ObjectiveTo explore the effect of serum containing Zhenwutang on myocardial mast cell apoptosis induced by angiotensin Ⅱ （AngⅡ） and the mechanism of the correlation between apoptosis and mitochondrial autophagy. MethodsIn this experiment， AngⅡ and serum containing Zhenwutang with different concentrations were used to interfere with H9C2 cardiomyocytes for 24 h， and the survival rate of H9C2 cardiomyocytes was detected by cell counting kit-8 （CCK-8） to screen the optimal concentration for the experiment. Enzyme-linked immunosorbent assay （ELISA） was used to detect the content of B-type natriuretic peptide （BNP） in cell culture supernatant， and immunofluorescence was used to detect the cell surface area to verify the construction of the myocardial mast cell model. Subsequently， the experiment was divided into a blank group （20% blank serum）， a model group （20% blank serum + 5×10^-5 mol·L^-1 AngⅡ）， low-， medium-， and high-dose （5%， 10% and 20%） serum containing Zhenwutang groups， an autophagy inhibitor group （1×10^-4 mol·L^-1 3-MA）， and autophagy inducer group （1×10^-7 mol·L^-1 rapamycin）. The apoptosis level of H9C2 cells and the changes of mitochondrial membrane potential were detected by flow cytometry. The lysosomal probe （Lyso Tracker） and mitochondrial probe （Mito Tracker） co-localization was employed to detect autophagy. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect Caspase-3， Caspase-9， B-cell lymphoma 2 （Bcl-2）， Bcl-2-related X protein （Bax）， and cytochrome C （Cyt C） in apoptosis-related pathways and the relative mRNA expression of ubiquitin ligase （Parkin）， phosphatase and tensin homolog （PTEN）-induced kinase 1 （PINK1）， and p62 protein in mitochondrial autophagy-related pathways. Western blot was used to detect cleaved Caspase-3， cleaved Caspase-9， Bax， Bcl-2， and Cyt C in apoptosis-related pathways， phosphorylated ubiquitin ligase （p-Parkin）， phosphorylated PTEN-induced kinase 1 （p-PINK1）， p62， and Bcl-2 homology domain protein Beclin1 in mitochondrial autophagy-related pathways， and the change of microtubule-associated protein 1 light chain 3 （LC3） Ⅱ/Ⅰ ratio. ResultsCCK-8 showed that when the concentration of AngⅡ was 5×10^-5 mol·L^-1， the cell activity was the lowest， and there was no cytotoxicity. At this concentration， the surface area of cardiomyocytes was significantly increased （P<0.01）， and the content of BNP in the supernatant of culture medium was significantly increased （P<0.05）. Therefore， AngⅡ with a concentration of 5×10^-5 mol·L^-1 was selected for the subsequent modeling of myocardial mast cells. Compared with the blank group， the model group and the autophagy inhibitor 3-MA group had a significantly increased apoptosis rate （P<0.01） and significantly decreased mitochondrial membrane potential （P<0.01）. The results of immunofluorescence co-localization showed that compared with the blank group， the model group had a significantly decreased number of red and green fluorescence spots. The results of Real-time PCR showed that compared with that in the blank group， the relative mRNA expression of Bax， Caspase-3， Caspase-9， Cyt C， and p62 in the model group was significantly up-regulated （P<0.01）， while the relative mRNA expression of Bcl-2， Parkin， and PINK1 was significantly down-regulated （P<0.01）. In addition， the relative protein expression of Bax， cleaved Caspase-3， cleaved Caspase-9， Cyt C， and p62 was significantly up-regulated （P<0.01）. The LC3Ⅱ/Ⅰ was significantly decreased， and the relative protein expression of Bcl-2， p-Parkin， p-PINK1， and Beclin1 was significantly down-regulated （P<0.01）. Compared with the model group， the serum containing Zhenwutang groups and the autophagy inducer group had significantly decreased apoptosis rate （P<0.01）， and the decrease ratio of mitochondrial membrane potential is significantly lowered （P<0.01） in a dose-dependent manner. Additionally， both red and green fluorescence spots became more in these groups. In the 3-MA group， the number of red and green fluorescence spots decreased significantly. The relative mRNA expression of Bax， Caspase-3， Caspase-9， Cyt C， and p62 was significantly down-regulated （P<0.05， P<0.01）， while that of Bcl-2， Parkin， and PINK1 was significantly up-regulated （P<0.01）. In the serum containing Zhenwutang groups， the relative protein expression levels of Bax， cleaved Caspase-3， cleaved Caspase-9， Cyt C， and p62 were significantly down-regulated （P<0.05，P<0.01）. The LC3Ⅱ/Ⅰ was significantly increased， and the relative protein expression levels of Bcl-2， p-Parkin， p-PINK1， and Beclin1 were significantly up-regulated （P<0.01）. ConclusionThe serum containing Zhenwutang can reduce the apoptosis of myocardial mast cells and increase mitochondrial autophagy. This is related to the inhibition of intracellular Bax/Bcl-2/Caspase-3 apoptosis pathway and regulation of Parkin/PINK1 mitochondrial autophagy pathway.

