Objective To explore the relationship between systemic immune-inflammation index(SⅡ)at admission and occurrence of early neurological deterioration(END)in patients with branch atheromatous disease(BAD).Methods A retrospective analysis was performed on 326 BAD patients admitted in Department of Neurology of Handan Central Hospital from October 2021 to February 2024.Based on occurrence of END or not,they were divided into END group(97 cases)and non-END group(229 cases).Clinical data of the patients were collected,and multivari-ate logistic regression analysis was used to identify the END risk variables in BAD patients.ROC curve was plotted to evaluate the value of NIHSS score,hs-CRP and SⅡ in predicting the inci-dence of END in the patients.Results Significantly advanced age,higher NIHSS score at admis-sion,and elevated hs-CRP level,neutrophil count and SⅡ,but lower platelet and lymphocyte counts were observed in the END group than the non-END group(P＜0.05,P＜0.01).Multi vari-ate logistic regression analysis indicated that NIHSS score at admission(OR=1.134,95％CI:1.050-1.226,P=0.001),hs-CRP(OR=1.131,95％CI:1.024-1.249,P=0.015),and SⅡ(OR=1.001,95％CI:1.001-1.002,P=0.003)were independent risk factors for END in BAD patients.The AUC value of SⅡ in the prediction of END was 0.660,which was significantly higher than that of NIHSS score and hs-CRP in BAD patients(P＜0.05).Conclusion SⅡ is an independent risk factor for END in BAD patients,and SⅡ at admission has a certain predictive value for the oc-currence of END in these patients.

Objective To study the expression of N6-methyladenosine(m6A)methyltransferase-like protein 16(METTL16),Ankyrin repeat and SOCS box containing protein 4(ASB13)in elderly breast cancer tissues and their relationship with clinicopathological features and prognosis.Methods 124 elderly patients with breast cancer diagnosed and treated in the Zibo 148 Hospital from January 2019 to January 2021 were selected.Immunohistochemistry(IHC)was used to detect the expression of METTL16 and ASB13 proteins in tissues.Real time fluorescence quantitative PCR(RT-qPCR)was used to detect the expression of METTL16 mRNA and ASB13 mRNA in tissues.Pearson correlation was used for correlation analysis.Survival analysis used Kaplan-Meier curves and Log Rank tests to compare the prognostic differences among patients with different METTL16 and ASB13 expression levels.COX regression analysis was used to analyze the prognostic factors of elderly patients with breast cancer.Results The positive rate of METTL16 in cancer tissue(70.97%)was higher than that in adjacent tissues(8.06%),while the positive rate of ASB13(22.58%)was lower than that in adjacent tissues(72.58%),the differences were statistically significant(χ2=102.642,62.146,all P<0.001).METTL16 mRNA,Snail mRNA and N-cadherin(N-cd)mRNA were higher in cancer tissues than in adjacent tissues,while ASB13 mRNA was lower in adjacent tissues,the differences were statistically significant(t=40.498～48.624,all P<0.001).METTL16 mRNA was positively correlated with Snail mRNA and N-cd mRNA in cancer tissue(r=0.712,0.669,all P<0.001),while ASB13 mRNA was negatively correlated with Snail mRNA and N-cd mRNA(r=-0.734,-0.759,all P<0.001).Compared with TNM stage Ⅰ-Ⅱ and patients with high to medium differentiation,patients with TNM stage Ⅲ and low differentiation had higher positive rate of METTL16 in cancer tissue and lower positive rate of ASB13,the differences were statistically significant(χ2=5.340～10.370,all P<0.05).The 3-year progression free survival rate(73.86%)of the METTL16 positive group was lower than that of the METTL16 negative group(88.89%),the 3-year progression free survival rate(92.86%)of the ASB13 positive group was higher than that of the ASB13 negative group(73.96%),and the differences were statistically significant(Log Rank χ2=4.483,4.882,all P<0.005).METTL16 positive,TNM stage Ⅲ,poor differentiation were risk factors affecting the prognosis of elderly breast cancer,and ASB13 positive was protective factors(Wald χ2=5.056～9.267,all P<0.001).Conclusion METTL16 expression is up-regulated and ASB13 expression is down-regulated in elderly breast cancer,both of which are related to the expression of invasion and metastasis genes,and are new prognostic markers for elderly breast cancer.

