Objective To investigate the clinical features of chronic hepatitis C(CHC)patients with hepatitis C virus genotype 3(HCV GT3)infection and the risk factors for disease progression.Methods A multicenter retrospective cohort study was conducted among 1 002 CHC patients from 11 clinical centers in Northwest China from December 2017 to November 2023,and according to their genotype,they were divided into GT1,GT2,GT3,and GT6 groups.Clinical features were compared between the patients with different genotypes.The one-way analysis of variance was used for comparison of normally distributed continuous data between groups,and the Scheffe test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of data with skewed distribution between groups;the chi-square test or Fisher test was used for comparison of categorical data between groups.The multivariate logistic regression analysis was used to explore the influencing factors for the progression of CHC to liver cirrhosis.Results In terms of the genotype,there were 427 patients with GT1 infection,242 with GT2 infection,299 with GT3 infection(210 patients with GT3a infection,87 with GT3b infection,and 2 with unclassified genotype),and 34 with GT6 infection.The patients with GT3 infection had a significantly younger age than those with GT1 infection(51.3±0.5 years vs 53.2±0.6 years,P<0.05)or GT2 infection(51.3±0.5 years vs 53.7±0.8 years,P<0.05),and for the patients with liver cirrhosis,the patients with GT3 infection had a significantly younger age than those with GT1 infection(52.1±0.5 years vs 59.4±0.9 years,P<0.001)or GT2 infection(52.1±0.5 years vs 58.1±1.1 years,P<0.001).Among the patients with GT3 infection,male patients accounted for 77.9%and the patients with liver cirrhosis accounted for 46.2%,which were significantly higher than those among the patients with GT1,GT2 or GT6 infection(all P<0.001).At baseline,the patients with GT3 infection had significantly higher levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)than those with GT1 or GT2 infection,significantly higher aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4(FIB4)than those with GT1,GT2 or GT6 infection,a significantly lower platelet count(PLT)than those with GT2 or GT6 infection,a significantly higher level of alpha-fetoprotein than those with GT2 or GT6 infection,and a significantly lower level of albumin(Alb)than those with GT6 infection(all P<0.05).There were no significant differences between the patients with GT3a infection and those with GT3b infection in age,sex,the proportion of patients with liver cirrhosis,comorbidities,HCV RNA quantification,PLT,ALT,AST,alkaline phosphatase,Alb,APRI,and FIB-4(all P>0.05).The multivariate logistic regression analysis showed that PLT≤150×109/L(odds ratio[OR]=10.72,95%confidence interval[CI]:5.76-35.86,P<0.001)and Alb≤35 g/L(OR=3.74,95%CI:1.22-11.45,P=0.021)were risk factors for liver cirrhosis.Conclusion Most CHC patients with GT3 infection are male in Northwest China,and compared with the patients with other genotypes,such patients tend to have a younger age of onset and higher degrees of liver inflammation activity and fibrosis.Low PLT and a low level of Alb are risk factors for progression to liver cirrhosis in CHC patients with GT3 infection.

