Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

The steps for installation and withdrawal of WYD2000 field surgical lamp were introduced.The failures and causes of broken cross-arm connector of WYD2000 field surgical lamp were analyzed.The problems of WYD2000 field surgical lamp in vulnerability to breaking and difficulty in maintenance were solved by designing and manufacturing a special maintenance tool and optimizing the materials and fixing mode of cross-arm connection.References were provided for main-tenance and improvement of WYD2000 field surgical lamp.[Chinese Medical Equipment Journal,2024,45(4):116-118]

Objective To explore clinical effect of single small incision with honeycomb titanium plate in treating acute acromioclavicular dislocation.Methods The clinical data of 40 patients with acute acromioclavicular dislocation admitted from December 2019 to December 2021 were retrospectively analyzed and divided into two groups according to different surgical methods.Among them,20 patients were fixed with single small incision with honeycomb titanium plate(titanium plate group),including 11 males and 9 females,aged from 23 to 65 years old with an average of(47.40±12.58)years old;12 patients on the left side,8 patients on the right side;11 patients with type Ⅲ,3 patients with type Ⅳ,and 6 patients with type Ⅴ according to Rockwood classification.Twenty patients were fixed with clavicular hook plate(clavicular hook group),including 8 males and 12 females,aged from 24 to 65 years old with an average of(48.40±12.08)years old;12 patients on the left side,8 patients on the right side;10 patients with type Ⅲ,2 patients with type Ⅳ,and 8 patients with type V according to Rockwood classifica-tion.Operative time,incision length,intraoperative blood loss,hospital stay,visual analogue scale(VAS)and Constant-Murley score of shoulder joint function were compared between two groups.Anteroposterior radiographs of the affected shoulder joint were recorded before,immediately and 6 months after surgery,and the coracoclavicular distance was measured and compared.Results Both groups of patients were successfully completed operation without serious complications.All patients were fol-lowed up for 6 to 15 months with an average of(11.9±4.8)months.There were no incisional infection,internal plant fracture or failure,bone tunnel fracture and other complications occurred.The incision length of titanium plate group(35.90±3.14)mm was significantly shorter than that of clavicular hook group(49.30±3.79)mm(P＜0.05).There were no significant difference in operative time,intraoperative blood loss and hospital stay between two groups(P＞0.05).At 1 and 3 months after operation,VAS of titanium plate group was lower than that of clavicular hook group(P＜0.05).Connstant-Murley scores in titanium plate group at 1,3 and 6 months after operation were(86.80±1.36),(91.60±2.32)and(94.90±2.22),respectively;and in clavicular hook group were(78.45±5.47),(85.55±2.01)and(90.25±1.92),which were higher than that of clavicular hook group(P＜0.05).There was no significant difference in coracoclavicular distance between two groups immediately and 6 months after op-eration(P＞0.05).Conclusion For the treatment of acute acromioclavicular joint dislocation,single small incision combined with honeycomb titanium plate have advantages of shorter incision,fast recovery of shoulder joint function without the second operation,and has good satisfaction of patient.

In this study, we investigated the anti-osteoporotic activity and mechanism of action of extract of Panax quiquefolium L. based on zebrafish model combined with metabolomics technology. A zebrafish model of prednisolone-induced osteoporosis was used to compare the anti-osteoporotic activity of Panax quiquefolium L., and the expression of osteoblast-associated genes and osteoclast-associated genes in zebrafish was detected by quantitative real-time PCR (qRT-PCR), using bone fluorescence area and fluorescence density as evaluation indexes. Metabolomics based on ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) was used to explore the change patterns of biomarkers and the metabolic pathways affected. The results showed that the 50% ethanol extracts of Panax quiquefolium L. from Jilin, Canada, Wenden and the United States can significantly improve the bone fluorescence area of zebrafish compared with model group. Furthermore, four sources 50% ethanol extracts of Panax quiquefolium L. except United States also can significantly improve the bone fluorescence density of zebrafish. In addition, PCR showed that extract of Panax quiquefolium L. can significantly up-regulated the expression of vitamin D receptor b (vdrb), collagen type I α2 (col1a2) and cysteine-rich acidic secreted protein (sparc) genes, and down-regulated the expression of matrix metalloproteinase 9 (mmp9), anti-tartrase acid phosphatase (trap) and cathepsin K (ctsk) genes. Metabolomic analysis identified 24 key differential metabolites. Furthermore, pathway analysis showed that Panax quiquefolium L. could regulate the levels of 10 key biomarkers by participating in purine metabolism, tricarboxylic acid cycle and pentose phosphate metabolism and improve the osteoporosis status of zebrafish. This study preliminically revealed the anti-osteoporosis mechanism of 50% ethanol extract from Panax quiquefolium L. through multi-component, multi-target and multi-pathway and also provides theoretical basis for clinical development and utilization of anti-osteoporosis products of Panax quiquefolium L. This experiment was approved by the Experimental Animal Welfare Ethics Committee of the Institute of Biology, Shandong Academy of Sciences (approval number: SWS20181002).