Refeeding syndrome(RFS)has a high incidence among critically ill patients and significantly impacts the re-covery and prognosis of the patients.In this paper,we reviewed the literature on the risk factors and risk prediction models for RFS,finding the risk factors of RFS included patient-related,treatment-related factors and disease-related factors and the risk prediction models encompassed risk stratification model,risk score models and the Logistic regression models.It was concluded from the review that early assessment was crucial to preventing the occurrence of RFS.However,there was still a lack of reliable RFS risk prediction models with good predictive performance.It was found as well that it was crucial for the prevention of RFS to attach importance to nutritional and serological indicators and other factors.It was expected to be a necessity to conduct prospec-tive and multicenter studies to develop a risk prediction model for predicting RFS for ICU patients.Our review provides a refer-ence for early assessment and intervention for critically ill patients with RFS.

The traditional Chinese medicine （TCM） in pediatric care has a long history，proven efficacy，and distinctive characteristics.The China Association of Chinese Medicine has organized a series of youth salons to discuss the clinical advantages of treating diseases.Experts at this seminar proposed that the superior disease categories in pediatric TCM are significant for showcasing the unique strengths and advantages of TCM in the treatment of pediatric diseases，enhancing diagnostic and treatment levels，inheriting TCM knowledge，promoting the integration of TCM and Western medicine，and meeting patients' needs.The strengths of pediatric TCM are summed up as "having what others do not，excelling at what others have，being special in what others excel at，and ensuring safety in what others specialize in." The scope of superiority in pediatric TCM covers multiple systems，including respiratory，digestive，endocrine，psychological，and dermatological systems.This article summarized the advantages of TCM in treating 13 diseases discussed in the salon，such as upper respiratory tract infections，coughs，pneumonia，allergic rhinitis，bronchial asthma，atopic dermatitis，functional dyspepsia，functional constipation，enuresis，marginal short stature，simple obesity，attention deficit hyperactivity disorder，and tic disorders.The overall advantages were reflected in three aspects：First，the holistic concept and treatment based on syndrome differentiation in TCM highlight the advantage of treating the root causes of diseases，making the treatment methodical and precise.Second，most traditional Chinese herbs are natural and have strong safety profiles.Third，TCM treatment methods are abundant，especially the external treatment methods，which are widely used in pediatrics，highly accepted by parents，and have definite efficacy，as well as good safety and compliance.

