ObjectiveTo explore the differences in the accumulation of secondary metabolites of Dendrobium nobile cultivated on epiphytic stones and trees， so as to elucidate the scientific connotation of "only those that grow on stones has superior quality"， and provide a direction for the cultivation and quality evaluation of D. nobile. MethodsUltra-performance liquid chromatography-triple quadrupole/linear ion trap mass spectrometry（UPLC-QTRAP-MS/MS）-based widely targeted metabolomics was used to detect the metabolites of D. nobile cultivated on epiphytic stones and trees. And the combination of principal component analysis（PCA）， hierarchical cluster analysis（HCA）， and orthogonal partial least squares-discriminant analysis（OPLS-DA） was performed for multivariate statistical analysis of metabolites. Differential metabolites were screened by variable importance in the projection（VIP） value≥1 and log₂fold change（FC）≥1 or ≤-1， and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis was conducted. ResultsA total of 1 267 metabolites were identified in the stems of D. nobile from the two cultivation modes， dominated by flavonoids（292）， phenolic acids（284）， and alkaloids（189）. Through OPLS-DA screening， 473 differential metabolites were obtained. Compared to epiphytic tree-cultivated D. nobile， epiphytic stone-cultivated D. nobile exhibited upregulation of flavonoids， phenolic acids， alkaloids， lignans and coumarins， while quinones and terpenoids were down-regulated. The differential metabolites mainly included flavonoid glycosides and alkaloids， and these differential metabolites significantly contributed to characterizing the two cultivation patterns. KEGG enrichment analysis revealed significant enrichment in pathways of flavone and flavonol biosynthesis， flavonoid biosynthesis， tyrosine metabolism， and phenylalanine metabolism in epiphytic stone-cultivated D. nobile. ConclusionEpiphytic stone cultivation is beneficial for the accumulation of phenolic acids， flavonoids， and alkaloids in D. nobile， indicating that the "only those that grow on stones has superior quality" documented in the materia medica has certain scientific basis， and the findings also provide a reference for quality evaluation and discrimination research between epiphytic stone and tree cultivated D. nobile.

ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design（QbD） and to assess its health risk. MethodsTaking whole iron content， Fe²⁺ dissolution content and looseness as critical quality attributes（CQAs）， and calcination temperature， calcination time， spreading thickness and particle size as critical process parameters（CPPs） determined by the failure mode and effect analysis（FMEA）， the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation（AHP-CRITIC） hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry， and the health risk assessment was carried out by daily exposure（EXP）， target hazard quotient（THQ） and lifetime cancer risk（LCR）， and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃， calcination time of 1 h， particle size of 0.2-0.5 cm， spreading thickness of 1 cm， and vinegar quenching for 1 time［Haematitum-vinegar（10：3）］. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1， while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10^-6-1×10^-4， and the LCR of the rest was<1×10^-6， and the LCRs of calcined Haematitum were all<1×10^-6， indicating that the carcinogenic risk of calcined Haematitum was low， but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg were formulated as 1 014， 25， 17， 27， 7 mg·kg^-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible， and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.

ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design（QbD） and to assess its health risk. MethodsTaking whole iron content， Fe²⁺ dissolution content and looseness as critical quality attributes（CQAs）， and calcination temperature， calcination time， spreading thickness and particle size as critical process parameters（CPPs） determined by the failure mode and effect analysis（FMEA）， the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation（AHP-CRITIC） hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry， and the health risk assessment was carried out by daily exposure（EXP）， target hazard quotient（THQ） and lifetime cancer risk（LCR）， and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃， calcination time of 1 h， particle size of 0.2-0.5 cm， spreading thickness of 1 cm， and vinegar quenching for 1 time［Haematitum-vinegar（10：3）］. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1， while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10^-6-1×10^-4， and the LCR of the rest was<1×10^-6， and the LCRs of calcined Haematitum were all<1×10^-6， indicating that the carcinogenic risk of calcined Haematitum was low， but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg were formulated as 1 014， 25， 17， 27， 7 mg·kg^-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible， and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objective To investigate the therapeutic effect and underlying mechanism of Qishishenshu Capsule on renal fibrosis in mice with early diabetic nephropathy(DN).Methods A DN mouse model was established by multiple injections of streptozotocin.The mice were randomly divided into a normal group(NC),model group(DN),and Qishi group(QS)(0.9 g/(kg·d)),with eight mice in each group.Mice were gavaged continuously for 4 weeks,and fasting blood glucose(FBG)was measured weekly.Four weeks later,urinary albumin/creatinine(UACR),serum creatinine,and blood urea nitrogen were measured.Hematoxylin-eosin,periodicacid-Schiff,and Sirius red staining were used to analyze renal pathological changes.Real-time fluorescence quantitative reverse-transcription polymerase chain reaction was used to detect the mRNA levels of fibronectin(FN),collagen type Ⅰ alpha 1(Col1a1),and α-smooth muscle actin(α-SMA).Immunohistochemistry and Western blot were performed to detect FN,collagen type Ⅰ(Collagen Ⅰ),collagen typeⅢ(Collagen Ⅲ),α-SMA,Podocin,Nephrin,and transforming growth factor-β1/SMAD family member2/3(TGF-β1/Smad2/3)pathway-related proteins.Results Compared with mice in the NC group,those in the DN group showed significantly higher levels of FBG and UACR(P＜0.001),and mesangial hyperplasia,basement membrane thickening,and collagen deposition in the renal tissue.The mRNA levels of FN,Col1a1,and α-SMA were increased(P＜0.05).Protein levels of Podocin and Nephrin were decreased(P＜0.05).The levels of FN,Collagen I,Collagen Ⅲ,α-SMA,and TGF-β1/Smad2/3 pathway proteins were increased(P＜0.05).Compared with the DN group,the QS group's level of UACR was decreased(P＜0.05),their renal pathological injury was alleviated,and mRNA levels of FN,Collagen Ⅰ,andα-SMA were attenuated(P＜0.05);whereas their protein levels of Podocin and Nephrin were elevated(P＜0.05).The levels of FN,Collagen Ⅰ,Collagen Ⅲ,α-SMA,and TGF-β1/Smad2/3 pathway proteins were also decreased(P＜0.05).Conclusions Qishishenshu Capsule improved renal fibrosis in DN mice,probably through the inhibition of the TGF-β1/Smad2/3 signaling pathway.

From November 2020 to November 2021, the TEST(Task-Experience- Supervise-Thinking) teaching model was adopted for general practice residency training in teaching clinic of Changfeng Health Service Center of Shanghai Putuo district. The satisfaction of mentors, residents and patients was surveyed with self-assessment questionnaire. The satisfaction scores of mentors, residents and patients were (79.89±0.40), (79.96±0.19) and (49.92±0.40). The adaption of model TEST in teaching clinic is more effective in training of clinical competency, communication ability, management ability and narrative ability for general practice residents. It is also beneficial for mentors to upgrade their teaching ability, as well as for patients to improve their experience and satisfaction for seeking medical service. It is worth popularizing in the community practice base of general resident training.

Objective:To analyze the status quo and influencing factors of non-alcoholic fatty liver disease in community-dwelling elderly women.Methods:A total of 9 754 female residents aged 60-79 years who attended health check-up in Anting Town Community Health Service Center from June 2019 to December 2021 were enrolled in the study. According to the ultrasound diagnosis, there were 5 220 cases of non-alcoholic fatty liver disease (NAFLD group) and 4 534 cases without NAFLD (non-NAFLD group). The general information, physiological and biochemical indicators were compared between two groups with Mann-Whitney U test and Chi-square test; the influence factors of NAFLD were analyzed with logistic regression. Results:The overall prevalence of NAFLD was 53.52%(5 220/9 754), prevalence in the 65-69 age group was the highest and that in the 75-79 age group was the lowest. Body mass index ( Z=47.667), waist circumference ( Z=45.949), waist-to-hip ratio ( Z=30.805), systolic blood pressure ( Z=7.543), diastolic blood pressure ( Z=7.621), fasting blood glucose ( Z=20.298), glycated hemoglobin ( Z=23.588), alanine aminotransferase ( Z=29.624), aspartate aminotransferase ( Z=7.824), total bilirubin ( Z=4.441), triglyceride ( Z=34.597), low-density lipoprotein cholesterol ( Z=2.476) and blood uric acid ( Z=29.934) levels of NAFLD group were significantly higher than those in non-NAFLD group (all P<0.05); the mean age ( Z=-3.885) and high density lipoprotein cholesterol ( Z=-23.553) in NAFLD group were significantly lower than those in non-NAFLD group (all P<0.001); there were no significant differences in the levels of total cholesterol ( Z=1.762)and creatinine ( Z=1.453) between the two groups (all P>0.05). The proportion of patients had type 2 diabetes mellitus ( χ2=368.395), hypertension ( χ2=208.503), hypertriglyceridemia ( χ2=883.831), hyperuricemia ( χ2=228.562), central obesity ( χ2=1 506.580), high risk of stroke ( χ2=605.322) and high risk of ASCVD ( χ 2=309.434) in NAFLD group were significantly higher than that of non-NAFLD group (all P<0.001). Logistic regression analysis showed that age ( OR=0.937, 95% CI: 0.928-0.946), body mass index ( OR=1.224, 95% CI:1.194-1.255), waist circumference ( OR=1.072, 95% CI: 1.062-1.082), glycosylated hemoglobin ( OR=1.348, 95% CI: 1.275-1.426), alanine aminotransferase ( OR=1.032, 95% CI: 1.026-1.037), triglyceride ( OR=1.757, 95% CI: 1.646-1.875) and serum uric acid ( OR=1.004, 95% CI: 1.004-1.005) levels were the influencing factors for NAFLD in elderly women (all P<0.001). Conclusion:The prevalence rate of non-alcoholic fatty liver disease in the community-dwelling elderly women is high, which are associated with multiple influencing factors.

