Metabolic dysfunction-associated fatty liver disease （MAFLD） has become one of the critical chronic liver diseases requiring global attention， and the degree of hepatic fibrosis in these patients is closely associated with their prognosis. Therefore， control or even reversal of hepatic fibrosis is an indispensable part of the long-term management of MAFLD patients. A large number of studies have shown that the Wnt signaling pathway is involved in the development and progression of MAFLD. This article systematically describes the Wnt signaling pathway and elaborates on its mechanism of action in MAFLD-associated hepatic fibrosis， in order to provide a reference for the treatment of hepatic fibrosis in patients with MAFLD.

ObjectiveTo study the effect of the herb pair Mori Folium-Ginseng Radix et Rhizoma （HMG） on glucose and lipid metabolism in the mouse model of type 2 diabetes mellitus and decipher the possible treatment mechanism. MethodsThe db/db mice were chosen as the mouse model of type 2 diabetes mellitus and then treated with HMG at low and high doses （1.56， 3.12 g∙kg^-1， respectively） or metformin （0.26 g∙kg^-1） by gavage for 6 weeks. The normal group and the model group were treated with double distilled water at the same time according to body weight. The 8-h fasting blood glucose and body weight were measured once a week. The oral glucose tolerance test （OGTT） was conducted at the 6th week of dosing. The mice were sacrificed after the end of dosing. Serum levels of lipids ［total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL）， and low-density lipoprotein cholesterol （LDL）］， liver function indicators ［aspartate aminotransferase （AST） and alanine aminotransferase （ALT）］， non-esterified fatty acids （NEFA）， glycosylated serum protein （GSP）， serum glucose （GLU）， fasting insulin （FINS）， and renal function indicators ［creatinine （Crea） and blood urea nitrogen （BUN）］ were measured by enzyme-linked immunosorbent assay. The protein levels of peroxidase proliferator-activating receptor gamma （PPARγ）， acetyl coenzyme A carboxylase （ACC）， and sterol regulatory element-binding protein-1 （SREBP-1） were determined by Western blot. The pathological changes in the liver and pancreas were examined. ResultsCompared with the normal group， the model group presented increased body weight， elevated levels of blood glucose， TG， TC， AST， ALT， GLU， NEFA， GSP， and HDL-C， up-regulated protein levels of ACC and SREBP-1， and down-regulated protein level of PPARγ （P<0.01）. Meanwhile， the model group presented a large amount of lipid droplets and steatosis in the liver， as well as karyopyknosis and lymphocyte infiltration in the pancreas. Compared with the model group， the high- and low-dose HMG groups showed decreased body weight， declined levels of blood glucose， TG， TC， AST， ALT， GLU， NEFA， and GSP， and elevate level of HDL-C （P<0.05， P<0.01）. Moreover， the two groups showcased reduced lipid droplets and steatosis in the liver， as well as enlarged islets with clear boundaries and alleviated lymphocyte infiltration and karyopyknosis. Western blot results showed that the high-dose herb pair group demonstrated down-regulated protein levels of ACC and SREBP-1 and up-regulated protein level of PPARγ （P<0.01）. ConclusionThe HMG can effectively improve the glucose and lipid metabolism in db/db mice by regulating the expression of PPARγ， SREBP-1， and ACC.

