OBJECTIVE: Anemoside B4 (AB4), the most abundant triterpenoidal saponin isolated from Pulsatilla chinensis, inhibited influenza virus FM1 or Klebsiella pneumoniae-induced pneumonia. However, the anti-SARS-CoV-2 effect of AB4 has not been unraveled. Therefore, this study aimed to determine the antiviral activity and potential mechanism of AB4 in inhibiting human coronavirus SARS-CoV-2 in vivo and in vitro. METHODS: The cytotoxicity of AB4 was evaluated using the Cell Counting Kit-8 (CCK8) assay. SARS-CoV-2 infected HEK293T, HPAEpiC, and Vero E6 cells were used for in vitro assays. The antiviral effect of AB4 in vivo was evaluated by SARS-CoV-2-infected hACE2-IRES-luc transgenic mouse model. Furthermore, label-free quantitative proteomics and bioinformatic analysis were performed to explore the potential antiviral mechanism of action of AB4. Type I IFN signaling-associated proteins were assessed using Western blotting or immumohistochemical staining. RESULTS: The data showed that AB4 reduced the propagation of SARS-CoV-2 along with the decreased Nucleocapsid protein (N), Spike protein (S), and 3C-like protease (3CLpro) in HEK293T cells. In vivo antiviral activity data revealed that AB4 inhibited viral replication and relieved pneumonia in a SARS-CoV-2 infected mouse model. We further disclosed that the antiviral activity of AB4 was associated with the enhanced interferon (IFN)-β response via the activation of retinoic acid-inducible gene I (RIG-1) like receptor (RLP) pathways. Additionally, label-free quantitative proteomic analyses discovered that 17 proteins were significantly altered by AB4 in the SARS-CoV-2 coronavirus infections cells. These proteins mainly clustered in RNA metabolism. CONCLUSION Our results indicated that AB4 inhibited SARS-CoV-2 replication through the RLR pathways and moderated the RNA metabolism, suggesting that it would be a potential lead compound for the development of anti-SARS-CoV-2 drugs.

Objective To investigate the prevalence and risk factors of cognitive impairment in the nursing home population in Changning District, Shanghai. Methods In this study, random cluster sampling method was used to select 570 elderly people from 5 nursing homes in Changning District. Multivariate logistic regression was used to analyze the risk factors influencing cognitive function. Results The total prevalence of cognitive impairment in Changning nursing home population was 22.5%. The prevalence rates of ≤80 and >80 age groups were 16.8% and 23.9%, respectively, and the prevalence rates of men and women were 19.2% and 23.9%, respectively. Multivariate analysis showed that age ≥ 80 years old (OR=1.839, 95% CI: 1.045~3.235), no habit of reading book or newspaper (OR=2.087, 95%CI: 1.282~3.398), limitation of daily activity ability (OR=1.577, 95% CI: 1.023~2.431), and having depressive symptoms (OR=2.809, 95% CI: 1.840~4.288) were all influencing factors for cognitive impairment. Conclusion More than one fifth of elderly people in nursing homes in Changning District have symptoms of cognitive impairment. It is necessary to carry out routine cognitive assessment and appropriate cognitive intervention for the nursing home population to reduce the health and economic losses caused by cognitive impairment.

