AIM To explore the effects of praeruptorin A from Suhuang antitussive capsules on cough variant asthma(CVA).METHODS The rats were randomly divided into the normal group,the model group,the dexamethasone group(0.5 mg/kg),the Suhuang antitussive capsules group(7 g/kg)and the low,medium and high dose praeruptorin A groups(15,30 and 60 mg/kg).The rat model of CVA was established by intraperitoneal injection of sensitizer(1 mg/mL ovalbumin and 10 mg/mL aluminum hydroxide)and aerosol inhalation of 1%ovalbumin followed by the corresponding dosing of drugs by gavage initiated on the 14th day.Another 14 days later,the rats had their pathological pulmonary changes observed by HE,Masson and PAS stainings;their number of inflammatory cells in bronchoalveolar lavage fluid(BALF)detected by hematology analyzer;and their levels of IL-4,IL-5,IL-13 and MUC5AC in BALF detected by ELISA.The RAW264.7 cell inflammatory model induced by lipopolysaccharide(LPS)was treated with 4,8,16 μmol/L praeruptorin A or 0.25 mg/mL Suhuang antitussive capsules,respectively.And the cells had their NO level detected by Griess method,and their ROS expression observed using fluorescence microscopy.The detections of the pulmonary and cellular mRNA expressions of IL-6,IL-1β,COX-2,iNOS and PPAR-γ by RT-qPCR;and the protein expressions of p-P65,P65,p-IκBα,IκBα,NLRP3,caspase-1(p20)and IL-1β by Western blot were conducted in both the cells and the rats.RESULTS The in vivo result showed that praeruptorin A reduced the cough frequency(P＜0.01);prolonged the cough latency(P＜0.05,P＜0.01);reduced the number of eosinophils and neutrophils in BALF(P＜0.05,P＜0.01);decreased the levels of IL-4,IL-5,IL-13 and MUC5AC in BALF and the pulmonary mRNA expressions of IL-6,IL-1β,COX-2 and iNOS(P＜0.05,P＜0.01);and decreased the phosphorylation of P65 and IκBα protein and NLRP3,caspase-1(p20)and IL-1β protein expressions(P＜0.05,P＜0.01)as well.The in vitro result showed that praeruptorin A inhibited the release of LPS-induced NO and reduce the ROS level(P＜0.01);decreased the mRNA expressions of IL-1β,COX-2 and iNOS(P＜0.05,P＜0.01);increased PPAR-γ mRNA expression(P＜0.05),and decreased the phosphorylation of P65 and IκBα protein and the expression of NLRP3 protein(P＜0.05,P＜0.01).CONCLUSION Praeruptorin A,one of the main antitussive components of Suhuang antitussive capsules,may improve CVA because of its anti-inflammatory and antitussive role by inhibiting the activation of NF-κB signaling pathway and reducing the expression of NLRP3 inflammatory corpuscles.

In the treatment of persistent atrial fibrillation with radiofrequency ablation,it is often necessary to add the ablation of external trigger foci of pulmonary vein on the basis of annular pulmonary vein isolation,including linear ablation,BOX ablation and fragmentation potential ablation.The isthmus of mitral valve is the most important component of linear ablation,but it is difficult to reach the isthmus of mitral valve for complete blockade by conventional radiofrequency ablation.The guide catheter was transported through the inferior vena cava to the coronary sinus,and the injection of Marshall vein anhydrous ethanol for ablation could achieve epicardial and myocardial block in the mitral isthmus,and the ablation combined with the endocardial patch ablation in the mitral isthmus could significantly improve the ablation effect,but there were disadvantages such as Marshall vein and coronary vein injury,high surgical cost and long time.This paper reports a case of persistent atrial fibrillation treated by self-made perforated balloon with Marshall intravenous anhydrous ethanol combined with individualized ablation strategy.No major adverse cardiovascular events or recurrence of atrial fibrillation occurred during 6 months of follow-up after discharge.