ObjectiveTo study the effect of the herb pair Mori Folium-Ginseng Radix et Rhizoma （HMG） on glucose and lipid metabolism in the mouse model of type 2 diabetes mellitus and decipher the possible treatment mechanism. MethodsThe db/db mice were chosen as the mouse model of type 2 diabetes mellitus and then treated with HMG at low and high doses （1.56， 3.12 g∙kg^-1， respectively） or metformin （0.26 g∙kg^-1） by gavage for 6 weeks. The normal group and the model group were treated with double distilled water at the same time according to body weight. The 8-h fasting blood glucose and body weight were measured once a week. The oral glucose tolerance test （OGTT） was conducted at the 6th week of dosing. The mice were sacrificed after the end of dosing. Serum levels of lipids ［total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL）， and low-density lipoprotein cholesterol （LDL）］， liver function indicators ［aspartate aminotransferase （AST） and alanine aminotransferase （ALT）］， non-esterified fatty acids （NEFA）， glycosylated serum protein （GSP）， serum glucose （GLU）， fasting insulin （FINS）， and renal function indicators ［creatinine （Crea） and blood urea nitrogen （BUN）］ were measured by enzyme-linked immunosorbent assay. The protein levels of peroxidase proliferator-activating receptor gamma （PPARγ）， acetyl coenzyme A carboxylase （ACC）， and sterol regulatory element-binding protein-1 （SREBP-1） were determined by Western blot. The pathological changes in the liver and pancreas were examined. ResultsCompared with the normal group， the model group presented increased body weight， elevated levels of blood glucose， TG， TC， AST， ALT， GLU， NEFA， GSP， and HDL-C， up-regulated protein levels of ACC and SREBP-1， and down-regulated protein level of PPARγ （P<0.01）. Meanwhile， the model group presented a large amount of lipid droplets and steatosis in the liver， as well as karyopyknosis and lymphocyte infiltration in the pancreas. Compared with the model group， the high- and low-dose HMG groups showed decreased body weight， declined levels of blood glucose， TG， TC， AST， ALT， GLU， NEFA， and GSP， and elevate level of HDL-C （P<0.05， P<0.01）. Moreover， the two groups showcased reduced lipid droplets and steatosis in the liver， as well as enlarged islets with clear boundaries and alleviated lymphocyte infiltration and karyopyknosis. Western blot results showed that the high-dose herb pair group demonstrated down-regulated protein levels of ACC and SREBP-1 and up-regulated protein level of PPARγ （P<0.01）. ConclusionThe HMG can effectively improve the glucose and lipid metabolism in db/db mice by regulating the expression of PPARγ， SREBP-1， and ACC.

Objective To explore the clinical characteristics of immune-related adverse events (irAEs) involving the pituitary gland in malignant tumor patients following the administration of immune checkpoint inhibitors (ICIs), and to compare characteristics of pituitary irAEs with primary hypophysitis. Methods A total of 753 malignant tumor patients who were hospitalized at Sir Run Run Shaw Hospital School of Medicine, Zhejiang University from January 2019 to November 2022 and received ICIs treatment were retrospectively included. The incidence of endocrine irAEs were statistically analyzed. The clinical characteristics of patients with pituitary irAEs were analyzed and compared with those of patients with primary hypophysitis (n＝18). Results Among the 753 patients treated with ICIs, the majority (742, 98.5%) received PD-1/PD-L1 inhibitors. The incidence of endocrine irAEs was 32.0% (241/753), with primary thyroid dysfunction being most common (212, 28.2%), followed by pituitary dysfunction (35, 4.6%). The median time to onset of pituitary irAEs was 5.8 months, with the majority presenting as secondary hypoadrenocorticism (33, 94.3%). Surgery was a protective factor for preventing pituitary irAEs (P＝0.002), whereas higher body mass index (BMI) and dual ICIs combination therapy were recognized as risk factors (P＜0.05). Compared to patients with primary hypophysitis, patients with pituitary irAEs had a higher proportion of males, lower BMI, lower rates of visual field defects and diabetes insipidus, higher rate of secondary hypoadrenocorticism and lower positive rate on MRI (P＜0.05). Conclusions Malignant tumor patients treated with ICIs exhibit a relatively high incidence of endocrine irAEs, with thyroid involvement being most common, followed by the pituitary gland. Pituitary irAEs primarily manifest as secondary hypoadrenocorticism, lacking specific clinical symptoms and exhibiting a low positive rate on MRI. These factors contribute to a high risk of misdiagnosis or missed diagnosis, necessitating heightened clinical vigilance.