OBJECTIVES: To investigate the reliability and accuracy of deep learning technology in automatic sex estimation using the 3D reconstructed images of the computed tomography (CT) from the Chinese Han population. METHODS: The pelvic CT images of 700 individuals (350 males and 350 females) of the Chinese Han population aged 20 to 85 years were collected and reconstructed into 3D virtual skeletal models. The feature region images of the medial aspect of the ischiopubic ramus (MIPR) were intercepted. The Inception v4 was adopted as the image recognition model, and two methods of initial learning and transfer learning were used for training. Eighty percent of the individuals' images were randomly selected as the training and validation dataset, and the remaining were used as the test dataset. The left and right sides of the MIPR images were trained separately and combinedly. Subsequently, the models' performance was evaluated by overall accuracy, female accuracy, male accuracy, etc. RESULTS: When both sides of the MIPR images were trained separately with initial learning, the overall accuracy of the right model was 95.7%, the female accuracy and male accuracy were both 95.7%; the overall accuracy of the left model was 92.1%, the female accuracy was 88.6% and the male accuracy was 95.7%. When the left and right MIPR images were combined to train with initial learning, the overall accuracy of the model was 94.6%, the female accuracy was 92.1% and the male accuracy was 97.1%. When the left and right MIPR images were combined to train with transfer learning, the model achieved an overall accuracy of 95.7%, and the female and male accuracies were both 95.7%. CONCLUSIONS The use of deep learning model of Inception v4 and transfer learning algorithm to construct a sex estimation model for pelvic MIPR images of Chinese Han population has high accuracy and well generalizability in human remains, which can effectively estimate the sex in adults.
Adult ; Female ; Humans ; Male ; Deep Learning ; Imaging, Three-Dimensional ; Pelvis ; Reproducibility of Results ; Tomography, X-Ray Computed ; Young Adult ; Middle Aged ; Aged ; Aged, 80 and over

Objective:To explore the association between atypical small acinar proliferation(ASAP)and subsequent diagnosis of intermediate and high risk prostate cancer(PCa),and analyze whether delaying repeat biopsy timing is safe and effective.Meth-ods:From June 2000 to June 2022,we retrospectively analyzed the clinical data of 276 patients accepting prostatic biopsy and diag-nosed with ASAP in China-Japan Union Hospital of Jilin University.54.7％(151/276)patients had a repeat biopsy.We used statis-tic methods to process the data.Results:25.2％(38/151)patients were diagnosed with PCa on repeat biopsy.Among them,78.9％(30/38)patients had Gleason score(GS)3+3 and 21.1％(8/38)had GS 3+4 disease.There were 4 and 6 patients got RP re-spectively in the two cohorts.Only 5.3％(8/151)of ASAP patients were diagnosed as intermediate risk PCa in repeated biopsy and specially,no high risk PCa was identified in our study.Conclusion:It was safe and valid to delay the repeat biopsy.

China ; Cognition ; Digestive System Surgical Procedures ; Enhanced Recovery After Surgery ; Humans ; Length of Stay

