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.

Although somatic cells can be reprogrammed to pluripotent stem cells (PSCs) with pure chemicals, authentic pluripotency of chemically induced pluripotent stem cells (CiPSCs) has never been achieved through tetraploid complementation assay. Spontaneous reprogramming of spermatogonial stem cells (SSCs) was another non-transgenic way to obtain PSCs, but this process lacks mechanistic explanation. Here, we reconstructed the trajectory of mouse SSC reprogramming and developed a five-chemical combination, boosting the reprogramming efficiency by nearly 80- to 100-folds. More importantly, chemical induced germline-derived PSCs (5C-gPSCs), but not gPSCs and chemical induced pluripotent stem cells, had authentic pluripotency, as determined by tetraploid complementation. Mechanistically, SSCs traversed through an inverted pathway of in vivo germ cell development, exhibiting the expression signatures and DNA methylation dynamics from spermatogonia to primordial germ cells and further to epiblasts. Besides, SSC-specific imprinting control regions switched from biallelic methylated states to monoallelic methylated states by imprinting demethylation and then re-methylation on one of the two alleles in 5C-gPSCs, which was apparently distinct with the imprinting reprogramming in vivo as DNA methylation simultaneously occurred on both alleles. Our work sheds light on the unique regulatory network underpinning SSC reprogramming, providing insights to understand generic mechanisms for cell-fate decision and epigenetic-related disorders in regenerative medicine.
Male ; Mice ; Animals ; Cellular Reprogramming/genetics* ; Tetraploidy ; Pluripotent Stem Cells/metabolism* ; Induced Pluripotent Stem Cells/metabolism* ; DNA Methylation ; Spermatogonia/metabolism* ; Germ Cells/metabolism*

Objective:To evaluate the efficacy and safety of disitamab vedotin combined with tislelizumab in the neoadjuvant treatment of bladder cancer.Methods:The clinical data of 16 bladder cancer patients who received neoadjuvant therapy with disitamab vedotin combined with tislelizumab from April 2022 to January 2023 at the First Hospital of Chongqing Medical University were retrospectively analyzed. There were 15 males and 1 female, aged (66.12±14.37) years old. The immunohistochemical staining of biopsy pathology showed that HER-2 (0), (+ ), (+ + ), and (+ + + ) were in 1, 6, 6, and 3 cases, respectively. Before neoadjuvant therapy, 5 cases were in T 2N 0M 0 stage, and 11 cases were in T 3N 0M 0 stage. Biopsy pathology showed 3 cases were low-grade uroepithelial carcinoma, and 13 cases were high-grade uroepithelial carcinoma. Neoadjuvant therapy regimens: Disitamab vedotin 120 mg, every 2 weeks for 1 cycle, a total of 4 cycles. Tislelizumab 200 mg, every 3 weeks for 1 cycle, a total of 3 cycles. Surgery was performed at 2-3 weeks after neoadjuvant therapy. The efficacy and adverse effects of neoadjuvant therapy were analyzed. Results:All 16 cases completed neoadjuvant therapy.Five cases achieved complete remission, 7 cases achieved partial remission, 3 cases had stable disease, and 1 case had disease progression.Twelve cases(75.0%) achieved objective remission, 15 cases (93.8%) had disease control, and 14 cases(87.5%) had a reduction in the target lesion from baseline. Complete remission was achieved in 2 (22.2%)of 9 HER-2-positive patients and and 3 (42.9%) of 7 HER-2-negative patients, respectively, and objective remission was achieved in 8 (88.9%) and 4 (57.1%). After neoadjuvant treatments, surgical treatments were refused in 6 cases, and bladder-preserving combination therapy was performed in 2 cases. Radical cystectomy were performed in 8 cases, with negative margins for surgical incision, of which 5 cases (62.5%) had postoperative pathologic stage

Objective:To observe the clinical effect of modified Shishi Niubangzi Decoction combined with strengthening muscle-waist exercise on lumbar disc herniation (LDH).Methods:Randomized controlled trial. A total of 60 patients with LDH admitted to the Pinggu Hospital, Beijing Traditional Chinese Medicine Hospital, were enrolled as the research objects between September 2020 and September 2021. According to the random number table, they were randomly divided into the treatment group and control group, 30 in each group. Both groups were given routine basic treatments (strengthening tendons-waist exercise and three-position six-step manipulation). On this basis, the treatment group was treated with modified Shishi Niubangzi Decoction, while the control group was treated with non-steroidal anti-inflammatory drugs (ibuprofen codeine sustained-release tablets). Both groups were treated for 4 weeks. The responsive rates, back pain intensity, leg pain and numbness by Visual Analogue Scale (VAS) and lumbar function by Oswestry Disability Index (ODI), and Japanese Orthopaedic Association (JOA) were compared between the two groups.Results:The response rate of treatment group was significantly higher than that of control group (93.3% vs. 73.3%; χ2=4.32, P=0.038). After treatment, scores of JOA (subjective symptoms, signs, activities of daily living) in the treatment group were significantly higher than those in the control group ( t=3.86, 2.71, 2.21, P<0.05). After treatment, scores of back pain (2.12±0.21 vs. 3.02±0.32, t=12.88), leg pain (2.04±0.64 vs. 2.64±0.66, t=3.58), lower limb numbness (1.75±0.24 vs. 2.41±0.70, t=4.89) in the treatment group were significantly lower than those in the control group ( P<0.01). At 1 week and 1 month after treatment, ODI scores in treatment group were significantly lower than those in control group ( t=10.22, 5.59; P<0.05). Conclusion:The modified Shishi Niubangzi Decoction combined with strengthening tendons-waist exercise can improve responsive rates, improve lumbar pain and function in LDH patients.

