Objective:To investigate the synergistic activity and mechanism of vinegar baked radix bupleurum polysaccharides(VBCP)in combination with oxaliplatin(OXA),and to provide new ideas for the clinical treatment of primary hepatocellular carci-noma.Methods:MTT assay was used to detect the cytotoxic effect of VBCP 3-4 and VBCP 3-3 in combination with OXA on Huh7 cells;ICP-MS was used to measure the uptake rate of OXA by Huh7 cells and evaluate the in vitro synergistic pathway of VBCP 3-4 in combination with OXA;Western blotting was used to measure the expression levels of related transporter proteins in Huh7 cells and explore the synergistic mechanism of VBCP 3-4 in combination and MRP1 in Huh7 cells,and the protein expression level of multidrug resistance-associated protein(MRP)2 was upregulated to 18.11%and 25.00%,respectively(P=0.008,P=0.001),while that of MRP1 was upregulated to 28.51%(P>0.05)and 39.70%(P=0.015),respectively.After the combination of VBCP 3-4 and OXA,the protein expression of MRP2,MRP1,and breast cancer resis-tance protein(BCRP)was inhibited;MRP2 was reduced by 47.38%in the high-dose combination group(P=0.000)and 15.18%in the low-dose combination group(P=0.049);MRP1 was reduced by 64.96%in the high-dose combination group(P=0.000)and 34.63%in the low-dose combination group(P=0.000);BCRP was reduced by 29.00%(P=0.020)in the high-dose combination group.Acting on Huh7 cells alone,VBCP 3-4 significantly reduced the protein expression levels of MRP2,MRP1,and BCRP,and in the high-dose VBCP 3-4 group,MRP2 and MRP1 were reduced by 24.91%and 20.79%,respectively(P=0.004,P=0.005).VBCP 3-4 downregu-lated the protein expression level of BCRP by 15.02%in the high-dose group(P=0.003)and 13.92%in the middle-dose group(P=0.030).Conclusion:VBCP 3-4 exerts a synergistic effect by inhibiting the expression of the efflux transporter proteins MRP1,MRP2,and BCRP,promoting the intake of OXA by Huh7 cells,and increasing the intracellular effective concentration.

Objective:To investigate the risk factors for aggravation of type 2 diabetic foot ulcer and the correlation between the level of infection and the severity of the disease,as well as the association of the detection rate of bacteria and the types of bacteria with disease severity in patients with type 2 diabetic foot ulcer,and to provide individualized guidance for the prevention,diagnosis,and treatment of type 2 diabetic foot.Methods:A retrospective analysis was performed for the data of 150 patients with type 2 diabetic foot who were treated in Department of Endocrinology,The First Affiliated Hospital of Kunming Medical University,from October 2021 to June 2023,and according to the Wagner grade of diabetic foot,these patients were divided into mild group A(35 patients with Wagner grade 2),moderate group B(58 patients with Wagner grade 3),and severe group C(57 patients with Wagner grade 4).The clinical data of the three groups were analyzed.Results:The severity of type 2 diabetic foot ulcer was correlated with white blood cell count,neutrophil count,platelet count,monocyte count,globulin,alkaline phosphatase,neutrophil-lymphocyte ratio,monocyte-lymphocyte ratio,platelet-lymphocyte ratio,high-sensitivity C-reactive protein,procalcitonin,interleukin-6,erythrocyte sedimentation rate,hemoglo-bin,albumin/globulin ratio,lymphocyte count,cholinesterase,albumin,fasting blood glucose,gamma-glutamyl transferase,glycated he-moglobin,blood uric acid,high-density lipoprotein cholesterol,total cholesterol,triglycerides,and low-density lipoprotein cholesterol(P<0.05).The multivariate ordinal logistic regression analysis showed that the neutrophil-lymphocyte ratio and erythrocyte sedi-mentation rate were independent risk factors for the progression of Wagner grade of diabetic foot(P<0.05).For groups A,B,and C,the detection rate of bacteria in foot ulcer secretion tended to increase with the severity of diabetic foot,with the highest detection rate in group C,followed by groups B and A.A total of 31 types of bacteria were detected in the three groups,and the proportion of Gram-positive bacteria was higher than that of Gram-negative bacteria,with Staphylococcus aureus accounting for the highest proportion of 27.72%in all samples.Conclusion:High-sensitivity C-reactive pro-tein,procalcitonin,interleukin-6,and erythrocyte sedimentation rate increase with the progression of the Wagner grade of diabetic foot,and neutrophil-lymphocyte ratio and erythrocyte sedimentation rate are independent risk factors for the progression of the Wagner grade of diabetic foot.The detection rate of bacteria in foot ulcer secretion tends to increase with the Wagner grade of diabetic foot,and Gram-positive bacteria account for a higher proportion than Gram-negative bacteria,with Staphylococcus aureus accounting for the highest proportion.