AIM: To explore the clinical features, diagnosis and treatment experience and the distribution characteristics of pathogenic microorganisms of primary canaliculitis, and provide reference for its diagnosis and treatment. METHODS: Retrospective clinical study. A total of 119 cases(120 eyes)diagnosed as primary canaliculitis in the department of ophthalmology of Wuxi No.2 People's Hospital from June 2019 to February 2023 were included. The treatment methods were mainly divided into conservative treatment(removing canaliculus stones through lacrimal punctum combined with injecting antibiotic eye ointment into the tube)and surgical treatment. The inspection methods of pathogenic microorganisms included secretion smear microscopy and microbial culture.RESULTS: Primary canaliculitis was more common in middle-aged and older female, mainly manifested by long-term red eye and increased secretion; however, the majority was not accompanied by tearing. Totally, 118 cases(99.2%)had monocular disease, while 63 cases(63 eyes; 52.5%)had inferior lacrimal canaliculus disease. Laboratory examination: Among 119 cases(120 eyes), 4 cases(4 eyes)did not undergo laboratory examination, and the other 115 cases(116 eyes)were as follows: Gram staining microscopy of secretion smear showed that Actinomyces were detected in 102 cases(103 eyes; 88.8%), while no fungus was detected; Microbial culture: 85 cases(86 eyes; 74.1%)were positive for bacterial culture. A total of 111 bacterial strains were cultured, which contained 26 types of bacteria. Among them, 32 strains were aerobic(28.8%); 26 strains were anaerobic(23.4%); and 53 strains were facultative anaerobic(47.7%). The most common bacteria were streptococcus(20 strains), staphylococcus(13 strains), Propionibacterium(10 strains), and capnocytophaga(10 strains). Only 4 cases(4 eyes; 3.4%)of microbial cultures were positive for Actinomyces. Fungus was negative in all microbial cultures. Treatment: Of the 119 cases(120 eyes), 114 cases(115 eyes; 95.8%)were cured by conservative treatment of removing lacrimal canaliculus stones through lacrimal punctum and intracanalicular ointment infiltration(IOI), while 5 cases(5 eyes)were not effective in conservative treatment; however, all of them were cured after surgical treatment, and the cure rate for primary canaliculitis was 100.0%.CONCLUSION: The incidence of primary canaliculitis is low, and it is prevalent in middle-aged and older female. Single lacrimal canaliculus is more common, which could be missed and misdiagnosed in clinic. Actinomyces is the major pathogen observed mostly in mixed infections, with heterogeneous strains, mainly anaerobic or facultative anaerobic bacteria. Streptococcus and Staphylococcus are the most common whereas fungal canaliculitis is rare. The cure rate of primary canaliculitis is high after diagnosis, and IOI method is recommended as the initial treatment of canaliculitis.

Objective To investigate the current situation of home environment safety of the elderly in Changning District, identify the risk factors related to the fall of the home environment of the elderly, and take targeted rectification measures, so as to create a safer environment for the elderly. Methods A phased random sampling method was used to select 201 elderly households from 10 streets in Changning District. Community doctors conducted on-the-spot investigation and assessment to collect information, and Epidata3.1 was used to input data and SAS 9.2 was used for statistical analysis. Results The incidence of falls in the past year was 19.90%, and the score of environmental risk factors/the number of environmental risk factors in each family ranged from 0 to 25, with an average of 9 items (standard deviation of 4.71). The results of multivariate logistic regression analysis show that the high level of falling environment (the number of falling risk factors in home environment ≥12) is still an independent risk factor for falls of the elderly, except for the influence of age and the number of drugs taken (OR=3.835, 95% CI:1.718-8.561). Conclusion The environmental risk factors causing falls are common in the home environment of the elderly in the community. It is necessary to focus on improving the home environment, reducing the risk of falls for the elderly, and creating a safe and comfortable home environment for the elderly.

Background::The Global Leadership Initiative on Malnutrition (GLIM) criteria were published to build a global consensus on nutritional diagnosis. Reduced muscle mass is a phenotypic criterion with strong evidence to support its inclusion in the GLIM consensus criteria. However, there is no consensus regarding how to accurately measure and define reduced muscle mass in clinical settings. This study aimed to investigate the optimal reference values of skeletal muscle mass index for diagnosing sarcopenia and GLIM-defined malnutrition, as well as the prevalence of GLIM-defined malnutrition in hospitalized cirrhotic patients.Methods::This retrospective study was conducted on 1002 adult patients with liver cirrhosis between January 1, 2018, and February 28, 2022, at Beijing You-An Hospital, Capital Medical University. Adult patients with a clinical diagnosis of liver cirrhosis and who underwent an abdominal computed tomography (CT) examination during hospitalization were included in the study. These patients were randomly divided into a modeling group (cohort 1, 667 patients) and a validation group (cohort 2, 335 patients). In cohort 1, optimal cut-off values of skeletal muscle index at the third lumbar skeletal muscle index (L3-SMI) were determined using receiver operating characteristic analyses against in-hospital mortality in different gender groups. Next, patients in cohort 2 were screened for nutritional risk using the Nutritional Risk Screening 2002 (NRS-2002), and malnutrition was diagnosed by GLIM criteria. Additionally, the reference values of reduced muscle mass in GLIM criteria were derived from the L3-SMI values from cohort 1. Multivariate logistic regression analysis was used to analyze the association between GLIM-defined malnutrition and clinical outcomes.Results::The optimal cut-off values of L3-SMI were 39.50 cm 2/m 2 for male patients and 33.06 cm 2/m 2 for female patients. Based on the cut-off values, 31.63% (68/215) of the male patients and 23.3% (28/120) of the female patients had CT-determined sarcopenia in cohort 2. The prevalence of GLIM-defined malnutrition in cirrhotic patients was 34.3% (115/335) and GLIM-defined malnutrition was an independent risk factor for in-hospital mortality in patients with liver cirrhosis ( Wald = 6.347, P = 0.012). Conclusions::This study provided reference values for skeletal muscle mass index and the prevalence of GLIM-defined malnutrition in hospitalized patients with liver cirrhosis. These reference values will contribute to applying the GLIM criteria in cirrhotic patients.

