SARS-CoV-2 and its emerging variants continue to pose a significant global public health threat. The SARS-CoV-2 main protease (M^pro) is a critical target for the development of antiviral agents that can inhibit viral replication and transcription. In this study, we identified chebulagic acid (CHLA), isolated from Terminalia chebula Retz., as a potent non-peptidomimetic and non-covalent M^pro inhibitor. CHLA exhibited intermolecular interactions and provided significant protection to Vero E6 cells against a range of SARS-CoV-2 variants, including the wild-type, Delta, Omicron BA.1.1, BA.2.3, BA.4, and BA.5, with EC₅₀ values below 2 μmol/L. Moreover, in vivo studies confirmed the antiviral efficacy of CHLA in K18-hACE2 mice. Notably, CHLA bound to a unique groove at the interface between M^pro domains I and II, which was revealed by the high-resolution crystal structure (1.4 Å) of the M^pro-CHLA complex, shrinking the substrate binding pocket of M^pro and inducing M^pro aggregation. CHLA was proposed to act as an allosteric inhibitor. Pharmacokinetic profiling and safety assessments underscore CHLA's potential as a promising broad-spectrum antiviral candidate. These findings report a novel binding site on M^pro and identify antiviral activity of CHLA, providing a robust framework for lead compounds discovery and elucidating the underlying molecular mechanisms of inhibition.

OBJECTIVE To investigate the epidemiological characteristics of infections in hemodialysis patients so as to provide bases for prevention and control of the infections in the hemodialysis patients.METHODS The patients who underwent maintenance hemodialysis in blood purification rooms of the Fifth Affiliated Hospital of Zhengzhou University in the first two working days each month from 2018 to 2022 were recruited as the research subjects.The incidence of hemodialysis-related events among the hemodialysis patients,including intravenous use of antibiotics,positive blood culture,exacerbation of pus,redness or swellings emerging at vascular access sites,were prospectively investigated.RESULTS A total of 386 case-times of hemodialysis-related events were moni-tored in 2018-2022,including 20 case-times of bloodstream infections,354 case-times of intravenous use of antibi-otics and 12 case-times of exacerbation of pus,redness or swellings emerging at vascular access sites.The inci-dence of hemodialysis-induced events was 4.19 per 100 patients each month,the average incidence rate of blood-stream infections was 0.22 per 100 patients each month.The patients with tunneled central venous catheter were 40.69 times the risk of bloodstream infections as the patients with intestinal fistula(95％CI:9.725～361.703,P＜0.001).The incidence of bloodstream infections was decreased by 53.85％among the hemodialysis patients in 2022 as compared with that in 2018.Staphylococcus aureus was the predominant species of pathogens causing the bloodstream infections.CONCLUSIONS The hemodialysis patients are the population at high risk of infections.The incidence of bloodstream infections and other infections is higher among the patients with tunneled central venous catheters than among the patients with other types of vascular accesses.The monitoring of hemodi-alysis-related infection events may reduce the incidence of bloodstream infections.

In this paper, the causes of dimethylacetamide poisoning in a small and micro enterprise were analyzed through on-site occupational health investigation, clinical data summary of poisoned patients and occupational hazard factors detection results. The incident was a group poisoning incident caused by exposure to dimethylacetamide, resulting in different degrees of toxic liver disease in 6 workers. Although the concentration of dimethylacetamide in the air in the workplace was excessive, percutaneous absorption may be the main cause of poisoning. The characteristics of percutaneous absorption of dimethylacetamide need to be paid great attention to, which can be used for reference to prevent similar incidents in the future.

Chronic liver disease remains a severe threat to human health. Furthermore, if left untreated promptly and effectively, it may gradually develop into end-stage liver disease, including decompensated cirrhosis and liver failure. Currently, mesenchymal stem cell technology is acting as a kind of an emerging treatment method, and multiple clinical trials have confirmed its promising application prospects in the treatment of decompensated cirrhosis and liver failure. Hence, stem cell therapy may offer a novel therapeutic option for these patients. This article summarizes the clinical research progress of stem cell therapy for decompensated cirrhosis and liver failure and analyzes present challenges and application prospects.