BACKGROUND:The capability of repairing articular cartilage damage is very limited,and tissue engineering technology provides new therapeutic options for repairing damaged cartilage,in which the interaction and induction between chondrocytes,bone marrow mesenchymal stem cells,and synovial mesenchymal stem cells is the basis of autologous healing of cartilage damage. OBJECTIVE:To construct the chondrocyte-bone marrow mesenchymal stem cell-synovial mesenchymal stem cell co-culture system to simulate the in vitro microenvironment of chondrocytes,and to explore the optimal cell inoculation ratio,meanwhile to observe the effects of icariin-containing serum on the proliferation of chondrocytes and the chondrogenic differentiation of stem cells in the system. METHODS:Rat knee chondrocytes,bone marrow mesenchymal stem cells and synovial mesenchymal stem cells were extracted,cultured and identified,and a chondrocyte-bone marrow mesenchymal stem cell-synovial mesenchymal stem cell non-contact co-culture system was constructed according to different cell inoculation ratios.After 72 hours of co-culturing,the chondrocyte proliferative activity and phenotypic ability were observed,and the co-culture system with the best overall effect was selected.New Zealand white rabbits were gavaged with icariin solution(0.25 mg/mL)to prepare icariin-containing serum,and cultured in conventional complete medium(high sugar DMEM culture medium containing 10%fetal bovine serum and 1%double antibody by volume)as the control group,while the experimental group was intervened by adding 10%icariin-containing serum by volume on the basis of above.The proliferative activity of chondrocytes and the expression of collagen type II were tested for the two groups after 24 and 48 hours.The differentiation of bone marrow mesenchymal stem cells and synovial mesenchymal stem cells into chondrocytes in the co-culture system was tested by immunofluorescence staining after 14 days. RESULTS AND CONCLUSION:(1)The three kinds of cells grew normally adherently to the wall in different ratios of co-culture,where chondrocytes showed the best proliferative activity and phenotypic ability in the co-culture system when chondrocytes:bone marrow mesenchymal stem cells:synovial mesenchymal stem cells=2:1:1.(2)Compared with the control group,the proliferative activity and type II collagen expression of chondrocytes in the experimental group were significantly increased after 24 hours(P<0.01),and the two groups still had difference after 48 hours(P<0.05).The two groups showed obvious chondrogenic differentiation of bone marrow mesenchymal stem cells and synovial mesenchymal stem cells after 14 days(P<0.01),and some of the cells appeared round or oval,and the cytoplasmic type II collagen immunofluorescence staining was positive.The fluorescence intensity of the experimental group was significantly higher than that of the control group(P<0.01).(3)The results showed that the chondrocyte-bone marrow mesenchymal stem cell-synovial mesenchymal stem cell co-culture system could be successfully established by the non-contact co-culture method,and the best chondrocyte proliferative activity and phenotypic ability could be obtained when the cell ratio was 2:1:1.Icariin-containing serum had the promoting effect on chondrocyte proliferation,and chondrogenic differentiation of bone marrow mesenchymal stem cells and synovial mesenchymal stem cells in the system.

Objective To explore the relationship between systemic immune-inflammation index(SⅡ)at admission and occurrence of early neurological deterioration(END)in patients with branch atheromatous disease(BAD).Methods A retrospective analysis was performed on 326 BAD patients admitted in Department of Neurology of Handan Central Hospital from October 2021 to February 2024.Based on occurrence of END or not,they were divided into END group(97 cases)and non-END group(229 cases).Clinical data of the patients were collected,and multivari-ate logistic regression analysis was used to identify the END risk variables in BAD patients.ROC curve was plotted to evaluate the value of NIHSS score,hs-CRP and SⅡ in predicting the inci-dence of END in the patients.Results Significantly advanced age,higher NIHSS score at admis-sion,and elevated hs-CRP level,neutrophil count and SⅡ,but lower platelet and lymphocyte counts were observed in the END group than the non-END group(P＜0.05,P＜0.01).Multi vari-ate logistic regression analysis indicated that NIHSS score at admission(OR=1.134,95％CI:1.050-1.226,P=0.001),hs-CRP(OR=1.131,95％CI:1.024-1.249,P=0.015),and SⅡ(OR=1.001,95％CI:1.001-1.002,P=0.003)were independent risk factors for END in BAD patients.The AUC value of SⅡ in the prediction of END was 0.660,which was significantly higher than that of NIHSS score and hs-CRP in BAD patients(P＜0.05).Conclusion SⅡ is an independent risk factor for END in BAD patients,and SⅡ at admission has a certain predictive value for the oc-currence of END in these patients.

