin sections of human brain frontal lobes were employed to determine the trend of changes in the target proteins.Further validation was performed by immunofluorescence and Western blotting.STAT1 phosphorylation was inhibited by creatine injection using eleven FAD4T mice and by cerebellar medullary pool puncture,and the expression of target proteins was examined by immunohistochemistry and immunofluorescence after postmortem sampling.Results Compared with the age controls,interferon-γ(IFN-γ),an activating cytokine of the STAT1 signaling pathway,and SOCS1,a negative regulator of STAT1 activation,were both significantly up-regulated,STAT1 phosphorylation was enhanced,and the ferroptosis markers ferritin light chain(FTL)and cystine/glutamate transporter(xCT)increased markedly in the cortex of AD human brains;Creatine treatment of FAD4T mice resulted in a reduction of both IFN-γ and SOCS1,and a significant decrease in the ferroptosis markers FTL and xCT(SLC7A11).Conclusion Creatine ameliorates neuronal ferroptosis in AD model mice by reducing neuronal STAT1-SOCS1 signalling activation.

Objective To investigate the status and developmental trends of clinical trials for weight control drugs in China,and to provide data support for sponsors,researchers,and regulatory authorities.Methods The drug clinical trial registration and information platform of the National Medical Products Administration was utilized to search for registered clinical trials of weight control drugs from November 2012 to June 2024.The search employed"overweight","obesity",and"weight loss"as keywords.The information collected included project registration time,drug name,dosage form,drug classification,indications,trial staging,study progress,design type,lead unit,and sponsor.Microsoft Office Excel software was employed for data entry,organization,and extraction.Results A total of 95 registered clinical trials of weight control drugs were identified,comprising 40 domestic multicenter trials,47 domestic single-center trials,and 8 international multicenter trials.Regarding trial phasing,46(48.4％)were phase Ⅰ clinical trials,17(17.9％)were phase Ⅱ clinical trials,19(20.0％)were phase Ⅲ clinical trials,and 13(13.7％)were bioequivalence trials.The drug categorization encompassed 22 chemical drugs,20 biological products,and 1 traditional Chinese medicine/natural drug.Concerning drug dosage forms,there were 32 items of injectable dosage forms,8 items of tablets,2 items of capsules,and 1 item of chewable tablets.Conclusions Registered clinical trials for weight-loss medications in China are predominantly concentrated in regions with developed medical resources.Injectable biologics constitute most test drugs,with most drugs in the early stages of research and development.The examination of the safety and efficacy of these drugs remains to be substantiated,and it is anticipated that a considerable period will elapse before their approval and market introduction.

Objective To investigate the status and developmental trends of clinical trials for weight control drugs in China,and to provide data support for sponsors,researchers,and regulatory authorities.Methods The drug clinical trial registration and information platform of the National Medical Products Administration was utilized to search for registered clinical trials of weight control drugs from November 2012 to June 2024.The search employed"overweight","obesity",and"weight loss"as keywords.The information collected included project registration time,drug name,dosage form,drug classification,indications,trial staging,study progress,design type,lead unit,and sponsor.Microsoft Office Excel software was employed for data entry,organization,and extraction.Results A total of 95 registered clinical trials of weight control drugs were identified,comprising 40 domestic multicenter trials,47 domestic single-center trials,and 8 international multicenter trials.Regarding trial phasing,46(48.4％)were phase Ⅰ clinical trials,17(17.9％)were phase Ⅱ clinical trials,19(20.0％)were phase Ⅲ clinical trials,and 13(13.7％)were bioequivalence trials.The drug categorization encompassed 22 chemical drugs,20 biological products,and 1 traditional Chinese medicine/natural drug.Concerning drug dosage forms,there were 32 items of injectable dosage forms,8 items of tablets,2 items of capsules,and 1 item of chewable tablets.Conclusions Registered clinical trials for weight-loss medications in China are predominantly concentrated in regions with developed medical resources.Injectable biologics constitute most test drugs,with most drugs in the early stages of research and development.The examination of the safety and efficacy of these drugs remains to be substantiated,and it is anticipated that a considerable period will elapse before their approval and market introduction.

