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 investigate the safety and clinical effect of testis-sparing microsurgery(TSMS)in the treatment of benign testis tumor(BTT).Methods:We retrospectively analyzed the clinical data on 16 cases of BTT treated in the Department of Andrology of the Affiliated Hospital of Qingdao University from October 2020 to February 2023.The median age of the patients was 23 years.All the tumors were unilateral,7 in the left and 9 in the right side,with a median diameter of 1.85 cm(1.0-3.5 cm).The patients all underwent color Doppler flow imaging(CDFI),MRI,semen analysis and examination of serum T,alpha-fetoprotein(AFP),human chorionic gonadotropin(HCG)and lactate dehydrogenase(LDH),followed by TSMS.The boundaries between the tumors and normal testis tissue were accurately identified under the microscope,and the tumors and the adjacent normal testis tissue 2 mm from their margins were excised completely.Bipolar coagulation forceps were used for wound hemostasis to maximally preserve the normal testis tissue.The resected specimens were subjected to fast frozen pathology intraoperatively,and the patients were followed up for 14-40 months by regular scrotal CDFI,MRI and examinations of serum T and semen parameters.Results:The levels of serum T,AFP,HCG and LDH and semen parameters were all within the normal range preoperatively.TSMS were successfully completed in all the cases,and all were pathologically confirmed as BTT according to the latest edition of WHO Classification of Tumors:Urinary and Male Genital Tumors.CDFI showed normal blood supply within the testis tissue at 1 month after surgery.No signs of intra-testicu-lar tumor residue,recurrence or metastasis,nor significant changes in the levels of serum T,AFP,HCG or LDH or semen parameters were observed during the follow-up as compared with the baseline.Natural conception was achieved in 2 cases at 16 and 18 months re-spectively after surgery.Conclusion:BTT can be differentially diagnosed by CDFI and MRI before surgery and confirmed by histo-pathology.TSMS can achieve complete excision of the tumor,maximal sparing of the normal testis tissue and thereby effective preserva-tion of male fertility.

The structures and activities of enzymes are influenced by pH of the environment. Understanding and distinguishing the adaptation mechanisms of enzymes to extreme pH values is of great significance for elucidating the molecular mechanisms and promoting the industrial applications of enzymes. In this study, the ESM-2 protein language model was used to encode the secreted microbial proteins with the optimal performance above pH 9 and below pH 5, which yielded 47 725 high-pH protein sequences and 66 079 low-pH protein sequences, respectively. A deep learning model was constructed to identify protein acid-base tolerance based on amino acid sequences. The model showcased significantly higher accuracy than other methods, with the overall accuracy of 94.8%, precision of 91.8%, and a recall rate of 93.4% on the test set. Furthermore, we built a website (https://enzymepred.biodesign.ac.cn), which enabled users to predict the acid-base tolerance by submitting the protein sequences of enzymes. This study has accelerated the application of enzymes in various fields, including biotechnology, pharmaceuticals, and chemicals. It provides a powerful tool for the rapid screening and optimization of industrial enzymes.
Deep Learning ; Hydrogen-Ion Concentration ; Amino Acid Sequence ; Enzymes/metabolism* ; Sequence Analysis, Protein ; Proteins/metabolism* ; Bacterial Proteins/metabolism*

Resection of oral and maxillofacial tumors is often accompanied by the inferior alveolar nerve neurectomy, resulting in abnormal sensation in lower lip. It is generally believed that spontaneous sensory recovery in this nerve injury is difficult. However, during our follow-up, patients with inferior alveolar nerve sacrifice showed different degrees of lower lip sensory recovery. In this study, a prospective cohort study was conducted to demonstrate this phenomenon and analyze the factors influencing sensory recovery. A mental nerve transection model of Thy1-YFP mice and tissue clearing technique were used to explore possible mechanisms in this process. Gene silencing and overexpression experiments were then conducted to detect the changes in cell morphology and molecular markers. In our follow-up, 75% of patients with unilateral inferior alveolar nerve neurectomy had complete sensory recovery of the lower lip 12 months postoperatively. Patients with younger age, malignant tumors, and preservation of ipsilateral buccal and lingual nerves had a shorter recovery time. The buccal nerve collateral sprouting compensation was observed in the lower lip tissue of Thy1-YFP mice. ApoD was demonstrated to be involved in axon growth and peripheral nerve sensory recovery in the animal model. TGF-β inhibited the expression of STAT3 and the transcription of ApoD in Schwann cells through Zfp423. Overall, after sacrificing the inferior alveolar nerve, the collateral compensation of the ipsilateral buccal nerve could innervate the sensation. And this process was regulated by TGF-β-Zfp423-ApoD pathway.
Mice ; Animals ; Lip/innervation* ; Prospective Studies ; Mandibular Nerve/pathology* ; Sensation/physiology* ; Trigeminal Nerve Injuries/pathology*

