ObjectiveTo understand the seropositivity of neutralizing antibodies (NAb) and low-level NAb against SARS-CoV-2 infection in the community residents, and to explore the impact of COVID-19 vaccination and SARS-CoV-2 infection on the levels of NAb in human serum. MethodsOn the ground of surveillance cohort for acute infectious diseases in community populations in Shanghai, a proportional stratified sampling method was used to enroll the subjects at a 20% proportion for each age group (0‒14, 15‒24, 25‒59, and ≥60 years old). Blood samples collection and serum SARS-CoV-2 NAb concentration testing were conducted from March to April 2023. Low-level NAb were defined as below the 25^th percentile of NAb. ResultsA total of 2 230 participants were included, the positive rate of NAb was 97.58%, and the proportion of low-level NAb was 25.02% (558/2 230). Multivariate logistic regression analysis indicated that age, infection history and vaccination status were correlated with low-level NAb (all P<0.05). Individuals aged 60 years and above had the highest risk of low-level NAb. There was a statistically significant interaction between booster vaccination and one single infection (aOR=0.38, 95%CI: 0.19‒0.77). Compared to individuals without vaccination, among individuals infected with SARS-CoV-2 once, both primary immunization (aOR=0.23, 95%CI: 0.16‒0.35) and booster immunization (aOR=0.12, 95%CI: 0.08‒0.17) significantly reduced the risk of low-level NAb; among individuals without infections, only booster immunization (aOR=0.28, 95%CI: 0.14‒0.52) showed a negative correlation with the risk of low-level NAb. ConclusionsThe population aged 60 and above had the highest risk of low-level NAb. Regardless of infection history, a booster immunization could reduce the risk of low-level NAb. It is recommended that eligible individuals , especially the elderly, should get vaccinated in a timely manner to exert the protective role of NAb.

Objective To investigate the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) for radiation-induced lung injury (RILI) and the underlying mechanism. Methods Forty-five healthy adult male C57BL/6 mice were randomly divided into control, model, and BMSCs groups. The model and BMSCs groups received a single irradiation dose of 20 Gy to the chest, while the control group did not receive X-ray irradiation. For the BMSCs group, an injection of 1 × 10⁶ BMSCs cells was administered via the tail vein within 6 h after irradiation. In the 5th week, the lung tissue was taken to observe pathological changes with HE staining; examine the expression of the inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) with immunohistochemical staining; observe the polarization of macrophages with immunofluorescence staining; and measure the expression of the epithelial-mesenchymal transition markers E-cadherin, N-cadherin, and vimentin proteins by Western blot. Results After radiation, the model group developed pulmonary vasodilation and congestion with septal thickening and inflammatory cell infiltration, and these changes were markedly reduced in the BMSCs group. The model group showed significantly down-regulated expression of IL-6 and TNF-α compared with significantly increased levels in the model group (P < 0.01, P < 0.05). Treatment with BMSCs significantly increased the polarization of lung macrophages towards the M2 type, while significantly decreasing the abnormally increased N-cadherin and vimentin levels in RILI mice (P < 0.05, P < 0.01). Conclusion BMSCs have therapeutic effects for RILI mice, which may be through promoting macrophage polarization from M1 to M2.

Objective To investigate the role of hydrogen therapy in reducing radiation-induced lung injury and the specific mechanism. Methods Forty C57BL/6 mice were randomly divided into four groups: normal control group, model group, hydrogen therapy group I, and hydrogen therapy group II. A mouse model of radiation-induced lung injury was established. The pathological changes in the lung tissue of the mice were examined with HE staining. Immunofluorescence staining was used to detect the expression of surface markers of M1 and M2 macrophages to observe macrophage polarization. The expression of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-10 in the lung tissue was measured by immunohistochemistry. The expression of nuclear factor-kappa B (NF-κB) p65 and phosphorylated NF-κB (P-NF-κB) p65 was measured by Western blot. Results HE staining showed that compared with the control group, the model group exhibited alveolar septal swelling and thickening, vascular dilatation and congestion, and inflammatory cell infiltration in the lung tissue; the hydrogen groups had significantly reduced pathological damage and inflammatory response than the model group, with more improvements in hydrogen group II than in hydrogen group I. Immunohistochemical results showed that compared with those in the control group, the levels of the inflammatory cytokines IL-6 and TNF-α were significantly increased in the model group; the hydrogen groups showed significantly decreased IL-6 and TNF-α levels and a significantly increased level of the anti-inflammatory factor IL-10 than the model group, which were more marked in hydrogen group II than in hydrogen group I. Immunofluorescence results showed that compared with the control group, the expression of the surface marker of M1 macrophages in the model group was significantly upregulated; the hydrogen groups showed significantly downregulated M1 marker and significantly upregulated M2 marker, and hydrogen group II showed significantly increased M2 marker compared with hydrogen group I. Western blot results showed that compared with that in the control group, the ratio of P-NF-κB p65/NF-κB p65 in the model group was significantly increased; the P-NF-κB p65/NF-κB p65 ratio was significantly reduced in the hydrogen groups than in the model group, and was significantly lower in hydrogen group II than in hydrogen group I. Conclusion Hydrogen inhalation therapy may reduce the inflammatory response of radiation-induced lung injury by inhibiting the NF-κB signaling pathway to promote the polarization of the macrophage M1 subtype to the M2 subtype.