OBJECTIVES: To explore the mechanism through which moxibustion promotes endometrial repair in rats with in thin endometrium (TE). METHODS: Female SD rats were randomized into control group, 95% anhydrous ethanol-induced TE model group and moxibustion (at "Guan Yuan") group. High-throughput sequencing was used to identify the target genes of TE, and the targeting relationship between miR-223-3p and NLRP3 was verified using a dual luciferase assay. Histopathological of rat uterus was observed with HE staining, and expressions of miR-223-3p and NLRP3 were detected using RT-qPCR; serum levels of IL-1β and IL-18 of the rats were detected using ELISA, and protein expressions of NLRP3, ASC, caspase-1 and GSDMD in the uterus were detected with Western blotting. The pregnancies of the rats after treatment were counted. RESULTS: Enrichment analysis of the differential genes suggested up-regulated inflammatory response in TE, and dual luciferase assay verified targeted inhibition of NLRP3 expression by miR-223-3p. The rat models of TE had significantly decreased endometrial thickness and reduced endometrial glands and blood vessels with enhanced mRNA expression of NLRP3, increased serum levels of IL-1β and IL-18, up-regulated protein expressions of NLRP3, ASC, caspase-1 and GSDMD, lowered pregnancy rates on both the affected and unaffected sides and the overall number of pregnancies. Treatment of the rat models with mo-xibustion obviously increased the endometrial thickness and the density of glands and blood vessels, up-regulated miR-223-3p expression, lowered serum IL-1β and IL-18 levels and the protein expressions of NLRP3, ASC, caspase-1 and GSDMD, and significantly increased the number of pregnancies. CONCLUSIONS Moxibustion at "Guan Yuan" acupoint up-regulates the expression of miR-223-3p, which results in targeted inhibition of NLRP3 to suppress pyroptosis and promote endometrial repair in rat models of TE.
Animals ; Female ; MicroRNAs/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Endometrium/pathology* ; Rats, Sprague-Dawley ; Rats ; Moxibustion ; Pyroptosis ; Up-Regulation ; Interleukin-1beta/metabolism* ; Interleukin-18 ; Caspase 1/metabolism*

Objective To investigate the correlation between insulin resistance and interleukin-6 (IL-6), chemerin, total cholesterol (TC)/high density lipoprotein cholesterol (HDL-C) ratio, triglyceride (TG)/HDL-C ratio, low density lipoprotein cholesterol (LDL-C)/HDL-C ratio and insulin resistance in obese patients with type 2 diabetes mellitus (T2DM), and to provide scientific basis for T2DM prevention and control. Methods A total of 355 obese T2DM patients in Songjiang Hospital Affiliated to Shanghai Jiaotong University School of Medicine were selected from January 2021 to December 2023. IL-6, chemerin and lipids were detected, and the assessment of insulin resistance was conducted through the homeostasis model assessment of insulin resistance (HOMA-IR). Results Among the 355 obese T2DM patients, there were 280 cases of insulin resistance, with the incidence rate of 78.87%. The BMI, IL-6, chemerin, TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C in the insulin resistance group were higher than those in the non-insulin resistance group (P<0.05). The above insulin resistant patients were divided into 4 subgroups by means of insulin resistance, and there were significant differences in BMI, IL-6, chemerin, and TG/HDL-C among the subgroups (P<0.05). IL-6, chemerin, and TG/HDL-C were positively correlated with HOMA-IR in obese T2DM patients (P<0.05), while TC/HDL-C and LDL-C/HDL-C had no significant correlation with HOMA-IR (P>0.05). BMI, IL-6, chemerin, and TG/HDL-C were all influencing factors of insulin resistance in obese T2DM patients (P<0.05). Conclusion IL-6, chemerin and TG/HDL-C are correlated with insulin resistance in obese patients with T2DM and are influencing factors for the occurrence of insulin resistance.