OBJECTIVE: To investigate risk factors of acute cerebrovascular events and effects on the prognosis within 1 year after hip fracture surgery. METHODS: A retrospective analysis was performed on 320 elderly patients with hip fracture treated from July 2017 to December 2020, including 111 males and 209 females, aged from 60 to 101 years old with an average of (79.05±8.48) years old. According to whether acute cerebrovascular events occurred within 1 year after surgery, patients were divided into cerebrovascular events and non-cerebrovascular events group. Clinical data of patients were collected, including age, sex, comorbidities, fracture type, white blood cell count, hemoglobin, albumin, activities of daily living (ADL) score, walking ability, type of anesthesia, type of surgery, and length of hospital stay, Univariate analysis and multivariate Logistic regression were used to analyze the independent risk factors of acute cerebrovascular events within 1 year after hip fracture in elderly patients. ADL, walking ability and mortality were compared between the two groups 1 year after surgery. RESULTS: Acute cerebrovascular events occurred in 38 patients (11.9%) within 1 year after surgery. In the cerebrovascular events group, there were 20 males and 18 females, aged (82.53±7.91) years. In the non-cerebrovascular event group, there were 91 males and 191 females, aged with an average of (78.59±8.46) years old . Univariate analysis showed that acute cerebrovascular events were associated with age (t=2.712, P=0.007), male (χ²=6.129, P=0.013), hypertension (χ²=8.449, P=0.004), arrhythmia (χ²=6.360, P=0.012), stroke history (χ²=34.887, P=0.000), diabetes mellitus (χ²=4.574, P=0.032) and length of hospital stay (t=2.249, P=0.025) were closely related. Multivariate Logistic regression analysis showed age (OR=1.068, P=0.018), male (OR=2.875, P=0.008), arrhythmia (OR=2.722, P=0.017) and stroke history (OR=7.382, P=0.000) was an independent risk factor for acute cerebrovascular events 1 year after surgery. The patients with cerebrovascular events died at 1 year after surgery (11 cases) compared with those without cerebrovascular events (41 cases), and the difference was statistically significant(χ²=5.108, P=0.024). ADL scores of patients with cerebrovascular events at 1 year after operation were (58.70±14.45) points compared with those without cerebrovascular events (67.83±10.45) points, and the difference was statistically significant(t=4.122, P=0.000). Independent walking, assisted walking and bed rest were 3, 17 and 7 cases in cerebrovascular event group, and 54, 174 and 13 cases in non-cerebrovascular event group, respectively;and the difference was statistically significant(χ²=11.030, P=0.003). CONCLUSION Acute cerebrovascular events were common in elderly patients 1 year after hip fracture. Age, male, arrhythmia and stroke history were independent risk factors for acute stroke. The patients in the cerebrovascular event group had higher mortality and worse self-care ability and walking ability one year after operation.
Female ; Humans ; Male ; Aged ; Middle Aged ; Aged, 80 and over ; Retrospective Studies ; Activities of Daily Living ; Hip Fractures ; Risk Factors ; Prognosis ; Stroke ; Arrhythmias, Cardiac

The regulation of spermatogonial proliferation and apoptosis is of great significance for maintaining spermatogenesis. The single-cell RNA sequencing (scRNA-seq) analysis of the testis was performed to identify genes upregulated in spermatogonia. Using scRNA-seq analysis, we identified the spermatogonia upregulated gene origin recognition complex subunit 6 (Orc6), which is involved in DNA replication and cell cycle regulation; its protein expression in the human and mouse testis was detected by western blot and immunofluorescence. To explore the potential function of Orc6 in spermatogonia, the C18-4 cell line was transfected with control or Orc6 siRNA. Subsequently, 5-ethynyl-2-deoxyuridine (EdU) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, flow cytometry, and western blot were used to evaluate its effects on proliferation and apoptosis. It was revealed that ORC6 could promote proliferation and inhibit apoptosis of C18-4 cells. Bulk RNA sequencing and bioinformatics analysis indicated that Orc6 was involved in the activation of wingless/integrated (Wnt)/ β-catenin signaling. Western blot revealed that the expression of β-catenin protein and its phosphorylation (Ser675) were significantly decreased when silencing the expression of ORC6. Our findings indicated that Orc6 was upregulated in spermatogonia, whereby it regulated proliferation and apoptosis by activating Wnt/β-catenin signaling.

Objective:To investigate a time series deep learning model for respiratory motion prediction.Methods:Eighty pieces of respiratory motion data from lung cancer patients were used in this study. They were divided into a training set and a test set at a ratio of 8∶2. The Informer deep learning network was employed to predict the respiratory motions with a latency of about 600 ms. The model performance was evaluated based on normalized root mean square errors (nRMSEs) and relative root mean square errors (rRMSEs).Results:The Informer model outperformed the conventional multilayer perceptron (MLP) and long short-term memory (LSTM) models. The Informer model yielded an average nRMSE and rRMSE of 0.270 and 0.365, respectively, at a prediction time of 423 ms, and 0.380 and 0.379, respectively, at a prediction time of 615 ms.Conclusions:The Informer model performs well in the case of a longer prediction time and has potential application value for improving the effects of the real-time tracking technology.

