AIM To establish a UPLC-MS/MS method for the simultaneous content determination of ellagic acid,gallic acid,dehydrodiisoeugenol,methyleugenol,agarotetrol,elemicin,chlorogenic acid,geniposide,rutin,ferulic acid,hydroysafflor-yellow A,deoxycholic acid,cholic acid,borneol and taurine in Zhuriheng Dropping Pills.METHODS The analysis of 50%methanol solution of this drug was performed on a 30℃thermostatic Thermo C18 column(2.1 mm×100 mm,1.9 μm),with the mobile phase comprising of acetonitrile-0.1%formic acid(containing 10 mmol/L ammonium acetate)flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning.RESULTS Fifteen constituents showed good linear relationships within their own ranges(R2>0.990 0),whose average recoveries were 75.91%-112.13%with the RSDs of 3.06%-10.66%.CONCLUSION This simple,sensitive and efficient method can be used for the quality control of Zhuriheng Dropping Pills.

Objective: To evaluate the success rate of His-Purkinje system pacing (HPSP) in patients with various sites of atrioventricular block (AVB) and provide clinical evidence for the selection of HPSP in patients with AVB. Methods: This is a retrospective case analysis. 637 patients with AVB who underwent permanent cardiac pacemaker implantation and requiring high proportion of ventricular pacing from March 2016 to September 2021 in the Department of Cardiology, General Hospital of Northern Theater Command were enrolled. The site of AVB was determined by electrophysiological examination. His bundle pacing (HBP) was performed in the first 130 patients (20.4%) who were classified as the HBP group and HPSP included HBP and/or left bundle branch pacing (LBBP) was performed in later 507 patients (79.6%) and these patients were classified as the HPSP group. The basic clinical information such as age and sex of the two groups was compared, and the success rates of HBP or HPSP in patients with different sites of AVB and QRS intervals were analyzed. Results: The age of HBP group was (66.4±15.9) years with 75 males (57.7%). The age of HPSP group was (66.8±13.6) years with 288 (56.8%) males. Among 637 patients, 63.0% (401/637) had atrioventricular node block; 22.9% (146/637) had intra-His block; 14.1% (90/637) had distal or inferior His bundle block. Totally, the success rate of HPSP was higher than that of HBP [93.9% (476/507) vs. 86.9% (113/130), P<0.05]. In each group of patients with various AVB sites, the success rate of HPSP was higher than that of HBP respectively and both success rates of HBP and HPSP showed a declining trend with the distant AVB site. The success rate of HBP in patients with atrioventricular node block and intra-His block was higher than that in patients with distal or inferior His bundle block [95.2% (79/83) vs. 47.1% (8/17), P<0.001; 86.7% (26/30) vs. 47.1% (8/17), P=0.010]. The success rate of HPSP was higher than that of HBP in patients with distal or inferior His bundle block [87.7% (64/73) vs 47.1% (8/17), P=0.001]. In patients with QRS<120 ms, 94.9% (520/548) of AVB sites were in atrioventricular node or intra-His, and HBP had a similar high success rate with HPSP [95.6% (109/114) vs. 96.3% (418/434), P=0.943] in these patients. In patients with QRS ≥ 120 ms, 69.7% (62/89) of AVB sites were at distal or inferior His bundle, and the success rate of HBP was only 25.0% (4/16), while the success rate of HPSP was as high as 79.5% (58/73), P<0.001. Conclusions: In patients with QRS<120 ms and atrioventricular node block or intra-His block, success rates of HBP and HPSP are similarly high and HBP might be considered as the first choice. In patients with QRS ≥ 120 ms and AVB site at distal or inferior His bundle, the success rate of HPSP is higher than that of HBP, suggesting LBBP should be considered as the first-line treatment option.
Aged ; Aged, 80 and over ; Atrioventricular Block/therapy* ; Bundle of His/physiology* ; Cardiac Pacing, Artificial ; Electrocardiography ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