Neurodegenerative diseases are a group of chronic progressive diseases characterized by inflammation,degenera-tion and apoptosis.Chronic neuroinflammation is gradually becoming a potential pathogenic and predisposing factor.As a widely expressed non-histone nucleoprotein,HMGB1 participates in inflammatory process of human body through receptors of advanced glycation end products and Toll-like receptors while maintaining chromosome homeostasis.As a key factor of neuroinflammation,HMGB1 is widely involved in development of neurodegenerative diseases and may become a biomarker and a potential therapeutic target of neurodegenerative diseases.This article reviews the role of HMGB1 in neurodegenerative diseases and tries to provide ground-work for basic research and clinical application for targeting HMGB1 in the treatment of neurodegenerative diseases.

Objective To analyze the clinical features of coronavirus disease 2019(COVID-19)complicated with probable sporadic Creutzfeldt-Jakob disease(sCJD).Methods The clinical data of one patient with COVID-19 complicated with probable sCJD were retrospectively analyzed,and the relevant literatures were reviewed.Results The patient was a 66-year-old male,onset with visual impairment and ataxia,and gradually developed rapid progressive cognitive impairment,mental and behavioral abnormalities,pyramidal tract signs and other manifestations.Serum anti-myelin oligodendrocyte glycoprotein immunoglobulin G antibody was positive(1∶32),CSF Tau protein was significantly increased,14-3-3 protein was positive,and cranial MRI had more than 2 cortical involvement,which was diagnosed as likely sCJD.The patient was infected with COVID-19 about 1 month after the onset of the disease,and the condition gradually worsened.Eleven cases of sCJD complicated with COVID-19 were reviewed form the literature.Combined with this case,the median age of 12 patients was 70 years old,and 66.67％were male.The total Tau level in CSF was significantly increased in 75％of sCJD patients,and positive pathogenic prion protein was detected by real-time quaking-induced conversion method in 66.67％of patients.83.33％of patients received early glucocorticoid or intravenous gamma globulin treatment,with no significant effect.72.7％of the patients died within 2-5 months of onset,and 18.2％of the patients developed shallow coma within 1-2 months of onset.Conclusions COVID-19 has the potential to accelerate the development of sCJD.Elevated level of protein Tau is a promising target for differentiating sCJD contaminant with COVID-19 and autoimmue encephalitis.

Objective:To analyze the relationship among thyroid autoimmunity (TAI), thyroid function, and gestational diabetes mellitus (GDM) in early pregnant women in Xi'an.Methods:A prospective study included pregnant women who underwent prenatal check-ups at the Northwest Women's and Children's Hospital from November 2020 to October 2021, with a gestational age of 6 to 14 weeks. Thyroid function, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), and urinary iodine levels were measured, and the prevalence of thyroid disease and GDM was monitored. The subjects were divided into four groups: TPOAb positive only, TgAb positive only, both TPOAb and TgAb positive, and both TPOAb and TgAb negative, to compare the differences in the prevalence of thyroid disease and GDM among the groups. Statistical analysis was performed using Kruskal-Wallis rank-sum test, Bonferroni correction, Chi-square test, and a multivariate logistic regression model was used to analyze the relationship between TAI, thyroid disease, and GDM. Results:A total of 20 243 early pregnant women were included in this study, among which 1 615 (7.98%) were positive for TPOAb only; 865 (4.27%) were positive for TgAb only; 1 672 (8.26%) were positive for both TPOAb and TgAb (both positive group); and 16 091 (79.49%) were negative for both TPOAb and TgAb (both negative group). The thyroid stimulating hormone levels in the TPOAb positive only group, TgAb positive only group, and both positive group were significantly higher than those in the both negative group, respectively (Bonferroni correction, all P<0.05); the free thyroxine level in the TPOAb positive only group was significantly lower than that in the both negative group ( P<0.05). After adjusting for age, pre-pregnancy body mass index, and urinary iodine levels, multivariate logistic regression analysis showed that compared to the both negative group, the risk of developing hypothyroidism during pregnancy was significantly increased in the both positive group ( OR=11.49, 95% CI: 2.84-46.39); the risk of developing subclinical hypothyroidism during pregnancy was significantly increased in the TgAb positive only group ( OR=1.99, 95% CI: 1.05-3.76) and the both positive group ( OR=3.74, 95% CI: 2.49-5.63); the risk of developing GDM was significantly increased in the TgAb positive only group ( OR=1.43, 95% CI: 1.04-1.96) and the both positive group ( OR=1.94, 95% CI: 1.53-2.46). Among early pregnant women with normal thyroid function, after adjusting for age, pre-pregnancy body mass index, and urinary iodine levels, multivariate logistic regression analysis showed that compared to the both negative group, the risk of developing GDM was significantly increased in the TgAb positive only group ( OR=1.46, 95% CI: 1.06-2.02) and the both positive group ( OR=1.80, 95% CI: 1.40-2.32). Conclusion:TgAb positive only is a risk factor for subclinical hypothyroidism and GDM. Screening for thyroid autoantibodies, especially TgAb, during pregnancy helps in the early identification of high-risk pregnant women for thyroid dysfunction and GDM.

