BACKGROUND:Studies have shown that metformin has anti-inflammatory,anti-tumor,anti-aging and vasoprotective effects,and can inhibit the progression of osteoarthritis,but its specific mechanism of action remains unclear. OBJECTIVE:To investigate the mechanism of metformin on cartilage protection in a rat model of osteoarthritis. METHODS:Forty male Sprague-Dawley rats were randomly divided into four groups(n=10 per group):blank,control,sham-operated,and metformin groups.The blank group did not undergo any surgery.In the sham-operated group,the joint cavity was exposed.In the model group and the metformin group,the modified Hulth method was used to establish the osteoarthritis model.At 1 day after modeling,the rats in the metformin group were given 200 mg/kg/d metformin by gavage,and the model,blank,and sham-operated groups were given normal saline by gavage.Administration in each group was given for 4 weeks consecutively.Hematoxylin-eosin staining,toluidine blue staining,and safranin O-fast green staining were used to observe the morphological structure of rat knee joints.Immunohistochemical staining and western blot were used to detect the protein expression of SOX9,type Ⅱ collagen,a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5),Beclin1,P62,phosphatidylinositol 3-kinase(PI3K),p-PI3K,protein kinase B(AKT),p-AKT,mammalian target of rapamycin(Mtor),and p-Mtor in rat cartilage tissue. RESULTS AND CONCLUSION:The results of hematoxylin-eosin,toluidine blue and safranin O-fast green staining showed smooth cartilage surface of the knee joints and normal histomorphology in the blank group and the sham-operated group,while in the model group,there was irregular cartilage surface of the knee joint and cartilage damage,with a decrease in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.In the metformin group,there was a significant improvement in the damage to the structure of the cartilage in the knee joints of the rats,and the cartilage surface tended to be smooth,with an increase in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.Immunohistochemistry staining and western blot results showed that compared with the control and sham-operated groups,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the model group was significantly decreased(P<0.05).Conversely,the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly increased(P<0.05).Furthermore,compared with the model group,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the metformin group was significantly increased(P<0.05),while the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly decreased(P<0.05).To conclude,Metformin can improve the autophagy activity of chondrocytes and reduce the degradation of cartilage matrix in osteoarthritis rats by inhibiting the activation of PI3K/AKT/Mtor signaling pathway,thus exerting a protective effect on articular cartilage.

Objective To discuss the value of clinical radiomic nomogram(CRN)and deep convolutional neural network(DCNN)in distinguishing atypical pulmonary hamartoma(APH)from atypical lung adenocarcinoma(ALA).Methods A total of 307 patients were retrospectively recruited from two institutions.Patients in institu-tion 1 were randomly divided into the training(n=184:APH=97,ALA=87)and internal validation sets(n=79:APH=41,ALA=38)in a ratio of 7∶3,and patients in institution 2 were assigned as the external validation set(n=44:APH=23,ALA=21).A CRN model and a DCNN model were established,respectively,and the performances of two models were compared by delong test and receiver operating characteristic(ROC)curves.A human-machine competition was conducted to evaluate the value of AI in the Lung-RADS classification.Results The areas under the curve(AUCs)of DCNN model were higher than those of CRN model in the training,internal and external validation sets(0.983 vs 0.968,0.973 vs 0.953,and 0.942 vs 0.932,respectively),however,the differences were not statistically significant(p=0.23,0.31 and 0.34,respectively).With a radiologist-AI com-petition experiment,AI tended to downgrade more Lung-RADS categories in APH and affirm more Lung-RADS cat-egories in ALA than radiologists.Conclusion Both DCNN and CRN have higher value in distinguishing APH from ALA,with the former performing better.AI is superior to radiologists in evaluating the Lung-RADS classification of pulmonary nodules.

To examine the molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) and investigate the horizontal transmission of blaKPC and blaNDM genes for the prevention and treatment of CRKP. A total of 49 clinically isolated CRKP strains were retrospectively analyzed from January to December 2022 at The First Hospital of Hunan University of Chinese Medicine. Phenotypic screening was performed using modified carbapenem inactivation assay (mCIM) and EDTA-carbapenem inactivation assay (eCIM). Polymerase chain reaction (PCR) was utilized to identify carbapenem resistance genes, β-lactamase resistance genes, and virulence genes, while multi-locus sequence analysis (MLST) was employed to assess the homology of CRKP strains. Conjugation experiments were conducted to infer the horizontal transmission mechanism of blaKPC and blaNDM genes. The results showed that the study included 49 CRKP strains, with 44 carrying blaKPC and 8 carrying blaNDM, Three strains were identified as blaKPC+ blaNDM-CRKP. In this study, 28 out of 49 CRKP strains (57.2%) were found to carry virulence genes. Additionally, one CRKP strain tested positive in the string test and was found to carry both Aerobactin and rmpA virulence genes. MLST results revealed a total of 5 ST types, with ST11 being predominant (41/49, 83.7%). Successful conjugation was observed in all 3 blaKPC-CRKP strains, while only 1 out of 3 blaNDM-CRKP strains showed successful conjugation. The transconjugant exhibited significantly reduced susceptibility to imipenem and cephalosporin antibiotics. In conclusion, the resistance mechanism of CRKP in this study is primarily attributed to the production of KPC enzymes, along with the presence of multiple β-lactamase resistance genes. Additionally, there is a local prevalence of hv-CRKP and blaKPC+ blaNDM-CRKP. blaKPC and blaNDM can be horizontally transmitted through plasmids, with varying efficiency among different strains.