ObjectivesTo assess the correlation between blastocyst morphology score， serum human chorionic gonadotropin β subunit （β-hCG） levels on day 12 after transfer and live birth outcomes among cycles tested HCG-positive after thawed single blastocyst transfer； to analyze the predictive value of serum β-hCG levels on live birth. MethodsWe reviewed the data of 519 frozen-thawed single blastocyst transfer cycles （FET） that had been tested HCG-positive from January 2016 to May 2020 at our IVF center. These FET cycles were firstly divided into 4 groups （AA， AB， BA， and BB） according to Gardner's grading system of inner cell mass （ICM） and trophectoderm cell （TE）， and then 4 groups （stages 3， 4， 5 and 6） according to the degree of blastocyst expansion. Serum β-hCG concentrations on day 12 after transfer and live birth rates were compared among groups transferred with different blastocysts grading and expansion stage. The relationship between Gardner’s grading or expansion stage of blastocysts and serum β-hCG levels was determined by correlation test， and ROC curves were plotted to determine the threshold values of serum β-hCG for predicting live birth. Results（1） The serum β-hCG concentration in the AA group and AB group on the 12th day after the transfer was significantly higher than that in the BB group （P <0.001， P <0.001）. However， there was no significant difference in the live birth rate when different ICM/TE-graded blastocysts were transferred （P = 0.120）. There were no significant differences in serum β-hCG concentration on day 12 after transfer and live birth rate among blastocysts with different expansion stages （P = 0.091， P = 0.557）. （2） There was a significant weak correlation between blastocyst ICM/TE grading and serum β-hCG concentration on day 12 （r_s = -0.221， P <0.001）， and even after controlling for confounding factors （ r_s = -0.228， P <0.001）；There was no significant correlation between blastocyst’s expansion stage and serum β-hCG concentration on day 12 after the transfer （r_s = -0.052， P = 0.240）， and the association remained insignificant after controlling for confounding factors （r_s = -0.029， P = 0.508）. （3） ROC curve analysis showed that the cut-off value for predicting live birth by serum β-hCG on day 12 was 657.5 mU/mL （P < 0.001）. ConclusionsNeither the ICM/TE grade nor the expansion stage of blastocysts affect the live birth rate，there is significant difference in the level of β-hCG produced by blastocyst with different ICM/TE grade；Our results suggest that early serum β-hCG level can predict live birth.

Objective: To investigate the relationship between the mechanical circulatory support (MCS) combined with immunomodulation and the prognosis of patients with fulminant myocarditis. Methods: This is a retrospective study. A total of 88 patients with fulminant myocarditis admitted to Dongguan Kanghua hospital from Aug. 2008 to Dec. 2020 were included. Medical histories, results of laboratory tests, treatment regimens and clinical outcomes of these patients during their hospitalization were collected from the medical record system. According to the treatment methods, the patients were divided into MCS+immunomodulation group (38 cases), MCS group (20 cases) and traditional treatment group (30 cases). Patients in the MCS+immunomodulation group received intra-aortic balloon pump (IABP) or IABP combined with extracorporeal membrane oxygenation (ECMO) and immunoglobulin or glucocorticoid. Patients in the MCS group only received mechanical circulatory support. Patients in the traditional treatment group received neither mechanical circulatory support nor immunomodulatory therapy, and only used vasoactive drugs and cardiotonic drugs. The in-hospital mortality and length of stay were compared among the three groups. Results: A total of 88 patients with fulminant myocarditis aged (35.0±10.8) years were included, and there were 46 males (52.3%). The mortality of MCS+immunomodulation group (7.9% (3/38) vs. 56.7% (17/30), P=0.001 2) and MCS group (30.0% (6/20) vs. 56.7% (17/30), P=0.002 8) were lower than that of traditional treatment group. Compared with the MCS group, the in-hospital mortality in the MCS+immunomodulation group was lower (P=0.005 4). The most common cause of death was multiple organ dysfunction syndrome (MODS). The constituent ratios of death in MCS+immunomodulation group, MCS group and traditional treatment group were 3/3, 4/6 and 12/17, respectively. The incidence of MODS in the MCS group (20% (4/20)) and the traditional treatment group (40% (12/30)) was significantly higher than that in the MCS+immunomodulation group (7.9% (3/38)) (both P<0.01). In discharged patients, the hospitalization time of MCS+immunomodulation group was shorter than that of traditional treatment group ((13.4±5.5)d vs. (18.5±7.4)d, P<0.05) and MCS group ((13.4±5.5)d vs. (16.9±8.5)d, P<0.05). Conclusion: MCS combined with immunomodulatory therapy is associated with lower in-hospital mortality and shorter hospital stay in patients with fulminant myocarditis.
Adult ; Heart-Assist Devices ; Humans ; Immunomodulation ; Male ; Middle Aged ; Myocarditis/therapy* ; Retrospective Studies ; Treatment Outcome ; Young Adult

