ObjectiveTo observe the effects of modified Chaihu Shugansan on the calmodulin-dependent protein kinase Ⅱ（CaMKⅡ）/cAMP-response element binding protein （CREB） signaling pathway in the hippocampus and heart tissue of a rat model with myocardial ischemia and depression and explore the mechanism by which this formula prevents and treats coronary heart disease combined with depression. MethodsThe model of myocardial ischemia combined with depression was established by high-fat diet， intraperitoneal injection of isoproterenol （ISO）， and chronic unpredictable mild stress （CUMS）. A total of 108 SD male rats were randomly divided into normal group， model group， high （23.4 g·kg^-1）， medium （11.7 g·kg^-1）， and low （5.85 g·kg^-1） dose groups of modified Chaihu Shugansan， CaMKⅡ inhibitor （KN93） group， and KN93 + high， medium， and low dose groups of modified Chaihu Shugansan， with 12 rats in each group. From the first day of modeling to the end of modeling， drugs were administered once a day. In the seventh and eighth weeks， the KN93 group and the KN93 + high， medium， and low dose groups of modified Chaihu Shugansan were intraperitoneally injected with KN93 three times weekly. At the end of the eighth week， behavioral tests including sucrose preference， open field， and elevated plus maze were conducted. Electrocardiogram （ECG） lead Ⅱ changes were observed in each group of rats， and hematoxylin-eosin （HE） staining was performed to observe changes in heart tissue. Serum levels of triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein （HDL）， low-density lipoprotein （LDL）， and lactate dehydrogenase （LDH） were measured by using an enzyme-labeled instrument. Creatine kinase （CK） and creatine kinase-MB （CK-MB） were detected by ultraviolet spectrophotometry， while serum monocyte chemoattractant protein-1 （MCP-1） was measured by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression of CaMKⅡ and CREB in hippocampal and heart tissue， and Western blot was performed to assess protein expression of CaMKⅡ， phosphorylated （p）-CaMKⅡ， CREB， and p-CREB. ResultsCompared to the normal group， the model group showed significant reductions in sucrose preference rate， total activity distance in the open field， number of entries into the center area of the open field， and percentage of entries into the open arms of the elevated plus maze （P<0.01）. The ECG showed ST-segment elevation， and HE staining showed serious degeneration of myocardial fibers， disordered arrangement， and infiltration of a large number of inflammatory cells. In addition， serum TC and LDL levels increased （P<0.01）， and HDL level decreased （P<0.01）. CK， CK-MB， LDH， and MCP-1 levels significantly increased （P<0.05， P<0.01）. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB decreased in the hippocampal tissue （P<0.05， P<0.01）， but those increased in the heart tissue （P<0.01）. Compared to the model group， the high， medium， and low dose groups of modified Chaihu Shugansan showed improvements in these abnormalities. The KN93 group had reduced sucrose preference， total activity distance in the open field， number of entries into the center area of the open field， and percentage of entries into the open arms of the elevated plus maze （P<0.01）， as well as decreased serum CK， CK-MB， LDH， and MCP-1 levels （P<0.05， P<0.01）. KN93 also reduced ST-segment elevation， alleviated the degeneration degree of myocardial fibrosis， and lowered inflammatory cell infiltration. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB in both the hippocampal and heart tissue were reduced （P<0.05， P<0.01）. The KN93 + high， medium， and low dose groups of modified Chaihu Shugansan showed further improvements in these abnormalities compared to the KN93 group. ConclusionThe modified Chaihu Shugansan exerts antidepressant and myocardial protective effects in rats with myocardial ischemia and depression， possibly related to bidirectional regulation of the CaMKⅡ/CREB signaling pathway， with the high-dose modified Chaihu Shugansan showing the best effects.

