Objective To explore the mechanism of Yishen Jiangtang Decoction(YSJTD)in improving diabetic kidney disease(DKD)based on the apoptotic Bcl-2/Caspase-3 pathway mediated by endoplasmic reticulum stress(ERS).Methods Thirty 8-week-old SPF male db/db mice were used to establish the DKD model and were randomly divided into model,YSJTD,ERS inhibitor(4-phenylbutyric acid[4-PBA]),and control groups(db/m mice),with 10 mice per group.Mice in the YSJTD and 4-PBA groups were gavaged daily with 5.6 mg/(g·d)YSJTD or 0.5 mg/(g·d)4-PBA,respectively,whereas the model and control groups received sodium carboxymethyl cellulose.Each mouse was orally administered 0.01 mL/(g·d)for 8 weeks.The mice were administered 0.01 mL/(g·d)YSJTD or 0.5mg/(g·d)4-PBA via gavage for 8 weeks.The general condition of the mice was observed,and blood glucose and plasma lipid levels were measured.Oral glucose tolerance tests(OGTT)and insulin tolerance tests(ITT)were performed,and the area under the curve(AUC)was calculated.Renal pathological changes(assessed using hematoxylin and eosin,periodic acid-Schiff,and Masson staining)and cell apoptosis,evaluated via TUNEL staining,were examined.Protein expression levels of Caspase-3 and Bcl-2 in kidney tissues were analyzed using Western blotting.A DKD model was established using high-glucose-induced mouse glomerular mesangial cells,SV40 MES 13.The Cell Counting Kit-8 assay was used to screen for high glucose concentrations and to determine the concentration of the YSJTD drug-containing serum.Cells were divided into four groups:control,model(30 mmol/L high glucose),10％YSJTD drug-containing serum(30 mmol/L high glucose+10％drug-containing serum),and 1 mol/L 4-PBA(30 mmol/L high glucose+1 mmol/L 4-PBA).Western blotting was used to detect the protein levels of GRP78,Caspase-3,and Bcl-2 in the cells.Results Compared to the control group,the model,YSJTD,and 4-PBA groups exhibited significantly increased OGTT-AUC,ITT-AUC,triglyceride(TG),and cholesterol(CHOL)levels(P＜0.05).These groups also showed severe renal pathological damage,increased glycogen deposition,and exacerbated fibrosis in kidney tissues.Compared to the model group,both the YSJTD and 4-PBA groups showed significantly reduced OGTT-AUC,TG,and CHOL levels,alleviated renal pathological damage,and decreased glycogen deposition and fibrosis.The YSJTD group also exhibited significantly reduced ITT-AUC(P＜0.05).Compared to the control group,the model group exhibited an increased number of apoptotic cells in renal tissue,reduced Bcl-2 expression,and elevated Caspase-3 expression(P＜0.05).Compared to the model group,both the YSJTD and 4-PBA groups demonstrated a reduced number of apoptotic cells,decreased Caspase-3 expression,and increased Bcl-2 expression,with the YSJTD group showing a more pronounced decrease in apoptotic cells(P＜0.05).In vitro experiments revealed that,compared to the control group,the model group exhibited increased GRP78 and Caspase-3 expression,as well as decreased Bcl-2 expression(P＜0.05).Compared to the model group,the 10％YSJTD drug-containing serum and 1 mol/L 4-PBA groups showed reduced GRP78 and Caspase-3 expression,as well as upregulated Bcl-2 expression(P＜0.05).Conclusion YSJTD improves glucose and lipid metabolism disorders in DKD by inhibiting the ERS-induced apoptotic pathway mediated by Bcl-2/Caspase-3,thereby exerting protective effects on renal function.

