Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3％,and that of non-infected group was 23.1％,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2％(95％CI:-2.3％-22.8％).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P＞0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P＞0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.

Objective: To investigate the etiology, complications, and prognostic factors of stage 5 chronic kidney disease (CKD5) in children. Methods: A case series study was conducted to retrospectively analyze the general situation, clinical manifestations, laboratory tests, genetic testing, and follow-up data (until October 2022) of 174 children with CKD5 who were diagnosed and hospitalized at the Children's Hospital of Chongqing Medical University from April 2012 to April 2021. The characteristics of complications in the children were compared based on age, gender, and etiology. Based on the presence or absence of left ventricular hypertrophy (LVH), patients were divided into LVH group and non LVH group for analyzing the influencing factors of cardiovascular disease. Patients were also divided into death group and survival group, peritoneal dialysis group and hemodialysis group based on the follow-up data for analyzing the prognostic factors. The chi-square test, independent sample t-test, Fisher exact probability test, Mann-Whitney U test and Kruskal Wallis test were used to analyze data among different groups. Multivariate Logistic regression analysis was used to identify the prognostic factors. Results: A total of 174 children with CKD5 were enrolled in the study (96 boys and 78 girls), aged 11.2 (8.2, 13.0) years. Congenital kidney and urinary tract malformations (CAKUT) were the most common causes of the CKD5 (84 cases, 48.3%), followed by glomerular diseases (83 cases, 47.7%), and among which 28 cases (16.1%) were hereditary glomerular diseases. The common complications of CKD5 included anemia (98.2%, 165/168), mineral and bone disorder in chronic kidney disease (CKD-MBD) (97.7%, 170/174), lipid metabolism disorders (87.5%, 63/72), hypertension (81.4%, 127/156) and LVH (57.6%,57/99). The incidences of hypertension in primary glomerular disease were higher than that in CAKUT(93.8%(30/32) vs.73.7%(56/76),χ²=5.59,P<0.05). The incidences of hypertension in secondary glomerular disease were higher than that in CAKUT and that in hereditary kidney disease (100.0%(20/20) vs. 73.7%(56/76), 68.2%(15/22), both P<0.05). The incidence of hypocalcemia in CAKUT, primary glomerular disease, and hereditary kidney disease was higher than that in secondary glomerular disease (82.1%(69/84), 88.2%(30/34), 89.3%(25/28) vs. 47.6%(10/21), χ²=10.21, 10.75, 10.80, all P=0.001); the incidence of secondary hyperparathyroidism in women was higher than that in men (80.0%(64/80) vs. 95.0%(57/60), χ²=6.58, P=0.010). The incidence of LVH in children aged 6-<12 was higher than that in children aged 12-18 (73.5%(25/34) vs. 43.1%(22/51), χ²=7.62, P=0.006). Among 113 follow-up children, the mortality rate was 39.8% (45/113). Compared to the survival group, the children in the death group had lower hemoglobin, higher blood pressure, lower albumin, lower alkaline phosphatase and higher left ventricular mass index ((67±19) vs. (75±20) g/L, 142 (126, 154) vs. 128(113, 145) mmHg(1 mmHg=0.133 kPa), (91±21) vs. (82±22) mmHg, 32 (26, 41) vs. 40 (31, 43) g/L, 151 (82, 214) vs. 215 (129, 37) U/L, 48 (38, 66) vs. 38(32, 50) g/m^2.7,t=2.03, Z=2.89, t=2.70, Z=2.49, 2.79, 2.29,all P<0.05), but no independent risk factors were identified (all P>0.05). The peritoneal dialysis group had better alleviation for anemia, low calcium, and high phosphorus than the hemodialysis group ((87±22) vs. (72±16) g/L, (1.9±0.5) vs. (1.7±0.4) mmol/L, (2.2±0.7) vs. (2.8±0.9) mmol/L, t=2.92, 2.29, 2.82, all P<0.05), and the survival rate of the peritoneal dialysis group was significantly higher than that of the hemodialysis group (77.8% (28/36) vs. 48.4% (30/62), χ²=8.14, P=0.004). Conclusions: CAKUT is the most common etiology in children with CKD 5, and anemia is the most common complication. The incidence of complications in children with CKD 5 varies with age, gender and etiology. Anemia, hypertension, hypoalbuminemia, reduced alkaline phosphatase and elevated LVMI may be the prognostic factors in children with CKD5. Peritoneal dialysis may be more beneficial for improving the long-term survival rate.
Male ; Humans ; Child ; Female ; Retrospective Studies ; Alkaline Phosphatase ; Kidney Failure, Chronic/therapy* ; Renal Insufficiency, Chronic/therapy* ; Hypertension ; Risk Factors ; Hypertrophy, Left Ventricular/etiology* ; Anemia/etiology*

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40％of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated he-patic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and ther-apeutic targets for liver protection.