The liver is abundant in blood supply and receives 25% of the cardiac output via the hepatic artery and portal vein. Circulatory disorders may cause hepatic injury, resulting in congestive hepatopathy(CH) and ischemic hepatitis(IH). Hepatic congestion arising from increased hepatic venous pressure and decreased cardiac output is the common pathophysiological basis of both CH and IH. In addition, extensive arteriovenous shunts affect portal pressure and cardiac function, leading to alterations of hepatic blood supply. The current review summarizes the pathophysiology, clinical manifestations and therapeutic interventions of the above diseases, in order to provide reference for clinical practice.
Cardiovascular Diseases ; Hepatic Artery ; Humans ; Liver ; Liver Diseases ; Portal Pressure ; Portal Vein

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

Abstract: Objective　To investigate the molecular characteristic and evolutionary trends of full-genome sequences of coxsackievirus A2 (CV-A2) and A5 (CV-A5) in Changsha City. Methods　The CV-A2 and CV-A5 strains were isolated and detected from patients with hand, foot and mouth disease (HFMD) cases. The full-genome sequences of CV-A2 and CV-A5 strains were obtained using NGS sequencing. Homology and phylogenetic tree analysis were performed, and the recombination regions of the strains were examined by SimPlot software. Results　The full-genome sequences of CV-A2 and CV-A5 strains were obtained from routine surveillance cases of HFMD in Changsha in 2019. The CV-A2 strain was named S281/Changsha/CHN/2019 with the full-genome sequence of 7 422 bp long; the CV-A5 strain was named S272/Changsha/CHN/2019 with the full-genome sequence of 7 425 bp long. Homology analysis of the isolates by comparison with the nucleic acid sequences of CV-A2 and other CV-A2 strains in China showed that the non-structural protein region shared lower similarity than that of structural protein region. The CV-A2 showed 79.20% similarity with Fleetwood strain (NC038306), showed the highest similarity 95.60% with MN419014 strain from Hubei Province. The non-structural protein 3C and 3D region shared the lowest similarity with MN419014, 90.51 and 92.06%, respectively. Phylogenetic tree analysis showed that 3C and 3D regions were located in the CV-A4 branch. Amino acid mutation sites were found in non-structural protein region, and the amino acid sequence in structural protein region was conserved. SimPlot analysis showed that genetic recombination was found in the 3C and 3D region of CV-A2 strains. The full-genome sequence of CV-A5 showed 80.7% similarity with the Swartz (AY421763) and 97.43% similarity with the strain (MH111030) from Australian. Homology analysis showed that the non-structural protein region shared lower similarity than that of structural protein region, based on full-genome of CV-A5. Phylogenetic tree analysis showed that CV-A5 and MH111030 were in the same branch, indicating that CV-A5 strain not from local. The amino acid sequence of CV-A5 strain was conserved. Conclusions　The CV-A2 strain in Changsha City shared genome sequence information with CV-A4, and the CV-A5 strain was imported from abroad. Our findings are expected to understand the molecular and recombination characteristics of CV-A2 and CV-A5, provided the data of evolution and genetic features of the coxsackievirus, and interrupt disease transmission in a timely and effective manner.