This study explored the effect of the Mycobacterium tuberculosis(Mtb)PE/PPE family protein PE_PGRS37 on the growth of Mycobacterium smegmatis(Ms)and macrophage autophagy during Mtb infection.The pe_pgrs37 gene was amplified from Mtb genome through PCR,and the recombinant vector pAIN-PE_PGRS37 was successfully constructed through homologous recombi-nation.pAIN-PE_PGRS37 and pAIN were integrated into Ms through electroshock to construct pAIN-PGRS37/Ms and pAIN/Ms re-combinant bacteria.Western blotting indicated that the PE_PGRS37 protein was correctly expressed in pAIN-PE_PGRS37/Ms.The re-combinant bacteria were inoculated in 7H9/7H10 medium,and their colony morphology and growth curves were observed.No signifi-cant difference in colony morphology was observed between pAIN-PE_PGRS37/Ms and pAIN/Ms.The growth rate significantly in-creased between 10 and 16 h,and a plateau was reached at 26 h.After infection of U937 cells with pAIN-PE_PGRS37/Ms and pAIN/Ms,macrophage autophagy flow was detected with western blotting and immunofluorescence.In the pAIN-PE_PGRS37/Ms-infected group,compared with the pAIN/Ms-infected group,macrophage LC3-II and p62 protein expression was significantly up-regulated(P<0.001)and inhibited autophagosome and lysosome fusion.The intracellular survival of the recombinant bacteria was detected through colony counting,and pAIN-PE_PGRS37/Ms showed significantly greater survival in macrophages at 12 h,24 h,and 48 h than pAIN/Ms(P<0.05).Our results suggested that PE_PGRS37 protein promotes Mycobacterium survival in macrophages by blocking macro-phage autophagy flow,thus inhibiting macrophage autophagy.

Objective:To explore the impact of Epstein-Barr Virus(EBV) infection on treatment response and survival in newly diagnosed multiple myeloma(MM).Methods:The clinical data of 196 patients with newly diagnosed MM admitted to Zhongshan Hospital of Fudan University from June 1st, 2019 to February 25th,2021 were analyzed retrospectively and divided into EBV-positive group (106 cases) and negative group (90 cases) according to the primary EBV DNA results in peripheral blood mononuclear cells.To analyse the distribution of EBV positive rates in each type and in each stage of the Revised International Staging System (R-ISS), and to compare EBV DNA loads in EBV-positive patients among R-ISS stages.Rank sum test, 2×2 chi-square test and independent sample t-test were used to compare laboratory findings, such as liver and kidney function, immunohistochemistry and cytogenetics, treatment efficacy and survival prognosis between the two groups.The clinical prognosis of EBV-positive patients was summarized through survival analysis and Cox regression.Results:The EBV positive rate in patients with newly diagnosed MM was 54% (106/196), with the highest rate in patients with κ light chain type (9/12).Patients with R-ISS stage Ⅲ had a significantly higher positive rate than with stage Ⅰ ( χ2=4.68, P=0.031) and stage Ⅱ ( χ2=6.04, P=0.014), but there was no significant difference in EBV DNA loads between EBV-positive MM patients by stage ( Z=3.27, P=0.195).Serum creatinine (Scr) and β 2-microglobulin (β 2-MG) levels were higher in the EBV-positive group than in the EBV-negative group ( Z=1.98, P=0.048 and Z=2.08, P=0.038), and the occurrence of t(4;14) was also higher in the EBV-positive group ( χ2=3.93, P=0.047).The proportion of complete response (CR)/stringent complete response(sCR) and very good partial response(VGPR) after completion of the fourth chemotherapy were significantly lower in the EBV-positive group than in the EBV-negative group ( χ2=12.82, P=0.001 and χ2=8.30, P=0.004), and a higher rate of progressive disease (PD) occurred in the EBV-positive group ( χ2=4.48, P=0.046).The 2-year progression-free survival (PFS) of MM patients was shorter in the EBV-positive group compared to that in the EBV-negative group ( Z=-4.50, P0.01).Cox regression analysis showed that R-ISS stage Ⅲ ( HR=5.38, 95% CI 1.28-22.56, P=0.021), failure to achieve VGPR after the fourth chemotherapy ( HR=3.02, 95% CI 1.42-6.46, P=0.004), EBV-positive ( HR=1.98, 95% CI 1.02-3.87, P=0.045), with 1q21 amplification ( HR=2.35, 95% CI 1.16-4.75, P=0.017) and 13q14 deletion ( HR=1.93, 95% CI 1.01-3.67, P=0.046) were independent risk factors for PFS in newly diagnosed MM. Conclusions:EBV infection is an independent risk factor for poor prognosis, which has important clinical implications for the outcome and prognosis of patients with newly diagnosed MM, and may become a novel clinical assessment indicator.