Background/Aims: Obstacles exist in facilitating hepatitis C virus (HCV) care cascade. To increase timely and accurate diagnosis, disease awareness and accessibility, in-hospital HCV reflex testing followed by automatic appointments and a late call-back strategy (R.N.A. model) was applied. We aimed to compare the HCV treatment rate of patients treated with this strategy compared to those without. Methods: One hundred and twenty-five anti-HCV seropositive patients who adopted the R.N.A. model in 2020 and another 1,396 controls treated in 2019 were enrolled to compare the gaps in accurate HCV RNA diagnosis to final treatment allocation. Results: The HCV RNA testing rate was significantly higher in patients who received reflex testing than in those without reflex testing (100% vs. 84.8%, P<0.001). When patients were stratified according to the referring outpatient department, a significant improvement in the HCV RNA testing rate was particularly noted in patients from non-hepatology departments (100% vs. 23.3%, P<0.001). The treatment rate in HCV RNA seropositive patients was 83% (83/100) after the adoption of the R.N.A. model, among whom 96.1% and 73.9% of patients were from the hepatology and non-hepatology departments, respectively. Compared to subjects without R.N.A. model application, a significant improvement in the treatment rate was observed for patients from non-hepatology departments (73.9% vs. 27.8%, P=0.001). The application of the R.N.A. model significantly increased the in-hospital HCV treatment uptake from 6.4% to 73.9% for patients from non-hepatology departments (P<0.001). Conclusions The care cascade increased the treatment uptake and set up a model for enhancing in-hospital HCV elimination.

OBJECTIVETo examine whether transforming growth factor-β (TGF-β) pathway and adaptive T cell immunity play roles in the anti-atherosclerotic effects of pioglitazone (PIO) in ApoEmice.

METHODSApoEmice with atherosclerosis induced by high-fat feeding were treated daily with PIO (20 mg/kg) or vehicle for 8 weeks. The protein expressions of TGF-β pathway in the atheromatous lesions of the aorta and the percentages of IFN-γand Foxp3cells in the spleen of the mice were examined with immunohistochemical staining. In the in vitro experiment, primary cultured splenocytes were stimulated with oxidized low-density lipoproteins (oxLDL) and treated with PIO either alone or in combination with the PPARγ antagonist GW9662, after which the changes in percentages of CD4IFN-γcells and CD4CD25Foxp3cells were analyzed with flow cytometry.

RESULTSPIO treatment of ApoEmice with high-fat feeding significantly attenuated the progression of atheromatous lesions (P<0.05) and resulted in increased expressions of TGFβ1 (P<0.01), TGFβRII (P<0.05), and p-Smad3 (P<0.05) and a decreased expression of Smad7 (P<0.05) in the lesions. PIO treatment also led to decreased percentage of IFN-γcells (P<0.05) and increased percentage of Foxp3cells (P<0.01) in the spleen of the mice. In primary cultured splenocytes, PIO treatment caused significant down-regulation of IFN-γ mRNA (P<0.05) and up-regulation of Foxp3 mRNA (P<0.05) and obviously increased the percentages of CD4IFN-γcells (P<0.05) and CD4CD25Foxp3(P<0.05); the effects of PIO on CD4IFN-γand CD4CD25Foxp3cells were abolished by treatment of the cells with GW9662.

CONCLUSIONThe anti-atherosclerotic effect of PIO is probably mediated by the TGF-β/Smad signaling pathway and PPAR-γ-dependent modulation of Th1/Treg population.

Cycloartenol, a phytosterol compound, also one of the key precusor substances for biosynthesis of numerous sterol compounds, has a variety of pharmacological activities such as anti-inflammatory, anti-tumor, antioxidant, antibiosis and anti-alzheimer's disease. Furthermore, cycloartenol also plays an important role in the process of plant growth and development. This article reviewed the research progress on cycloartenol pharmacological activity in domestic and foreign articles, and summarized the effect of cycloartenol and "cycloartenol pathway" on the plant growth and development, laying foundation for the its further study, development and utilization.