Objective:To investigate the clinical characteristics, prognosis, and the impact of different secondary prevention strategies on stroke recurrence in patients with carotid web (CaW)-associated acute anterior circulation large vessel occlusion (LVO).Methods:A retrospective analysis was conducted on 401 patients with acute anterior circulation LVO who underwent mechanical thrombectomy at 2 advanced stroke centers, Xingtai Central Hospital and Xingtai People′s Hospital, from January 2018 to June 2024. CaW was identified using digital subtraction angiography (DSA) and other imaging modalities. Based on the presence of CaW, patients were divided into CaW group and non-CaW group. Differences between the 2 groups in baseline characteristics, clinical features, and clinical outcomes were compared, and long-term follow-up was conducted for the CaW group.Results:Among the 401 patients, the CaW group consisted of 16 patients (4.0%), while the non-CaW group included 385 patients (96.0%). Compared to the non-CaW group, patients in the CaW group were younger [53 (46, 58) years vs 65 (56, 76) years, Z=-3.811, P<0.001], had a higher proportion of M1 segment middle cerebral artery occlusion [13/16 vs 54.0% (208/385), χ2=4.602, P=0.032] and a lower proportion of internal carotid artery terminus occlusion [1/16 vs 40.0% (154/385), χ2=6.024, P=0.014]; the 90-day modified Rankin Scale (mRS) score was significantly lower in the CaW group [1.00 (0, 1.75) vs 3.00 (1.00, 4.00), Z=14.210, P<0.001], and the proportion of patients with favorable functional independence (mRS score 0-2) was significantly higher [15/16 vs 45.7% (176/385), χ2=12.350, P<0.001] in the CaW group; the incidence of pneumonia in the CaW group was significantly lower [2/16 vs 42.6% (164/385), χ2=4.562, P=0.033]. Among the 16 CaW patients, 10 received antiplatelet therapy, 4 underwent carotid artery stenting (CAS), and 2 underwent carotid endarterectomy (CEA). During a median follow-up of 29 months, patients who underwent CAS and CEA had no stroke recurrence, while 2 patients who received antiplatelet therapy had stroke recurrence and subsequently underwent CAS and CEA. Conclusions:The proportion of CaW among patients with acute anterior circulation LVO was 4.0%. The patients with CaW were younger and had a higher proportion of M1 segment middle cerebral artery occlusion. Following mechanical thrombectomy, patients in the CaW group had good functional outcomes. Simple drug therapy may be insufficient to prevent stroke recurrence in CaW patients, and CAS and CEA may be effective therapeutic options.

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

Objective To study the expression of N6-methyladenosine(m6A)methyltransferase-like protein 16(METTL16),Ankyrin repeat and SOCS box containing protein 4(ASB13)in elderly breast cancer tissues and their relationship with clinicopathological features and prognosis.Methods 124 elderly patients with breast cancer diagnosed and treated in the Zibo 148 Hospital from January 2019 to January 2021 were selected.Immunohistochemistry(IHC)was used to detect the expression of METTL16 and ASB13 proteins in tissues.Real time fluorescence quantitative PCR(RT-qPCR)was used to detect the expression of METTL16 mRNA and ASB13 mRNA in tissues.Pearson correlation was used for correlation analysis.Survival analysis used Kaplan-Meier curves and Log Rank tests to compare the prognostic differences among patients with different METTL16 and ASB13 expression levels.COX regression analysis was used to analyze the prognostic factors of elderly patients with breast cancer.Results The positive rate of METTL16 in cancer tissue(70.97%)was higher than that in adjacent tissues(8.06%),while the positive rate of ASB13(22.58%)was lower than that in adjacent tissues(72.58%),the differences were statistically significant(χ2=102.642,62.146,all P<0.001).METTL16 mRNA,Snail mRNA and N-cadherin(N-cd)mRNA were higher in cancer tissues than in adjacent tissues,while ASB13 mRNA was lower in adjacent tissues,the differences were statistically significant(t=40.498～48.624,all P<0.001).METTL16 mRNA was positively correlated with Snail mRNA and N-cd mRNA in cancer tissue(r=0.712,0.669,all P<0.001),while ASB13 mRNA was negatively correlated with Snail mRNA and N-cd mRNA(r=-0.734,-0.759,all P<0.001).Compared with TNM stage Ⅰ-Ⅱ and patients with high to medium differentiation,patients with TNM stage Ⅲ and low differentiation had higher positive rate of METTL16 in cancer tissue and lower positive rate of ASB13,the differences were statistically significant(χ2=5.340～10.370,all P<0.05).The 3-year progression free survival rate(73.86%)of the METTL16 positive group was lower than that of the METTL16 negative group(88.89%),the 3-year progression free survival rate(92.86%)of the ASB13 positive group was higher than that of the ASB13 negative group(73.96%),and the differences were statistically significant(Log Rank χ2=4.483,4.882,all P<0.005).METTL16 positive,TNM stage Ⅲ,poor differentiation were risk factors affecting the prognosis of elderly breast cancer,and ASB13 positive was protective factors(Wald χ2=5.056～9.267,all P<0.001).Conclusion METTL16 expression is up-regulated and ASB13 expression is down-regulated in elderly breast cancer,both of which are related to the expression of invasion and metastasis genes,and are new prognostic markers for elderly breast cancer.

