Objective To systematically analyze the disease burden, long-term trends, and age-sex distribution of major valvular heart disease (VHD) subtypes—rheumatic heart disease (RHD), non-rheumatic valvular disease (NRVD), and non-rheumatic calcific aortic valve disease (CAVD)—in global, Chinese, and US populations from 1990 to 2021, providing evidence for public health strategies and clinical resource allocation. Methods Based on publicly available data from the Global Burden of Disease (GBD) Study 2021, we extracted incidence, mortality, and disability-adjusted life years (DALYs) for VHD from 1990 to 2021. Age-standardized rates (ASRs) were calculated using the GBD 2021 global standard population, and the estimated annual percentage change (EAPC) with its 95% uncertainty interval (UI) was computed for the period. Data from the Agency for Healthcare Research and Quality (AHRQ), the European Society of Cardiology (ESC)/Eurostat surveys, and Chinese national registries were used for trend triangulation and contextual background. Results From 1990 to 2021, the ASR and disease burden of RHD significantly decreased globally and in China (EAPC for DALYs in China: −4.8%, 95%UI: −5.0% to −4.6%). In contrast, the burden of NRVD and CAVD steadily increased in aging populations like those in China and the US, with a higher burden observed in older adults and males. In 2021, the incidence of NRVD and CAVD peaked in individuals aged ≥65 years, with rates being significantly higher in men than in women. RHD burden was concentrated in low socio-demographic index (SDI) regions, whereas NRVD/CAVD burden was strongly associated with high-SDI regions. Conclusion The global VHD epidemiological landscape is transitioning from an RHD-dominant to an NRVD/CAVD-dominant pattern. China faces a dual challenge of a residual RHD burden and a rapidly growing burden of degenerative valvular diseases. Developing tailored screening, prevention, and treatment strategies for different disease subtypes and populations is crucial.

OBJECTIVE: To characterize a glycosyltransferase (RpUGT1) from Rheum palmatum and investigate its specificity toward flavonoid compounds. METHODS: The RpUGT1 was expressed in Escherichia coli and screened for catalytic activity against a range of flavonoid substrates using a high-throughput HPLC assay method. Mass spectrometry (MS) and nuclear magnetic resonance (NMR) were used to determine the structure of the product. Homology modeling, molecular docking analyses and site-directed mutagenesis studies were conducted to identify key residues responsible for its function. RESULTS: The recombinant RpUGT1 protein exhibited catalytic activity towards various flavonoids. Notably, RpUGT1 catalyzed the glycosylation of isorhamnetin to form 3-O-glucoside and kaempferol to form 7-O-glucoside, utilizing uridine diphosphate (UDP) glucose as the sugar donor. The homology modeling and molecular docking analyses identified key residues responsible for its activity. Subsequent site-directed mutagenesis studies highlighted the crucial role of K307 in catalysis. CONCLUSION These discoveries offer valuable perspectives on the role of the UGT family and establish a groundwork for forthcoming research on the synthesis of flavonoids in plants.