Objective:To investigate the effect of sakubatril/valsartan on left ventricular systolic dyssynchrony in young patients with dilated cardiomyopathy (DCM).Methods:Forty-nine patients with left ventricular systolic asynchronism DCM from July 2017 to July 2018 in Guangdong Medical University Affiliated Hospital were randomly divided into two groups. The experimental group was treated with sakubatra valsartan and the control group was treated with lotensin for 12 months. Left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVESd) and ejection fraction (EF) were measured by two-dimensional color Doppler echocardiography. The left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), ejection fraction (EF) and systolic dyssynchrony index (SDI) of 16 segments were measured by three-dimensional color Doppler ultrasound. Plasma NT-proBNP was tested before and after treatment.Results:After treated for 12 months, three-dimensional color Doppler ultrasonography showed the LVEDV in the experimental group decreased significantly: (180.5 ± 42.7) ml vs. (160.5 ± 45.6) ml, P<0.05. The left ventricular systolic asynchronism (SDI) of 16 segments in the experimental group significantly improved, and the value of left ventricular SDI significantly decreased compared with that of the control group: (8.2 ± 3.6)% vs. (10.8 ± 4.1)%, P<0.05. Plasma NT-proBNP decreased more significantly in the experimental group compared with that in the control group: (105.54 ± 13.25) ng/L vs. (137.27 ± 14.36) ng/L, P<0.05. Conclusions:Sakubatril/valsartan can effectively improve left ventricular systolic dyssynchrony in young patients with dilated cardiomyopathy.

Objective: To observe the effect of combining whole body vibration with botulinum neurotoxin A injections on tiptoe and the gross motor function of children with spastic diplegic cerebral palsy. Methods: Sixty spastic diplegic children with tipped foot aged between 2 to 5 were equally divided into a control group and an experimental group randomly. The control group received 3 IU/kg botulinum neurotoxin A injections to the medial and lateral heads of the gastrocnemius muscle. Then 5 daily courses of conventional training were administered 5 days a week for 3 weeks beginning 24 hours after the injections. The experimental group additionally received 2min of whole body vibration 3 or 4 times per day with one-minute rests, 5 days per week for 5 weeks. All of the children were assessed before the experiment and 1, 3 and 6 months later using the modified Tardieu scale (MTS) and the R1 and R2 ankle and dimensions D and E of the gross motor function measurement scale (GMFM-88). Results: There were no significant differences between the two groups before the treatment. Afterward, the average MTS, R1, R2 and GMFM-88 scores of both groups were significantly improved. The average MTS, R1 and R2 scores of the experimental group after treatment were significantly better than the control group′s averages. The average GMFM-88 score of the experimental group was not significantly different from that of the control group after 1 month, but after 3 and 6 months significant differences emerged. Conclusion Whole body vibration improves the effectiveness of botulinum neurotoxin A injections in relieving tiptoe and improving the gross motor function of children with spastic diplegic cerebral palsy.

OBJECTIVE:To investigate therapeutic efficacy of ezetimibe combined with tirofiban in the treatment of acute coronary syndrome patients and its influence on the content of ischemia modified albumin (IMA) in peripheral blood.METHODS:A total of 82 patients with acute coronary syndrome in our hospital from Jan.2016 to Jan.2017 were divided into observe group and control group according to random number table,with 41 cases in each groups.All patients were given general treatment containing statins,glyceryl trinitrate and so on.Control group was additionally given Ezetimibe tablet 10 mg orally once a day.Observation group was additionally given Tirofiban hydrochloride sodium chloride injection 5 mg intravenously once a day,on the basis of control group,for consecutive 15 d.Clinical efficacies of 2 groups were evaluated.The dose of glyceryl trinitrate,duration and frequency of angina pectoris attack,left ventricular function indexes (SV,LVDD,CO,LVEF) were compared before treatment and after last medication.The contents of IMA in peripheral blood were detected before treatment and 3,6,9,12,15 h after the first day medication.ADR of the 2 groups were observed closely during the treatment.RESULTS:The total response rate of observation group was 92.7％,which was significantly higher than 72.3％ of control group (P＜0.05).Compared with before treatment,dose of glyceryl trinitrate and the content of IMA in 2 groups were decreased significantly after last medication,duration and frequency of angina pectoris attack were shortened significantly;the levels of SV,CO and LVEF were increased significantly while the level of LVDD was decrease significantly;the effect of observation group was significantly better than that of control group,with statistical significance (P＜0.05).No severe ADR was found in all patients during the treatment.CONCLUSIONS:Based on general treatment of glyceryl trinitrate therapeutic efficacy of ezetimibe combined with tirofiban is better than that of ezetimibe alone in the treatment acute coronary syndrome patients,and can decrease the content of IMA in peripheral blood more quickly.