ObjectiveTo find out whether there is any difference in the monitoring results of mosq-ovitraps placed in different orientations in multi-storey residential areas, so as to provide a scientific basis for routine and emergency monitoring of Aedes albopictus with mosq-ovitraps in residential areas. MethodsFrom July 6th to October 26th 2023, one mosquito ovitrap was set up in each of the 4 orientations of east, south, west and north around the buildings in a multi-storey residential area in Jinhui Town, Fengxian District, Shanghai. Data was collected and recorded 72 hours after placement. The chi-square test was used to compare the mosquito ovitrap indices (MOIs) of two independent samples, and the Kruskal⁃Wallis H test was used to compare the MOIs of multiple independent samples. ResultsAfter 16 weeks of surveillance, 997 mosquito ovitraps were recovered, of which 211 were positive, with the mosquito ovitrap index (MOI) of 21.16% and the Aedes albopictus density index of 1.03 mosquitoes·ovitrap^-1. The MOIs were higher in September (24.22%) and October (23.96%), and the MOIs in the west, south and north within the two months were all above 20.00%. From July to October, the MOIs in the east, west, south and north were 20.70%, 22.20%, 25.50% and 16.20%, respectively, and the difference in MOIs among the 4 orientations was not statistically significant (χ²=6.647, P=0.084). Stratified analysis by month showed that in August, the south side of the multi-storey residential areas had the highest MOI (31.30%), the north side had the lowest MOI (1.30%), and there was a statistically significant difference in MOI in the east, west, south and north (χ²=25.986, P<0.001). In October, the MOI in the west was the highest (33.30%) and the MOI in the east was the lowest (6.30%), the difference in MOIs of the 4 orientations was statistically significant (χ²=12.007, P=0.007). The MOIs in the south side of the building in the outskirts of the residential area from the 1st week in July to the 4th week in October was lower (19.20%) than that in the south side of the inner building (31.70%), and the difference in MOI was statistically significant (χ²=5.118, P=0.024). ConclusionThe study of MOI in different orientations in a multi-storey residential area is a preliminary exploration based on field work, and the results show that there is a difference in MOIs in different orientations during the peak breeding period of mosquitoes. Further indicators such as temperature, humidity and wind speed in different orientations can be collected to explore the influencing factors of MOIs.

Elevated glucose metabolism is a prominent characteristic of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). However, the efficacy of inhibiting a single target of glucose metabolism in FLS using small molecular inhibitors is limited for RA treatment. Herein, the synergistic inhibition of FLS' survival, proliferation, and activation by combining two glucose metabolism inhibitors, diclofenac (DC) and lonidamine (LND) was first verified. Subsequently, DC and LND were individually conjugated to cystamine-modified hyaluronic acid (HA) to prepare two polymer-prodrug conjugates. A HAP-1 peptide-modified dual polymer-prodrug conjugates-assembled nanoparticles system (^HAP-1NP_DC+LND) was further tailored in the optimal synergistic ratio for targeted and synergistic metabolic modulation of FLS to alleviate RA symptoms. Upon targeted uptake by FLS in inflamed joints, ^HAP-1NP_DC+LND released DC and LND within the intracellular reductive microenvironment, where DC hinders glucose uptake and LND suppresses glycolytic enzymes to eliminate FLS synergistically. Additionally, the secretion of lactic acid and pro-inflammatory factors from FLS were reduced, thereby disrupting the crosstalk between FLS and pro-inflammatory macrophages. Finally, ^HAP-1NP_DC+LND demonstrated promising efficacy in a mouse model of collagen-induced arthritis (CIA). Overall, this research provides valuable insights into novel therapeutic strategies for the safe and effective of treatment RA through targeted and synergistic metabolic modulation of FLS.