When partial nephrectomy is performed by posterior abdominal approach, the surgical field is poorly exposed, resulting in increased surgical difficulty and risk of injury.In this study, 28 patients with T 1a stage kidney tumors underwent retroperitoneal laparoscopic partial nephrectomy. Intraoperatively, exposure of the surgical field was achieved using the percutaneous puncture of the renal fascia suspension technique. There were no dissatisfactory exposures due to peritoneal damage during the surgery, no additional tubes were inserted, and no conversions to open surgery were needed. The operation time was (76.5±20.3) minutes, blood loss was (92.1±18.7) ml, renal artery clamping time was (19.5±4.3) minutes. Postoperatively, there were no complications such as bleeding, infection, or hematuria.

Objective:To investigate the epidemiological characteristics, genotypes and genetic evolution of respiratory syncytial virus (RSV) isolated in Shanghai from April 2020 to December 2021, which was a period from the COVID-19 outbreak to the phase of regular epidemic prevention and control.Methods:This retrospective study collected the nasopharyngeal secretions or nasopharyngeal aspirates of children with acute respiratory tract infection (ARTI) admitted to the Shanghai Children′s Hospital from April 2020 to December 2021. PCR-capillary electrophoresis and RT-PCR were used for virus identification and the amplification of the gene fragment of the second hypervariable region of RSV G protein. Homology analysis and phylogenetic analysis were conducted using bioinformatics software. Chi-square test was used to compare the detection rates of RSV. Results:A total of 6 211 samples were collected and 13.62% (846/6 211) of them were positive for RSV. The positive rates of RSV in male and female patients were 14.07% (503/3 574) and 13.01% (343/2 637), respectively, with no significant gender difference (χ 2=1.467, P=0.226). The highest detection rate of RSV was found in children ≤6 months of age, and the rate of RSV infection decreased gradually with age (χ 2=352.942, P<0.001). No RSV-positive specimens were detected from April 2020 to August 2020, after which the detection rate of RSV gradually increased with two epidemic peaks occurring from December 2020 to February 2021 and from August to October 2021. The predominant epidemic subtype was RSV subtype B in 2020 and the first 9 months of 2021, which was gradually replaced by RSV subtype A in the last 3 months of 2021. The 176 strains of RSV subtype A obtained in this study were all ON1 genotype, and the nucleotide homology of the Shanghai epidemic strains was 90.20%-99.50%. All of the 250 strains of RSV subtype B were BA9 genotype, and the nucleotide homology of the Shanghai epidemic strains was 90.10%-100.00%. Conclusions:From April 2020 to December 2021, with the regular prevention and control of COVID-19, there is a change in the epidemic season of RSV. The prevalent genotypes of RSV subtypes A and B are ON1 and BA9, respectively, and the subtype A gradually replaces subtype B as the most prevalent subtype.

Objective To evaluate the bioequivalence and safety of ibuprofen arginine granules test and reference formulations in Chinese healthy volunteers under fasting and postprandial conditions,and to provide evidence for consistency evaluation and clinical application of the drugs.Methods A single-center,single-dose,randomized,open-label,fasting and postprandial,two-period,two-crossover trial design was used.Twenty-four healthy Chinese volunteers were enrolled in the fasting and postprandial trial,respectively.The test preparation and reference preparation of ibuprofen arginine granules 0.4 g were taken orally in a randomized crossover single dose.Data analysis was performed using Phoenix WinNonlin 8.3.Results In the fasting group,the main pharmacokinetic parameters of ibuprofen in plasma after administration of the test and reference formulations of ibuprofen arginine granules were as follows:Cmax were(51.07±7.43)and(50.10±7.64)μg·mL-1;AUC0-,were(122.78±20.62)and(119.94±21.03)μg·h·mL-1;AUC0_∞ were(125.84±21.31)and(122.64±21.87)μg·h·mL-1,respectively.In the postprandial group,the main pharmacokinetic parameters of ibuprofen in plasma after administration of the test and reference formulations of ibuprofen arginine granules were as follows:Cmax were(17.47±3.56)and(17.89±4.47)μg·mL-1;AUC0-twere(114.33±17.12)and(122.13±29.46)μg·h·mL-1;AUC0_∞ were(134.04±36.72)and(133.96±30.35)μg·h·mL-1,respectively.The 90％confidence intervals of the geometric mean ratio of the two preparations were as follows:Cmax 97.96％-106.02％,AUC0_t 98.77％-105.14％,AUC0-∞ 99.34％-105.19％in fasting group;in postprandial group,Cmax was 92.37％-103.05％,AUC0-t was 93.31％-99.56％,AUC0-∞ was 93.89％-102.91％.Conclusion The test preparation and reference preparation of ibuprofen arginine granules in this study are bioequivalent in healthy adult Chinese volunteers.