To examine the molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) and investigate the horizontal transmission of blaKPC and blaNDM genes for the prevention and treatment of CRKP. A total of 49 clinically isolated CRKP strains were retrospectively analyzed from January to December 2022 at The First Hospital of Hunan University of Chinese Medicine. Phenotypic screening was performed using modified carbapenem inactivation assay (mCIM) and EDTA-carbapenem inactivation assay (eCIM). Polymerase chain reaction (PCR) was utilized to identify carbapenem resistance genes, β-lactamase resistance genes, and virulence genes, while multi-locus sequence analysis (MLST) was employed to assess the homology of CRKP strains. Conjugation experiments were conducted to infer the horizontal transmission mechanism of blaKPC and blaNDM genes. The results showed that the study included 49 CRKP strains, with 44 carrying blaKPC and 8 carrying blaNDM, Three strains were identified as blaKPC+ blaNDM-CRKP. In this study, 28 out of 49 CRKP strains (57.2%) were found to carry virulence genes. Additionally, one CRKP strain tested positive in the string test and was found to carry both Aerobactin and rmpA virulence genes. MLST results revealed a total of 5 ST types, with ST11 being predominant (41/49, 83.7%). Successful conjugation was observed in all 3 blaKPC-CRKP strains, while only 1 out of 3 blaNDM-CRKP strains showed successful conjugation. The transconjugant exhibited significantly reduced susceptibility to imipenem and cephalosporin antibiotics. In conclusion, the resistance mechanism of CRKP in this study is primarily attributed to the production of KPC enzymes, along with the presence of multiple β-lactamase resistance genes. Additionally, there is a local prevalence of hv-CRKP and blaKPC+ blaNDM-CRKP. blaKPC and blaNDM can be horizontally transmitted through plasmids, with varying efficiency among different strains.

Objective To explore the value of combined prediction model based on clinical and CT radiomics features in discriminating atypical pulmonary hamartoma(APH)from atypical lung adenocarcinoma(ALA).Methods A total of 290 patients with APH and ALA confirmed by pathology were retrospectively selected.250 patients from the First Affiliated Hospital of Anhui Medical University were randomly assigned into a training set(APH=91,ALA=84)and an internal validation set(APH=39,ALA=36)at a ratio of 7∶3,and other 40 patients from the First Affiliated Hospital of USTC were assigned as an external validation set(APH=21,ALA=19).The independent model and multivariate logistic regression combined model were constructed using the selected clinical-CT features and radiomics features,respectively,and a nomogram was drawn.Receiver operating characteristic(ROC)curve and DeLong test were used to evaluate and compare the performances of the models.Results The area under the curve(AUC)of the combined model established by 3 clinical-CT features and 4 radiomics features in the training set was 0.980,which was higher than that of clinical-CT model(AUC=0.885,P＜0.001)and radiomics model(AUC=0.975,P=0.042).The AUC of the combined model in the internal and external validation sets(0.963 vs 0.917)were also higher than those of clinical-CT model(0.858 vs 0.774)and radiomics model(0.953 vs 0.897),respectively.Conclusion The combined prediction model based on clinical and CT radiomics features can improve the differential diagnosis ability of APH and ALA.