Objective: To analyze the characteristics of road traffic injuries (RTI) among urban and rural residents in Zhejiang Province, so as to provide a basis for developing targeted RTI prevention and control strategies. Methods: In April 2023, permanent residents from 13 counties (cities, districts) in Zhejiang Province were selected using a multistage stratified random sampling method. Basic information and RTI occurrences within the past 12 months were collected through questionnaire surveys. RTI incidence and characteristics of RTI among urban and rural residents were analyzed. Results: A total of 36 980 individuals were surveyed, including 18 327 males (49.56%) and 18 653 females (50.44%). The median age was 56.00 (interquartile range, 28.00) years. There were 442 person-times of RTI, with an incidence of 1.20%. The rural incidence was significantly higher than the urban (1.33% vs. 1.05%, P<0.05). The incidence of RTI increased with age and decreased with higher educational attainment (both P<0.05). The majority of RTI occurred on streets/urban areas, accounting for 59.28%. In urban, streets/urban areas were the primary locations, accounting for 76.84%. In rural, streets/urban areas and intercity highways were the main sites, accounting for 46.03% and 40.48%, respectively. There was a statistically significant difference in the composition of RTI locations between urban and rural (P<0.05). The primary treatment approach of RTI was outpatient/emergency care, accounting for 61.99%. There was a statistically significant difference in the proportion of treatment approaches of RTI between urban and rural (P<0.05). Electric bicycles were involved in 67.87% of RTI, and 54.29% of motor vehicle occupants used seat belts. No statistically significant differences were observed in the composition of transportation modes or seat belt usage rates between urban and rural (both P>0.05). The lower limb was the most commonly injured sites, accounting for 42.31%. Mild injury was predominant, accounting for 50.90%, and complete recovery was predominant outcome, accounting fo 69.68%. The median rest period was 13.50 (interquartile range, 27.25) days. The median medical expenses was 1 200.00 (interquartile range, 5 700.00) yuan. No statistically significant differences were observed between urban and rural in terms of injury sites, injury severity, outcome, rest period, or medical expenses (all P>0.05). Conclusions RTI incidence is higher among rural residents, the elderly, and lower education levels residents in Zhejiang Province. It is recommend optimizing road safety infrastructure on streets/urban areas and intercity highways, prioritizing prevention of electric bicycles RTI, strengthening safety education for high-risk population, and increasing the usage rate of safety devices.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

OBJECTIVE: To develop and validate a predictive model for the risk of bloodstream infection (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). METHODS: A literature search was conducted in PubMed, Cochrane Library, and Embase databases from inception to July 2022 to identify studies reporting statistically significant risk factors for CRKP-BSI. Relative risks (RR) were extracted and pooled. Based on factor weights, a risk-scoring model was established. For external validation, hospitalized CRKP-infected patients from January 2016 to January 2022 at Shanghai First People's Hospital were included. Clinical data were used to calculate individual risk scores. The predictive accuracy was assessed using receiver operator characteristic curve (ROC curve). Patients were stratified into low-to-intermediate-risk and high-risk groups based on the optimal cut-off, and CRKP BSI incidence was compared between groups. RESULTS: The literatures related to the risk factors of CRKP-BSI published from database inception to July 2022 was retrieved and screened from PubMed, Cochrane Library, and Embase. Fourteen risk factors were included in the scoring model: cardiovascular disease, severe neutropenia or immunosuppression, intensive care unit (ICU) stay history, prior hospitalization, carbapenem exposure, aminoglycoside exposure, antifungal exposure, endotracheal intubation or tracheostomy, mechanical ventilation, hemodialysis, central venous catheter, indwelling urinary catheter, CRKP colonization, and Klebsiella pneumoniae positivity at non infection sites. The total score ranged from 0 to 173.5 points. In the validation cohort of 230 CRKP-infected patients, 41 developed CRKP BSI. The model yielded an area under the curve (AUC) of 0.783 (95%CI was 0.689-0.876). The optimal cut off was 81.25 points, with sensitivity of 75.6% and specificity of 81.0%. Based on this cut off, 163 patients were categorized as low-to-intermediate risk and 67 patients as high risk. The incidence of CRKP BSI in the high-risk group was significantly higher than in the low-to-intermediate-risk group [64.2% (43/67) vs. 4.9% (8/163); RR = 13.175 (95%CI was 5.920-29.319), P < 0.001]. CONCLUSIONS The model, based on 14 routinely available clinical parameters, demonstrated good performance in predicting CRKP BSI risk and may assist clinicians in early identification of high risk patients.