Forty adult male C57BL/6 mice were randomly divided into four groups:the control group,Salmonella typhimurium(S.typhimurium)(ST)group,phlorizin(PHZ)+S.typhimuri-um(ST)group,and PHZ(80 mg/kg)group,with 10 mice in each group.Morphological observa-tion,HE staining,ELISA,immunofluorescence and Western blot were performed,the results showed that PHZ significantly increased the cecal index,decreased the spleen index of S.typhi-murium-induced mice(P＜0.05),and reduce the pathological damage of cecum in mice.Mean-while,PHZ treatment also significantly reduced colonization of S.typhimurium in the cecum,spleen,mesenteric lymph nodes and liver(P＜0.05).The results of ELISA showed that PHZ treatment also significantly inhibited the S.ty phimurium-induced increase in the expression of IL-1β,INF-γ,TNF-a and IL-6 in the cecum of mice(P＜0.05).Immunofluorescence and Western blot results showed that PHZ significantly increased the protein expression levels of Occludin,Claudin-3,and ZO-1 in the cecal barrier of mice induced by S.typhimurium(P＜0.05).These results con-firmed that phlorizin could improve cecal inflammation and intestinal barrier damage induced by S.typhimurium in mice.

Objective To evaluate the effectiveness and feasibility of a remote medication treatment management model for elderly patients with chronic disease at home based on mobile technology.Methods A convenient and elderly-friendly mo-bile application(hereinafter referred to as Yaoshiyi APP)was developed,and a remote medication treatment management team consisting of clinical pharmacists from tertiary hospitals,community pharmacists,and community physicians was formed.Patients from communities were selected for practical research,led by pharmacists.Based on the Yaoshiyi APP,patients were subjected to 6 months of medication treatment management practice,and the effectiveness and feasibility of the practice were evaluated.Re-sults The Yaoshiyi APP can be integrated with a variety of medical-grade wearable devices to realize the functions of automati-cally uploading monitoring data,abnormal value reminding,medication reminding,medication consultation,and medication sci-ence popularization.A total of 302 elderly patients with chronic disease at home completed the study.The results showed that phar-macists have identified and intervened in 695 cases of medication-related problems.According to the classification of medication-related problems,the top three were 247 cases(35.5％)of additional treatment,97 cases(14.0％)of unnecessary drug treat-ment,and 93 cases(13.4％)of medication compliance problems.The patient's medication adherence score(Morisky medication adherence scale-8,MMAS-8)increased from(5.85±1.57)at enrollment to(6.74±1.23)6 months after enrollment(P＜0.01).After 6 months of enrollment,the patient's satisfaction with the pharmacist's work reached a score of(4.99±0.08)out of 5.The average reduction in drug costs for patients caused by pharmacists intervening in irrational medication is(20.9±18.0)％.At the end of follow-up,93.4％of patients were proficient in using the Yaoshiyi APP.Conclusion The remote medication treatment management model for elderly patients with chronic disease at home based on mobile technology constructed in this study can ef-fectively improve patient compliance with disease monitoring and medication,ensure rational drug use,reduce medical resource waste,and receive high patient acceptance.