We revisited the "Xiao Chaihu Decoction event (XCHDE)" occurred in late 1980s in Japan and the Bupleuri Radix related adverse drug reaction (ADR) reports in China After careful review, comparison, analysis and evaluation, we think the interstitial pneumonitis, drug induced Liver injury (DILI) and other severe adverse drug envents (ADEs) including death happened in Japan is probably results from multiple factors, including combinatory use of XCHDE with interferon, Kampo usage under modern medicine theory guidance, and use of XCHD on the basis of disease diagnosis instead of traditional Chinese syndrome complex differentiation. There are less ADE case reports related to XCHD preparation in China compared to Japan, mostly manifest with hypersensitivity responses of skin and perfuse perspiration. The symptoms of Radix Bupleuri injection related ADEs mainly manifest hypersensitivity-like response, 2 cases of intravenous infusion instead of intramuscular injection developed hypokalemia and renal failure. One case died from severe hypersensitivity shock. In Chinese literatures, there is no report of the interstitial pneumonitis and DILI associated with XCHDG in Japan. So far, there is no voluntary monitoring data and large sample clinical research data available. The author elaborated the classification of "reevaluation" and clarified "re-evaluation upon events" included the reaction to the suspected safety and efficacy events. Based on the current status of the clinical research on the Radix Bupleuri preparations, the author points out that post-marketing "re-evaluation upon suspected event" is not only a necessity of continuous evaluation of the safety, efficacy of drugs, it is also a necessity for providing objective clinical research data to share with the international and domestic drug administrations in the risk-benefit evaluation. It is also the unavoidable pathway to culture and push the excellent species and famous brands of TCM to the international market, in that it enhances the pharmaceutical manufactures the ability to control enterprise risk and eliminate the negative impact on traditional Chinese medicine. With the widely used and ADR report concentrated Radix Bupleuri injection as an example, the author provide a new approach to post-marketing clinical research.
Bupleurum ; chemistry ; Drug Compounding ; Drug-Related Side Effects and Adverse Reactions ; etiology ; Drugs, Chinese Herbal ; adverse effects ; Humans ; Product Surveillance, Postmarketing ; methods ; Safety

OBJECTIVETo analyze the etiological and epidemiological characteristics of hand-foot-and-mouth disease (HFMD) seen in Jiangsu province from 2008 to 2010, and provide evidence for its prevention and control.

METHODSBased on the requirement of supervision program of HFMD, surveillance and report were done according to National Disease Supervision Information Management System. Descriptive epidemiological method, performed between 2008 and 2010, was used to analyze the time, region and population distribution and results of etiologic analysis of HFMD. Nucleic acid of enterovirus (EV) genome was detected by real-time RT-PCR.

RESULTSThe average incidence rate of HFMD was 86.70 per million between 2008 and 2010, the peak incidence occurred in April to July. There were significant differences among the incidence in different districts (P<0.05), and the highest incidence was seen in the densely inhabited southern areas of Jiangsu province. Most of the cases were infants and children aged less than 5 years. The number of male cases (2008: 17,008, 2009: 48 768, 2010: 50,231) was much larger than that of the female cases 2008: 9662, 2009: 29 151, 2010: 30,655. The HFMD cases with mild symptoms were caused mainly by enterovirus 71 (EV71) and coxsackievirus A16 (Cox A16) and there was difference among different years. The severe HFMD cases and deaths were mainly caused by EV71 infection.

CONCLUSIONSThe epidemiologic characteristics of HFMD in Jiangsu province from 2008 to 2010 had close relationship with season, population and region. The mild cases of HFMD were mainly infected with EV71 and Cox A16. However, EV71 illness seemed to be more severe and had significantly greater frequency of serious complications and fatality than the illness caused by Cox A16.

Child, Preschool ; China ; epidemiology ; Disease Outbreaks ; Enterovirus A, Human ; pathogenicity ; Female ; Hand, Foot and Mouth Disease ; epidemiology ; virology ; Humans ; Infant ; Male

BACKGROUNDTransplantation of mensenchymal stem cells (MSCs) has been proposed as a promising way for tissue engineering. However, the application of MSCs for transplantation will undergo apoptosis due to the extremely harsh microenvironment such as excessive inflammation. Apigenin (API) has been reported to protect cells against inflammatory damage and cell death by exhibiting anti-inflammatory and anti-oxidative capacity. Here we investigated the modulatory effects of API in lipopolysaccharide (LPS)-mediated inflammation and apoptosis of MSCs, and further defined the underlying mechanism.