Humans ; Klebsiella pneumoniae/drug effects* ; Klebsiella Infections/microbiology* ; Carbapenems/pharmacology* ; Risk Factors ; Bacteremia/microbiology* ; ROC Curve ; Carbapenem-Resistant Enterobacteriaceae

This study aims to investigate the potential of oncolytic nanoparticles encapsulating Coxsackievirus A21 (CVA21) full-genome mRNA (CVA21@ONP) to resurrect CVA21 and induce apoptosis in host cells, as well as the antitumor immune effects of CVA21@ONP in immunocompetent tumor-bearing BALB/c mice. We used lipid nanoparticles (LNPs) to encapsulate CVA21 full-genome mRNA, thus preparing CVA21@ONP. The killing efficacy of CVA21@ONP was determined by the plaque assay and cell counting kit-8 (CCK-8), and the apoptosis in HT29 and CT26-iRFP cells was evaluated by flow cytometry. Mice were administrated with CVA21@ONP at high and low doses intratumorally, and the growth of tumors expressing infra-red fluorescent protein (iRFP) was monitored. Additionally, the types and changes of immune cells in the spleen were analyzed by flow cytometry. The results demonstrated that CVA21@ONP successfully resurrected CVA21 in both HT29 and U87MG cells. The plaque assay revealed robust killing effects of CVA21@ONP against both human and murine cell lines, and flow cytometry results showed increased early and late apoptotic cells. Notably, intratumoral detection revealed significantly down-regulated expression of iRFP in both high- and low-dose CVA21@ONP groups. Flow cytometry results further indicated that CVA21@ONP treatment effectively reduced the levels of immunosuppressive cells, including myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), in the spleen, while enhancing T cell-dependent antitumor immune responses. These findings suggest that CVA21@ONP can replicate and survive extensively both in vitro and in vivo, activating the immune system of mice administrated with CVA21@ONP to target cells at the tumor site, thereby remodeling the tumor immune microenvironment and accelerating the suppression or even complete regression of tumors. The oncolytic performance of CVA21@ONP has been verified through intratumoral injection administration in this study, aimed at further exploring its therapeutic potential and promoting the development of the field of tumor treatment.
Animals ; Nanoparticles/chemistry* ; Mice ; Mice, Inbred BALB C ; Humans ; Apoptosis ; Oncolytic Viruses/genetics* ; Oncolytic Virotherapy/methods* ; Cell Line, Tumor ; RNA, Messenger/genetics* ; HT29 Cells

Objective:To discuss the relationship between three proinflammatory factors and muscle mass(MM)in the elderly patients with sarcopenic obesity and diabetes,and to provide theoretical basis for the development of clinical treatment protocols in the elderly patients with sarcopenic obesity and diabetes.Methods:The elderly patients with diabetes who visited our hospital from January 2021 to May 2023 were selected,including 41 patients with obesity and diabetes(OD group)and 46 patients with sarcopenic obesity and diabetes(SOD group);80 healthy subjects(control group)and 62 subjects with simple obesity(SO group)who underwent physical examination in our hospital during the same period were included.The clinical data of the subjects in four groups were compared,and the correlations between proinflammatory factors and MM and fat mass(FM)were analyzed.All the subjects were divided into sarcopenia group and normal group based on the presence of sarcopenia.Logistic regression model was used to analyze the independent influencing factors of sarcopenia;receiver operating characteristic(ROC)curve was drawn to determine the predictive value of the above factors for sarcopenia.Results:Compared with control group,the body mass index(BMI),FM and body fat percentage(BFP)of the subjects in SOD,OD and SO groups were significantly increased(P＜0.05);compared with control group,OD group and SO group,the appendicular skeletal muscle mass(ASM),appendicular skeletal muscle mass index(ASMI)and grip strength(GS)of the subjects in SOD group were significantly decreased(P＜0.05),and the levels of serum interleukin-6(IL-6),C-reactive protein(CRP)and tumor necrosis factor-α(TNF-α)were significantly increased(P＜0.05).In all the subjects,the IL-6,CRP and TNF-α were negatively correlated with ASMI(r=-0.589,r=-0.621,r=-0.620;P＜0.05),and positively correlated with BFP(r=0.252,r=0.221,r=0.147;P＜0.05).Compared with normal group,the ASM,ASMI and GS of the subjects in sarcopenia group were significantly decreased(P＜0.05),and the levels of serum proinflammatory factors IL-6,CRP and TNF-α were significantly increased(P＜0.05).The univariate Logistic regression analysis results showed that IL-6,CRP and TNF-α were the influencing factors of sarcopenia(P＜0.05).The multivariate Logistic regression analysis results showed that the increased levels of IL-6 and TNF-α were the independent risk factors for sarcopenia(OR＞1,P＜0.05).The ROC curve results showed that the area under the curve(AUC)values of IL-6,CRP and TNF-α were all＞0.700,indicating that the above indicators had good predictive value for sarcopenia.Conclusion:The increased levels of proinflammatory factors IL-6,CRP and TNF-α are associated with the decrease of MM in the elderly patients with sarcopenic obesity and diabetes,and IL-6 and TNF-α are the independent risk factors for the sarcopenia.