ObjectiveTo observe the effect of natural moxibustion at "Feishu （BL 13）" on immune balance of T helper cell 17 （Th17） / regulatory T cell （Treg） in healthy rats. MethodsForty-eight rats were randomly divided into 10 rats in the sham moxibustion group and 38 rats in natural moxibustion group. The rats in the sham moxibustion group applied blank acupoint stickers to bilateral "Feishu （BL 13）"， and the rats in natural moxibustion group applied acupoint stickers filled with Compound Banmao Ointment （复方斑蝥膏） to bilateral "Feishu （BL 13）" for a period of 8 h. Thirty rats in natural moxibustion group were successfully blistered after 8 h， and then were randomly divided into 1-day， 3-day and 7-day groups with 10 rats in each group. The general condition of rats was recorded during the experiment； different time groups of natural moxibustion were sampled at the corresponding time， and HE staining was used to observe the pathological changes of the skin in the area of application； flow cytometry was used to detect the subpopulations of Th17 and Treg in peripheral blood， and the value of Th17/Treg was calculated； and ELISA was used to detect the serum interleukin 17A （IL-17A） and interleukin 6 （IL-6）， interleukin 10 （IL-10） levels. ResultsCompared with sham moxibustion group， blisters can be seen in the application area of rats in 1-day natural moxibustion group， and the rats often scratched the skin of the moxibustion area， which showed loose stratum corneum， thickening of the stratum spinosum and stratum granulosum， absence of cells in the basal layer， inflammatory cell infiltration， and elevation of Treg in peripheral blood， and serum IL-17A， IL-6； in 3-day natural moxibustion group， the moxibustion area of the rats was scabbed and partially detached， with the most obvious dermatopathological changes， and elevated peripheral blood Th17 and Treg， and serum IL-17A， IL-6， IL-10； in 7-day natural moxibustion group， skin damage and pathological changes in the area of moxibustion were basically restored； Th17/Treg values were reduced in 1-， 3- and 7-day moxibustion groups after blistering （P＜0.05 or P＜0.01）. Compared with the 1-day moxibustion group， peripheral blood Th17， Treg， and serum IL-17A elevated in the 3-day moxibustion group； peripheral blood Treg， serum IL-17A， and IL-6 decreased， and Th17/Treg values elevated in the 7-day moxibustion group （P＜0.05 or P＜0.01）. Compared with the 3-day moxibustion group， the 7-day moxibustion group had lower peripheral blood Th17 and Treg， serum IL-17A， IL-6， and IL-10， and higher Th17/Treg values （P＜0.05 or P＜0.01）. ConclusionNatural moxibustion at "Feishu （BL 13）" can shift the Th17/Treg balance towards Treg of healthy rats， which will gradually lead to immune homeostasis， and regulate the relevant inflammatory factors in the serum to prevent inflammation from occurring and developing.

Objective:To establish a method for the determination of eight N-nitrosamines (N-nitrosodimethylamine, N-nitrosodimethylamine, N-nitrosomethylmethylamine, N-nitrosodibutylamine, N-nitrosopropylamine, N-nitrosomorpholine, N-nitrosodianiline and N-nitrosopiperidine) in the air of workplace by gas chromatography-tandem mass spectrometry (GC-MS/MS) .Methods:From January to August 2023, eight N-nitrosamines in the air of workplace were collected by ThermoSorb/N column, eluted with 4 ml methanol-dichloromethane (1∶1 volume ratio), separated by VF-624 ms capillary column, detected by multiple reaction monitoring mode and quantified by external standard method. The detection limit and precision of the method were also analyzed.Results:The linear range of the method for the determination of eight N-nitrosamines was 1.0-20.0 μg/L, the correlation coefficient was 0.9993-0.9999, the detection limit was 0.051-0.132 μg/L, and the minimum quantitative concentration was 0.030-0.078 μg/m 3 (calculated by collecting 22.5 L of air sample and eluting with 4.0 ml stripping liquid). The within-run precisions were 2.05%-6.89% and the between-run precisions were 2.41%-8.26%. The desorption rates were 67.20%-102.60%. The sample can be kept at least 7 days at 4 ℃. Conclusion:GC-MS/MS method for the determination of eight N-nitrosamines in workplace air has high sensitivity and good precision, and can accurately determine the content of eight N-nitrosamines in workplace air.

Objective:To establish a method for the determination of eight N-nitrosamines (N-nitrosodimethylamine, N-nitrosodimethylamine, N-nitrosomethylmethylamine, N-nitrosodibutylamine, N-nitrosopropylamine, N-nitrosomorpholine, N-nitrosodianiline and N-nitrosopiperidine) in the air of workplace by gas chromatography-tandem mass spectrometry (GC-MS/MS) .Methods:From January to August 2023, eight N-nitrosamines in the air of workplace were collected by ThermoSorb/N column, eluted with 4 ml methanol-dichloromethane (1∶1 volume ratio), separated by VF-624 ms capillary column, detected by multiple reaction monitoring mode and quantified by external standard method. The detection limit and precision of the method were also analyzed.Results:The linear range of the method for the determination of eight N-nitrosamines was 1.0-20.0 μg/L, the correlation coefficient was 0.9993-0.9999, the detection limit was 0.051-0.132 μg/L, and the minimum quantitative concentration was 0.030-0.078 μg/m 3 (calculated by collecting 22.5 L of air sample and eluting with 4.0 ml stripping liquid). The within-run precisions were 2.05%-6.89% and the between-run precisions were 2.41%-8.26%. The desorption rates were 67.20%-102.60%. The sample can be kept at least 7 days at 4 ℃. Conclusion:GC-MS/MS method for the determination of eight N-nitrosamines in workplace air has high sensitivity and good precision, and can accurately determine the content of eight N-nitrosamines in workplace air.