【Objective】 To summarize the clinicopathological features and prognosis of young patients (18-40 years old) with non-clear cell renal cell carcinoma (nccRCC) treated in a single center to provide reference for the diagnosis and treatment of similar patients. 【Methods】 Clinical data of 113 nccRCC patients treated during Jan. 2012 and Aug. 2022 were retrospectively analyzed, including 57 males (50.4%) and 56 females (49.6%). The average age of onset was (31.6±5.8) years. Among all patients, 57 had lesions (50.4%) on the left side, and 56 (49.6%) on the right side. Young patients undergoing renal cancer surgery accounted for approximately 12.4% of the total number of renal cancer patients undergoing surgery, and nccRCC accounted for 34.8% of the total number of cases. 【Results】 Minimally invasive surgery (laparoscopic or robot-assisted) was performed in 102 cases (90.3%), and open surgery in 11 cases (9.7%). Fifty-five cases (48.7%) underwent partial nephrectomy and 58 (51.3%) radical nephrectomy. Among them, 11 patients (9.7%) developed tumor thrombi. All surgeries were successful with no serious complications. The pathological types included 32 cases (28.3%) of chromophobe renal cell carcinoma, 25 cases (22.1%) of MiT family translocation renal cell carcinoma, and 20 cases (17.7%) of papillary renal cell carcinoma. The total proportion of the three pathological subtypes reached 68.1%. After 46 (2-115) months of follow-up, 8 cases (7.8%, 8/102) developed tumor metastasis and 2 died. 【Conclusion】 The nccRCC is rare in young patients. The major pathological type is chromophobe, and the major treatment method is minimally invasive surgery. Most pathological types have good long-term prognosis, while patients with tumor thrombi have a high risk of metastasis and poor prognosis.

As the understanding of the pathogenic mechanisms of gastric cancer deepens and the identification of gastric cancer driver genes advances,drugs targeting gastric cancer driver genes have been applied in clinical practice.Among them,trastuzumab,as the first targeted drug for gastric cancer,effectively inhibits the proliferation and metastasis of tumor cells by targeting overexpressed human epidermal growth factor receptor 2(HER2).Trastuzumab has become the standard treatment for HER2-positive gastric cancer patients.Ramucirumab,on the other hand,inhibits tumor angiogenesis by targeting vascular endothelial growth factor receptor 2(VEGFR2)and has been used as second-line therapy for advanced gastric cancer patients.In addition,bemarituzumab targets overexpressed fibroblast growth factor receptor 2(FGFR2),while zolbetuximab targets overexpressed claudin 18.2(CLDN18.2),significantly extending progression-free survival and overall survival in patients with gastric cancer in clinical trials.This article reviews the roles of tumor driver genes in the progression of gastric cancer,and the treatment strategies for gastric cancer primarily based on targeting HER2,VEGF,FGFR2,CLDN18.2 and MET.This provides a reference for clinical application of targeted therapy for gastric cancer.

Acceleration of tooth movement during orthodontic treatment is challenging,with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step.Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages,especially adhesion G protein-coupled receptors(aGPCRs),play important roles in force sensing.However,its role in the regulation of osteoclast differentiation remains unclear.Herein,through single-cell analysis,we revealed that CD97,a novel mechanosensitive aGPCR,was expressed in macrophages.Compression upregulated CD97 expression and inhibited osteoclast differentiation;while knockdown of CD97 partially rescued osteoclast differentiation.It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation.RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression.Consistently,we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity,thereby accelerating tooth movement.In conclusion,our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.