Objective To observe the clinical efficacy of Shengdi Xiexin Decoction combined with proton pump inhibitors(PPIs)in the treatment of acute non-variceal upper gastrointestinal bleeding(ANVUGIB)with stomach-heat congestion syndrome.Methods Sixty-two patients with ANVUGIB of stomach-heat congestion syndrome admitted to Dongguan Hospital of Guangzhou University of Chinese Medicine between January and December 2024 were randomly divided into a treatment group(n=31)and a control group(n=31)using a random number table.The control group received conventional western therapy(e.g.,Omeprazole Sodium),while the treatment group additionally received Shengdi Xiexin Decoction.Both groups were treated for 7 days,followed by 8 weeks of follow-up.The changes in traditional Chinese medicine(TCM)syndrome scores,hematological parameters[hemoglobin(Hb),red blood cells(RBC),hematocrit(Hct),albumin(ALB)],tissue perfusion and metabolic markers[blood urea nitrogen/creatinine ratio(BUN/Cr),lactate(Lac)levels],hemostasis time,time to resume oral diet,hospital stay duration,hospitalization costs,and rebleeding rates were observed to evaluate the clinical efficacy and drug safety.Results(1)After 7 days of treatment,the total effective rate was significantly higher in the treatment group(90.32％,28/31)than that in the control group(74.19％,23/31).The intergroup comparison(by chi-square test)showed that the treatment group,efficacy was superior to that of the control group(P＜0.05).(2)The treatment group showed significantly short hemostasis time,time to resume oral diet,and hospital stay duration(P＜0.05),as well as significantly low hospitalization costs(P＜0.05)compared to the control group.(3)Both groups exhibited significant reductions in the scores of epigastric burning pain,abdominal distension,acid regurgitation,restlessness,excessive thirst,scanty dark uring and dry stools,and total TCM syndrome scores(P＜0.05).The treatment group demonstrated significantly greater improvements in the scores of abdominal distension,acid regurgitation,restlessness,dark uring and dry stools,and total TCM syndrome scores(P＜0.05),while no significant differences were observed in epigastric burning pain and excessive thirst(P＞0.05).(4)Hb and Hct levels increased significantly in both groups(P＜0.05),with a greater increase in the treatment group(P＜0.05).Although RBC and ALB levels showed an upward trend,no significant differences were observed between groups(P＞0.05).Following treatment,intergroup comparisons revealed that the treatment group demonstrated significantly greater increases in Hb and Hct levels than the control group(P＜0.05).In contrast,the two groups showed comparable effects in elevating RBC and ALB levels,with no statistically significant differences(P＞0.05).(5)BUN/Cr ratio and Lac levels decreased significantly in both groups(P＜0.05),with a more pronounced reduction in the treatment group(P＜0.05).(6)No significant differences were found in early or delayed rebleeding rates between groups(P＞0.05).(7)Neither group experienced significant adverse events.Conclusion Shengdi Xiexin Decoction combined with PPIs significantly improves clinical outcomes in ANVUGIB patients with stomach-heat congestion syndrome.It is effective on enhancing hematological parameters,correcting tissue hypoperfusion,alleviating symptoms,shortening hemostasis time and hospitalization durations,and reducing medical costs,demonstrating excellent safety.