Statistical analysis was conducted on the quantity of Chinese medicine material and sliced herbal medicine,the species types and medicinal parts of Chinese medicine material and sliced herbal medicine,and the quantity and composition of Chinese patent medicines and single-herb preparations in Chinese Pharmacopoeia of the 2020 edition.The statistical results are available on the web site(http://itcm.hzau.edu.cn/yd/zgyd.htm)for reference.The analysis results showed that:(1)Chinese Pharmacopoeia(Part I)contained a total of 616 kinds of Chinese medicine material and sliced herbal medicine and 47 kinds of plant oils and extracts.The 616 kinds of Chinese medicine material and sliced herbal medicine originated from plants,animals,minerals,microorganisms,artificial or synthetic raw materials,human-sourced products,and products having the origin of both animal and plants.Of the 47 kinds of plant oils and extracts,46 were made from plant sources,and the remaining one,i.e.Cornu Bubali concentrated powder,was made from the animal sources.(2)A total of 421(73.60%)from the 616 kinds of Chinese medicine material and sliced herbal medicine originated from the single species,96(16.78%)originated from 2 kinds of species,40(6.99%)originated from 3 kinds of species,11(1.92%)originated from 4 kinds of species,2(0.35%)originated from 5 kinds of species,and 2(0.35%)originated from 6 kinds of species.Of the 47 kinds of plant oils and extracts,34 originated from the single species,5 originated from 2 kinds of species and 5 originated from 3 kinds of species.(3)The Chinese Pharmacopoeia(Part I)contained a total of 1 605 Chinese patent medicines and single-herb preparations.Except that the composition of Yunnan Baiyao Powder and Yunnan Baiyao Capsules was not issued,the remaining 1 603 types of Chinese patent medicines and single-herb preparations involved a total of 14 329 kinds of medicinal materials.The Chinese medicines with the leading 20 frequency used in the Chinese patent medicines and single-herb preparations recorded in the Chinese Pharmacopoeia of 2020 edition were Glycyrrhizae Radix et Rhizoma,Angelicae Sinensis Radix,Poria,Chuanxiong Rhizoma,Scutellariae Radix,Paeoniae Radix Alba,Astragali Radix,Citri Reticulatae Pericarpium,Rehmanniae Radix,Atractylodis Macrocephalae Rhizoma,Salviae Miltiorrhizae Radix et Rhizoma,Borneolum Syntheticum,Platycodonis Radix,Rhei Radix et Rhizoma,Rehmanniae Radix Preparata,Aucklandiae Radix,Carthami Flos,Ophiopogonis Radix,Codonopsis Radix and Angelicae Dahuricae Radix.The results suggest that there were still problems existing in Chinese Pharmacopoeia of the 2020 edition,i.e.,some of the drugs of Chinese patent medicines were not listed in the Chinese medicine material and sliced herbal medicine,and some of the prepared drugs of Chinese patent medicines were not listed in the Chinese medicine material and sliced herbal medicine,either.The systemic analysis of the general information of Chinese medicinal materials as well as their correlation with Chinese patent medicines in Chinese Pharmacopoeia will provide a reference for further research on the production of Chinese medicine material and sliced herbal medicine and the complete list of drugs in Chinese patent medicines.

Objective To observe the pharmacokinetic effect of amoxicillin and clavulanate potassium tablets on amoxicillin in Chinese healthy subjects under fasting and high fat and high calorie diet.Methods 71 healthy subjects were given a single dose of amoxicillin potassium clavulanate tablets(0.375 g)on fasting or high fat diet,and venous blood samples were collected at different time points.The concentrations of amoxicillin in human plasma were determined by HPLC-MS/MS method,and the pharmacokinetic parameters were calculated by non-atrioventricular model using PhoenixWinNonlin 8.0 software.Results The main pharmacokinetic parameters of amoxicillin potassium clavulanate tablets after fasting and high fat diet were(5 105.00±1 444.00),(4 593.00±1 327.00)ng·mL-1,and postprandial-fasting ratio 89.40％,90％confidence interval(79.55％-100.19％);t1/2 were(1.52±0.16),(1.39±0.22)h;AUC0-t were(12 969.00±1 841.00),(11 577.00±1 663.00)ng·mL-1·h,and postdietary/fasting ratio 89.20％,90％confidence interval(83.92％-94.28％);AUC0-∞ were(13 024.00±1 846.00),(11 532.00±1 545.00)ng·mL-1·h,and postprandial-fasting ratio 88.60％,90％confidence interval(83.48％-93.50％).The median Tmax(range)were 1.63(0.75,3.00)and 2.50(0.75,6.00)h,respectively,and the Tmax of postprandial medication was delayed(P＜0.01).Conclusion Compared with fasting condition,amoxicillin Tmax was significantly delayed after high fat diet,while Cmax,AUC0-t and AUC0-∞ were not significantly changed,indicating that food could delay the absorption of amoxicillin,but did not affect the degree of absorption.

