Objective:To detect the pathogen and clinically diagnose for a suspected case of Neisseria meningitidis with positive blood culture result, and assess the risk of disease transmission among the community. Methods:Blood sample was collected for Neisseria meningitidis isolation and culture. Pathogen identification and serogroup typing were conducted by colony morphology, Gram staining, biochemical tests, latex agglutination test, slide agglutination test, and nucleic acid testing. The susceptibility to 12 antibiotics was also tested. Epidemiological investigation was conducted on the case, and epidemic control measures were also implemented. Results:Through various detection, the suspected case was diagnosed as Neisseria meningitidis invasive infection. The isolated strain belonged to group Y serotype, type 767 (multilocus sequence typing), and the ST167 clonal complex. The strain was sensitive to nine antibiotics, including penicillin, ampicillin, and meropenem. It exhibited intermediate sensitivity to ciprofloxacin and levofloxacin, and resistance to methicillin/sulfamethoxazole. Close contacts of the case and environmental testing results were negative. Conclusions:The case is confirmed to be an invasive infection caused by group Y Neisseria meningitidis, the ST167 clonal complex. Epidemiological investigation shows a relatively low risk of epidemic transmission. Continuous monitoring and surveillance are necessary for further assessment.

Objective To explore the application effect of air bag compression combined with multi-step automatic decompression in radial artery hemostasis after coronary angiography in elderly patients. Methods A total of 630 elderly patients who underwent transradial coronary angiography in our hospital from March 2023 to April 2024 were selected as study subjects and randomly divided into control group, observation group 1, and observation group 2, with 210 patients in each group. The control group received manual compression hemostasis with a three-step air bag compressor after surgery, while the observation group 1 and observation group 2 received automatic compression hemostasis with a customized pressure step compressor for three-step and five-step compression, respectively, on the air bag compressor after surgery. The bleeding rate, delayed pressure release rate, radial artery stenosis rate, radial artery occlusion rate, and nursing work time were compared among the three groups after surgery (after CAG and before removal of the air bag compressor). Pain scores, heart rate, and blood pressure were recorded after surgery and before pressure release at 1 h after surgery. Results The observation group 2 had better results in bleeding rates, delayed pressure release rates, radial artery stenosis rates, and occlusion rates at the puncture site compared with the control group and observation group 1(P < 0.05). The nursing work time in the observation group 1 and observation group 2 was shorter than that in the control group (P < 0.05). The pain scores, heart rate, and systolic blood pressures before pressure release at 1 h after surgery were better in all three groups compared with those after surgery (P < 0.05). The pain scores, heart rates, and blood pressures before pressure release at 1 h after surgery in the observation group 2 were better than those in the control group and observation group 1 (P < 0.05). Conclusion The application of air bag compression combined with a five-step gradual automatic decompression method for compression hemostasis can effectively reduce the incidence of radial artery complications, shorten nursing work time, and improve patients' comfort.

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*

Objective:To explore the value of 68Ga-prostate specific membrane antigen (PSMA)-11 PET/CT in newly diagnosed prostate cancer patients with different risk stratifications, and to compare the performance of this modality with conventional imaging in detecting metastases. Methods:From June 2019 to July 2020, the clinical and imaging data of 60 patients (age range: 44-88 years, median age 69 years) who underwent 68Ga-PSMA-11 PET/CT imaging in Fudan University Shanghai Cancer Center were retrospectively analyzed. Spearman rank correlation analysis was used to explore the correlation of SUV max in primary foci with prostate specific antigen (PSA) and Gleason score (GS). Based on the D′Amico risk stratification (PSA>20 μg/L and ≤20 μg/L, GS>7 and ≤7), the detection rates of 68Ga-PSMA-11 PET/CT for metastases were evaluated by χ2 test, and the differences of SUV max were analyzed by Mann-Whitney U test. Patients were divided into high-risk (PSA>20 μg/L and GS>7), medium-risk (PSA>20 μg/L and GS≤7, or PSA≤20 μg/L and GS>7), and low-risk (PSA<20 μg/L and GS<7) groups according to PSA levels and GS. Compared with conventional imaging (bone imaging, CT or MRI), the ability of 68Ga-PSMA-11 PET/CT to detect metastatic tumors, and the utility to change the prostate cancer stage were evaluated by Fisher′s exact test. Results:High uptake of 68Ga-PSMA-11 was observed in primary lesions of 60 patients, and SUV max was positively correlated with GS or PSA ( rs values: 0.42, 0.38; P values: 0.001, 0.002). The detection rates of lymph node and bone metastases in the group with PSA>20 μg/L were 11/18 and 13/18, respectively, which were higher than those in the group with PSA≤20 μg/L (28.57%(12/42) and 35.71%(15/42); χ2 values: 6.56, 7.56, P values: 0.010, 0.006. However, there was no statistical significance in the SUV max of these lesions( z values: -1.04, -0.96; P values: 0.299, 0.337). There was a statistical difference in the detection rates of lymph node and bone metastases between the group with GS>7 and the group with GS≤7 (lymph node: 54.05%(20/37) vs 13.04%(3/23), χ2=10.09, P=0.001; bone metastases: 59.46%(22/37) vs 26.09%(6/23), χ2=8.19, P=0.004), as well as the SUV max of bone metastases( z=-2.02, P=0.044). In the high-risk group, 68Ga-PSMA-11 PET/CT had the higher detection rate of metastases than conventional imaging (16/17 vs 10/17; P=0.039) and it changed 25.0%(15/60) of the patients′ staging. Conclusions:PSA and GS affect the detection rate of 68Ga-PSMA-11 PET/CT. In patients with high-risk prostate cancer, 68Ga-PSMA-11 PET/CT is superior to conventional imaging in detecting metastases. When PSA>20 μg/L and GS>7, it is better to use 68Ga-PSMA-11 PET/CT in prostate cancer staging.