OBJECTIVE: To investigate the effects of melatonin on the growth and metastasis of MDA-MB-231 breast cancer cells and explore the mechanism. METHODS: MDA-MB-231 cells were treated with 1, 3 or 5 mmol/L melatonin, and the changes in cell proliferation were examined using CCK-8 assay. Colony-forming assay and wound healing assay were used to assess the effects of melatonin treatmnent on colony-forming ability and migration of the cells. Flow cytometry and immunofluoresnce assay were employed to examine apoptosis and positive staining for autophagy-related proteins in the cells treated with 3 mmol/L melatonin. The effects of melatonin treatment alone or in combination with 3-methyladenine (3-MA) on the expressions of the proteins associated with autophagy (LC3, P62 and Beclin1), apoptosis (Bcl2 and Bax) and epithelial-mesenchymal transition (E-cadherin and Snail) were examined with Western blotting. RESULTS: Melatonin treatment significantly inhibited the proliferation of breast cancer cells in a concentration- and time-dependent manner (P < 0.05), suppressed colony-forming ability and migration (P < 0.01), and promoted apoptosis of the cells (P < 0.01). Melatonin treatment alone significantly increased the expressions of Bax (P < 0.05), E-cadherin, LC3-II/LC3-I, and Beclin1 and lowered the expressions of Bcl2 (P < 0.05), Snail, P62 (P < 0.05), and Bcl2/Bax ratio (P < 0.01) in the cells, and caused enhanced positive staining of Beclin1 protein and attenuated staining of P62 protein. Compared with melatonin treatment alone, melatonin treatment combined with 3-MA significantly decreased the expressions of Beclin1 (P < 0.001), LC3-II/LC3-I (P < 0.05), Bax (P < 0.01), and E-cadherin (P < 0.001) and increased the expressions of Bcl2 (P < 0.05), Snail, and Bcl2/Bax ratio (P < 0.01). CONCLUSION Melatonin can induce autophagy of MDA-MB-231 breast cancer cells to inhibit cell proliferation and metastasis and promote cell apoptosis, and suppressing autophagy can weaken the inhibitory effect of melatonin on the growth and metastasis of breast cancer cells.
Autophagy ; Autophagy-Related Proteins/metabolism* ; Breast Neoplasms ; Cell Line, Tumor ; Female ; Humans ; Melatonin/pharmacology*

BACKGROUND: Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment. METHODS: This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR. RESULTS: A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities. CONCLUSION: Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; Bendamustine Hydrochloride/therapeutic use* ; China ; Humans ; Lymphoma, Non-Hodgkin/drug therapy* ; Neoplasm Recurrence, Local/drug therapy* ; Prospective Studies ; Rituximab/therapeutic use*

Objective:To explore the effect of upregulating CXC-chemokine receptor 7 (CXCR7) in endothelial progenitor cells (EPCs) on angiogenesis after cerebral ischemia-reperfusion injury. Methods:EPCs were isolated and cultured from human umbilical cord blood and identified. Then, the EPCs were transfected with CXCR7 overexpression lentiviral vector, and the expression of CXCR7 was identified with real-time PCR and Western blotting. The tube-like structure formation and apoptosis of EPCs under oxidized low density lipoprotein (ox-LDL) were detected with tube-like structure formation test and Annexin V/PI staining. Cerebral ischemia-reperfusion injury model in rats was established, and the qualified model rats were randomly divided into three groups after 24 hours reperfusion: PBS group (n = 12) was injected with phosphate buffers through tail vein, control group (n = 12) was injected the EPCs infected with control lentiviral vector, and CXCR7 group (n = 12) was injected with EPCs infected with CXCR7 overexpression lentiviral vector. Neurological function scores were determined seven and 14 days after transplantation. The cerebral infarct volume was measured, the number of GFP-positive cells in the ischemic site and the density of capillary were observed. Results:The expression of CXCR7 in EPCs increased after transfection (P < 0.01). Overexpression of CXCR7 improved tube formation and reduced apoptosis of EPCs under ox-LDL (P < 0.05). Compared with PBS and control groups , neurological function improved in CXCR7 group, with less infarct volume, more GFP-positive cells and density of capillary (P < 0.05). Conclusion:Up-regulating CXCR7 can improve the survival and angiogenesis of EPCs, and improve the repair of cerebral ischemia-reperfusion injury.

