Objective To study the pharmacokinetic and pharmacodynamic characteristics of compound levodopa/carbidopa(250 mg/25 mg)and levodopa/benserazide(200 mg/50 mg)in patients with Parkinson's disease(PD).Methods This experiment used a levodopa challenge test with a randomized crossover design.In the first week,20 PD patients orally received either 275 mg of compound levodopa/carbidopa or 250 mg of levodopa/benserazide on an empty stomach,and in the second week,they received the other treatment.The levodopa blood concentration was measured using high-performance liquid chromatography-tandem mass spectrometry,and motor symptoms were evaluated using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Ⅲ.Results Data from 17 patients in the compound levodopa/carbidopa group and 18 patients in the levodopa/benserazide group was included in the analysis.After administration,the Cmax values of compound levodopa/carbidopa and levodopa/benserazide groups were(3 563.76±1 003.06)and(3 642.44±1 192.70)ng·mL-1;the tmax values were(1.10±0.44)and(1.03±0.55)h;the t1/2 values were(1.52±0.15)and(1.68±0.27)h;the AUC0-t values were(7 625.19±1 706.85)and(5 846.07±1 191.16)ng·mL-1·h;the mean residence time(MRT)values were(2.39±0.361)and(2.14±0.37)h,respectively.There were no statistically significant differences in the Cmax,tmax,and t1/2 values between the two groups(all P＞0.05).Compared with the levodopa/benserazide group,the compound levodopa/carbidopa group increased levodopa AUC and prolonged MRT(all P＜0.05).The improvement in motor symptoms and levodopa blood concentration showed consistent trends at various time points in both groups.The compound levodopa/carbidopa group showed significantly better improvement in motor function at 6 and 8 hours after medication compared to the levodopa/benserazide group[(-10.82±8.91)points vs(-5.17±6.78)points,(-7.88±10.05)points vs(-2.11±4.84)points;both P＜0.05].Conclusion The pharmacokinetic and pharmacodynamic characteristics of compound levodopa/carbidopa are similar to those of levodopa/benserazide.

Evaluate the interventional effect of Lycium barbarum leaves extract on cataract rats and its effects on plasma and liver tissue metabolites. The ultimate goal is to explore the scientific connotation of Lycium barbarum leaves extract on vision improvement. All experiments were approved by the experimental animal ethics committee from Nanjing University of Chinese Medicine (202306A067). D-Galactose (D-gal) induced cataract model in rats was established. The lens opacity, lens and liver tissue pathology, level of oxidative stress and polyol metabolism regulation in the lens, level of oxidative stress in serum and liver tissue, and the content of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum and liver tissue were analysed to evaluate the effect of Lycium barbarum leaves extract on cataract. The metabolite profiles of plasma and liver tissue of rats were analyzed by UPLC-QTOF-MS/MS. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to compare and analyze the metabolic data in control group and cataract group, and screen potential biomarkers. The related metabolic pathways were further constructed by KEGG database analysis. The results showed that lens and liver pathology of cataract rats were improved after being intervened by the leaves extract of Lycium barbarum. The contents of AR and Ca²⁺ were significantly decreased in lens, and the contents of SDH and GSH and the ability of CAT were significantly increased; the content of GSH and the ability of SOD were significantly improved in serum and liver tissue, the content of MDA, the abilities of ALT and AST and the level of inflammatory factors were significantly reduced. The metabolomics results showed that there were 15 different metabolites in plasma and liver tissue of cataract rats, and 9 different biomarkers including retinyl ester, stearic acid, and palmitic acid, were returned by Lycium barbarum leaves extract. As revealed by pathway enrichment in plasma and liver tissue, it was found that the retinol metabolic pathway was mainly regulated by Lycium barbarum leaves extract. In summary, Lycium barbarum leaves can effectively alleviate the pathological changes of cataract, inhibit inflammation and improve antioxidant capacity, which may relate to the retinol metabolic pathway. It provides scientific basis and support for revealing the scientific connotation of the effect of Lycium barbarum leaves on vision improvement.