Osteosarcoma is the most common primary solid bone malignancy. The main factor leading to recurrence and metastasis of osteosarcoma is resistance to chemotherapy drugs. Long non-coding RNAs can affect drug resistance in osteosarcoma by regulating epithelial-mesenchymal transition, cell autophagy, apoptosis, drug efflux, and cell cycle, suggesting that long non-coding RNAs may become new targets for drug resistance in osteosarcoma treatment.

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

ObjectiveTo automatically measure the wrist range of motion using the somatosensory capture device Azure Kinect. MethodsAzure Kinect was used to recognize the spatial coordinates of human elbow, wrist, palm, fingertip and other joint points, and the best measurement posture was determined by orthogonal experiment. Holt's double-parameter exponential smoothing method and bone length constraint method were used to smooth the joint point data to eliminate the jitter. The average angle of multiple frames was calculated through the spatial vector relationship to realize the automatic measurement of wrist joint range of motion. From May to October, 2021, 5 times × 10 groups of measurement were performed on each subject of wrist joint of five healthy subjects using the above method. ResultsThe R1 of each subject of wrist joint was between 83 and 127, and the value was in the middle. This method contrasted well with measurements made on augmented reality ruler, 2D images (r > 0.990), and the maximum error was within 1.61°. ConclusionThe wrist joint angle measurement modality using Azure Kinect is consistent to conventional measurement modality, and can meet the requirements of real-time measurement.

Objective To establish a small liver cancer biobank with a standard operating procedure and the function of informationized management. Methods According to the inclusion and exclusion criteria, blood, tissue, and stool samples were collected from the patients with liver cancer who attended Liver Surgery Center, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, from August 2012 to December 2020 and signed the informed consent. In-and-out-of-storage management was performed based on the standard procedure for whole blood, serum, frozen tissue, paraffin-embedded tissue, and stool samples, and related clinical and follow-up data were collected. The frozen samples of liver cancer tissue and adjacent tissue in different years were randomly selected, and the concentration and completeness of total RNA were examined to ensure the quality of frozen samples stored in the biobank. Results The samples were collected from 4190 liver cancer patients who underwent surgery within a period of 101 natural months, and there were 41718 frozen tissue samples, 18950 paraffin-embedded tissue samples, 24389 whole blood samples, 20060 serum samples, and 5392 stool samples. The liver cancer patients had an age range of 13-88 years, and male patients accounted for 85.1%. The patients with hepatitis B accounted for 83.3%, and those with liver cirrhosis accounted for 73.5%. A standard operating procedure and an electronic data capture system were developed according to the collection, processing, storage, application, and informationized management of samples. Among the 18 frozen tissue samples randomly selected from the biobank, 16 samples had high RNA quality, which could meet the requirements of subsequent experiments. Conclusion A standardized and informationized biobank has been established for liver cancer, which provides high-quality samples for the basic research on liver cancer and helps to explore the research value of samples.

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

Background::Pancreatic adenocarcinoma (PAAD) is an extremely lethal malignancy. Identification of the functional genes and genetic variants related to PAAD prognosis is important and challenging. Previously identified prognostic genes from several expression profile analyses were inconsistent. The regulatory genetic variants that affect PAAD prognosis were largely unknown.Methods::Firstly, a meta-analysis was performed with seven published datasets to systematically explore the candidate prognostic genes for PAAD. Next, to identify the regulatory variants for those candidate genes, expression quantitative trait loci analysis was implemented with PAAD data resources from The Cancer Genome Atlas. Then, a two-stage association study in a total of 893 PAAD patients was conducted to interrogate the regulatory variants and find the prognostic locus. Finally, a series of biochemical experiments and phenotype assays were carried out to demonstrate the biological function of variation and genes in PAAD progression process.Results::A total of 128 genes were identified associated with the PAAD prognosis in the meta-analysis. Fourteen regulatory loci in 12 of the 128 genes were discovered, among which, only rs4887783, the functional variant in the promoter of Ring Finger and WD Repeat Domain 3 ( RFWD3), presented significant association with PAAD prognosis in both stages of the population study. Dual-luciferase reporter and electrophoretic mobility shift assays demonstrated that rs4887783-G allele, which predicts the worse prognosis, enhanced the binding of transcript factor REST, thus elevating RFWD3 expression. Further phenotypic assays revealed that excess expression of RFWD3 promoted tumor cell migration without affecting their proliferation rate. RFWD3 was highly expressed in PAAD and might orchestrate the genes in the DNA repair process. Conclusions::RFWD3 and its regulatory variant are novel genetic factors for PAAD prognosis.