Objective To evaluate the effect and cost-effectiveness of three commonly used molluscicides, 4% "Luo-wei" (tea-seed distilled saponins, TDS), 50% niclosamide ethanolamine salt wettable powder (NESWP), and 26% metaldehyde and niclosamide suspension concentrate (MNSC) in large-scale field application, so as to provide the references for formulating the strategy of snail control. Methods The field test and parallel comparison were implemented. A marshland with Oncomelania hupensis snails of the Yangtze River was divided into 4 parts (10 hm²) for the research, and three of them were experimental areas while the last one was a blank control area. The experimental areas were sprayed with 4% "Luo-wei", 50% NESWP and 26% MNSC respectively for 3 times and the interval was 1 week. Seven days after each spraying the effect of snail control was investigated, and the costs of molluscicides, labor, transportation, fuel consumption and mechanical loss were recorded. The cost of each molluscicide, snail mortality, snail density, and the cost of increasing 1% of snail mortality per 100 m² were analyzed and compared. Results After the first, second and third spraying, the corrected snail mortality rates were 67.34%, 76.55% and 84.60% respectively in the 4% "Luo-wei" group; the corrected snail mortality rates were 64.71%, 75.17% and 83.89% respectively in the 50% NESWP group; the corrected snail mortality rates were 66.55%, 76.27% and 86.67% respectively in the 26% MNSC group. There was no significant difference among the 3 groups in the snail mortality at the same spraying time (χ² = 1.590, 0.571, 3.238, all P > 0.05) . In addition, along with the increase of the spraying times, the snail mortality of each group was increased significantly compared to that of the control group (χ² = 79.333, 94.718, 117.020, all P < 0.01) . After the first, second and third spraying, the reduction rates of snail density were 69.82%–86.60% in the 4% "Luo-wei" group, 68.66%–86.55% in the 50% NESWP group, and 71.89%–88.87% in the 26% MNSC group respectively. The decreasing amplitude of the snail density was more than 85% in all the experimental areas after 3 rounds of spraying molluscicide. The snail control costs per 100 hm² were 19.57, 11.97 Yuan and 10.47 Yuan in the 4% "Luo-wei" group, 50% NESWP group, and 26% MNSC group respectively. After the first, second and third spraying, the costs of increasing 1% of snail mortality per 100 m² were 0.30, 2.08 Yuan and 2.38 Yuan in the 4% "Luo-wei" group, 0.20, 1.10 Yuan and 1.32 Yuan in the 50% NESWP group, and 0.17, 1.04 Yuan and 0.97 Yuan in the 26% MNSC group respectively, and the cost-effectiveness was the highest at the first spraying in all the three groups. Conclusions The effects of the three molluscicides for snail control are similar, but the efficacy of snail control is reduced as the spraying time increases.

Objective To investigate the effect of ZnO nanoparticles on the expressions of plasma membrane calcium ATPasel (PMCA1) of human lens epithelial cell B-3 (HLEB-3) at both mRNA and protein levels in the presence and absence of ultraviolet B (UVB) irradiation.Methods HLEB-3 was cultured in RPMI 1640 medium,and the cytotoxic effect of different concentrations of ZnO (0 μg · mL-1,2.5 μg · mL-1,5.0μg · mL-1,10.0 μg · mL-1) on HLEB-3 was investigated in the presence and absence of UVB irradiation.DAPI staining was used to monitor the effect of ZnO on HLECB-3 nuclei,and cell apoptosis was evaluated using annexin V-FITC/PI staining in the presence and absence of UVB irradiation.In addition,the intracellular calcium ion (Ca2 +)levels were assayed using Fluo-3/AM staining,and the expression levels of both PMCA1 mRNA and protein within HLEB-3 were detected by real-time PCR and Western blot,respectively.Results DAPI staining showed that the ZnO-treated HLEB-3 displayed a concentration-dependent apoptosis,and UVB irradiation could further aggravate the cytotoxic effect of ZnO on HLEB-3.In addition,in the presence of UVB irradiation,concentration gradient of ZnO (2.5 μg · mL-1,5.0 μg · mL-1,10.0 μg · mL-1) increased the intracellular calcium ion levels [from (156.34 ±4.59) nmol · L-1 to (173.88 ±7.17)umol · L-1,(289.02 ± 9.09) nmol · L-1,(488.36 ± 48.16) nmol · L 1,respectively] and upregulated HLEB-3 apoptosis,with statistical difference (all P ＜ 0.05).Moreover,the expression level of PMCA1 in the 2.5 μg · mL-1,5.0 μg · mL-1,10.0 μg · mL-1 ZnO-treated epithelial cells was accordingly 0.75,0.57 and 0.41 as much as that in the 0μg · mL-1 ZnO-treated cells in the absence of UVB irradiation (all P ＜ 0.05),and was accordingly 0.64,0.24 and 0.09 in the present of UVB irradiation,with significant difference (all P ＜ 0.05).Conclusion Both ZnO nanoparticle and UVB irradiation can exert cosuppression effect on HLEB-3 via calcium-mediated signaling pathway,indicating it has great potential for the treatment of posterior capsular opacification with UVB irradiation.