Osteoarthritis is a chronic degenerative disease characterized by cartilage degeneration, synovial inflammation, and subchondral bone remodeling. Its pathogenesis involves multiple links such as joint mechanical stress imbalance, extracellular matrix degradation, and inflammatory responses. Physical exercise has been widely recognized in the treatment of osteoarthritis. Although mechanism of action remains incompletely understood, appropriate exercise can effectively relieve pain caused by osteoarthritis, improve joint dysfunction, and reduce inflammation. In recent years, pyroptosis has been proven to exacerbate the pathological process of osteoarthritis by promoting the release of pro-inflammatory factors such as IL-1β and HMGB1 from synovial fibroblasts (FLSs) and chondrocytes. The pyroptosis of FLSs is regulated by the NLRP1/3 inflammasome, HIF-1α, and the SDF-1/AMPK pathway. In contrast, chondrocyte pyroptosis is closely related to the activation of the P2X7 receptor, the NF-κB/NLRP3 signaling axis, microRNAs (for example, miR-140-5p inhibits CTSB/NLRP3, while miR-155 promotes pyroptosis), and certain traditional Chinese medicine extracts (such as morroniside and loganin). Both exercise and pyroptosis are closely associated with the inflammatory response in osteoarthritis. Recent studies have found that exercise/mechanical stress stimulation can directly or indirectly regulate chondrocyte pyroptosis and delay the progression of osteoarthritis. In terms of direct regulation, moderate-intensity exercise can downregulate the expression of the P2X7 receptor, activate the AMPK/mTOR pathway to promote autophagy, and thereby inhibit chondrocyte pyroptosis. Mechanical stretch stimulation can upregulate TGF-β1 to activate the Smad2/3 pathway and inhibit the NF-κB/NLRP3 signaling axis. In terms of indirect regulation, exercise can inhibit the PI3K/Akt/NF-κB pathway by increasing the secretion of irisin, and simultaneously promote the production of lipoxin A4 (LXA4) to induce the polarization of synovial macrophages into the anti-inflammatory M2 type. In addition, exercise can also upregulate the expression of Metrnl protein and block the NLRP3/caspase-1/GSDMD pyroptosis signaling cascade.

Osteoarthritis is a chronic degenerative disease characterized by cartilage degeneration, synovial inflammation, and subchondral bone remodeling. Its pathogenesis involves multiple links such as joint mechanical stress imbalance, extracellular matrix degradation, and inflammatory responses. Physical exercise has been widely recognized in the treatment of osteoarthritis. Although mechanism of action remains incompletely understood, appropriate exercise can effectively relieve pain caused by osteoarthritis, improve joint dysfunction, and reduce inflammation. In recent years, pyroptosis has been proven to exacerbate the pathological process of osteoarthritis by promoting the release of pro-inflammatory factors such as IL-1β and HMGB1 from synovial fibroblasts (FLSs) and chondrocytes. The pyroptosis of FLSs is regulated by the NLRP1/3 inflammasome, HIF-1α, and the SDF-1/AMPK pathway. In contrast, chondrocyte pyroptosis is closely related to the activation of the P2X7 receptor, the NF-κB/NLRP3 signaling axis, microRNAs (for example, miR-140-5p inhibits CTSB/NLRP3, while miR-155 promotes pyroptosis), and certain traditional Chinese medicine extracts (such as morroniside and loganin). Both exercise and pyroptosis are closely associated with the inflammatory response in osteoarthritis. Recent studies have found that exercise/mechanical stress stimulation can directly or indirectly regulate chondrocyte pyroptosis and delay the progression of osteoarthritis. In terms of direct regulation, moderate-intensity exercise can downregulate the expression of the P2X7 receptor, activate the AMPK/mTOR pathway to promote autophagy, and thereby inhibit chondrocyte pyroptosis. Mechanical stretch stimulation can upregulate TGF-β1 to activate the Smad2/3 pathway and inhibit the NF-κB/NLRP3 signaling axis. In terms of indirect regulation, exercise can inhibit the PI3K/Akt/NF-κB pathway by increasing the secretion of irisin, and simultaneously promote the production of lipoxin A4 (LXA4) to induce the polarization of synovial macrophages into the anti-inflammatory M2 type. In addition, exercise can also upregulate the expression of Metrnl protein and block the NLRP3/caspase-1/GSDMD pyroptosis signaling cascade.

Objective : To investigate the role and related mechanisms of IgD on the viability , proliferation , apoptosis , and other functions of Molm_13 cells. Methods: Peripheral blood serum was collected from AML patients and healthy controls. The sIgD levels were quantified by ELISA. For in vitro studies , Molm_13 cells were treated with varying concentrations of IgD. Cell viability and proliferation were assessed via CCK_8 assays , CFSE staining , and colony formation assays. Apoptosis rates were determined using an Annexin V/PI apoptosis detection kit. Preliminary exploration of the mechanisms related to IgD_induced proliferation of Molm_13 were analyzed through differential gene analysis. Results: Compared with healthy controls , the levels of sIgD in AML patients were significantly el_ evated (P < 0. 001 ) . IgD treatment dose_dependently increased Molm_13 cell viability and proliferation ( P < 0. 05) , inhibited apoptosis rates (P < 0. 001) . Conclusion IgD promotes the viability and proliferation of Molm_ 13 cells , and reduces apoptosis.