ObjectiveProtein arginine methyltransferases (PRMTs) play pivotal roles in numerous cellular biological processes. However, the precise regulatory effects of PRMTs on the fate determination of mesenchymal stromal/stem cells (MSCs) remain elusive. Our previous studies have shed light on the regulatory role and molecular mechanism of PRMT5 in MSC osteogenic differentiation. This study aims to clarify the role and corresponding regulatory mechanism of PRMT7 during the adipogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Methods(1) Human bone marrow-derived mesenchymal stem cells (hBMSCs) were cultured in a medium that induces adipogenesis. We used qRT-PCR and Western blot to monitor changes in PRMT7 expression during adipogenic differentiation. (2) We created a cell line with PRMT7 knocked down and assessed changes in PRMT7 expression and adipogenic capacity using Oil Red O staining, qRT-PCR and Western blot. (3) We implanted hBMSCs cell lines mixed with a collagen membrane subcutaneously into nude mice and performed Oil Red O staining to observe ectopic lipogenesis in vivo. (4) A cell line overexpressing PRMT7 was generated, and we examined changes in PRMT7 expression using qRT-PCR and Western blot. We also performed Oil Red O staining and quantitative analysis after inducing the cells in lipogenic medium. Additionally, we assessed changes in PPARγ expression. (5) We investigated changes in insulin-like growth factor 1 (IGF-1) expression in both PRMT7 knockdown and overexpressing cell lines using qRT-PCR and Western blot, to understand PRMT7’s regulatory effect on IGF-1 expression. siIGF-1 was transfected into the PRMT7 knockdown cell line to inhibit IGF-1 expression, and knockdown efficiency was confirmed. Then, we induced cells from the control and knockdown groups transfected with siIGF-1 in lipogenic medium and performed Oil Red O staining and quantitative analysis. Finally, we assessed PPARγ expression to explore IGF-1’s involvement in PRMT7’s regulation of adipogenic differentiation in hBMSCs. Results(1) During the adipogenesis process of hBMSCs, the expression level of PRMT7 was significantly reduced (P<0.01). (2) The adipogenic differentiation ability of PRMT7 knockdown group was significantly stronger than that of control group (P<0.001). (3) The ectopic adipogenic differentiation ability of PRMT7 knockdown group was significantly stronger than that of control group. (4) The adipogenic differentiation ability of the PRMT7 overexpression group was significantly weaker than that of the control group (P<0.01). (5) The expression level of IGF-1 increased after PRMT7 knockdown (P<0.000 1). The expression level of IGF-1 decreased after PRMT7 overexpression (P<0.000 1), indicating that PRMT7 regulates the expression of IGF-1. After siIGF-1 transfection, the expression level of IGF-1 in all cell lines decreased significantly (P<0.001). The ability of adipogenic differentiation of knockdown group transfected with siIGF-1 was significantly reduced (P<0.01), indicating that IGF-1 affects the regulation of PRMT7 on adipogenic differentiation of hBMSCs. ConclusionIn this investigation, our findings elucidate the inhibitory role of PRMT7 in the adipogenic differentiation of hBMSCs, as demonstrated through both in vitro cell-level experiments and in vivo subcutaneous transplantation experiments conducted in nude mice. Mechanistic exploration revealed that PRMT7’s regulatory effect on the adipogenic differentiation of hBMSCs operates via modulation of IGF-1 signaling pathway. These collective findings underscore PRMT7 as a potential therapeutic target for fatty metabolic disorders, thereby offering a novel avenue for leveraging PRMT7 and hBMSCs in the therapeutic landscape of relevant diseases.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective:To investigate the concern about pollen broadcasting in Chinese population from multiple dimensions and to understand the information about allergic rhinitis (AR) in China by analyzing related factors.Methods:From March 1 to September 30, 2022, a large-scale multi-center cross-sectional survey was conducted based on the Questionnaire Star platform in 21 Chinese hospitals. A total of 7 056 subjects from 7 regions in China: Northeast, North, East, Central, South, Southwest, and Northwest China were included. Basic characteristics (including social demographic characteristics and disease characteristics of AR patients), concern about pollen broadcasting, the willingness of pollen-induced AR (PiAR) patients to receive pollen broadcasting, and the treatment satisfaction rate of AR patients were collected. The chi-square test, multivariate linear regression model, and Logistic regression analysis were used to analyze the concern about pollen broadcasting in the Chinese population and related factors from multiple dimensions.Results:Among 7 056 subjects, 23.02% were concerned about pollen broadcasting. Among 