Objective:To investigate the therapeutic effects of dapagliflozin on renal fibrosis in patients with type 2 diabetic nephropathy (T2DN) and the underlying mechanisms involved.Methods:A randomized controlled study was conducted involving 152 patients with T2DN who received treatment at The First People's Hospital of Huzhou from April 2021 to May 2023. The patients were divided into an observation group and a control group, with 76 participants in each group, using a random number table method. The control group received conventional hypoglycemic therapy, while the observation group received dapagliflozin in addition to the conventional hypoglycemic therapy. Both groups were treated for 3 months. Before and after treatment, glycated hemoglobin, blood glucose, renal function indicators, and renal fibrosis markers (hyaluronic acid, type Ⅳ collagen, type Ⅲ procollagen, and laminin) were measured. Additionally, the levels of transforming growth factor-beta 1 (TGF-β 1), phosphorylated p38 mitogen-activated protein kinase (MAPK) pathway components [phosphorylated extracellular signal-regulated kinase (p-ERK),phosphorylated p38 mitogen-activated protein kinase (p-P38), phosphorylated c-Jun N-terminal Kinase (p-JNK)], and inflammatory factors (interleukin-6, interleukin-1 beta, and cyclooxygenase-2) in the patients' peripheral blood were measured. Transcriptome sequencing was performed to construct libraries and sequence the total RNA from kidney biopsy samples of the patients. Results:After treatment, the levels of hyaluronic acid, laminin, type Ⅳ collagen, and type Ⅲ procollagen in the observation group were (167.42 ± 17.91) μg/L, (106.10 ± 14.57) μg/L, (95.98 ± 10.03) μg/L, and (89.38 ± 9.75) μg/L, respectively. These values were significantly lower than those in the control group [(243.17 ± 24.38) μg/L, (147.43 ± 17.09) μg/L, (147.71 ± 14.59) μg/L, and (121.81 ± 14.88) μg/L, t = 21.83, 16.04, 25.47, 15.89, all P < 0.001]. The levels of interleukin-6, interleukin-1 beta, cyclooxygenase-2, TGF-β 1, and p-ERK, p-P38, and p-JNK in the observation group were significantly lower than those in the control group ( t = 9.45, 3.49, 11.30, 6.11, 4.26, 4.21, 2.04, all P < 0.05). Transcriptome sequencing enrichment analysis identified "fibronectin," "inflammatory response," and "TGF-β 1/P38 MAPK signaling pathway" as the differentially expressed signaling pathways. In kidney biopsy samples, the protein levels of TGF-β 1, p-ERK, and p-P38 in the observation group were (0.38 ± 0.15), (0.17 ± 0.10), and (0.58 ± 0.18), respectively, all of which were significantly lower than those in the control group [(0.16 ± 0.10), (0.07 ± 0.02), (0.19 ± 0.11), t = 2.99, 2.40, 4.53, all P < 0.05]. The overall response rate in the observation group was 93.43% (71/76), which was significantly higher than that in the control group [81.58% (62/76), χ2 = 7.02, P = 0.030]. Conclusions:Dapagliflozin has a beneficial therapeutic effect on renal fibrosis in patients with T2DN, as it can inhibit the expression of the TGF-β 1/p38 MAPK signaling pathway and reduce inflammation.

In this paper, the causes of dimethylacetamide poisoning in a small and micro enterprise were analyzed through on-site occupational health investigation, clinical data summary of poisoned patients and occupational hazard factors detection results. The incident was a group poisoning incident caused by exposure to dimethylacetamide, resulting in different degrees of toxic liver disease in 6 workers. Although the concentration of dimethylacetamide in the air in the workplace was excessive, percutaneous absorption may be the main cause of poisoning. The characteristics of percutaneous absorption of dimethylacetamide need to be paid great attention to, which can be used for reference to prevent similar incidents in the future.

Objective:To investigate the therapeutic effects of dapagliflozin on renal fibrosis in patients with type 2 diabetic nephropathy (T2DN) and the underlying mechanisms involved.Methods:A randomized controlled study was conducted involving 152 patients with T2DN who received treatment at The First People's Hospital of Huzhou from April 2021 to May 2023. The patients were divided into an observation group and a control group, with 76 participants in each group, using a random number table method. The control group received conventional hypoglycemic therapy, while the observation group received dapagliflozin in addition to the conventional hypoglycemic therapy. Both groups were treated for 3 months. Before and after treatment, glycated hemoglobin, blood glucose, renal function indicators, and renal fibrosis markers (hyaluronic acid, type Ⅳ collagen, type Ⅲ procollagen, and laminin) were measured. Additionally, the levels of transforming growth factor-beta 1 (TGF-β 1), phosphorylated p38 mitogen-activated protein kinase (MAPK) pathway components [phosphorylated extracellular signal-regulated kinase (p-ERK),phosphorylated p38 mitogen-activated protein kinase (p-P38), phosphorylated c-Jun N-terminal Kinase (p-JNK)], and inflammatory factors (interleukin-6, interleukin-1 beta, and cyclooxygenase-2) in the patients' peripheral blood were measured. Transcriptome sequencing was performed to construct libraries and sequence the total RNA from kidney biopsy samples of the patients. Results:After treatment, the levels of hyaluronic acid, laminin, type Ⅳ collagen, and type Ⅲ procollagen in the observation group were (167.42 ± 17.91) μg/L, (106.10 ± 14.57) μg/L, (95.98 ± 10.03) μg/L, and (89.38 ± 9.75) μg/L, respectively. These values were significantly lower than those in the control group [(243.17 ± 24.38) μg/L, (147.43 ± 17.09) μg/L, (147.71 ± 14.59) μg/L, and (121.81 ± 14.88) μg/L, t = 21.83, 16.04, 25.47, 15.89, all P < 0.001]. The levels of interleukin-6, interleukin-1 beta, cyclooxygenase-2, TGF-β 1, and p-ERK, p-P38, and p-JNK in the observation group were significantly lower than those in the control group ( t = 9.45, 3.49, 11.30, 6.11, 4.26, 4.21, 2.04, all P < 0.05). Transcriptome sequencing enrichment analysis identified "fibronectin," "inflammatory response," and "TGF-β 1/P38 MAPK signaling pathway" as the differentially expressed signaling pathways. In kidney biopsy samples, the protein levels of TGF-β 1, p-ERK, and p-P38 in the observation group were (0.38 ± 0.15), (0.17 ± 0.10), and (0.58 ± 0.18), respectively, all of which were significantly lower than those in the control group [(0.16 ± 0.10), (0.07 ± 0.02), (0.19 ± 0.11), t = 2.99, 2.40, 4.53, all P < 0.05]. The overall response rate in the observation group was 93.43% (71/76), which was significantly higher than that in the control group [81.58% (62/76), χ2 = 7.02, P = 0.030]. Conclusions:Dapagliflozin has a beneficial therapeutic effect on renal fibrosis in patients with T2DN, as it can inhibit the expression of the TGF-β 1/p38 MAPK signaling pathway and reduce inflammation.