Objective To investigate the prevalence of food intolerance among children in Zhuzhou area and its relationship with age,gender,systemic diseases,and food allergies,so as to provide a basis for the scientific adjustment of children's dietary structure.Methods A retrospective analysis was conducted on totally 1 592 children who underwent food intolerance and food allergen testing in the hospital,the positive rate and distri-bution of 14 kinds of food intolerance were assessed,and their correlation with various factors was analyzed.Results Among 14 kinds of food tested,milk and eggs had the highest positive rates of intolerance,at 82.22％and 55.78％,respectively.The majority of children were intolerant to 1 to 2 kinds of food,with a de-creasing trend in the number of children intolerant to multiple kinds of food.Among the 14 types of food,ex-cept for mushrooms and pork,there were statistically significant differences in the distribution of negative,mild,moderate,and severe intolerance in other foods(P＜0.05).Children tended to have moderate or even se-vere intolerance to milk and eggs,while they tended to have mild intolerance to other foods.There was no sta-tistically significant difference in the overall food intolerance rate between boys and girls(P=0.654),but the positive rate of tomato intolerance in girls was slightly higher than that in boys(P=0.043).Except for pork,there were statistically significant differences in the positive rates of intolerance to 14 different foods among different age groups(P＜0.05).The positive rates of intolerance to cod,mushrooms,and crabs increased with age,while the positive rates of intolerance to beef decreased with age.There was a statistically significant difference in the positive rate of milk intolerance between healthy children and children with skin allergies(P＜0.05).There was a statistically significant difference in the proportion of individuals who were tolerant and not allergic to milk compared to hose who were intolerant and allergic to milk(P＜0.05).There was a statistically significant difference in the proportion of individuals who were tolerant and not allergic to eggs compared to those who were intolerant and allergic to eggs(P＜0.05).Conclusion The positive rate of food intolerance among children in Zhuzhou area is relatively high,with milk and eggs being the main intolerant foods.There are differences in the positive rate of intolerance among different gender and age groups,and in-tolerance to milk and eggs is associated with food allergies to some extent.

Objective To investigate the clinical features of chronic hepatitis C(CHC)patients with hepatitis C virus genotype 3(HCV GT3)infection and the risk factors for disease progression.Methods A multicenter retrospective cohort study was conducted among 1 002 CHC patients from 11 clinical centers in Northwest China from December 2017 to November 2023,and according to their genotype,they were divided into GT1,GT2,GT3,and GT6 groups.Clinical features were compared between the patients with different genotypes.The one-way analysis of variance was used for comparison of normally distributed continuous data between groups,and the Scheffe test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of data with skewed distribution between groups;the chi-square test or Fisher test was used for comparison of categorical data between groups.The multivariate logistic regression analysis was used to explore the influencing factors for the progression of CHC to liver cirrhosis.Results In terms of the genotype,there were 427 patients with GT1 infection,242 with GT2 infection,299 with GT3 infection(210 patients with GT3a infection,87 with GT3b infection,and 2 with unclassified genotype),and 34 with GT6 infection.The patients with GT3 infection had a significantly younger age than those with GT1 infection(51.3±0.5 years vs 53.2±0.6 years,P<0.05)or GT2 infection(51.3±0.5 years vs 53.7±0.8 years,P<0.05),and for the patients with liver cirrhosis,the patients with GT3 infection had a significantly younger age than those with GT1 infection(52.1±0.5 years vs 59.4±0.9 years,P<0.001)or GT2 infection(52.1±0.5 years vs 58.1±1.1 years,P<0.001).Among the patients with GT3 infection,male patients accounted for 77.9%and the patients with liver cirrhosis accounted for 46.2%,which were significantly higher than those among the patients with GT1,GT2 or GT6 infection(all P<0.001).At baseline,the patients with GT3 infection had significantly higher levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)than those with GT1 or GT2 infection,significantly higher aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4(FIB4)than those with GT1,GT2 or GT6 infection,a significantly lower platelet count(PLT)than those with GT2 or GT6 infection,a significantly higher level of alpha-fetoprotein than those with GT2 or GT6 infection,and a significantly lower level of albumin(Alb)than those with GT6 infection(all P<0.05).There were no significant differences between the patients with GT3a infection and those with GT3b infection in age,sex,the proportion of patients with liver cirrhosis,comorbidities,HCV RNA quantification,PLT,ALT,AST,alkaline phosphatase,Alb,APRI,and FIB-4(all P>0.05).The multivariate logistic regression analysis showed that PLT≤150×109/L(odds ratio[OR]=10.72,95%confidence interval[CI]:5.76-35.86,P<0.001)and Alb≤35 g/L(OR=3.74,95%CI:1.22-11.45,P=0.021)were risk factors for liver cirrhosis.Conclusion Most CHC patients with GT3 infection are male in Northwest China,and compared with the patients with other genotypes,such patients tend to have a younger age of onset and higher degrees of liver inflammation activity and fibrosis.Low PLT and a low level of Alb are risk factors for progression to liver cirrhosis in CHC patients with GT3 infection.