Objective To comprehensively evaluate the quality of Croci Stigma from different regions by using the entropy weighted TOPSIS,and to provide evidence for the quality evaluation and regions selection of Croci Stigma.Methods The contents of picrocrocin,crocin I,crocin II and crocin III were determined by HPLC wavelength switching method.The total content of four components,loss on drying,total ash,absorbance and extract were chosen as detection indexes for Croci Stigma,and the weight was calculated by entropy weight method,and the indexes were statistically analyzed by TOPSIS method.The quality of Croci Stigma was comprehensively evaluated.Results The analysis results of entropy weighted TOPSIS method showed that the mean values of relative closeness(Ci)values of Croci Stigma from Zhejiang,Tibet,Anhui,Jiangsu provinces and shanghai city were 0.654,0.396,0.426,0.326 and 0.341,respectively.Overall,the quality of Croci Stigma in Zhejiang province was the highest.Conclusion The established entropy weighted TOPSIS method is objective,comprehensive and effective,which can be used for the comprehensive quality evaluation of Croci Stigma.

Hypertension has a high global prevalence rate,which is the main preventable risk factor for cardiovascular disease.Home blood pressure monitoring plays an important role in diagnosis,adjustment of treatment strategies and long-term follow-up of hypertension.However,there are still enormous challenges for the popularization and standardized application of home blood pressure monitoring.Therefore,this review article describes indication,standardized implementation protocol,current status and influencing factors of implementation and management forms of home blood pressure monitoring.It can provide a reference for promoting the implementation of practical guidelines for home blood pressure monitoring and optimizing the application of home blood pressure monitoring.

It is an urgent demand worldwide to control the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The 3-chymotrypsin-like protease (3CL^pro) and papain-like protease (PL^pro) are key targets to discover SARS-CoV-2 inhibitors. After screening 12 Chinese herbal medicines and 125 compounds from licorice, we found that a popular natural product schaftoside inhibited 3CL^pro and PL^pro with IC₅₀ values of 1.73 ± 0.22 and 3.91 ± 0.19 μmol/L, respectively, and inhibited SARS-CoV-2 virus in Vero E6 cells with EC₅₀ of 11.83 ± 3.23 μmol/L. Hydrogen-deuterium exchange mass spectrometry analysis, quantum mechanics/molecular mechanics calculations, together with site-directed mutagenesis indicated the antiviral activities of schaftoside were related with non-covalent interactions with H41, G143 and R188 of 3CL^pro, and K157, E167 and A246 of PL^pro. Moreover, proteomics analysis and cytokine assay revealed that schaftoside also regulated immune response and inflammation of the host cells. The anti-inflammatory activities of schaftoside were confirmed on lipopolysaccharide-induced acute lung injury mice. Schaftoside showed good safety and pharmacokinetic property, and could be a promising drug candidate for the prevention and treatment of COVID-19.