Objective To investigate the correlation between the clinical characteristics of allergic rhinitis(AR)in adults located in Shenzhen area and the traditional Chinese medicine(TCM)constitutions.Methods A cross-sectional survey of adult AR patients in Shenzhen was conducted.From June 2022 to December 2023,adult AR patients admitted to the Department of Otolaryngology outpatient clinic of Bao'an Traditional Chinese Medicine Hospital Affiliated to Guangzhou University of Chinese Medicine(Shenzhen Bao'an District Hospital of Traditional Chinese Medicine)were selected as the study subjects.The clinical baseline data,Total Nasal Symptoms Score(TNSS),and Total Non-Nasal Symptoms Score(TNNSS)of the patients were collected for the analysis of clinical characteristics,and TCM constitutions were differentiated based on the information collected by TCM constitutions questionnaire.After that,the correlation between the biased TCM constitutions and clinical characteristics were explored by using analysis of variance,non-parametric test and Logistic regression analysis.Results(1)A total of 215 cases of adult AR patients from Shenzhen were included.Most of the patients were male(60.93％),and the patients were usually aged 18-29 years old(accounting for 48.84％).AR in adults often arose in the spring(33.49％)and fall(30.70％).(2)Lung qi deficiency-cold syndrome was the predominated TCM syndrome type of AR in adults,accounting for 40.93％,and then came kidney yang deficiency syndrome(26.98％),spleen qi deficiency syndrome(20.00％),and heat accumulation in lung meridian syndrome(12.09％).Lung qi deficiency-cold syndrome and heat accumulation in lung meridian syndrome were more common in young males,and kidney yang deficiency syndrome was frequently seen in middle-aged and elderly males.(3)The leading three TCM constitution types of AR in adults were qi deficiency constitution(30.23％),yang deficiency constitution(24.65％),and inherited special constitution(15.81％).In adult AR patients with lung qi deficiency-cold syndrome,the commonly-seen TCM constitution types were qi deficiency constitution,inherited special constitution,and balanced constitution.In adult AR patients with spleen qi deficiency syndrome,the commonly-seen TCM constitution types were inherited special constitution,phlegm-damp constitution,and yang deficiency constitution.In adult AR patients with kidney yang deficiency syndrome,the commonly-seen TCM constitution types were yang deficiency constitution,qi stagnation constitution,and inherited special constitution.In adult AR patients with heat accumulation in lung meridian syndrome,the commonly-seen TCM constitution types were damp-heat constitution,yin deficiency constitution,and blood-stasis constitution.The leading five TNSS scores were shown in adult AR patients with inherited special constitution,qi deficiency constitution,yang deficiency constitution,phlegm-damp constitution,and qi stagnation constitution,respectively.And the leading five TNNSS scores were shown in adult AR patients with yang deficiency constitution,inherited special constitution,qi stagnation constitution,yin deficiency constitution,and damp-heat constitution,respectively.(4)The results of statistical analysis showed that the differences in gender among the adult AR patients with various TCM constitution types were not statistically significant(P＞0.05),but the differences in age groups,TCM syndrome types,TNSS scores and TNNSS scores were statistically significant(P＜0.01 or P＜0.001).(5)The results of Logistic regression analysis showed that the TNSS scores and TNNSS scores were all positively correlated with qi deficiency constitution,yang deficiency constitution,and inherited special constitution,and spleen qi deficiency syndrome was negatively correlated with damp-heat constitution,the differences being all statistically significant(P＜0.01 or P＜0.001).Conclusion The onset of AR in adults from Shenzhen area is closely related to age,gender,season,and TCM constitutions.The adult AR patients usually have the biased constitutions,in particular qi deficiency constitution,yang deficiency constitution,and inherited special constitution.In adult AR patients,higher TNSS scores are correlated with inherited special constitution,higher TNNSS scores are correlated with yang deficiency constitution,and the primary TCM syndrome type of lung qi deficiency-cold syndrome is correlated with qi deficiency constitution.

Objective To investigate the therapeutic effects and mechanisms of Aurantii Fructus Immaturus(AFI)on slow-transit constipation(STC)in mice.Methods A STC model was established via intragastric administration of Loperamide Hydrochloride.Successfully modeled mice were randomized into a model group,low-and high-dose AFI groups,a high-dose AFI+Masitinib[tyrosine kinase(c-Kit)inhibitor]group,additionally,a normal group was set up.After intervention,intestinal transit rate,6-hour fecal pellet number,fecal water content,and colonic histomorphology(hematoxylin-eosin staining)were assessed.Enzyme-linked immunosorbent assay(ELISA)was used to measure levels of 5-hydroxytryptamine(5-HT),vasoactive intestinal polypeptide(VIP),substance P(SP),nitric oxide(NO),and nitric oxide synthase(NOS)activity in colon tissue.Quantitative real-time PCR(qRT-PCR)was used to evaluate mRNA expression of stem cell factor(SCF)and c-Kit in colon tissue,Western Blot was used to analyze relative protein expression of aquaporin 3(AQP3),aquaporin 8(AQP8),SCF,and c-Kit in colon tissue.Results Compared with the normal group,there was devere colonic damage observed in the colon tissue of the mice in the model group,the fecal pellet number,fecal water content,intestinal transit rate,colon tissue SP content,c-Kit and SCF gene and protein expression levels were reduced.The contents of 5-HT,VIP and NO,NOS activity and the protein expression levels of AQP3 and AQP8 in colon tissue were increased,and the differences were statistically significant(P＜0.05).Compared with the model group,the colonic injury of mice in the low-and high-does AFI groups showed obvious improvement,the fecal pellet number,fecal water content,intestinal transit rate,colon tissue SP content,c-Kit and SCF gene and protein expression levels were increased,the contents of 5-HT,VIP and NO,NOS activity and the protein expression levels of AQP3 and AQP8 in colon tissue were decreased(P＜0.05).Masitinib partially reversed the laxative effects of AFI(P＜0.05).Conclusion AFI enhances intestinal motility,alleviates colonic injury,and improves defecation in STC mice,potentially via activation of the SCF/c-Kit pathway.