Objective To investigate the correlations of serum Apelin-13 and fatty acid binding protein 4 (FABP4) levels with metabolic and bone metabolic indicators in postmenopausal women with different bone mass. Methods A total of 145 postmenopausal women were selected as subjects and divided into three groups based on bone mineral density (BMD) test results: normal bone mass group(49 cases), osteopenia (ON) group(51 cases), and osteoporosis (OP) group(45 cases). Serum Apelin-13, FABP4 levels, bone metabolic indicators, and biochemical indicators were measured and compared among the three groups. Spearman correlation analysis was used to analyze the correlations of Apelin-13, FABP4, and other indicators with BMD. Multivariate Logistic regression analysis was performed to analyze the risk factors for OP, and the receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of serum Apelin-13 for postmenopausal osteoporosis (PMOP). Results The serum Apelin-13 level in the OP group was lower than that in the ON group and the normal bone mass group (P < 0.05). No significant difference in serum FABP4 levels was found among the three groups (P>0.05). The levels of serum parathyroid hormone (PTH), alkaline phosphatase (ALP), type Ⅰ procollagen amino-terminal propeptide (PⅠNP), type Ⅰ collagen cross-linked C-terminal peptide (CTXⅠ), and bone-specific alkaline phosphatase (BALP) in the OP group were higher than those in the ON group and the normal bone mass group (P < 0.05). Lumbar post-menopause BMD was positively correlated with serum Apelin-13 levels (P < 0.05), but had no correlation with serum FABP4 levels (P>0.05). Lumbar BMD was negatively correlated with serum PTH, ALP, PⅠNP, CTXⅠ, BALP, and age (P < 0.05), but positively correlated with body weight, body mass index, T-score, fasting insulin, and insulin resistance index (P < 0.05). Multivariate Logistic regression analysis showed that serum Apelin-13, PTH, ALP, PⅠNP, CTXⅠ, and BALP levels were independent factors influencing the occurrence of OP in postmenopausal women (P < 0.05). ROC curve results showed that the optimal cut-off value of serum Apelin-13 for predicting PMOP was 18.51 pg/mL, with an area under the curve of 0.716, a sensitivity of 70.0%, and a specificity of 64.4%. Conclusion Apelin-13 is lowly expressed in the serum of PMOP patients, and its expression level is closely related to lumbar BMD, which may serve as an early screening indicator and potential therapeutic target for PMOP.

