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.

Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

Alzheimer's disease (AD), a neurodegenerative disorder with complex etiologies, manifests through a cascade of pathological changes before clinical symptoms become apparent. Among these early changes, alterations in the expression of non-coding RNAs (ncRNAs) have emerged as pivotal events. In this study, we focused on the aberrant expression of ncRNAs and revealed that Lamr1-ps1, a pseudogene of the laminin receptor, significantly exacerbates early spatial learning and memory deficits in APP/PS1 mice. Through a combination of bioinformatics prediction and experimental validation, we identified the miR-29c/Bace1 pathway as a potential regulatory mechanism by which Lamr1-ps1 influences AD pathology. Importantly, augmenting the miR-29c-3p levels in mice ameliorated memory deficits, underscoring the therapeutic potential of targeting miR-29c-3p in early AD intervention. This study not only provides new insights into the role of pseudogenes in AD but also consolidates a foundational basis for considering miR-29c as a viable therapeutic target, offering a novel avenue for AD research and treatment strategies.
Animals ; Alzheimer Disease/pathology* ; Pseudogenes/genetics* ; Mice ; Memory Disorders/metabolism* ; MicroRNAs/genetics* ; Disease Models, Animal ; Spatial Learning/physiology* ; Mice, Transgenic ; Presenilin-1/genetics* ; Male ; Amyloid Precursor Protein Secretases/metabolism* ; Mice, Inbred C57BL ; Aspartic Acid Endopeptidases/metabolism*

Normal heart function depends on complex regulation by the brain, and abnormalities in the brain‒heart axis affect various diseases, such as myocardial infarction and anxiety disorders. However, systematic tracking of the brain regions associated with the input and output of the heart is lacking. In this study, we injected retrograde transsynaptic pseudorabies virus (PRV) and anterograde transsynaptic herpes simplex virus (HSV) into the left ventricular wall of mice to identify the whole-brain regions associated with the input to and output from the heart. We successfully detected PRV and HSV expression in at least 170 brain subregions in both male and female mice. Sex differences were discovered mainly in the hypothalamus and medulla, with male mice exhibiting greater correlation and hierarchical clustering than female mice, indicating reduced similarity and increased modularity of virus expression patterns in male mice. Further graph theory and multiple linear regression analysis of different injection timelines revealed that hub regions of PRV had highly similar clusters, with different brain levels, suggesting a top-down, hierarchically transmitted neural control pattern of the heart. Hub regions of HSV had scattered clusters, with brain regions gathered in the cortex and brainstem, suggesting a bottom-up, leapfrog, multipoint neural sensing pattern of the heart. Both patterns contain many hub brain regions that have been previously overlooked in brain‒heart axis studies. These results provide brain targets for future research and will lead to deeper insight into the brain mechanisms involved in specific heart conditions.
Animals ; Male ; Female ; Heart/physiology* ; Mice ; Herpesvirus 1, Suid ; Brain/physiology* ; Mice, Inbred C57BL ; Brain Mapping ; Efferent Pathways/physiology* ; Afferent Pathways/physiology* ; Simplexvirus ; Sex Characteristics

Objective:To explore the perioperative safety and postoperative short-and long-term efficacy of stomach-partitioning gastrojejunostomy (SPGJ) with distal selective vagotomy (DSV) for treating benign gastric outlet obstruction (GOO).Methods:The clinical data of 26 benign GOO patients treated by Beijing Friendship Hospital, Capital Medical University from January 2019 to July 2023 were retrospectively analyzed. There were 20 males (76.9%) and 6 females (23.1%), aged from 25 to 75 years, with an average age of (55.8±13.6) years, and an average body mass index (BMI) of (20.1±3.4) kg/m 2. There were 12 cases in SPGJ-DSV group and 14 cases in SPGJ group. The main outcome was the gastrointestinal quality of life index (GIQLI) 1 year after surgery in both groups. Independent sample t-test was used to test the difference between the continuous variables with normal distribution. The comparison between groups of non-normal distribution continuous variables was tested by Mann-Whitney U test. Counting data were compared using Chi-square test or Fisher exact test. Results:There were no significant differences between the two groups in terms of operative time ( P=0.071), intraoperative blood loss ( P=0.422), time to pass gas ( P=0.538), time to liquid intake ( P=0.386), postoperative hospitalization ( P=0.431), complications within 30 days after surgery ( P=0.999), and postoperative GOOSS grade ( P=0.483). Among them, postoperative DGE occurred in one patient in each of the two groups, both of which were grade A. In the follow-up results, compared with the SPGJ group, SPGJ-DSV group had a significant advantage in GIQLI score, and the difference was statistically significant ( P=0.028). The incidence of gastric ulcer, reflux esophagitis, bile reflux and gastritis in SPGJ-DSV group was 8.3%, 8.3%, 8.3% and 58.3%, while that in SPGJ group was 35.7%, 21.4%, 21.4% and 57.1%, respectively, but there was no statistical significance between groups. Conclusion:In the treatment of benign GOO patients, SPGJ with DSV did not significantly increase the difficulty of laparoscopic procedures, operative time and intraoperative blood loss. Moreover, it showed a significant advantage in gastrointestinal quality of life 1 year after surgery. In addition, the incidence rates of gastric ulcers and reflux esophagitis were lower in the SPGJ-DSV group 1 year after surgery, but further confirmation is needed in large sample studies.