Objective To investigate the effects of different clipping time of first time using permanent aneurysm clips on common carotid artery wall in rabbitsMethods Sixty healthy male Japanese white rabbits were selected.The first time permanent aneurysm clips were used to clip common carotid artery for 30 min or 60 min respectively according to the random number method (n=30 in each group).Thirty segments of common carotid artery specimens clipped by aneurysm clips were collected respectively.Mean-Whitney U test was used to conduct the comparison of histopathological damage grade of vascular wall.Results The aneurysm clips were use to clip 30 min and 60 min caused vascular wall injury could observe the middle elastic plastic plate deformation and endothelial denudation.The vascular walls in the clipping 60 min group had local necrosis with inflammatory response,and even rupture of vascular wall.There were significant differences in overall damage degree of vascular wall (U=324.00,P=0.045) and severe injury rate (0%[0/30] vs.20.0%[6/30],P=0.031) between the clipping 30 min group and the clipping 60 min group (all P<0.05).Conclusion The vascular wall injury of using disposable permanent aneurysm clips for clipping 60 min was more severe than 30 min.Attention should be paid to shortening the time of carotid artery occlusion in operation.

Objective To explore the effect of Src on cervical cancer cells through ERK signal transduction pathway.Methods Experimental study was carried out in vitro.Cervical cancer cell lines Hela (HPV-positive) and C33A (HPV-negative) were treated with Src kinase inhibitor PP2.Then,the cell cycle and apoptosis of each group were evaluated by using flow cytometry (FCM).Western blotting and Real-time PCR were used to detect the levels of the expression of ERK 1/2,c-Fos and c-Jun mRNA and protein respectively.The database was established and analyzed with SPSS statistical software (version 20.0).Results After down-regulating Src,the cell proliferation was inhibited and cell apoptosis was induced.The proportions of G0/G 1 stage of Hela and C33A cell in cell cycle increased while G2/M and S stages decreased.Meanwhile,the mRNA levels of ERK 1,ERK 2,c-Fos and c-Jun increased.And the expression levels of ERK 1/2,phosphorylated ERK 1/2 (p-ERK 1/2)and phosphorylated c-Fos (p-c-Fos) protein decreased,while c-Jun and phosphorylated c-Jun (p-c-Jun)protein expression increased.In addtion,the change level of Hela cell,p-ERK 1/2 and c-Fos protein were lower than that of C33A cell before and after the Src inhibition.Conclusions Src,involved in regulating the expression of key factors of the ERK signal transduction pathway including p-ERK 1/2 and p-c-Fos,might be capable of promoting the proliferation of cervical cancer cells and inhibiting their apoptosis.The infection with HPV might have adjustable effect on this process.

Objective To observe the incidence of adverse reactions and short-term efficacy of S-1 and concurrent intensity-modulated radiotherapy ( IMRT) for locally advanced gastric cancer in a phase Ⅱclinical trial based on the phase I clinical trial.Methods Patients pathologically diagnosed with stage TN (+) gastric adenocarcinoma with local or distal metastasis after R0 resection were enrolled as subjects.IMRT was delivered 5 times per week with a total dose of 45 Gy in 25 fractions.S-1 was orally administered on the day of radiotherapy at a dose of 80 mg/m2 .Results A total of 40 patients, consisting of 6 patients from the phase I trial and 34 patients from the phaseⅡtrial, were enrolled in this study.In those patients, the age ranged between 27 and 73 years ( median age 50 years) and the male-to-female ratio was 3:1.Thirty-nine ( 98%) out of the forty patients completed radiotherapy and thirty-five ( 88%) completed concurrent chemotherapy.The most common grade 3-4 adverse reactions were nausea/anorexia ( 13%) , leukopenia ( 10%) , vomiting ( 8%) , radiation esophagitis ( 5%) , and neutropenia ( 5%) .There was no perioperative death.The 2-year overall survival and disease-free survival rates were 74% and 77%, respectively. Conclusions Postoperative S-1 and concurrent IMRT achieve satisfactory outcomes and tolerable toxicity in patients with locally advanced gastric cancer.