Objective To explore the mechanism of Yishen Jiangtang Decoction(YSJTD)in improving diabetic kidney disease(DKD)based on the apoptotic Bcl-2/Caspase-3 pathway mediated by endoplasmic reticulum stress(ERS).Methods Thirty 8-week-old SPF male db/db mice were used to establish the DKD model and were randomly divided into model,YSJTD,ERS inhibitor(4-phenylbutyric acid[4-PBA]),and control groups(db/m mice),with 10 mice per group.Mice in the YSJTD and 4-PBA groups were gavaged daily with 5.6 mg/(g·d)YSJTD or 0.5 mg/(g·d)4-PBA,respectively,whereas the model and control groups received sodium carboxymethyl cellulose.Each mouse was orally administered 0.01 mL/(g·d)for 8 weeks.The mice were administered 0.01 mL/(g·d)YSJTD or 0.5mg/(g·d)4-PBA via gavage for 8 weeks.The general condition of the mice was observed,and blood glucose and plasma lipid levels were measured.Oral glucose tolerance tests(OGTT)and insulin tolerance tests(ITT)were performed,and the area under the curve(AUC)was calculated.Renal pathological changes(assessed using hematoxylin and eosin,periodic acid-Schiff,and Masson staining)and cell apoptosis,evaluated via TUNEL staining,were examined.Protein expression levels of Caspase-3 and Bcl-2 in kidney tissues were analyzed using Western blotting.A DKD model was established using high-glucose-induced mouse glomerular mesangial cells,SV40 MES 13.The Cell Counting Kit-8 assay was used to screen for high glucose concentrations and to determine the concentration of the YSJTD drug-containing serum.Cells were divided into four groups:control,model(30 mmol/L high glucose),10％YSJTD drug-containing serum(30 mmol/L high glucose+10％drug-containing serum),and 1 mol/L 4-PBA(30 mmol/L high glucose+1 mmol/L 4-PBA).Western blotting was used to detect the protein levels of GRP78,Caspase-3,and Bcl-2 in the cells.Results Compared to the control group,the model,YSJTD,and 4-PBA groups exhibited significantly increased OGTT-AUC,ITT-AUC,triglyceride(TG),and cholesterol(CHOL)levels(P＜0.05).These groups also showed severe renal pathological damage,increased glycogen deposition,and exacerbated fibrosis in kidney tissues.Compared to the model group,both the YSJTD and 4-PBA groups showed significantly reduced OGTT-AUC,TG,and CHOL levels,alleviated renal pathological damage,and decreased glycogen deposition and fibrosis.The YSJTD group also exhibited significantly reduced ITT-AUC(P＜0.05).Compared to the control group,the model group exhibited an increased number of apoptotic cells in renal tissue,reduced Bcl-2 expression,and elevated Caspase-3 expression(P＜0.05).Compared to the model group,both the YSJTD and 4-PBA groups demonstrated a reduced number of apoptotic cells,decreased Caspase-3 expression,and increased Bcl-2 expression,with the YSJTD group showing a more pronounced decrease in apoptotic cells(P＜0.05).In vitro experiments revealed that,compared to the control group,the model group exhibited increased GRP78 and Caspase-3 expression,as well as decreased Bcl-2 expression(P＜0.05).Compared to the model group,the 10％YSJTD drug-containing serum and 1 mol/L 4-PBA groups showed reduced GRP78 and Caspase-3 expression,as well as upregulated Bcl-2 expression(P＜0.05).Conclusion YSJTD improves glucose and lipid metabolism disorders in DKD by inhibiting the ERS-induced apoptotic pathway mediated by Bcl-2/Caspase-3,thereby exerting protective effects on renal function.

After the optimization of control measures in December 2022，low-level SARS-CoV-2 infections have persisted in China.The predominant circulating variants globally are Omicron and its sublineages.Due to differences in mutation sites，various Omicron subvariants exhibit distinct characteristics in viral properties，clinical manifestations，and the effectiveness of vaccines and therapeutics.This review synthesizes the latest literature and epidemiological data on the six Omicron subviriants，including BA.5.2，BF.7，BA.2.75，XBB.1.5，EG.5 and JN.1，review their origin，virological characteristics，clinical characteristics in pediatric infection and prevention and control strategies，aiming to provide references for the prevention and control management of these variants and their offspring variants.