Respiratory syncytial virus (RSV) is an enveloped, negative-sense, single-stranded RNA virus of the Orthopneumovirus  genus of the Pneumoviridae family in the order Mononegavirales. RSV can cause acute upper and lower respiratory tract infections, sometimes with extrapulmonary complications. The disease burden of RSV infection is enormous, mainly affecting infants and older adults aged 75 years or above. Currently, treatment options for RSV are largely supportive. Prevention strategies remain a critical focus, with efforts centered on vaccine development and the use of prophylactic monoclonal antibodies. To date, three RSV vaccines have been approved for active immunization among individuals aged 60 years and above. For children who are not eligible for these vaccines, passive immunization is recommended. A newly approved prophylactic monoclonal antibody, Nirsevimab, which offers enhanced neutralizing activity and an extended half-life, provides exceptional protection for high-risk infants and young children. This review provides a comprehensive and detailed exploration of RSV's virology, immunology, pathogenesis, epidemiology, clinical manifestations, treatment options, and prevention strategies.
Humans ; Respiratory Syncytial Virus Infections/prevention & control* ; Respiratory Syncytial Viruses/pathogenicity* ; Respiratory Syncytial Virus, Human/pathogenicity* ; Antiviral Agents/therapeutic use*

Objective:To explore the correlation between serum NLR and SII levels and postmenopausal osteoporotic vertebral compression fracture (OVCF) and to analyze the short-term prognostic value.Methods:A total of 132 patients with postmenopausal OVCF admitted to our hospital from Dec. 2018 to Dec. 2021 were selected as the study group, and 98 patients with postmenopausal osteoporosis but did not suffer from OVCF were selected as the control group. According to the recurrence of postmenopausal OVCF fractures, the ROC curves of NLR and SII were plotted, and their prognostic value for postmenopausal osteoporosis OVCF was analyzed.Results:NLR level was 2.96±0.41 and STI level was 39.41±23.45 in the control group. The level of NLR was 3.42±0.32 and SII was 431.77±31.14 in the research group ( P<0.05) . Multivariate Logistic regression analysis showed that lumbar bone density ( OR=0.030, 95%CI: 0.001-0.832, P=0.042) , NLR level ( OR=29.43, 95%CI: 9.840-103.6, P=0.001) and SII level ( OR=1.048, 95%CI: 1.034-1.066, P=0.001) were all risk factors affecting postmenopausal OVCF. NLR (3.77±0.22) and SII (441.32±29.68) in the recurrent fracture group were higher than NLR (3.27±0.22) and SII (426.87±30.57) in the non-recurrent fracture group, and the differences were statistically significant (all P<0.05) , multivariate Logistic regression analysis showed lumbar spine bone density ( OR=8.56×10 4, 95% CI: 3.884-2.992×10 10, P=0.045) , NLR level ( OR=1.243×10 -8, 95% CI: 2.911×10 -13-1.072×10 -5, P=0.001) and SII level ( OR=0.938, 95% CI: 0.885-0.976, P=0.008) were all influencing factors affecting the postoperative treatment effect of postmenopausal OVCF, and ROC results showed that both NLR (AUC=0.86, 95% CI: 0.77-0.94, P<0.001) and SII (AUC=0.76, 95% CI: 0.67-0.85, P<0.001) had good prognostic value for postmenopausal OVCF. Conclusion:NLR and SII are risk factors for OVCF in postmenopausal osteoporosis patients, and have good short-term prognostic value.