3 176 self-reported AR and 1 019 PiAR patients, 25.60% and 39.16% were concerned about pollen broadcasting, respectively, which was higher than that of non-AR or non-PiAR subjects ( χ2 value was 21.74 and 175.11, respectively, both P<0.001). Among AR patients, the proportion of spring and autumn allergen-positive patients concerned about pollen broadcasting was higher than that in perennial allergen-positive patients ( χ2 value was 20.90 and 19.51, respectively, both P<0.001). The proportion of AR patients with asthma, sinusitis, allergic conjunctivitis, and cardiovascular and cerebrovascular diseases was higher than those without complications ( χ2 value was 50.83, 21.97, 56.78, 7.62, respectively, all P<0.05). The proportion of AR patients in North China who could find pollen broadcasting locally was 31.01%, significantly higher than those in other regions (all P<0.05). Multivariate linear regression model analysis showed that among PiAR patients, those with higher per capita household income and higher AR disease cognition levels had been concerned about pollen broadcasting in the past, and those complicated with allergic conjunctivitis had stronger intention to receive pollen broadcasting (B value was 0.24, 0.13, 0.66, 0.47, respectively, all P<0.05). The higher the disease cognition level of PiAR patients, the stronger their willingness to actively participate in treatment ( R2=0.72, P<0.001). Only 18.89% of AR patients felt satisfied with the treatment effect. Logistic regression analysis showed that in AR patients, the treatment satisfaction rate was significantly higher among those concerned about pollen broadcasting compared to those who were not ( OR=1.83, P<0.001). Conclusions:Currently, the dissemination of pollen broadcasting in China is hindered by various factors such as disease cognition level. The treatment satisfaction among AR patients remains unsatisfactory.

Objective To investigate the differences in levels of serum gastrin(GAS)and gastric inhibitory peptide(GIP)in patients with irritable bowel syndrome(IBS)at different ages and their correlation with dis-ease severity.Methods A total of 108 patients with IBS who were treated in the hospital from February 2021 to March 2023 were selected as the research objects.IBS patients were divided into diarrhea type IBS group(n=60)and constipation type IBS group(n=48)according to their clinical types,and were divided into elder-ly group and non elderly group according to whether the patients were older than 60 years at enrollment.The severity of disease was assessed by the IBS Symptom Severity Scale(IBS-SSS).Serum gastrointestinal related hormones such as GAS,GIP,motilin(MTL)and 5-hydroxytryptamine(5-HT)were detected.Inflammatory markers such as interleukin(IL)-8,IL-10,IL-18 and calcitonin gene-related peptide(CGRP)were detected.Pearson correlation test was used to analyze the correlation between IBS-SSS and gastrointestinal related hor-mones and inflammatory markers.Multivariate Logistic regression analysis was used to screen the independ-ent risk factors of severe IBS.Results Among diarrhea type IBS patients and constipation type IBS patients,the mean IBS-SSS score in the non elderly group was significantly higher than that in the elderly group,and the proportion of patients with moderate IBS was higher than that in the elderly group,and the differences were statistically significant(P＜0.05).The mean levels of GAS and 5-HT in the non elderly group were sig-nificantly higher than those in the elderly group,and the differences were statistically significant(P＜0.05),but there were no significant differences in the levels of GIP and MTL between the two groups(P＞0.05).The mean levels of IL-18 and CGRP in the non elderly group were significantly higher than those in the elder-ly group,and the mean level of IL-10 in the non elderly group was significantly lower,and the differences were statistically significant(P＜0.05),but there was no significant difference in the level of IL-8 between the two groups(P＞0.05).Pearson correlation analysis showed that IBS-SSS scores were positively correlated with serum levels of 5-HT,IL-18 and CGRP in non-elderly IBS patients,elderly IBS patients and all enrolled IBS patients(P＜0.05).Multivariate Logistic regression analysis showed that the elevated serum levels of 5-HT,IL-18 and CGRP were independent risk factors for severe IBS in non-elderly patients(P＜0.05).Among all patients,only elevated serum 5-HT level was an independent risk factor for severe IBS(P＜0.05).Conclusion Regardless of the type of IBS,the severity of IBS in elderly patients is less than that in non-elderly patients.The levels of gastrointestinal hormones and inflammation markers are different in patients at different ages.The serum levels of 5-HT,IL-18 and CGRP are positively correlated with the severity of IBS,which are poten-tial biological indicators to reflect the severity of IBS.