Objective To study the relationship between the changes of sagittal spinopelvic parameters and facet joint-derived low back pain in patients with hip osteoarthritis after hip arthroplasty.Methods The clinical data of 30 patients with facet joint-derived low back pain induced by hip osteoarthritis who underwent unilateral hip arthroplasty(observation group)from June 2019 to November 2020 in our hospital were retrospectively analyzed,and 50 healthy subjects who underwent lumbar X-ray examination in the physical examination center of our hospital at the same time were randomly selected as the control group.The sagittal spinopelvic parameters were measured based on the X-ray,including pelvic incidence(PI),pelvic tilt(PT),sacral slope(SS),lumbar lordosis(LL),sacrum pubic incidence(SPI)and sacrum pubic posterior angle(SPPA).The correlation between the changes of sagittal spinopelvic parameters and facet joint-derived low back pain was analyzed by multiple linear regression,and its diagnostic efficacy to facet joint-derived low back pain was analyzed by receiver operating characteristic(ROC)curve.Results The PI,LL,SPI or SPA before and 1 year after surgery of the observation group had no significant difference combined with those of the control group(P>0.05).The PT before surgery of the observation group was smaller than that of the control group(P<0.05),and the SS before surgery was larger than that of the control group(P<0.05).Multiple linear regression analysis showed that PT and SS before surgery were correlated with facet joint-derived low back pain(P<0.05).The sensitivity of PT and SS before surgery in diagnosing facet joint-derived low back pain were 50.00%and 73.30%,with the specificity of 88.00%and 78.00%,respectively.ROC curve analysis showed that the area under the curve of PT and SS before surgery in diagnosing facet joint-derived low back pain were 0.708(95%CI:0.595 to 0.822)and 0.775(95%CI:0.673 to 0.877),respectively.Conclusion Patients with hip osteoarthritis pain have significantly larger SS and significantly smaller PT.Hip arthroplasty can alleviate the symptoms of low back pain without affecting the sagittal spinopelvic balance;the PT and SS before surgery are correlated with the facet joint-derived low back pain,and they are of high value in the diagnosing facet joint-derived low back pain.

Objective To standardize the management of clinical trials in our hospital,reduce the incidence of protocol deviations,and provide a reference for improving the quality of clinical trials.Methods The healthcare failure mode and effect analysis(HFMEA)method was used to determine the potential failure modes of the current protocol deviation.The frequency,severity and detectability of failure modes were quantified and evaluated.The risk priority number(RPN)was calculated and the corresponding improvement measures were proposed.The RPN values before and after the implementation of HFMEA were statistically analyzed to evaluate the improvement effect.Results After the implementation of HFMEA activities,the RPN values of 14 potential failure modes decreased significantly(P<0.05);The risk level of 12 potential failure modes decreased.The HFMEA team members'ability in finding and solving problems,communication and cooperation were significantly improved.Conclusions The implementation of HFMEA activities contributes to the management of protocol deviation in clinical trials,can effectively reduce the occurrence of protocol deviation,and provides experience for improving the quality of drug clinical trials.

Objective:To investigate the impact of ionizing radiation(IR)on the structure and function of the testis and pro-vide some strategies for the prevention and treatment of IR-induced damage(IRD).Methods:Using radiation dose simulation,se-men analysis,hormone testing,electron microscopy and single-cell transcriptome sequencing,we assessed and analyzed a case of IRD.We established a mouse model of IRD to validate the results of single-cell sequencing,and investigated the specific biological mecha-nisms of IRD and potential strategies for its intervention.Results:IR at 1-2 Gy significantly reduced sperm concentration and mo-tility,which gradually recovered after 12 months but the percentage of morphologically normal sperm remained low.It also caused im-balanced levels of various steroid hormones,decreased testosterone and dehydroepiandrosterone sulfate,increased progesterone,prolac-tin,luteinizing hormone,and follicle-stimulating hormone.Electron microscopy revealed damages to the testis structure,including loss of germ cells,atrophy of the seminiferous tubules,nuclear membrane depression of the spermatocytes,mitochondrial atrophy and de-formation,and reduction of mitochondrial cristae.Single-cell sequencing indicated significant changes in the function of the Leydig cells and macrophages and disrupted lipid-related metabolic pathways after IRD.Administration of L-carnitine to the mouse model im-proved lipid metabolism disorders and partially alleviated IRD to the germ cells.Conclusion:Ionizing radiation can cause disorders of testicular spermatogenesis and sexual hormones and inhibit lipid metabolism pathways in Leydig cells and macrophages.Improving lipid metabolism can alleviate IRD to germ cells.