Objective:To investigate the high-risk factors affecting the prognosis of patients with pT 1-2N 1M 0 after mastectomy, establish a nomogram prediction model, perform risk stratification, and screen the radiotherapy benefit populations. Methods:Clinical data of 936 patients with pT 1-2N 1M 0 breast cancer undergoing mastectomy in the Fourth Hospital of Hebei Medical University from January 2010 to December 2016 were retrospectively analyzed and 908 cases had complete follow-up data. They were divided into the radiotherapy (RT) group ( n=583) and non radiotherapy (NRT) group ( n=325) according to the radiotherapy. After propensity score matching (PSM) was performed 1 vs. 1, 298 cases were assigned into the RT group and 298 in the NRT group. Overall survival (OS) and disease-free survival (DFS) were compared between two groups using log-rank test. Nomogram prediction model was established, the survival differences were compared among different risk groups, and the radiotherapy benefit populations were screened. Results:Univariate analysis showed that the 5- and 8-year OS and DFS in the RT group were significantly better than those in the NRT group (both P<0.001). Multivariate analysis showed that age, tumor quadrant, number of lymph node metastases, T staging, and Ki-67 level were the independent prognostic factors for OS. Age, tumor quadrant, and T staging were the independent prognostic factors for DFS. The OS nomogram analysis showed that the OS of patients in the high-risk group was significantly improved by post-mastectomy radiotherapy (PMRT) ( P=0.001), while PMRT did not show an advantage in the low- and medium-risk groups ( P=0.057, P=0.099). The DFS nomogram analysis showed that DFS was significantly improved by PMRT in patients in the medium- and high-risk groups ( P=0.036, P=0.001), whereas the benefits from PMRT were not significant in the low-risk group ( P=0.475). Conclusions:For patients with pT 1-2N 1M 0 breast cancer after mastectomy, age ≤ 40 years, tumor located in the inner quadrant or central area, T 2 staging, 2-3 lymph node metastases, Ki-67>30% are the high-risk factors affecting clinical prognosis. The nomogram prediction model can screen the populations that can benefit from PMRT, providing reference for clinical decision-making.

Objective:To investigate the predictive value of myoglobin (Mb) for the prognosis of sepsis related chronic critical illness (CCI).Methods:Retrospective study was conducted on septic patients with the length of ICU stay equal or greater than 14 days, and sepsis-related organ failure assessment (SOFA) score equal or greater than 2 on the 14th day in ICU in the First Department of Critical Care Medicine at the First Affiliated Hospital of Sun Yat-sen University from January 2017 to March 2020. Patients′ clinical and laboratory data were collected on the 1st and 14th day in ICU. The survival on day 28 in ICU was recorded. According to the myoglobin levels on day 1 and day 14, all subjects were divided into myoglobin elevation group and decline group. Kaplan-Meier survival curve was used to compare the cumulative survival rate at day 28. Cox regression analysis was used to analyze the independent risk factors of mortality. Receiver operating characteristic (ROC) curve was used to analyze the prognostic value of myoglobin.Results:A total of 131 patients with sepsis related CCI were recruited, including 58 patients in the elevation group and 73 in the decline group. The Mb level in elevation group on day 1 was significantly lower than that in decline group [172.40(59.99, 430.53) μg/L vs. 413.60(184.40, 1 328.50) μg/L, Z=3.749, P=0.000], and the Mb level on day 14 was the opposite change in two groups [483.65(230.38, 1 471.75)μg/L in elevation group vs. 132.20(76.86, 274.35)μg/L in decline group, Z=5.595, P=0.000]. Kaplan-Meier survival curve analysis showed that the 28-day cumulative survival rate of the elevation group was significantly lower than that of decline group (χ2=7.051, P=0.008). Cox ratio regression analysis suggested that elevated myoglobin was an independent risk factor for 28-day mortality in septic patients with CCI ( OR=2.534, 95% CI 1.212-5.295, P=0.013). ROC curve analysis suggested that the sensitivity of myoglobin elevation in predicting mortality related to CCI within 28 days was 64.5%, and the specificity was 32.0% with area under the curve(AUC) 0.661(95% CI 0.550-0.773, P=0.007) and Jorden Index was 0.325. Conclusion:Elevated myoglobin, an independent risk factor for mortality within 28 days in ICU, can predict the prognosis of sepsis related chronic critical illness.