Background::Acute-on-chronic liver failure (ACLF) is a severe liver disease with complex pathogenesis. Clinical hypoglycemia is common in patients with ACLF and often predicts a worse prognosis. Accumulating evidence suggests that glucose metabolic disturbance, especially gluconeogenesis dysfunction, plays a critical role in the disease progression of ACLF. Lon protease-1 (LONP1) is a novel mediator of energy and glucose metabolism. However, whether gluconeogenesis is a potential mechanism through which LONP1 modulates ACLF remains unknown.Methods::In this study, we collected liver tissues from ACLF patients, established an ACLF mouse model with carbon tetrachloride (CCl 4), lipopolysaccharide (LPS), and D-galactose (D-gal), and constructed an in vitro hypoxia and hyperammonemia-triggered hepatocyte injury model. LONP1 overexpression and knockdown adenovirus were used to assess the protective effect of LONP1 on liver injury and gluconeogenesis regulation. Liver histopathology, biochemical index, mitochondrial morphology, cell viability and apoptosis, and the expression and activity of key gluconeogenic enzymes were detected to explore the underlying protective mechanisms of LONP1 in ACLF. Results::We found that LONP1 and the expressions of gluconeogenic enzymes were downregulated in clinical ACLF liver tissues. Furthermore, LONP1 overexpression remarkably attenuated liver injury, which was characterized by improved liver histopathological lesions and decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in ACLF mice. Moreover, mitochondrial morphology was improved upon overexpression of LONP1. Meanwhile, the expression and activity of the key gluconeogenic enzymes were restored by LONP1 overexpression. Similarly, the hepatoprotective effect was also observed in the hepatocyte injury model, as evidenced by improved cell viability, reduced cell apoptosis, and improved gluconeogenesis level and activity, while LONP1 knockdown worsened liver injury and gluconeogenesis disorders.Conclusion::We demonstrated that gluconeogenesis dysfunction exists in ACLF, and LONP1 could ameliorate liver injury and improve gluconeogenic dysfunction, which would provide a promising therapeutic target for patients with ACLF.

【Objective】 To analyze the effects of different fortified feeding methods on nutritional metabolism and growth rate of preterm very low birth weight infants (VLBWI), in order to provide new clues for improving the prognosis of the preterm infants. 【Methods】 A total of 115 cases of premature VLBWI admitted to Department of Neonatology, The First Affiliated Hospital of Kunming Medical University from January 2019 to December 2020 were included in this study, and were divided into fortified breastfeeding group (HFM group), mixed feeding group, and premature formula feeding group (PF group) based on their feeding methods. The effects of different feeding methods on the nutritional metabolism and growth rate of premature VLBWI were analyzed. 【Results】 1) The hospitalization time of infants in the HFM group was shorter than that in PF group and mixed feeding group (t=7.185, 6.924, P<0.05). 2) The proportion of necrotizing enterocolitis (NEC) in the HFM group during hospitalization was lower than that in the PF group (P<0.05); the proportions of late onset septicemia(LOS) and extra uterine growth restriction(EUGR) in the HFM group during hospitalization were lower than those in the PF group (χ²=5.030, 4.147, P<0.05); the proportion of LOS was lower than that of the mixed feeding group(χ²=6.589, P<0.05). 3) During hospitalization, the proportions of abdominal distension, bloody stools and increased eosinophils in the HFM group were lower than those in the PF group (P<0.05), which in mixed feeding group was lower than those in PF group (Fisher exact test, P<0.05). 4) At discharge, the weight and length growth rate of the HFM group were higher than those of the mixed feeding group (t=3.722, 0.425, P<0.001) and the PF group (t =6.015, 0.496, P< 0.001). 【Conclusion】 Fortified breastfeeding can more effectively increase the growth rate of VLBWI in premature infants, improve nutritional metabolism, reduce complications and adverse feeding reactions related to premature infants, and is safer and more effective.