Objective:To construct a novel dual-specific antibody targeting human CD123 (CD123 DuAb) and study its effects in acute myeloid leukemia (AML) .Methods:Based on the variable region of the CD123 monoclonal antibody independently developed at our institution, the CD123 DuAb expression plasmid was constructed by molecular cloning and transfected into ExpiCHO-S cells to prepare the antibody protein. Through a series of in vitro experiments, its activation and proliferation effect on T cells, as well as the effect of promoting T-cell killing of AML cells, were verified.Results:① A novel CD123 DuAb plasmid targeting CD123 was successfully constructed and expressed in the Expi-CHO eukaryotic system. ②The CD123 DuAb could bind both CD3 on T cells and CD123 on CD123 + tumor cells. ③When T cells were co-cultured with MV4-11 cells with addition of the CD123 DuAb at a concentration of 1 nmol/L, the positive expression rates of CD69 and CD25 on T cells were 68.0% and 44.3%, respectively, which were significantly higher than those of the control group ( P<0.05). ④Co-culture with CD123 DuAb at 1 nmol/L promoted T-cell proliferation, and the absolute T-cell count increased from 5×10 5/ml to 3.2×10 6/ml on day 9, and CFSE fluorescence intensity decreased significantly. ⑤ With the increase in CD123 DuAb concentration in the culture system, T-cell exhaustion and apoptosis increased. When the CD123 DuAb was added at a concentration of 1 nmol/L to the culture system, the proportion of CD8 + PD-1 + LAG-3 + T cells was 10.90%, and the proportion of propidium iodide (PI) - Annexin Ⅴ + T cells and PI + Annexin Ⅴ + T cells was 18.27% and 11.43%, respectively, which were significantly higher than those in the control group ( P<0.05). ⑥ The CD123 DuAb significantly activated T cells, and the activation intensity was positively correlated with its concentration. The expression rate of CD107a on T cells reached 16.05% with 1 nmol/L CD123 DuAb, which was significantly higher than that of the control group ( P<0.05). ⑦The CD123 DuAb promoted cytokine secretion by T cells at a concentration of 1 nmol/L, and the concentration of IFN-γ and TNF-α in the supernatant of the co-culture system reached 193.8 pg/ml and 169.8 pg/ml, respectively, which was significantly higher than that of the control group ( P<0.05). ⑧When CD123 DuAb was added at a concentration of 1 nmol/L to the co-culture system of T cells and CD123 + tumor cells, the killing intensity of T cells significantly increased, and the residual rates of CD123 + MV4-11 cells, CD123 + Molm13 cells, and CD123 + THP-1 cells were 7.4%, 6.7%, and 14.6% on day 3, respectively, which were significantly lower than those in the control group ( P<0.05) . Conclusion:In this study, a novel CD123 DuAb was constructed and expressed. In vitro experiments verified that the DuAb binds to CD123 + tumor cells and T cells simultaneously, promotes T-cell activation and proliferation, and facilitates their anti-leukemia effect, which provides a basis for further clinical research.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective To investigate the serum C-type lectin domain family 4 member G(CLEC4G)level and its clinical value in patients with Atopic Dermatitis(AD).Methods The blood samples of 60 AD patients and 29 control patients were collected,and CLEC4G,Interleukin-33(IL-33),total immunoglobulin E(tIgE),specific IgE(specific IgE),and eosinophil levels were detected.The correlation between CLEC4G level and clinical data of AD patients and IL-33 was analyzed.The risk of AD was evaluated by Logistic regression analysis of CLEC4G,IL-33 and other indicators.Results Compared with the control group,the serum CLEC4G level in AD patients was significantly decreased(359.4±57.3 vs.521.8±48.1)pg/mL.There was no significant difference in CLEC4G level between child-hood,adolescent and adult,male and female AD patients.Compared with tIgE≤100 kU/L group,CLEC4G level was significantly decreased in 100～200 kU/L group and tIgE≥200 kU/L group,but there was no significant difference between 100～200 kU/L group and tIgE≥200 kU/L group.Serum CLEC4G level decreased significantly only in the moderate AD group,but had no significant difference among the other groups.The serum level of IL-33 was increased in AD patients,but there was no significant correlation between CLEC4G and IL-33(r = 0.090,P = 0.495).Age less than 14 years old and IL-33 were risk factors for the incidence of AD,with OR values of 2.756 and 1.241,95%CI of 1.076～7.060 and 1.030～1.495,respectively.CLEC4G was a protective factor for AD(OR = 0.890,95%CI:0.809～0.979).Conclusion CLEC4G may be a protective factor independent of IL-33 mediated AD pathogenesis.