Background: s/Aims: Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant is closely associated with the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the role and mechanism of TM6SF2 E167K variant during MASLD progression are not yet fully understood. Methods: The Tm6sf2167K knock-in (KI) mice were subjected to high-fat diet (HFD). Hepatic lipid levels of Tm6sf2167K KI mice were detected by lipidomics analysis. Thin-layer chromatography (TLC) was used to measure the newly synthesized triglyceride (TG) and phosphatidylcholine (PC). Results: The TM6SF2 E167K variant significantly aggravated hepatic steatosis and injury in HFD-induced mice. Decreased polyunsaturated PC level and increased polyunsaturated TG level were found in liver tissue of HFDinduced Tm6sf2167K KI mice. Mechanistic studies demonstrated that the TM6SF2 E167K variant increased the interaction between TM6SF2 and PNPLA3, and impaired PNPLA3-mediated transfer of polyunsaturated fatty acids (PUFAs) from TG to PC. The TM6SF2 E167K variant increased the level of fatty acid-induced malondialdehyde and reactive oxygen species, and decreased fatty acid-downregulated cell membrane fluidity. Additionally, the TM6SF2 E167K variant decreased the level of hepatic PC containing C18:3, and dietary supplementation of PC containing C18:3 significantly attenuated the TM6SF2 E167K-induced hepatic steatosis and injury in HFD-fed mice. Conclusions The TM6SF2 E167K variant could promote its interaction with PNPLA3 and inhibit PNPLA3-mediated transfer of PUFAs from TG to PC, resulting in the hepatic steatosis and injury during MASLD progression. PC containing C18:3 could act as a potential therapeutic supplement for MASLD patients carrying the TM6SF2 E167K variant.

Objective:To screen the differentially expressed genes (DEG) related to inflammatory response associated with the prognosis of colon cancer based on the bioinformatics approach, and to construct and validate a prognostic model for colon cancer.Methods:RNA sequencing and clinical data of 472 colon cancer patients and normal colon tissues of 41 healthy people were retrieved from the Cancer Genome Atlas (TCGA) database. Gene expression related to prognosis of colon cancer and clinical data were retrieved from the International Cancer Genome Consortium (ICGC) database. The retrieval time was all from the establishment of library to November 2022. A total of 200 genes associated with inflammatory response obtained from the Gene Set Enrichment Analysis (GSEA) database were compared with the RNA sequencing gene dataset of colon cancer and normal colon tissues obtained from the TCGA database, and then DEG associated with inflammatory response were obtained. The prognosis-related DEG in the TCGA database were analyzed by using Cox proportional risk model, and the inflammatory response-related DEG were intersected with the prognosis-related DEG to obtain the prognosis-related inflammatory response-related DEG. The prognostic model of colon cancer was constructed by using LASSO Cox regression. Risk scores were calculated, and colon cancer patients in the TCGA database were divided into two groups of low risk (< the median value) and high risk (≥the median value) according to the median value of risk scores. Principal component analysis (PCA) was performed on patients in both groups, and survival analysis was performed by using Kaplan-Meier method. The efficacy of risk score in predicting the overall survival (OS) of colon cancer patients in the TCGA database was analyzed based on the R software timeROC program package. Clinical data from the ICGC database were applied to externally validate the constructed prognostic model, and patients with colon cancer in the ICGC database were classified into high and low risk groups based on the median risk score of patients with colon cancer in the TCGA database. By using R software, single-sample gene set enrichment analysis (ssGESA), immunophenotyping difference analysis, immune microenvironment correlation analysis, and immune checkpoint gene difference analysis of immune cells and immune function were performed for prognosis-related inflammation response-related DEG in the TCGA database.Results:A total of 60 inflammatory response-related DEG and 12 prognosis-related DEG were obtained; and 6 prognosis-related inflammatory response-related DEG (CCL24, GP1BA, SLC4A4, SRI, SPHK1, TIMP1) were obtained by taking the intersection set. LASSO Cox regression analysis showed that a prognostic model for colon cancer was constructed based on 6 prognosis-related inflammatory response-related DEG, and the risk score was calculated as = -0.113×CCL24+0.568×GP1BA+ (-0.375)×SLC4A4+(-0.051)×SRI+0.287×SPHK1+0.345×TIMP1. PCA results showed that patients with colon cancer could be better classified into 2 clusters. The OS in the high-risk group was worse than that in the low-risk group in the TCGA database ( P < 0.001); the area of the curve (AUC) of the prognostic risk score for predicting the OS rates of 1-year, 3-year, 5-year was 0.701, 0.685, and 0.675, respectively. The OS of the low-risk group was better than that of the high-risk group in the ICGC database; AUC of the prognostic risk score for predicting the OS rates of 1-year, 2-year, 3-year was 0.760, 0.788, and 0.743, respectively. ssGSEA analysis showed that the level of immune cell infiltration in the high-risk group in the TCGA database was high, especially the scores of activated dendritic cells, macrophages, neutrophils, plasmacytoid dendritic cells, T helper cells, and follicular helper T cells in the high-risk group were higher than those in the low-risk group, while the score of helper T cells 2 (Th2) in the high-risk group was lower compared with that in the low-risk group (all P < 0.05); in terms of immune function, the high-risk group had higher scores of antigen-presenting cell (APC) co-inhibition, APC co-stimulation, immune checkpoint, human leukocyte antigen (HLA), promotion of inflammation, parainflammation, T-cell stimulation, type Ⅰ interferon (IFN) response, and type ⅡIFN response scores compared with those in the low-risk group (all P < 0.05). The results of immunophenotyping analysis showed that IFN-γ-dominant type (C2) had the highest inflammatory response score, and the differences were statistically significant when compared with trauma healing type (C1) and inflammatory response type (C3), respectively (all P < 0.05). Immune microenvironment stromal cells and immune cells were all positively correlated with prognostic risk scores ( r values were 0.35 and 0.21, respectively, both P < 0.01). The results of immune checkpoint difference analysis showed there was a statistically significant difference in programmed-death receptor ligand 1 (PD-L1) expression level between high-risk group and low-risk group ( P = 0.002), and PD-L1 expression level was positively correlated with prognostic risk score ( r = 0.23, P < 0.01). Conclusions:Inflammatory response-related genes may play an important role in tumor immunity of colon cancer and can be used in the prognostic analysis and immunotherapy of colon cancer patients.