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues. Magnesium has been proved to promote bone healing under normal conditions. Here, we elucidate the mechanism by which Mg²⁺ promotes angiogenesis and osseointegration in diabetic status. We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised, with significantly decreased angiogenesis. We then developed Mg-coating implants with hydrothermal synthesis. These implants successfully improved the vascularization and osseointegration in diabetic status. Mechanically, Mg²⁺ promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells, thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia. Altogether, our data suggested that Mg²⁺ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.
Mice ; Animals ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Magnesium/metabolism* ; Osseointegration ; Diabetes Mellitus, Experimental/metabolism* ; Endothelial Cells/metabolism* ; NF-E2-Related Factor 2/metabolism*

ObjectiveThe lung mesenchymal stem cells （LMSCs） induced by D-galactose （D-gal） were intervened by Wenfei Huaxian decoction-containing serum to explore the mechanism of Wenfei Huaxian decoction in delaying the senescence of LMSCs through the nicotinamide phosphoribosyltransferase/silent information regulator 1 （NAMPT/SIRT1） signaling pathway. MethodWenfei Huaxian decoction-containing serum was prepared. LMSCs were isolated by gradient density centrifugation， and they were cultured and identified in vitro. The senescence model in vitro was established by stimulating cells via D-gal for 24 h. LMSCs cells were modeled after being treated with different volume fractions （5%， 10%， 20%， 40%， and 80%） of Wenfei Huaxian decoction-containing serum for 24 h， and the cell proliferation level was detected by methyl thiazolyl tetrazolium （MTT） method. The cells were randomly divided into blank serum group， model group， and high， medium， and low dose groups of Wenfei Huaxian decoction-containing serum. Senescence-associated β-galactosidase （SA-β-gal） staining was used to detect the senescence of LMSCs in each group. The content of NAD + was detected by colorimetry. The levels of senescence-associated factors （p16 and p53）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in cell culture supernatant were detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the relative expression of senescence-associated proteins and NAMPT/SIRT1 signaling pathway-related proteins. ResultCompared with the blank serum group， the proliferation of LMSCs was significantly inhibited after D-gal stimulation for 24 h （P<0.01）. Compared with the model group， the proliferation of LMSCs could be promoted after intervention with the corresponding Wenfei Huaxian decoction-containing serum （P<0.05， P<0.01）. Compared with the blank serum group， the SA-β-gal staining of LMSCs in the model group after D-gal stimulation was enhanced， and the content of NAD⁺ was increased （P<0.01）. The expression levels of senescence factors p16 and p53， as well as SASP pro-inflammatory factors IL-6 and TNF-α in the cell culture supernatant， were significantly increased （P<0.01）. The expression of senescence-associated proteins p16， p21， and p53 increased （P<0.01）， and the protein expression of NAMPT， SIRT1， peroxisome proliferator-activated receptor γ coactivator 1α （PGC-1α）， and forkhead box family transcription factor O1 （FoxO1） decreased （P<0.01）. Compared with the model group， the SA-β-gal staining of LMSCs in each group of Wenfei Huaxian decoction-containing serum was significantly reduced， and the content of NAD⁺ was decreased （P<0.01）. The senescence factors （p16 and p53） and inflammatory factors （IL-6 and TNF-α） in the cell culture supernatant were significantly decreased （P<0.01）. The expression of senescence-associated proteins （P16， P21， and P53） decreased （P<0.05， P<0.01）. The protein expressions of NAMPT， SIRT1， PGC-1α， and FoxO1 were significantly up-regulated （P<0.05， P<0.01）. ConclusionWenfei Huaxian decoction can alleviate senescence and inflammatory response damage of D-gal-induced LMSCs， and its mechanism may be related to the regulation of the NAMPT/SIRT1 signaling pathway.