Objective:To investigate the clinical significance of elevated cytokeratin 19 fragment (CYFRA21-1) in patients with dermatomyositis associated with positive anti-melanoma differentiation-associated gene 5 (MDA5) antibody.Methods:142 consecutive cases with newly onset anti-MDA5(+) (MADEDM)-DM admitted to the first affiliated hospital of Zhengzhou University from June 2018 to October 2021 were enrolled. They were divided into two groups, the low serum CYFRA21-1 group (CYFRA21-1≤4 ng/ml) and the high serum CYFRA21-1 group (CYFRA21-1>4 ng/ml). The clinical manifestations, laboratory tests results, imaging examinations treatment and outcome were collected for statistical analysis. Enumeration data were expressed as the number of cases and percentage (%). Normally distributed parameters were tested by t-test. Parameters with skewed distribution were tested by Mann-Whitney Wilcoxon analysis. Categorical variables were compared by the Chi-square test or Fisher′s exact test. Risk factor analysis was performed using Logistic regression. Cumulative survivals were described by Kaplan-Meier curves. Results:The age of onset in the high CYFRA21-1 group [(56±9)years vs. (50±10) years, t=-3.50, P=0.001] was higher than that in the low CYFRA21-1 group. Fever [63.3% (38/60) vs. 40.2% (33/82), χ2=7.39, P=0.007] was more common in the high CYFRA21-1 group, and arthritis [41.7% (25/60) vs. 69.5%(57/82), χ2=11.01, P=0.001] was less common. Myalgia, myasthenia, rashes, Raynaud′s phenomenon and skin ulcers had no significant difference between the two groups. The WBC count [5.2(4.1, 6.9)×10 9/L vs. 4.3(3.2, 6.2)×10 9/L, Z=-2.57, P=0.010], neutrophil count [4.0(2.9, 5.5)×10 9/L vs. 2.9(2.1, 4.5)×10 9/L, Z=-3.25, P=0.001] and neutrophil/lymphocyte ratio [5.75(3.50, 9.20) vs. 3.55(2.64, 5.41), Z=-3.77, P<0.001] in high CYFRA21-1 group were significantly higher than those in low CYFRA21-1 group. At the same time, LDH [384(302, 519)U/L vs. 318(260, 405)U/L, Z=-2.98, P=0.003], ferritin [1 204(677, 2 039)ng/ml vs. 570(229, 846)ng/ml, Z=-4.78, P<0.001], KL-6 [995(658, 1 491)U/ml vs. 750(563, 1 197)U/ml, Z=-2.49, P=0.013], ESR [36(22, 61)mm/1 h vs. 28(15, 46)mm/1 h, Z=-2.18, P=0.029] and CRP [9.2(4.7, 31.5)mg/L vs. 3.1(1.1, 11.6)mg/L, Z=-3.53, P<0.001] were significantly increased in the high level of CYFRA21-1 group, while serum albumin[(32±5)g/L vs. (35±5)g/L, t=3.92, P<0.001] was significantly decreased. There was no significant difference in the titers of serum anti-MDA5 antibodies between the two groups. The positive rate of anti-RO52 antibody [44(74.6%) vs. 44(53.7%), χ2=6.40, P=0.011] in high CYFRA21-1 group was higher than that in low CYFRA21-1 group. The ground glass opacity (GGO) score [1.75(1.33, 2.42) vs. 1.09(0.67, 1.67), Z=-4.60, P<0.001] based on high resolution CT (HRCT) was also significantly increased in the CYFRA21-1 high level group. Compared with the low CYFRA21-1 group, the high CYFRA21-1 group had a higher probability of RP-ILD [48.3%(29/60) vs. 23.2%(19/82), χ2=9.80, P=0.002] and a higher 6-month mortality rate[48.3%(29/60) vs.13.4%(11/82), χ2=19.70, P<0.001]. Logistic regression analysis showed that age ≥53 years old [ OR(95% CI)=5.197(1.781, 15.165), P=0.003], duration < 2 months [ OR(95% CI)=3.314 (1.058, 10.378), P=0.040], NE/LYMP >5 [ OR(95% CI)=3.443(1.120, 10.586), P=0.031], CRP>5 mg/L[ OR(95% CI)=6.271(1.749, 22.480), P=0.005], CA125>14 U/ml[ OR(95% CI)=7.500 (2.409, 23.345), P=0.001] and CYFRA21-1>4 ng/ml[ OR(95% CI)=3.665(1.258, 10.676), P=0.017] were independent risk factors for death within 6 months in MDA5-DM patients. Kaplan-Meier survival curve showed that the survival rate of the high CYFRA21-1 group was significantly lower than that of the low CYFRA21-1 group( P<0.001). Conclusion:Elevated CYFRA21-1 is an independent risk factor for early mortality in MDA5-DM patients and can serve as a novel serological marker for risk stratification in these patients.