Objective To investigate the effect of silment information regulator factor related enzymes 1 (SIRT1) on the apoptosis of retinal ganglion cells (RGCs) in rats with diabetic retinopathy and its downstream molecular mechanisms.Methods Together 60 healthy male Sprague-Dawley rats were collected and randomly divided into normal group,diabetic group,SIRTI activator-resveratrol treatment group (treatment group),and diabetic rat model was induced by intraperitoneal injection of streptozotocin at 60 mg · kg-1 in the latter two group rats,while the normal group was injected with sodium citrate buffer at 60 mg · kg-1.Then,after 72 h,rats with blood glucose ＞ 16.7 mmol · L-1 were designated as diabetic rats by blood glucose test.Then each rat in the treatment group was treated with SIRT1 activator-resveratrol at 20 g · kg-1 once a day at the 2nd day after the success of the model,and the normal group and diabetic group were given methylene chloride.Finally,after immunohistochemical staining for retina,TUNEL assay was used to evaluate the apoptosis of RGCs,while the expression of SIRTI,p38 MAPK and Caspase-3 protein was detected by Western blot.Results The apoptotic index of RGCs in the normal group,diabetic group and treatment group was (0.848+0.131)％,(19.038 + 1.327)％,(10.461 + 1.089)％ respectively at 8 weeks,and the difference among the three groups was statistically significant (F =670.497,P =0.000),while the differences between each two groups were also statistically significant (all P =0.000).Furthermore,when compared with the normal group (0.132 ± 0.043),the expression of SIRT1 protein in the diabetic group (0.060 ± 0.028) and the treatment group (0.073 ± 0.026) was significantly decreased,and the overall difference among the three groups was statistically significant (F =1 310.663,P =0.000),while the differences between each two groups were also statistically significant (all P =0.000).The expression levels of p38 MAPK and Caspase-3 were increased in diabetic group (1.121 ± 0.082,0.266 ± 0.005) and treatment group (0.574 ± 0.012,0.190 ±0.060) respectively,and the overall difference and pairwise comparison in the three groups approached statistically significance (all P =0.000,0.000).Conelusion Up-regulation of SIRT1,can inhibit the apoptosis of RGCs,and protect RGCs against apoptosis in rat model of diabetic retinopathy,which may be correlated with the downregulation of p38 MAPK signal pathway.

Objective To investigate the relationship between the levels of plasma adrenaline and norepinephrine and gene polymorphism of β1 adrenergic receptor G1165C in children with enterovirus 71 (EV71) infection in hand foot and mouth disease (HFMD). Methods The polymerase chain reaction (PCR) was used to detect the expression of gene polymorphism of β1 adrenergic receptor G1165C in vitro. The levels of plasma adrenaline and norepinephrine were measured by enzyme-linked immunosorbent assay (ELISA). Results The plasma norepinephrine level of severe group was significantly higher than the mild group in children with EV71 infection in HFMD (P < 0.05); however, the levels of plasma adrenaline in two groups had no statistical differences (P > 0.05); There was no significant difference in the distribution of β1 adrenergic receptor G1165C genotype and allele between EV71 infection group and healthy control group (P > 0.05). Further analysis of EV71 infection group by dividing it into mild and severe groups showed that there was no significant difference in the distribution of genotype and allele between these two groups as well (P > 0.05). There was no significant difference in the levels of epinephrine and norepinephrine in different genotypes of EV71 infection group (P > 0.05), and in the levels of plasma epinephrine and norepinephrine in the mild and severe groups (P > 0.05). Conclusions As the disease gets worse, the plasma norepinephrine level has a rising trend in children with EV71 infection in HFMD, which is an important indicator to evaluate the progress of the disease. However, the gene polymorphism of β1 adrenergic receptor G1165C have no significant correlation, not only with the susceptibility and severity of EV71 infection in hand, foot and mouth disease, but also with the levels of catecholamine.