Objective To analyze and discuss the current research status,hotspots,frontiers,and progress in work practice of family pharmacists both in domestic and abroad by Citespace.Methods The database of Web of Science Core Collection and CNKI were selected for data extraction.They searched for literature from the database from establishment to April 1,2023 using the topic words"family pharmacist"and"home pharmaceutical care"both in Chinese and English.The network diagrams of essential nodes such as authors,countries,institutions,and key words were analyzed and drawn Results A total of 439 Chinese and 572 English literatures were included in the study.Scholars such as Mei Shen,Shihui Bao,Zhongzhuang Wang,Hughes Carmel M,Jamieson Hamish A,and Chen Timothy F have significantly contributed.The UK and the United States were leading countries in family pharmacists.Most of China's top ten research institutions were from Shanghai,Beijing.The top five Chinese literature keywords were pharmaceutical care,community,pharmacist,rational drug use,family pharmacist.The top five English literature keywords were pharmaceutical care,care,management,older people,and impact.Conclusions According to keyword clustering and burst analysis,research hotspots in foreign countries mainly focus on pharmaceutical services,adverse drug reactions,adherence,etc.,which is consistent with the development direction of pharmaceutical services in China.However,domestic pharmacy's development and literature publication are slightly behind those of foreign countries,and there is still some development space for pharmaceutical services in China.

Objective:To explore the clinical phenotype and genetic etiology of a child with Developmental epileptic encephalopathy type 104 (DEE 104).Methods:A child who had presented at the Children′s Medical Center of the Affiliated Hospital of Guangdong Medical University in February 2021 for recurrent seizures over 1 month was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Results:The child, a five-month-old male, had presented with frequent focal seizures with severe developmental retardation from infancy. Physical examination showed emaciation, microcephaly, oblique palpebral fissures, Stahl′s ears, and hypotonia in the limbs. Electroencephalogram revealed multi-focal sharp waves, slow waves and slow spinal waves. Cranial magnetic resonance imaging revealed enlargement of bilateral lateral ventricles and the third ventricle, along with widening of brain sulci, fissure and cisterna. WES revealed that he had harbored a heterozygous c. 2401C>T (p.His801Tyr) missense variant of the ATP6V0A1 gene. Sanger sequencing showed that both of his parents were of the wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS2+ PM2_Supporting+ PP3). The proband was diagnosed with DEE 104. Early treatment with sodium valproate has failed, but the child had become seizure free after the addition of levetiracetam and topiramate. He still had abnormal EEG discharges and severe psychomotor retardation. Combining our case and a review of literature, DEE104 is mainly caused by de novo heterozygous variants of the ATP6V0A1 gene with an autosomal dominant inheritance. The patients may show refractory epilepsy and severe global developmental delay from infancy. Conclusion:The c. 2401C>T (p.His801Tyr) variant probably underlay the DEE104 in this child.