Objective:To systematically review the related factors of depressive symptoms among men who have sex with men(MSM)in China.Methods:CNKI,Wanfang Data,VIP,CBM,EMbase,Pubmed,CINAHL,Web of Science and the Cochrane Library were searched from inception to February 17,2023.After literature screening and data extraction,two researchers independently assessed the quality of included studies according to the Agency for Healthcare Research and Quality.Results:A total of 21 articles with 11 822 participants were includ-ed.The results of meta-analysis showed that month income ≥3 000 yuan(OR=0.59),college degree or above(OR=0.59)and high self-esteem(OR=0.83)were protective factors,sexual role as the recipient(OR=1.68),dual sexual role(OR=1.41),multiple sexual partners(OR=1.65),sexual violence experience(OR=3.44),self-rated poor health status(OR=3.93),HIV/AIDS related discrimination(OR=1.13),HIV/AIDS related stress(OR=1.11)and suicidal tendency(OR=2.86)were risk factors for depressive symptoms.Conclusion:There are many related factors to the depressive symptoms of MSM.It is necessary to carry out early intervention on the basis of personalized assessment to reduce the occurrence of depressive symptoms among MSM.

Objective: To examine the association of hypertension onset age with diabetes, so as to provide insights into reducing the the risk of cardiovascular events. Methods: Permanent residents aged 35 to 75 years were selected through the program of early screening and comprehensive intervention for the high-risk cardiovascular disease population in Changning District and Baoshan District, Shanghai Municipality from 2016 to 2020. Demographic information, disease history, hypertension onset age, blood pressure and fasting blood glucose were collected through questionnaire surveys, physical examination and laboratory tests. The residents were divided into four groups based on the onset age of hypertension: <45, 45-<55, 55-<65 and ≥65 years old, and the residents with normal blood pressure were selected as control. The association of hypertension onset age with prediabetes and diabetes were identified using a multivariable logistic regression model. Results: A total of 25 228 residents were recruited, including 8 753 males (34.70%) and 16 475 females (65.30%). The prevalence of hypertension was 43.80%. There were 1 779, 3 274, 3 781 and 2 217 cases with hypertension onset age of <45, 45-<55, 55-<65 and ≥65 years old, respectively, and 14 177 residents with normal blood pressure. The prevalence of prediabetes and diabetes were 24.01% and 11.29%, respectively. Multivariable logistic regression analysis showed that after adjusting for confounding factors such as gender, marital status and educational level, compared with the normal blood pressure group, the risk of prediabetes was higher in the hypertension onset age groups of <45 (OR=1.345, 95%CI: 1.164-1.553), 45-<55 (OR=1.365, 95%CI: 1.212-1.536) and 55-<65 years old (OR=1.376, 95%CI: 1.239-1.527), and the risk of diabetes was higher in the hypertension onset age groups of <45 (OR=2.302, 95%CI: 1.906-2.775), 45-<55 (OR=2.349, 95%CI: 2.016-2.734), 55-<65 (OR=1.909, 95%CI: 1.667-2.184) and ≥65 years old (OR=1.315, 95%CI: 1.131-1.526). Conclusion There are statistically significant associations between hypertension onset age with prediabetes and diabetes.

Based on the natures and flavors of herbal medicinals recorded in Shen Nong's Classic of the Materia Medica （《神农本草经》）； Miscellaneous Records of Famous Physicians （《名医别录》）， this study analyzed the characte-ristics of the natures， flavors and combination of medicinals of the two-herb compound formulas in Treatise on Cold Damage and Miscellaneous Diseases （《伤寒杂病论》）.Finally， 31 compound formulas were included， and it was found that the nature and flavor of the herbs in these two-herb compound formulas are closely related to the functions of the compound formulas， such as the common pairing of the acrid and the sweet herbs to warm yang and transform qi， the acrid and the bitter herbs in pairs to regulate and harmonize cold and heat， the sweet and the bitter in pairs to remove dampness and clear heat， the acrid and the acrid in pairs to arrest vomiting and direct qi downward， and the sour and the sweet in pairs to slow the urgent and relieve pain. Regardless of the deficiency or excess nature of the disease， the corresponding two-herb compound formulas often aim to reinforce healthy qi while eliminating pathogenic factors， with some formulas showcasing a unique correspondence between the disease pattern and the symptoms addressed.