Metabolic associated fatty liver disease （MAFLD） has become one of the most prevalent chronic liver diseases worldwide， with the core pathological feature of pathological accumulation of triglycerides in hepatocytes， and as a key rate-limiting enzyme for triglyceride synthesis in the liver， 2-acylglycerol O-acyltransferase 2 （DGAT2） plays a central role in this process. Cell and animal model studies have confirmed that inhibition of DGAT2 can effectively alleviate hepatic steatosis and delay disease progression， and subsequent clinical trials have also shown the potential clinical application value in the treatment of MAFLD. This article systematically reviews the mechanism of action of DGAT2 in the development and progression of MAFLD and comprehensively summarizes the therapeutic strategies targeting DGAT2， including the advances in both monotherapy and drug combinations， in order to provide new ideas for individualized treatment of MAFLD patients.

Nanocarrier-based drug delivery systems can provide new research strategies for targeted intervention at atherosclerosis （AS） lesions by regulating the in vivo distribution and release behavior of drugs. Existing studies have shown that polymeric and lipid nanocarriers， cell membrane-coated systems， and microenvironment-responsive drug delivery strategies can intervene in the pathological progression of AS by modulating macrophage function， promoting cholesterol efflux， and controlling inflammation and oxidative stress； some systems have attempted to achieve multi-target synergistic intervention through combined delivery and theranostics； some drug delivery systems can improve drug enrichment in lesions and modulate related pathological processes. However， their long-term safety， lesion-targeting stability， scale-up manufacturing， and incremental clinical benefit remain to be validated. In the future， it is necessary to strengthen the matching between delivery mechanisms and pathological features and to establish evaluation systems for pharmacokinetics and safety， thereby providing a basis for the clinical translation of nanocarrier-based drug delivery systems.

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.

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

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.

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.

Objective To explore the effects of nail-tail transverse connection in the treatment of atlantoaxial dislocation(AAD)and its impacts on bone metabolism,serum vascular endothelial growth factor(VEGF),and fibroblast growth factor-2(FGF-2)levels.Methods A total of 150 pa-tients with AAD were selected as the research subjects and divided into two groups using the random number table method,with 75 cases in each group.The observation group was treated with nail-tail transverse connection combined with posterior atlantoaxial pedicle screw internal fixation(C1-C2 PSR),while the control group was treated with C1-C2 PSR alone.Serum bone metabolism indicators[osteocalcin(BGP),type Ⅰ collagen N-terminal peptide(NTX),bone alkaline phosphatase(BALP),tartrate-resistant acid phosphatase(TRAP),type Ⅰ collagen carboxy-terminal peptide(CTX)],VEGF and FGF-2 levels were compared between the two groups at different time points.The Japanese Orthopaedic Association(JOA)score was used to evaluate the patients' neurological function before surgery and 3 years after surgery.Bone graft fusion was evaluated at 6 months,1 year,2 years,and 3 years after surgery.Results At 1,3 and 6 months after surgery,the serum VEGF and FGF-2 levels in the observation group were higher than those in the control group,and the differences were statistically significant(P＜0.05).After treatment,the BALP,BGP,NTX,TRAP and CTX levels in both groups were lower than those before treatment,and their levels in the observation group were lower than those in the control group,with statistically significant differences(P＜0.05).Before surgery,there was no statistically significant difference in the JOA scores be-tween the two groups(P＞0.05).At 3 years after surgery,the JOA scores in both groups were higher than those before surgery,and the JOA score and the score improvement rate in the observa-tion group were higher than those in the control group,with statistically significant differences(P＜0.05).At 6 months,1 year,2 years and 3 years after surgery,the success rate of bone graft fusion in the observation group was higher than that in the control group,with statistically significant differ-ences(P＜0.05).Conclusion Nail-tail transverse connection has significant effects in the treat-ment of AAD,which can effectively improve patients' bone metabolism and increase the serum VEGF and FGF-2 levels.