OBJECTIVE To investigate the epidemiological characteristics of infections in hemodialysis patients so as to provide bases for prevention and control of the infections in the hemodialysis patients.METHODS The patients who underwent maintenance hemodialysis in blood purification rooms of the Fifth Affiliated Hospital of Zhengzhou University in the first two working days each month from 2018 to 2022 were recruited as the research subjects.The incidence of hemodialysis-related events among the hemodialysis patients,including intravenous use of antibiotics,positive blood culture,exacerbation of pus,redness or swellings emerging at vascular access sites,were prospectively investigated.RESULTS A total of 386 case-times of hemodialysis-related events were moni-tored in 2018-2022,including 20 case-times of bloodstream infections,354 case-times of intravenous use of antibi-otics and 12 case-times of exacerbation of pus,redness or swellings emerging at vascular access sites.The inci-dence of hemodialysis-induced events was 4.19 per 100 patients each month,the average incidence rate of blood-stream infections was 0.22 per 100 patients each month.The patients with tunneled central venous catheter were 40.69 times the risk of bloodstream infections as the patients with intestinal fistula(95％CI:9.725～361.703,P＜0.001).The incidence of bloodstream infections was decreased by 53.85％among the hemodialysis patients in 2022 as compared with that in 2018.Staphylococcus aureus was the predominant species of pathogens causing the bloodstream infections.CONCLUSIONS The hemodialysis patients are the population at high risk of infections.The incidence of bloodstream infections and other infections is higher among the patients with tunneled central venous catheters than among the patients with other types of vascular accesses.The monitoring of hemodi-alysis-related infection events may reduce the incidence of bloodstream infections.

Chronic liver disease remains a severe threat to human health. Furthermore, if left untreated promptly and effectively, it may gradually develop into end-stage liver disease, including decompensated cirrhosis and liver failure. Currently, mesenchymal stem cell technology is acting as a kind of an emerging treatment method, and multiple clinical trials have confirmed its promising application prospects in the treatment of decompensated cirrhosis and liver failure. Hence, stem cell therapy may offer a novel therapeutic option for these patients. This article summarizes the clinical research progress of stem cell therapy for decompensated cirrhosis and liver failure and analyzes present challenges and application prospects.

Objective:To understand the epidemiological characteristics and spatiotemporal distribution of viral encephalitis in children and adolescents in Henan Province from 2012 to 2023.Methods:The information about viral encephalitis cases from October 1, 2012 to July 26, 2023 were collected from Zhengzhou Children's Hospital (National Children's Regional Medical Center),Henan Provincial Children's Hospital for the analyses on temporal distribution the cases, the severe illness rate, age distribution, pathogen type and imaging findings of the cases.Results:A total of 6 276 cases of viral encephalitis were included in this study after excluding cases with incomplete information. The cases mainly originated from Zhengzhou (38.96%), followed by Zhoukou (9.93%), Xuchang (8.68%), Zhumadian (7.90%) and Pingdingshan (7.39%). The cases in boys accounted for 62.13% and the cases in girls accounted for 37.87%. Most cases (72.45%) occurred in age group 7-13 years. The overall rate of severe illness cases was 4.51% from 2012 to 2023. There were significant differences in severe illness cases among different areas and years ( χ2=5.33, P=0.021; χ2=48.14, P<0.001). Enteroviruses were mainly detected (31.57%), in which Coxsackie virus was predominant (58.37%). Imaging findings showed that cerebral hemisphere damage was most common in children and adolescents with viral encephalitis (54.93%). Conclusions:From 2012 to 2023, more cases of viral encephalitis occurred in boys in Henan. Children and adolescents aged 7-13 years were the main affected group. The prevention of enteroviruses infection, especially Coxsackie virus, needs to be strengthened. Special attention should be paid to the prevention of cerebral hemisphere damage after viral encephalitis diagnosis.