This study explored the effect of the Mycobacterium tuberculosis(Mtb)PE/PPE family protein PE_PGRS37 on the growth of Mycobacterium smegmatis(Ms)and macrophage autophagy during Mtb infection.The pe_pgrs37 gene was amplified from Mtb genome through PCR,and the recombinant vector pAIN-PE_PGRS37 was successfully constructed through homologous recombi-nation.pAIN-PE_PGRS37 and pAIN were integrated into Ms through electroshock to construct pAIN-PGRS37/Ms and pAIN/Ms re-combinant bacteria.Western blotting indicated that the PE_PGRS37 protein was correctly expressed in pAIN-PE_PGRS37/Ms.The re-combinant bacteria were inoculated in 7H9/7H10 medium,and their colony morphology and growth curves were observed.No signifi-cant difference in colony morphology was observed between pAIN-PE_PGRS37/Ms and pAIN/Ms.The growth rate significantly in-creased between 10 and 16 h,and a plateau was reached at 26 h.After infection of U937 cells with pAIN-PE_PGRS37/Ms and pAIN/Ms,macrophage autophagy flow was detected with western blotting and immunofluorescence.In the pAIN-PE_PGRS37/Ms-infected group,compared with the pAIN/Ms-infected group,macrophage LC3-II and p62 protein expression was significantly up-regulated(P<0.001)and inhibited autophagosome and lysosome fusion.The intracellular survival of the recombinant bacteria was detected through colony counting,and pAIN-PE_PGRS37/Ms showed significantly greater survival in macrophages at 12 h,24 h,and 48 h than pAIN/Ms(P<0.05).Our results suggested that PE_PGRS37 protein promotes Mycobacterium survival in macrophages by blocking macro-phage autophagy flow,thus inhibiting macrophage autophagy.

Objective:To explore the impact of Epstein-Barr Virus(EBV) infection on treatment response and survival in newly diagnosed multiple myeloma(MM).Methods:The clinical data of 196 patients with newly diagnosed MM admitted to Zhongshan Hospital of Fudan University from June 1st, 2019 to February 25th,2021 were analyzed retrospectively and divided into EBV-positive group (106 cases) and negative group (90 cases) according to the primary EBV DNA results in peripheral blood mononuclear cells.To analyse the distribution of EBV positive rates in each type and in each stage of the Revised International Staging System (R-ISS), and to compare EBV DNA loads in EBV-positive patients among R-ISS stages.Rank sum test, 2×2 chi-square test and independent sample t-test were used to compare laboratory findings, such as liver and kidney function, immunohistochemistry and cytogenetics, treatment efficacy and survival prognosis between the two groups.The clinical prognosis of EBV-positive patients was summarized through survival analysis and Cox regression.Results:The EBV positive rate in patients with newly diagnosed MM was 54% (106/196), with the highest rate in patients with κ light chain type (9/12).Patients with R-ISS stage Ⅲ had a significantly higher positive rate than with stage Ⅰ ( χ2=4.68, P=0.031) and stage Ⅱ ( χ2=6.04, P=0.014), but there was no significant difference in EBV DNA loads between EBV-positive MM patients by stage ( Z=3.27, P=0.195).Serum creatinine (Scr) and β 2-microglobulin (β 2-MG) levels were higher in the EBV-positive group than in the EBV-negative group ( Z=1.98, P=0.048 and Z=2.08, P=0.038), and the occurrence of t(4;14) was also higher in the EBV-positive group ( χ2=3.93, P=0.047).The proportion of complete response (CR)/stringent complete response(sCR) and very good partial response(VGPR) after completion of the fourth chemotherapy were significantly lower in the EBV-positive group than in the EBV-negative group ( χ2=12.82, P=0.001 and χ2=8.30, P=0.004), and a higher rate of progressive disease (PD) occurred in the EBV-positive group ( χ2=4.48, P=0.046).The 2-year progression-free survival (PFS) of MM patients was shorter in the EBV-positive group compared to that in the EBV-negative group ( Z=-4.50, P0.01).Cox regression analysis showed that R-ISS stage Ⅲ ( HR=5.38, 95% CI 1.28-22.56, P=0.021), failure to achieve VGPR after the fourth chemotherapy ( HR=3.02, 95% CI 1.42-6.46, P=0.004), EBV-positive ( HR=1.98, 95% CI 1.02-3.87, P=0.045), with 1q21 amplification ( HR=2.35, 95% CI 1.16-4.75, P=0.017) and 13q14 deletion ( HR=1.93, 95% CI 1.01-3.67, P=0.046) were independent risk factors for PFS in newly diagnosed MM. Conclusions:EBV infection is an independent risk factor for poor prognosis, which has important clinical implications for the outcome and prognosis of patients with newly diagnosed MM, and may become a novel clinical assessment indicator.