Objective:To explore the impact of multimorbidity on disability in older adults, providing a reference for formulating strategies for the management and nursing of multimorbidity and disability in older adults.Methods:Adopting the method of cross-sectional survey research, the data of 6 469 older adults (≥60 years old) were collected from the 2018 Chinese Longitudinal Healthy Longevity Survey database in July 2023, including basic information, chronic disease prevalence, and disability measured by basic activities of daily living (BADL), and instrumental activities of daily living (IADL). They were divided into multimorbidity and non-multimorbidity groups based on whether they had two or more chronic diseases. The propensity score matching (PSM) method was used to match the basic conditions of the two groups of older adults with the proportion of 1∶1. Binary logistic regression was applied to analyze the effects of multimorbidity on BADL disability and IADL disability.Results:Among 6 469 older adults, there were 2 882 males and 3 582 females, with 3 158 aged 60-84 years old and 3 311 aged over 84 years old. BADL disability accounted for 26.5% (1 712/6 469), while IADL disability accounted for 66.8% (4 324/6 469). There were 2 335 patients in the multimorbidity group and 4 134 patients in the non-multimorbidity group. Binary Logistic regression analysis showed that the risk of BADL disability in older adults in multimorbidity group was 1.511 times higher than that in the non-multimorbidity group (95% CI 1.317-1.734, P<0.01); the risk of IADL disability in older adults in the multimorbidity group was 1.618 times higher than that in the non-multimorbidity group (95% CI 1.426-1.835, P<0.01). Conclusions:Multimorbidity would increase the risk of disability in older adults. Relevant authorities should develop relevant interventions and nursing responses to enhance the prevention and management of multimorbidity and disability in older adults.

TGF-β1 is considered a key mediator in the formation of hepatic fibrosis and mainly acts by activating the downstream Smad signaling pathway.Smad2 and Smad3 are two major downstream regulators that promote TGF-β1-mediated tissue fibrosis,while Smad7 is a negative-feedback regulator of the TGF-β1/Smad pathway and inhibits TGF-β1-mediated hepatic fibrosis.A growing number of studies are showing that natural products can delay the progression of hepatic fibrosis by regulating the TGF-β1/Smad pathway,inhibiting HSC activation,and reducing ECM deposition.This article reviews the molecular mechanism of the TGF-β1/Smad signaling pathway in hepatic fibrosis,and summarizes the natural products that target the regulation of this pathway,providing a reference for research into the treatment of hepatic fibrosis.

Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC₅₀ values and achieved picomolar DC₅₀ values and >99% of maximum degradation (D_max) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-MET^Y1230H and c-MET^D1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.

Objective:To observe any effect of virtual reality (VR) training on the cognitive functioning and functional fitness of nursing home residents with subjective cognitive decline (SCD).Methods:Fifty-six of such residents were randomly divided into an observation group and a control group, each of 28. Both groups received health education and routine care, but the observation group was additionally provided with 45 minutes of VR training three times a week for 6 months. The training included Baduanjin, magic, flying bird, supermarket shopping, gravity ball and gym episodes. Both groups′ cognition was evaluated using the subjective cognitive decline questionnaire (SCD-Q), the Montreal cognitive assessment (MoCA), the Rivermead Behavioural Memory Test (second edition) (RBMT-Ⅱ), a digit symbol substitution test (DSST), an animal fluency test (AFT) and trail-making test A-B (TMT A-B). Functional fitness was quantified using the 8-foot up-and-go test (8UGT), a 30-second arm curl test (30sACT), a 30-second chair stand test (30sCST), a back scratching test (BST), the sit-and-reach test (CSRT) and a 2-minute step test (2MST) before and after the 6-month intervention.Results:After the intervention, the average SCD-Q, MoCA, RBMT-Ⅱ, DSST, TMT-A, and TMT-B scores of the observation group were significantly better than before the intervention, and significantly better than the control group′s averages. And except for the back scratching their functional results were also significantly better, on average, than those of the control group.Conclusions:VR training can effectively improve the cognition and functional fitness of nur-sing home residents with SCD. Such training is worthy of promotion and wider application in nursing homes.