Objective: To explore the effects and mechanism of water-soluble chitosan hydrogel on infected full-thickness skin defect wounds in diabetic mice. Methods: The experimental research method was adopted. The control hydrogel composed of polyvinyl alcohol and gelatin, and the water-soluble chitosan hydrogel composed of the aforementioned two materials and water-soluble chitosan were prepared by the cyclic freeze-thaw method. The fluidity of the two dressings in test tube before and after the first freeze-thawing was generally observed, and the difference in appearance of the final state of two dressings in 12-well plates were compared. According to random number table (the same grouping method below), the cell strains of L929 and HaCaT were both divided into water-soluble chitosan hydrogel group and control hydrogel group, respectively. After adding corresponding dressings and culturing for 24 h, the cell proliferation activity was measured using cell counting kit 8. Rabbit blood erythrocyte suspensions were divided into normal saline group, polyethylene glycol octyl phenyl ether (Triton X-100) group, water-soluble chitosan hydrogel group, and control hydrogel group, which were treated accordingly and incubated for 1 hour, and then the hemolysis degree of erythrocyte was detected by a microplate reader. Twenty-four female db/db mice aged 11-14 weeks were selected, and full-thickness skin defect wounds on their backs were inflicted and inoculated with the methicillin-resistant Staphylococcus aureus (MRSA), 72 h later, the mice were divided into blank control group, sulfadiazine silver hydrogel group, control hydrogel group, and water-soluble chitosan hydrogel group, which were treated accordingly. On post injury day (PID) 0 (immediately), 7, 14, and 21, the healing of the wound was observed. On PID 14 and 21, the wound healing rate was calculated. On PID 14, MRSA concentration in wounds was determined. On PID 21, the wounds were histologically analyzed by hematoxylin and eosin staining; the expression of CD31 in the wounds was detected by immunofluorescence method, and its positive percentage was calculated. Raw264.7 cells were taken and divided into interleukin-4 (IL-4) group, blank control group, control hydrogel group, and water-soluble chitosan hydrogel group, which were treated accordingly. At 48 h of culture, the percentages of CD206 positive cells were detected by flow cytometry. The number of samples was all 3. Data were statistically analyzed with independent sample t test, one-way analysis of variance, analysis of variance for repeated measurement, least significant difference test, and Dunnett T3 test. Results: Two dressings in test tube had certain fluidity before freeze-thawing and formed semi-solid gels after freeze-thawing for once. The final forms of two dressings in 12-well plates were basically stable and translucent sheets, with little difference in transparency. At 24 h of culture, the cell proliferation activities of L929 and HaCaT in water-soluble chitosan hydrogel group were significantly higher than those in control hydrogel group (with t values of 6.37 and 7.50, respectively, P<0.01). At 1 h of incubation, the hemolysis degree of erythrocyte in water-soluble chitosan hydrogel group was significantly lower than that in Triton X-100 group (P<0.01), but similar to that in normal saline group and control hydrogel group (P>0.05). On PID 0, the traumatic conditions of mice in the 4 groups were similar. On PID 7, more yellowish exudates were observed inside the wound in blank control group and control hydrogel group, while a small amount of exudates were observed in the wound in sulfadiazine silver hydrogel group and water-soluble chitosan hydrogel group. On PID 14, the wounds in blank control group and control hydrogel group were dry and crusted without obvious epithelial coverage; in sulfadiazine silver hydrogel group, the scabs fell off and purulent exudate was visible on the wound; in water-soluble chitosan hydrogel group, the base of wound was light red and obvious epithelial coverage could be observed on the wound. On PID 14, the wound healing rate in water-soluble chitosan hydrogel group was significantly higher than that in the other 3 groups (all P<0.01). On PID 21, the wound in water-soluble chitosan hydrogel group was completely closed, while the wounds in the other 3 groups were not completely healed; the wound healing rate in water-soluble chitosan hydrogel group was significantly higher than that in the other 3 groups (all P<0.01). On PID 14, the concentration of MRSA in the wound in water-soluble chitosan hydrogel group was significantly lower than that in blank control group (P<0.01), but similar to that in control hydrogel group and sulfadiazine silver hydrogel group (P>0.05). On PID 21, the new epidermis was severely damaged in blank control group; the epidermis on the wound in control hydrogel group also had a large area of defect; complete new epidermis had not yet being formed on the wound in sulfadiazine silver hydrogel group; the wound in water-soluble chitosan hydrogel group was not only completely covered by the new epidermis, the basal cells of the new epidermis were also regularly aligned. On PID 21, the percentage of CD31 positivity in the wound in water-soluble chitosan hydrogel group was (2.19±0.35)%, which was significantly higher than (0.18±0.05)% in blank control group, (0.23±0.06)% in control hydrogel group, and (0.62±0.25)% in sulfadiazine silver hydrogel group, all P<0.01. At 48 h of culture, the percentage of CD206 positive Raw264.7 cells in water-soluble chitosan hydrogel group was lower than that in IL-4 group (P>0.01) but significantly higher than that in blank control group and control hydrogel group (P<0.05 or P<0.01). Conclusions: The water-soluble chitosan hydrogel has good biosafety and can induce higher level of macrophage M2 polarization than control hydrogel without water-soluble chitosan, so it can enhance the repair effect of MRSA-infected full-thickness skin defect wounds in diabetic mice and promote rapid wound healing.
Mice ; Female ; Animals ; Rabbits ; Interleukin-4 ; Hydrogels/pharmacology* ; Wound Healing ; Chitosan/pharmacology* ; Diabetes Mellitus, Experimental ; Water ; Methicillin-Resistant Staphylococcus aureus ; Gelatin ; Polyvinyl Alcohol ; Hemolysis ; Saline Solution ; Eosine Yellowish-(YS) ; Hematoxylin ; Octoxynol ; Silver ; Phenyl Ethers ; Sulfadiazine