Objective To observe the effect of abdominal massage combined with thumb-tack needling for subcutaeous embedding on sleep homeostasis system in rats with anxiety insomnia.Methods Forty rats were randomly divided into normal group,model group,abdominal massage group,thumb-tack needling for subcutaeous embedding group and abdominal massage plus thumb-tack needling for subcutaeous embedding group,with 8 rats in each group.Except for the normal group,the rats in the other groups were used to replicate the model of anxiety insomnia by multi-factor compound stimulation.After the corresponding intervention,Morris water maze test was used to detect the level of learning and memory.Open field test was used to detect the degree of anxiety stress.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of hypothalamic ventral lateral preoptic nucleus(VLPO)neurons.Immunohistochemistry,real-time quantitative polymerase chain reaction(qRT-PCR)and Western Blot were used to detect the protein and mRNA expression of N-methyl-D-aspartate(NMDA)receptor subunits NR1,NR2B and calmodulin kinase Ⅱ(CaMK Ⅱ)in hypothalamic VLPO area,respectively.Results Compared with the normal group,the daytime anxiety symptoms of the rats in the model group were aggravated,the sleep latency was prolonged and the duration was shortened(P＜0.01).The average total swimming distance and average escape latency of the water maze directional navigation experiment were increased(P＜0.01).The number of crossing the hidden platform and the retention time of the target quadrant in the space exploration experiment were decreased(P＜0.01).The movement distance,the number of central grid crossings and the retention time of the central grid in the open field experiment were significantly reduced(P＜0.01).There was no significant difference in the modification frequency and the number of uprights(P＞0.05).Neurons in the VLPO brain region showed pathological damage.The protein and mRNA expression levels of NR1 and CaMK Ⅱ were decreased(P＜0.01)in VLPO brain region,and the protein and mRNA expression levels of NR2B were increased(P＜0.01).Compared with the model group,the level of learning and memory in the water maze test and the degree of anxiety stress in the open field test were significantly restored in the abdominal massage group,the thumb-tack needling for subcutaeous embedding group and the abdominal massage combined with thumb-tack needling for subcutaeous embedding group(P＜0.05 or P＜0.01),the neuronal damage in the VLPO brain region was improved,the protein and mRNA expression levels of NR1,CaMK Ⅱ were increased(P＜0.05 or P＜0.01),and the protein and mRNA expression levels of NR2B were decreased(P＜0.05 or P＜0.01).The improvement effect of the above indexes in the abdominal massage plus thumb-tack needling for subcutaeous embedding group was superior to that in the abdominal massage group or thumb-tack needling for subcutaeous embedding group(P＜0.05 or P＜0.01).Conclusion Abdominal massage combined with thumb-tack needling for subcutaeous embedding can promote sleep and anti-anxiety in rats with anxiety insomnia.The related mechanism may be related to adjusting the dynamic balance between NR1/NR2B in VLPO brain area and up-regulating the expression level of CaMK Ⅱ,improving the function of neurons in VLPO brain area,and then restoring the regulation of sleep homeostasis system.

Objective To design an anti-inversion performance evaluation system for ankle braces and validate its performance.Methods The system was composed of a simulation system,an inversion angle acquisition system,a lateral tension acquisition system for ankle joint and a data collection and procession system.The simulation platform made of aluminum alloy consisted of a standing platform and a landing pad,and the landing pad was made up of a platform and a slope for landing;the inversion angle acquisition system included markers,an image acquisition device and a fill light.The lateral tension acquisition system involved in a tension sensor,a detection sensor and an elastic cloth for fixation.The data collection and procession system comprised of a computer or smartphone,iXControl software,iXViewer software and a cell phone App that received real-time data from the lateral ankle tension acquisition device.The system developed underwent performance validation when applied to evaluating anti-inversion performance of volunteers without or with flexible or new braces.The traditional EMG testing method was used for EMG data acquisition for volunteers without or with flexible or new braces,and the consistency was explored between the testing results by the traditional method and the system.Results The system developed could evaluate the anti-inversion performance of ankle braces by simulating the process of ankle inversion during human high-altitude landing,and the results had high consistency with those by traditional EMG testing methods.Conclusion The system developed with simple structure and easy operation evaluates the anti-inversion performance of ankle braces.[Chinese Medical Equipment Journal,2024,45(11):21-26]

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.