Hepatitis B virus （HBV） has the characteristics of wide transmission， a high chronic infection rate， and a low cure rate， and improving the cure rate of HBV may help to improve the long－term prognosis of patients. Heat shock protein 90 （Hsp90） is a chaperone protein widely present in organisms. In recent years， more and more studies have shown that Hsp90 is associated with HBV infection and plays an important role in HBV replication. It can not only interact with specific proteins of the virus to promote its replication， but also interact with the host’s own proteins to perform its function. This article reviews the role of Hsp90 in HBV replication in recent studies， so as to provide new theoretical guidance and directions for the development of new anti－HBV drugs targeting Hsp90 and the prevention and treatment of HBV infection in the future.

Objective:To investigate whether stress hyperglycemia (SH) is an independent risk factor for the occurrence and mortality of sepsis-associated encephalopathy (SAE).Methods:From August 2016 to October 2021, sepsis patients admitted to the ICU of Guangdong Provincial People's Hospital were selected as the study subjects. According to whether they developed to SH (RBG>11.1 mmol/L) within 7 days of enrollment, the pat ients were divided into the SH group and the non-SH group for analysis. Logistic regression was used to analyze whether SH was an independent risk factor for SAE occurrence, and ROC curve was used to analyze the predictive value of SH to SAE. Kaplan-Meier curve was used to compare the 90-day survival of SAE patients with or without SH. Cox regression analysis was used to analyze the risk factors of 28-day and 90-day death in SAE patients.Results:A total of 183 sepsis patients were included, including 62 patients in the SH group and 121 in the non-SH group. Logistic regression analysis demonstrated that SH was an independent risk factor for SAE ( OR=4.452, 95% CI: 2.021-9.808, P <0.001). ROC curve demonstrated that SH could accurately predict SAE (AUC=0.831; Sensitivity=78.4%; Specificity=76.8%; and Yoden index=0.553). Kaplan-Meier curve demonstrated that the 90-day survival of SAE patients with SH significantly declined (log-rank test: P<0.01). Cox regression analysis suggested that SH was a risk factor for death at day 28 and day 90 in SAE patients (28 d, HR=2.272, 95% CI: 1.212-4.260, P=0.010; 90 d, HR=2.456, 95% CI: 1.400-4.306, P<0.01). Conclusions:SH is an independent risk factor for SAE and can predict SAE occurrence. SH significantly reduces 90-day survival and increase mortality at 28 and 90 days in SAE patients.