【Objective】 To explore the effects of early application of erythropoietin (EPO) in patients with anemia after renal transplantation. 【Methods】 Patients who underwent renal transplantation in the First Affiliated Hospital of Soochow University were retrospectively analyzed. According to whether EPO was applied after operation, the patients were divided into EPO group and routine group. Patients with delayed renal function recovery were excluded, and the remaining patients were further analyzed. The general, laboratory and follow-up data of the two groups were compared, and adverse drug reactions were observed. 【Results】 The hemoglobin (P=0.026), red blood cell count (P=0.038) and hematocrit (P=0.011) in EPO group were higher than those in the routine group 2 weeks after operation, while the postoperative serum creatinine level was lower (P=0.001). Since the first week after operation, the reticulocyte count in EPO group was significantly higher than that in routine group (P<0.01). There was a negative correlation between hemoglobin and serum creatinine in EPO group at week 1 (r=-0.375, P=0.010) and week 2 (r=-0.386, P=0.008). During the treatment, 6 patients showed transient elevation of serum potassium, which returned to normal after symptomatic treatment, and no obvious adverse drug reactions were observed. 【Conclusion】 Continuous application of erythropoietin in the early stage after renal transplantation can significantly improve anemia in renal transplant patients and promote the recovery of renal function.

Objective:To investigate the prevalence of thyroid nodules among students aged 8 - 17 years in Jintan District, Changzhou City, Jiangsu Province, and to explore the risk factors of thyroid nodules among underage students.Methods:In September 2018, two primary and middle schools, one ordinary high school and one vocational high school in Jintan District were selected as the survey sites. Students aged 8 - 17 years were selected as the survey subjects, and questionnaire survey, physical examination and thyroid ultrasound examination were conducted. At the same time, drinking water samples from schools and towns were collected to test water iodine, and urine samples from students and family salt samples were collected to test urinary iodine and salt iodine. Multivariate logistic regression was used to analyze related factors that may affect the occurrence of thyroid nodules.Results:A total of 725 students were surveyed, including 359 (49.5%) boys and 366 (50.5%) girls. Two water samples were collected from each of the four schools, and the mean values of water iodine were 0.3, 8.5, 0.2 and 0.2 μg/L, respectively; two water samples were collected from each of the towns where the four schools were located, and the mean values of water iodine were 6.8, 8.1, 4.8 and 3.7 μg/L, respectively. A total of 725 urine samples were collected, and the median urinary iodine was 209.92 μg/L, ranging from 8.60 to 932.00 μg/L. A total of 725 edible salt samples were collected from students' families, and the salt iodine content was (23.75 ± 7.10) mg/kg, ranging from 0.00 to 60.30 mg/kg, and 95.0% (689/725) of students' families ate iodized salt. A total of 725 students were examined for thyroid gland, and 22 were diagnosed with goiter, with an enlargement rate of 3.0%; and 155 were diagnosed with thyroid nodules, with a detection rate of 21.4%. The detection rates of thyroid nodules in boys and girls were 20.9% (75/359) and 21.9% (80/366), respectively; the detection rates of thyroid nodules in students who participated and did not participate in extracurricular tuition/interest classes in the past month were 28.2% (71/252) and 17.8% (84/473), respectively. The results of multivariate logistic regression analysis showed that girls and participating in extracurricular tuition/interest classes in the past month were independent risk factors for the occurrence of thyroid nodules [odds ratio ( OR) = 2.057, 2.538, 95% confidence interval ( CI): 1.226 - 3.451, 1.532 - 4.204, P < 0.05). Conclusions:The detection rate of thyroid nodules in students aged 8 - 17 years in Jintan District is at a high level. Girls and participating in extracurricular tuition/interest classes in the past month are independent risk factors for the occurrence of thyroid nodules.