METHODSEffects of different concentrations of API (0, 5, 10, 20, 40 and 80 µmol/L) for 24 hours, and LPS (0, 0.5 and 5.0 µg/ml) for 6 hours and 24 hours on MSCs viability were assayed by MTT. Based on this, MSCs were pretreated with different concentrations of API (0 - 40 µmol/L) at the indicated times (6, 12 and 24 hours) followed by exposure to 5 µg/ml LPS for 24 hours. MTT, phase-contrast microscopy, annexinV/propidium iodide (PI) double stain flow cytometry (FCM) and Hoechst staining were applied to explore the effects of API on MSCs induced by 5 µg/ml LPS for 24 hours. In addition, reverse-transcription polymerase chain reaction (RT-PCR) was applied to detect the mRNA expression of pro-inflammatory factors including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB), pro-apoptotic gene caspase-3, Bad, and anti-apoptotic gene Bcl-2. Moreover, AutoDock software was used to imitate the docking score of API and vitamin D receptor (VDR). In parallel, Western blotting and RT-PCR were used to investigate protein and mRNA expression of VDR.

RESULTSMSCs stimulated with LPS 5 µg/ml for 24 hours was used as a model of apoptosis induced by over inflammatory stimulus. API (0 - 40 µmol/L) had non-toxic effect on MSCs; however, it could decrease mRNA expression of COX-2, iNOS and NF-κB at different time points in MSCs induced by LPS, except for API at the concentration of 5 µmol/L.

RESULTSfrom phase-contrast microscopy, MTT, Hoechst staining and AnnexinV/PI double stain FCM demonstrated that with the increasing concentrations of API and extension of administrating time, significant morphological changes of MSCs occurred, viability of cells was strongly inhibited, and meanwhile, apoptosis of LPS-administrated MSCs was exacerbated, compared with LPS individual group. In addition, API promoted caspase-3, Bad mRNA expression and inhibited Bcl-2 mRNA expression in a time-dependent and concentration- dependent manner. Further study found that pro-apoptosis effect of API was related to suppress VDR expression.

CONCLUSIONSAPI could inhibit the expression of inducible inflammatory factors, therefore exert the strong anti-inflammatory function. However, API could not protect MSC apoptosis induced by LPS but amplified the apoptosis. The apoptosis is related to Bad/Bcl-2 increasing and caspase-3 activation, which is mediated through suppressing VDR expression.

Animals ; Apigenin ; pharmacology ; Apoptosis ; drug effects ; Blotting, Western ; Cell Survival ; drug effects ; Cells, Cultured ; Flow Cytometry ; Lipopolysaccharides ; pharmacology ; Male ; Mesenchymal Stromal Cells ; cytology ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Calcitriol ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

ObjectiveTo investigate norovirus infection status and indentify its epidemiological characteristics and genotype distribution in infantile viral diarrhea in Jiangsu.MethodsFour hundred and ninety-eight fecal specimens of infantile virus diarrhea cases were collected from Suzhou Children's hospital and Nanjing Children's hospital in 2010.Norovirus genegroup were detected by real-time RT-PCR,and genetype were determined by sequence analysis.Results Among all fecal specimens,2 (0.4％) cases were positive for norovirus G Ⅰ,and 190 (38％) cases for G Ⅱ.Nucleotide sequence analysis revealed that in the 2 samples for G Ⅰ,one strain was G Ⅰ 1 and another was G Ⅰ 3.Twenty-one strains were belonged to G Ⅱ 4 and 2 strains were G Ⅱ 3 in the 23 samples for G Ⅱ.ConclusionAs one of the most important pathogens causing infantile viral diarrhea in Jiangsu province,subtype G Ⅱ 4 was the main epidemic strain of norovirus,meanwhile other genotypes also existed.