A 5-year-old girl was admitted due to one episode of melena and one episode of hematemesis.Upon admission,gastroscopy revealed esophageal and gastric varices.Abdominal CT scan,MRI,and color Doppler ultrasound suggested cirrhosis,intrahepatic bile duct dilation,and bilateral kidney enlargement.Genetic testing identified compound heterozygous mutations in the PKHD1 gene:c.2264C>T(p.Pro755Leu)and c.1886T>C(p.Val629Ala).The c.2264C>T(p.Pro755Leu)mutation is a known pathogenic variant with previous reports,while c.1886T>C(p.Val629Ala)is a novel mutation predicted to have pathogenic potential according to Mutation Taster and PolyPhen2.The child was diagnosed with autosomal recessive polycystic kidney disease.In children presenting with gastrointestinal bleeding without obvious causes,particularly those with liver or kidney disease,consideration should be given to the possibility of autosomal recessive polycystic kidney disease,and genetic testing should be conducted for definitive diagnosis when necessary.

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.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective:To explore the pathogenesis of flunarizine-induced parkinsonism from gut-brain axis perspective.Methods:Thirty male C57BL/6 mice were randomly divided into control group and flunarizine group ( n=15). Mice in the control group were given 0.1 mL 50% polyethylene glycol 400+50% saline by gavage once/d for 2 weeks, while mice in the flunarizine group were given 6 mg/mL flunarizine+50% polyethylene glycol 400+50% saline by gavage at a daily dose of 30 mg/kg for 2 weeks. Body mass was recorded 1, 3, 5, 7, 10 and 14 d after drug administration, and motor function was assessed by rotarod test 14 d after drug administration; 16s RNA sequencing was performed in the feces to observe the intestinal flora; intestinal transit function was detected by Evans blue by gavage; and then, the mice were sacrificed and homogenate or frozen sections (brain and intestinal tissues) were prepared; dopamine-ergic neuron expression was detected by Western blotting; RT-qPCR was applied to detect the expressions of inflammatory factors in the substantia nigra, and immunofluorescent staining was used to detect the expressions of ZO-1 and Claudin-5 in the intestinal epithelial tissues. Results:Compared with the control group, the flunarizine group had lower body mass ratio 1, 3, 5, 7, 10 and 14 d after drug administration (ratio to body mass before drug administration). Compared with the control group, the flunarizine group had significantly shortened residence time in rod rotating and lower rotational speed when falling ( P<0.05). Compared with the control group, the flunarizine group had decreased tyrosine hydroxylase protein in the substantia nigra without significant difference ( P>0.05). Compared with the control group, the flunarizine group had significantly increased interleukin-6 and tumor necrosis factor-α in the substantia nigra (1.00±0.00 vs. 2.79±0.83; 1.00±0.00 vs. 3.39±1.37), significantly lower intestinal Evans blue propulsion rate (80.67%±4.51% vs. 50.67%±6.03%), and statistically decreased ZO-1 and Claudin-5 expressions in the colonic epithelial tissues (27.01±1.41 vs. 16.32±2.83; 37.00±2.80 vs. 24.52±2.12, P<0.05). Totally, 576 microorganisms were noted in both control group and flunarizine group, 744 in the control group alone, and 634 in the flunarizine group alone. The intestinal flora β diversity indices in the 2 groups were significantly different based on weighted Unifrac-principle coordinates analysis (PCoA, PCoA1: 39.88%; PCoA2: 30.69%). Compared with the control group, the microbial colony structure of mice in flunarizine group was dominated by phylum thick-walled bacteria and phylum warty microbacteria, and by families Muribaculaceae, Lachnospiraceae and Akkermansiaceae. Compared with the control group, the flunarizine group had significantly decreased relative abundance of Ackermannia spp. and Lactobacillus spp. in the intestinal flora ( P<0.05). Conclusion:Flunarizine may contribute to the pathogenesis of DIP by causing structural disturbances in the intestinal flora and inducing neuroinflammation based on the gut-brain axis.