Objective:To explore the predictive value of renal resistive index (RRI) joint with semiquantitative power Doppler ultrasound (PDU) score to acute kidney injury (AKI) in non-septic critically ill patients.Methods:This prospective observational study enrolled non-septic critically ill patients admitted to the Emergency Intensive Care Unit of Cangzhou Central Hospital from January 2018 to August 2019. In addition to general data, RRI and PDU scores were measured with medical ultrasonic instrument within 6 h after admission. Renal function was assessed on the 5th day in accordance with kidney disease: Improving Global Outcomes criteria. The patients who progressed to AKI stage 3 within 5 days after admission were classified into the AKI 3 group, and the rest were classified into the AKI 0-2 group. The difference of each index was compared between the two groups in non-septic critically ill patients and patients with acute heart failure (AHF). Normal distributed continuous variables were compared using independent sample t-tests, whereas Mann-Whitney U tests were used to examine the differences in variables without a normal distribution. Categorical data were compared with the Chi-square test. Receiver operator characteristic curves were plotted to examine the values of RRI, PDU score, RRI-RDU/10 (subtraction of RRI and 1/10 of PDU score), RRI/PDU (the ratio of RRI to PDU score), and RRI+PDU (the prediction probability of the combination of RRI and PDU score for AKI stage 3 obtained by logistic regression analysis) in predicting AKI 3. Delong's test was used to compare the area under the curve (AUC) between predictors. Results:A total of 110 non-septic critically ill patients (51 patients with no AKI, 21 with AKI stage 1, 11 with AKI stage 2, and 27 with AKI stage 3) were recruited. Among them, there were 63 patients with AHF (21 patients with no AKI, 15 with AKI stage 1, 7 with AKI stage 2, and 20 with AKI stage 3). Among the non-septic critically ill patients as well as its subgroup of AHF, compared with the AKI 0-2 group, acute physiology and chronic health evaluation-Ⅱ score, sequential organ failure assessment score, arterial lactate concentration, mechanical ventilation rate, proportion of vasoactive drugs, 28-day mortality, serum creatinine, RRI, RRI-RDU/10, RRI/PDU, RRI+PDU, and rate of continuous renal replacement therapy were higher in the AKI 3 group, and urine output and PDU score were lower ( all P<0.05). As for non-septic critically ill patients, RRI/PDU [AUC=0.915, 95% confidence interval ( CI): 0.846-0.959, P<0.01] and RRI+PDU (AUC=0.914, 95% CI: 0.845-0.959, P<0.01) performed best in predicting AKI 3, and the AUCs were higher than RRI (AUC=0.804, 95% CI: 0.718-0.874, P<0.01) and PDU score (AUC=0.868, 95% CI: 0.791-0.925, P<0.01). The optimal cutoff for RRI/PDU was > 0.355 (sensitivity 92.6%, specificity 81.9%, Youden index 0.745). The predictive value of RRI-RDU/10 for AKI 3 (AUC=0.899, 95% CI: 0.827-0.948, P<0.01) was also better than RRI and PDU scores, but slightly worse than RRI/PDU and RRI+PDU, with statistically difference only between RRI and RRI-RDU/10 ( P<0.05). As for patients with AHF, RRI/PDU (AUC=0.962, 95% CI: 0.880-0.994, P<0.01) and RRI+PDU (AUC=0.962, 95% CI: 0.880-0.994, P<0.01) also performed best in predicting AKI 3, and the AUCs were higher than RRI (AUC=0.845, 95% CI: 0.731-0.924, P<0.01) and PDU score (AUC=0.913, 95% CI: 0.814-0.969, P<0.01) with statistically differences (all P<0.05). The optimal cutoff for RRI/PDU was > 0.360 (sensitivity 95.0%, specificity 90.7%, Youden index 0.857). The predictive value of RRI-RDU/10 for AKI 3 (AUC=0.950, 95% CI: 0.864-0.989, P<0.01) was also better than RRI and PDU score, but slightly worse than RRI/PDU and RRI+PDU, with statistically difference only between RRI and RRI-RDU/10 ( P<0.05). Conclusions:The combination of RRI and PDU score could effectively predict AKI 3 in non-septic critically ill patients, especially in patients with AHF. The ratio of RRI to PDU score is recommended for clinical application because of its excellent predictive value for AKI and its practicability.