ObjectiveTo investigate the possible mechanism of Wenfei Huaxian Decoction （温肺化纤汤） in treatment of pulmonary fibrosis in systemic sclerosis-associated interstitial lung disease （SSc-ILD）. MethodsSixty C3H/He female rats were randomly divided into a control group， a model group， a pirfenidone group， and low-， medium-， and high-dose Wenfei Huaxian Decoction groups. The SSc-ILD model mice was established by subcutaneous injection of bleomycin solution 0.04 mg/d into the back of mice for 28 days in all groups but the control group. After successful modelling， the pirfenidone group was given pirfenidone capsule 300 mg/（kg·d） by gavage， the low-， medium- and high-dose Wenfei Huaxian Decoction groups were given Wenfei Huaxian Decoction 7.81， 15.62， and 31.24 g/（kg·d） by gavage， respectively， and the control group as well as the model group were given normal saline 0.1 ml/10 g by gavage， for a total of 21 days. At the end of the intervention， HE staining and Masson staining were used to observe the pathological changes in the skin and lung tissues； the hydroxyproline content of the skin and lung tissues was detected； the protein expression levels of endoplasmic reticulum stress-related proteins glucose-regulated protein 78 （BIP） and C/EBP homologous protein （CHOP） as well as those of nuclear factor kappa B （NF-κB） pathway p65 were measured by western blot； ELISA was performed to determine the expression levels of interferon gamma （IFN-γ）， interleukin 6 （IL-6） and tumour necrosis factor alpha （TNF-α） in serum of rats. ResultsThe results of HE and Masson staining indicated that compared with the control group， the dermis significantly thickened， the number of collagen fibers significantly enlarged， and the number of inflammatory cells significantly increased in the model group； the lung tissue showed a marked inflammatory cellular response with massive collagen fibre proliferation with inflammatory cell infiltration. Compared with the model group， the skin tissue and lung tissue collagen fibre proliferation significantly reduced and inflammatory cell infiltration reduced in the pirfenidone group and all dose groups of Wenfei Huaxian Decoction， and the effects of pirfenidone group and Wenfei Huaxian Decoction medium- and high-dose groups were basically comparable. Compared with the model group， the content of hydroxyproline in skin and lung tissue， the serum level of IFN-γ， IL-6 and TNF-α， and the expression levels of BIP and CHOP protein in lung tissue increased in model group （P＜0.05）. Compared with model group， the content of hydroxyproline in skin tissue of pirfenidone group， low-and medium-dose Wenfei Huaxian Decoction groups decreased， and the content of hydroxyproline in lung tissue of medium-dose Wenfei Huaxian Decoction group decreased. The serum level of IFN-γ， IL-6， TNF-α and the expression levels of BIP， CHOP and p65 protein in lung tissue of rats in pirfenidone group and high-dose Wenfei Huaxian Decoction group decreased （P＜0.05）. The content of hydroxyproline in lung tissue of medium-dose Wenfei Huaxian Decoction group was significantly lower than that of low-dose and high-dose Wenfei Huaxian Decoction group， and the serum level of IFN-γ， IL-6， TNF-α in low- and medium-dose Wenfei Huaxian Decoction group were higher than those in high-dose Wenfei Huaxian Decoction group. The expression level of BIP protein in high-dose group was significantly lower than that in low- and medium-dose Wenfei Huaxian Decoction groups （P＜0.05）. ConclusionWenfei Huaxian Decoction can improve the skin and lung fibrosis of SSc-ILD rats， which may act through anti-inflammation， inhibition of NF-κB pathway， and then inhibition of endoplasmic reticulum stress， which ultimately blocked the fibrotic process.

Objective To evaluate the effect of driving pressure(DP)-guided individualized positive end-expiratory pressure(PEEP)combined with regular lung recruitment maneuvers(RMs)on atelectasis in elderly patients undergoing laparoscopic surgery in the Trendelenburg position using lung ultrasound.Methods A total of 62 patients aged 65-85 years old and classified by ASA status Ⅰ-Ⅲ undergoing laparoscopic radical resection of colorectal cancer were included and randomly divided into the experimental group(n=31)and the control group(n=31).Both groups received one RM after the beginning of pneumoperitoneum,followed immediately by titration of individualized PEEP with the lowest DP,and both groups received another RM after the end of pneumoperitoneum.The experimental group received additional RM every 30 min from the beginning of pneumoperitoneum,while the control group received no intervention.Recording time points for observation were:before induction of anesthesia(T0),30 min after pneumoperitoneum(T1),90 min after pneumoperitoneum(T2),at the end of surgery(T3)and 45 min after entering the postanesthesia care unit(PACU,T4).Lung ultrasound score(LUS)was recorded at T0,T3 and T4.Dynamic lung compliance(Cdyn)was recorded at T1-T3.Oxygenation index(OI),mean arterial pressure(MAP)and heart rate(HR)were recorded at T0-T4.Hypotension during RM,hypoxic saturation events in PACU and the incidence of pulmonary complications(POPC)within the first 7 days after surgery were recorded.Results Compared with the control group,LUSs at T3 and T4 were significantly decreased in the experimental group(P<0.05),and OI and Cdyn at T2 and T3 were significantly increased(P<0.05).In addition,the incidence of hypoxia saturation events in PACU was lower in the experimental group than that in the control group(P<0.05).There were no significant differences in the incidence of hypotension during lung recruitment and the incidence of POPC within 7 days after surgery between the two groups.Conclusion The individualized PEEP combined with regular RMs can effectively reduce the atelectasis observed by lung ultrasound immediately after laparoscopic radical resection of colorectal cancer and in PACU in elderly patients.