OBJECTIVE: To compare the efficacy on insomnia between Fang 's scalp acupuncture combined with conventional acupuncture and the simple conventional acupuncture. METHODS: A total of 66 patients with insomnia were randomly divided into an observation group (33 cases, 1 case dropped off) and a control group (33 cases, 2 cases dropped off). In the control group, the routine acupuncture therapy was applied to Shenmen (HT 7), Baihui (GV 20), Zhaohai (KI 6) and Sanyinjiao (SP 6), etc. Based on the treatment as the control group, Fang's scalp acupuncture therapy was supplemented at fuxiang tou, fuzang shangjiao, fuzang zhongjiao, siwei, etc. At these scalp points, the needles were inserted perpendicularly with flying needling technique and manipulated with trembling one. In either group, the treatment was given once daily, continuously for 2 weeks. Before and after treatment, separately, the score of Pittsburgh sleep quality index (PSQI) and the score of Chinese perceived stress scale (CPSS) were observed, as well as the parameters monitored by polysomnography, i.g. total sleep time (TST), sleep onset latency (SOL), wakefulness after the sleep onset (WASO), sleep efficiency (SE), the percentages of the time of rapid eye movement sleep phase (REM) and non-rapid eye movement sleep phase 1, 2, 3 and 4 in TST (REM%, N1%, N2%, N3%). The efficacy was compared between two groups. RESULTS: After treatment, the scores of each factor and the total scores of PSQI, as well as CPSS scores were all lower than those before treatment in the two groups (P<0.01, P<0.05); except the score for sleep quality, the score of each factor and the total score of PSQI, as well as CPSS score in the observation group were lower than those in the control group (P<0.01, P<0.05). After treatment, TST, SE%, REM% and N3% were increased and SOL, WASO, N1% were decreased as compared with before treatment in the two groups (P<0.01, P<0.05), and N2% in the observation group was decreased (P<0.01); SE%, REM% and N3% in the observation group were higher than the control group (P<0.05) and N1% and N2% were lower than the control group (P<0.05). The total effective rate was 93.8% (30/32) in the observation group, higher than 87.1% (27/31) in the control group (P<0.05). CONCLUSION Fang 's scalp acupuncture, on the base of routine acupuncture, obviously improves the sleep quality and perceived stress and adjusts the sleep structure in the patients with insomnia.
Acupuncture Points ; Acupuncture Therapy/methods* ; Humans ; Scalp ; Sleep ; Sleep Initiation and Maintenance Disorders/therapy* ; Stress, Psychological/therapy* ; Treatment Outcome

The clinical randomized controlled trial(RCT) of Chinese patent medicine in the treatment of influenza were reviewed and analyzed to provide basic information for clinical decision and related research. On the basis of the collection in the Traditional Chinese Medicine(TCM) Clinical Evidence Database System(EVDS), CNKI, Wanfang, VIP, SinoMed, EMbase, PubMed, and Cochrane Library were searched for RCTs of Chinese patent medicine for influenza published from database inception to July 25, 2021. The publication time, sample size, intervention and control measures, course of treatment, outcome indicators, and methodological quality of the trials were analyzed and evaluated. Ninety-two RCTs of Chinese patent medicine for influenza published between 2005 and 2021, were included, among which 17 RCTs(18.48%) had a sample size higher than 200 and the average sample size was about 145. Twenty-seven Chinese patent medicines were involved, including twenty-one oral medicines and six injections. The Chinese patent medicines in trials reported in more than five papers included Lianhua Qingwen Capsules/Gra-nules, Tanreqing Injection, and Reduning Injection. Fourteen intervention protocols were reported, of which Chinese patent medicine+western medicine+conventional treatment vs western medicine+conventional treatment(20.65%) was the most frequently employed. Additionally, 85.87% of the RCTs reported the course of treatment, and 80.43% of the RCTs determined 3-7 d as the intervention course. Forty-five outcome indicators were extracted, which were used 434 times, including symptoms/signs, physicochemical detection, safety events, TCM symptoms/syndromes, quality of life, long-term prognosis, and economic evaluation. Symptoms/signs(61.52%) exhibited the highest frequency. Methodological problems were prevalent in the included trials. The findings reveal that there are few clinical trials on influenza treatment by Chinese patent medicine, and the methodological problems are prominent, affec-ting the reliability and practicability of the trials. In the future research, the value characteristics of Chinese patent medicine should be highlighted and the quality control in the whole process should be strengthened based on the scientific and rigorous design.
China ; Clinical Trials as Topic ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Influenza, Human/drug therapy* ; Medicine, Chinese Traditional ; Nonprescription Drugs/therapeutic use* ; Quality of Life ; Reproducibility of Results