BACKGROUND: Concerns exist regarding the potential development of tuberculosis in patients with rheumatoid arthritis (RA) treated with biological and targeted drugs. We assessed systematically whether biological therapy increased the risk of tuberculosis in patients with RA by meta-analysis of randomized controlled trials (RCTs). METHODS: A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and China Biology Medicine disc for RCTs evaluating biological therapy in patients with RA from inception through August 2021. Traditional meta-analysis and network meta-analysis were performed to compare the risk of tuberculosis for each biologics class in patients with RA. Peto odds ratio (Peto OR) and its 95% confidence interval (CI) were calculated as the primary effect measure. RESULTS: In total, 39 studies with 20,354 patients were included in this meta-analysis, and 82 patients developed tuberculosis. The risk of tuberculosis was increased in patients treated with biologics compared with non-biologics (Peto OR: 3.86, 95% CI: 2.36-6.32, P < 0.001). Also, tumor necrosis factor-α (TNF-α) inhibitors had a higher probability of developing tuberculosis than placebo (Peto OR: 3.98, 95% CI: 2.30-6.88, P < 0.001). However, network meta-analysis demonstrated that there was no significant difference in the risk of tuberculosis for each biologics class in patients with RA. Noticeably, tuberculosis was significantly more common in patients treated with a high dose compared with patients receiving a low dose of tofacitinib (Peto OR: 7.39, 95% CI: 2.00-27.31, P = 0.003). CONCLUSION This meta-analysis demonstrates the evidence of an elevated risk of tuberculosis in patients with RA treated with TNF-α inhibitors, and a dose-dependent elevated risk of tuberculosis in patients treated with tofacitinib.
Antirheumatic Agents/adverse effects* ; Arthritis, Rheumatoid/drug therapy* ; Humans ; Network Meta-Analysis ; Pharmaceutical Preparations ; Randomized Controlled Trials as Topic ; Tuberculosis/drug therapy*

To investigate the relationship between serum C-reactive protein (CRP) levels and work impairment in patients with ankylosing spondylitis (AS) based on real-world evidence. Outpatients with confirmed AS at Chinese PLA General Hospital were recruited consecutively by Smart-phone SpondyloArthritis Management System (SpAMS) from April 2016 to April 2018. The relationship between CRP and work productivity and activity impairment questionnaire (WPAI) were evaluated. Five hundred and fifty-one outpatients with AS in paid employment were recruited. The presenteeism, overall work impairment, and activity impairment rates increased by 1.4% (1.1%, 1.8%), 1.1% (0.5%, 1.6%), and 1.7% (1.3%, 2.1%), respectively, for every 10 mg/L increase in the CRP level (all P value<0.01). However, the CRP level was not associated with absenteeism after adjusting for covariates [0.5%(-0.4%, 1.0%), P>0.05]. There is a significant association between increased serum CRP levels at baseline and the previous 7-day work impairment in patients with AS. Higher CRP levels contribute to worse presenteeism, overall work impairment, and activity impairment rates, which suggests the necessity of monitoring CRP on treatment, and also indicates that anti-inflammatory therapy may be effective for improving work productivity.

We report a case of mucormycosis induced by Cunninghamella spp. infection in a ten-year-old girl with acute lymphoblastic leukemia, who developed fever and respiratory symptoms after chemotherapy and was diagnosed with invasive fungal disease. Peripheral blood DNA sequences were analyzed using metagenomic next-generation sequencing (mNGS), and by comparison with the Pathogens Metagenomics Database (PMDB), we identified Cunninghamella spp. with sequence number 514 as the pathogen. The patient was treated with amphotericin B combined with posaconazole and showed a favorable response. We searched Pubmed, Embase, CNKI, and Wanfang database for reports of cases of Cunninghamella spp. infection in children and retrieved 22 reported cases (including 12 males) with a median age of 13.5 (3-18) years. In these 22 cases, hematological malignancy was the most common underlying condition (19/22), and most of patients experienced an acute onset and rapid progression with respiratory symptoms (14/20) and fever (16/20) as the most common symptoms. CT imaging often showed unilateral lesions with varying imaging findings, including pulmonary nodules or masses, infiltrative changes, and pleural effusion. Definite diagnoses were established in 18 of the cases, and 4 had probable diagnoses; the lungs and skin were the most frequent organs compromised by the infection. A definite diagnosis of Cunninghamella spp. infection still relied on histopathological examination and fungal culture, but the molecular techniques including PCR and mNGS had shown potentials in the diagnosis. Almost all the cases received antifungal treatment after diagnosis (21/22), and 13 patients also underwent surgeries. Death occurred in 9 (42%) of the cases at a median of 19 (4-54) days after onset of the signs or symptoms. The patients receiving antifungal therapy combined with surgery had a high survival rate (9/13, 69%) than those with antifungal therapy alone (3/8, 37%). Invasive fungal disease is a common complication in immunoco-mpromised patients, but Cunninghamella spp. infection is rare and has a high mortality rate. In cases highly suspected of this disease, active diagnosis and early treatment are critical to improve the survival outcomes of the patients.
Adolescent ; Amphotericin B/therapeutic use* ; Antifungal Agents/therapeutic use* ; Child ; Cunninghamella ; Female ; Humans ; Male ; Mucormycosis/etiology*