Objective:To investigate the pseudo-CT generation from cone beam CT (CBCT) by a deep learning method for the clinical need of adaptive radiotherapy.Methods:CBCT data from 74 prostate cancer patients collected by Varian On-Board Imager and their simulated positioning CT images were used for this study. The deformable registration was implemented by MIM software. And the data were randomly divided into the training set ( n=59) and test set ( n=15). U-net, Pix2PixGAN and CycleGAN were employed to learn the mapping from CBCT to simulated positioning CT. The evaluation indexes included mean absolute error (MAE), structural similarity index (SSIM) and peak signal to noise ratio (PSNR), with the deformed CT chosen as the reference. In addition, the quality of image was analyzed separately, including soft tissue resolution, image noise and artifacts, etc. Results:The MAE of images generated by U-net, Pix2PixGAN and CycleGAN were (29.4±16.1) HU, (37.1±14.4) HU and (34.3±17.3) HU, respectively. In terms of image quality, the images generated by U-net and Pix2PixGAN had excessive blur, resulting in image distortion; while the images generated by CycleGAN retained the CBCT image structure and improved the image quality.Conclusion:CycleGAN is able to effectively improve the quality of CBCT images, and has potential to be used in adaptive radiotherapy.

Objective: To analyze the safety, effectiveness, economics, innovation, suitability and accessibility of tetrandrine in the treatment of pneumoconiosis, and provide evidence-based basis for health policy decision-making and clinical practice. Methods: In July 2022, the system searched PubMed, Embase, the Cochrane Library, CNKI, Wanfang, SinoMed databases (the retrieval time was from the establishment of the database to June 30, 2022), screened the documents that meet the standards, extracted and evaluated the data, and used the "HTA checklist" developed by the International Network of Agencies for Health Technology Assessment (INAHTA) to evaluate the HTA report. AMSTAR-2 Scale was used to evaluate the quality of systematic evaluation/Meta analysis. CHEERS Scale was used to evaluate the quality of pharmacoeconomics research. The included cohort study or case-control study was evaluated with the Newcastle-Ottawa Scale. The included randomized controlled trial (RCT) studies were evaluated using the Cochrane Risk Bias Assessment Tool (Cochrane RCT) quality evaluation criteria. Comprehensive comparison and analysis based on the characteristics of the data included in the study. Results: A total of 882 related literatures were detected from the initial screening. According to relevant standards, 8 RCT studies were finally selected for analysis. Statistical results showed that basic treatment with tetrandrine could better improve FEV(1) (MD=0.13, 95%CI: 0.06-0.20, P<0.001), FEV(1)/FVC (MD=4.48, 95%CI: 0.61-8.35, P=0.02) and clinical treatment efficiency. Tetrandrine had a low incidence of adverse reactions. The affordability coefficient of tetrandrine tablets was 0.295-0.492. Conclusion: Tetrandrine can improve the clinical symptoms and pulmonary ventilation function of pneumoconiosis patients, most of the adverse reactions are mild, and the clinical application is safe.
Humans ; Pneumoconiosis/drug therapy* ; Benzylisoquinolines/therapeutic use* ; Drugs, Chinese Herbal ; Case-Control Studies

Patients with congenital unilateral absence of the vas deferens (CUAVD) manifest diverse symptoms from normospermia to azoospermia. Treatment for CUAVD patients with obstructive azoospermia (OA) is complicated, and there is a lack of relevant reports. In this study, we describe the clinical features and evaluate the treatments and outcomes of CUAVD patients with OA. From December 2015 to December 2020, 33 patients were diagnosed as CUAVD with OA in Shanghai General Hospital (Shanghai, China). Patient information, ultrasound findings, semen analysis, hormone profiles, and treatment information were collected, and the clinical outcomes were evaluated. Of 33 patients, 29 patients were retrospectively analyzed. Vasoepididymostomy (VE) or cross VE was performed in 12 patients, the patency rate was 41.7% (5/12), and natural pregnancy was achieved in one of the patients. The other 17 patients underwent testicular sperm extraction as the distal vas deferens (contralateral side) was obstructed. These findings showed that VE or cross VE remains an alternative treatment for CUAVD patients with OA, even with a relatively low rate of patency and natural pregnancy.
Pregnancy ; Female ; Humans ; Male ; Vas Deferens/abnormalities* ; Azoospermia/surgery* ; Epididymis/surgery* ; Retrospective Studies ; Tertiary Care Centers ; China ; Semen