Objective To compare the effects and prognosis between bivalirudin and heparin on coronary microcirculation in patients with acute coronary syndrome(ACS)during percutaneous coronary intervention(PCI).Methods A retrospective analysis was conducted on 312 ACS patients who underwent PCI treatment in the Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University from January 2020 to March 2023.General clinical data were analyzed and divided into a bivalvrudin group of 153 patients and a heparin group of 159 patients based on different anticoagulation regimens during the perioperative period.The postoperative thrombolysis in myocardial infarction(TIMI)blood flow grading,TIMI myocardial perfusion grading(TMPG),ST segment regression rate(STR)of electrocardiogram,and the number of angina pectoris episodes were observed and compared between the two groups The incidence of adverse events within 7 days after surgery,the incidence of major adverse cardiovascular events(MACE)within 3 months after surgery,and the incidence of bleeding events.Results There was no statistically significant difference in the general clinical data and intraoperative conditions between the two groups of patients(both P＞0.05).There was no statistically significant difference in TIMI blood flow grading between the two groups of patients after PCI(P=0.959).The TMPG grading of two groups of patients after PCI was statistically significant(P=0.001).The number of angina attacks and ST segment regression rate of electrocardiogram in both groups of patients after PCI were statistically significant(both P＜0.05).The incidence of adverse events within 7 days after PCI in two groups of patients was not statistically significant(P=0.285).There was no statistically significant difference in the total incidence of MACE events within 3 months after PCI between the two groups of patients(P=0.195).There was no statistically significant difference in the incidence of bleeding events within 3 months after PCI between the two groups of patients(all P＞0.05).Conclusions sivalirudin is safe and effective for PCI treatment,can improve coronary microcirculation,and does not increase the incidence of MACE events,bleeding events,and stent thrombosis events.

Objective:To determine the effect of community management based on the Roy′s adaptation model (RAM) in patients with chronic obstructive pulmonary disease (COPD).Methods:This study was a cluster randomized controlled study, with the community as the cluster unit, and selected 805 COPD patients from 8 communities in Xuzhou City who had completed community registration before June 2019. A total of 735 patients actually completed follow-up and participated in intervention evaluation. They were randomly divided into control group (362 cases) and intervention group (373 cases) by random number table method. The control group received routine follow-up, while the intervention group received RAM intervention for 6 months. The forced expiratory volume in 1 second (FEV1)/forced volume vital capacity (FVC) ratio (FEV 1/FVC) and the modified British medical research council (mMRC) were used to assess the pulmonary function. The hospital anxiety and depression scales (HADS) were used to evaluate the mental health. The Chinese version of the Short Form Coping and Adaption Processing Scale (CAP-15) was used to assess the adaptive capacity. And the St. George′s Respiratory Questionnaire (SGRQ) was used to evaluate the quality of life in COPD patients. The t test or χ 2 test was used for pre-intervention comparisons between groups, and the repetitive measure analysis of variance (ANOVA) was used for post-intervention comparisons between groups. Results:After 6 months intervention, there were no significant differences in FEV 1/FVC radio between the two groups [(0.61±0.11) vs (0.62±0.12)] ( P=0.172). The scores of mMRC [(2.04±0.33) vs (2.77±0.31) points], HAD-A [(5.28±4.28) vs (6.99±4.41) points], HAD-D [(5.82±5.12) vs (7.27±4.93) points] and SGRQ [(40.17±9.30) vs (53.69±9.77) points] were all lower in the intervention group than those in the control group (all P<0.001). The CAPS-15 score was higher in the intervention group than that in the control group [(35.87±3.62) vs (26.1±3.47)] ( P<0.001). Conclusion:RAM could be used in community management of COPD patients, which could improve their dyspnea symptoms and psychological and physiological functions, also improve their adaptability and quality of life.