Objective:To investigate the effect of different concentrations and infection durations of varicella-zoster virus (VZV) on nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome-related proteins in mouse brain astrocytes.Methods:Mouse brain astrocytes were infected with different dilutions (10 0 [undiluted original concentration] - 10 -7) of cell-free VZV suspension, and the cytopathic effect was observed under a microscope in each group to determine the concentration and infection duration of VZV for subsequent experiments. Some mouse brain astrocytes were infected with cell-free VZV suspension at dilutions of 10 0, 10 -2, 10 -4, and 10 -6, and samples were collected on day 5; some other mouse brain astrocytes were infected with cell-free VZV suspension at the median tissue culture infective dose (TCID 50) of 1.0 × 10 5/ml, and the samples were collected on days 3, 5, 7, and 9, separately; normally cultured mouse brain astrocytes served as control groups in the above experiments. Western blot analysis was performed to determine the protein expression of VZV glycoprotein E (gE), NLRP3, caspase-1, and interleukin-1β (IL-1β) in mouse brain astrocytes in each group. One-way analysis of variance was used for comparisons of data with a normal distribution, and least significant difference- t test was used for multiple comparisons. Results:On day 3 after infection with VZV at the dilution of 10 0, the number of cells decreased, some cells became irregular, lost their original shapes, and showed granular cytoplasm and an unclear nucleus structure, while some cells fused and formed multinucleated giant cells; on day 5, ≥ 50% of cells showed the aforementioned changes and some intercellular spaces were dilated giving a network-like appearance in the 10 0-dilution group; on day 9, the 10 0- - 10 -6- dilution groups all showed dilated intercellular spaces arranged in networks and cytopathic effect in ≥ 50% of cells; on day 10, some cells in the control group exhibited cytoplasmic vacuolation, exfoliation and flotation. Based on these results, the following experiments were conducted with VZV at a concentration gradient ranging from 10 0 to 10 -6 dilutions, and the observations were performed from day 3 to day 9. Western blot analysis showed increased protein expression of VZV gE, NLRP3, caspase-1, and IL-1β in the VZV infection groups compared with the control group, and there were significant differences among different VZV concentration groups ( F = 21.45, 43.82, 21.85, 29.53, respectively, all P < 0.05) and different infection duration groups ( F = 224.10, 78.79, 186.50, 85.08, respectively, all P < 0.05). With the increasing dilution ratios, the expression of inflammasome-related proteins (NLRP3, caspase-1, and IL-1β) decreased, with the highest expression observed in the 10 0-dilution group and the lowest in the 10 -6-dilution group (all P < 0.05). On days 3, 5, and 7 after VZV infection, the expression of NLRP3 inflammasome-related proteins increased over time, with the highest expression observed on day 7 and the lowest on day 3 (all P < 0.05), while their expression decreased on day 9. Conclusion:The expression of NLRP3 inflammasome-related proteins was up-regulated in mouse brain astrocytes after VZV infection, and their expression levels increased along with the increase in the VZV concentration and infection duration in a certain range.

China has classified the Corona Virus Disease 2019(COVID-19) as a statutory category B infectious disease and managed it according to Category B since January 8, 2023.In view that Omicron variant is currently the main epidemic strain in China, in order to guide the treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection in children with the times, refer to the Diagnosis and Treatment Protocol for Novel Coronavirus Infection (Trial 10 th Edition), Expert Consensus on Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fourth Edition) and the Diagnosis and Treatment Strategy for Pediatric Related Viral Infections.The Expert Consensus on the Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fifth Edition) has been formulated and updated accordingly on related etiology, epidemiology, pathogenic mechanism, clinical manifestations, auxiliary examination, diagnosis and treatment, and added key points for the treatment of COVID-19 related encephalopathy, fulminating myocarditis and other serious complications for clinical reference.

COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.

Polymyalgia rheumatica (PMR) is a syndrome characterized by pain and morning stiffness in the neck and shoulder and pelvic girdles, as well as raised acute-phase reactants, with or without systemic symptoms, such as fever. Giant cell arteritis (GCA) is a systemic vasculitis of unclear etiology that involves systemic arteries, principally affecting medium- and large-sized arteries with skipped, segmental alterations and granulomatous vasculitis seen on histopathology. In China, epidemiological data describing GCA are still limited; thus, the prevalence might be underestimated. The involvement of vessels in GCA can cause irreversible visual impairment or loss and stroke, which are serious complications. PMR is three times more prevalent than GCA, and other specific diseases should be excluded before the diagnosis is established. PMR symptoms can be present in 40%-60% of patients with GCA. Conversely, GCA can develop in 15% of patients with PMR. Chinese Rheumatology Association, based on the clinical diagnosis and treatment guidelines in 2005, utilizing the experience and guidelines of diagnosis and treatment at home and abroad, formulated this specification to standardize the diagnosis and treatment of GCA and PMR and improve the patient′s prognosis.

Antiviral treatment is the core part in the treatment of herpes zoster. Based on the latest studies, consensus and guidelines, this article aims to provide a basis and reference for clinicians to make a reasonable choice of types and doses of antiviral agents. Valacyclovir, a precursor of acyclovir with high oral bioavailability and great convenience of administration, is generally the first choice of oral antiviral agents; for some special cases, such as immunocompromised patients, intravenous drips of acyclovir should be selected when appropriate. Brivudine is often a better choice for patients with severe renal insufficiency; famciclovir or other antiviral agents should be considered for patients resistant to acyclovir; for immunocompromised patients resistant to acyclovir, intravenous drips of foscarnet sodium can be an option. Oral antiviral agents should be administered at adequate doses. Selecting appropriate antiviral agents and their doses can effectively relieve acute symptoms of patients and reduce the probability of postherpetic neuralgia.