BACKGROUND: Early clinical researches suggest that mediodespidine capsule can decrease blood pressure of patients with primary hypertension on the basis of yanggan qinggan pinggan technique.OBJECTIVE: To observe the effect of mediodespidine capsule on primary hypertension and angiotensin Ⅱ (Ang- Ⅱ ) of patients in the types of yin deficiency, yang excess and liver fire.DESIGN: Randomized controlled case observation.SETTING: Department of Cardiology, First Affiliated Hospital, Hunan University of Traditional Chinese Medicine.PARTICIPANTS: Patients were selected from the Inpatient Department and Out-patients Clinic of the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine between April 1999 and April 2000. Inclusion criteria: Patients, who were diagnosed with the criteria of primary hypertension, who belonged to the types of yin deficiency, yang excess and liver fire, who could endure this test, who were coincidence with the criteria of mental-stress test, were all consent. Exclusion criteria: Patients who had severe congestive heart failure, atrophic arthritis and unable tolerance were excluded. There were 60 cases in total, including 29 males and 31females. All patients were divided into mediodespidine group and verapamil group with 30 in each group on the basis of randomly digital table.METHODS: Patients who had positive results of awaken mental-stress test were involved in this study. Cases in mediodespidine group were treated with mediodespidine capsule, which was made of tall gastrodia tuber, spine date seed and fourstamen stephania root at the dosage of 0.43 g/pill and were provided by the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine (wei yao ji zi: 05-047, batch number: 990503), five pills each for 3 times a day. Cases in verapamil group were treatedwith verapamil (40 mg/pill, Shanghai Huanghe Liya PharmaceuticalCompany Limited,batch number: 980301B) 80 mg each for 3 times a day. The course in both groups was 4 weeks. ① Effect of blood pressure: Average value of blood pressure tested for 3 successive days were regarded as the blood pressure before treatment, and average value of blood pressure tested for 3 times after treatment was regarded as the blood pressure after treatment. ② Effect of symptom:Scores were recorded as four levels according to main symptoms, such as vertigo, headache, pain and weakness of waist and knees, before and after treatment. ③ Values of Ang- Ⅱ were measured with radioimmunoassay before and after cold pressor test. Effect on Ang- Ⅱ was evaluated with effect of decompression, effect of clinical symptom and criteria of clinical effect.MAIN OUTCOME MEARUSES: Clinical symptoms, values of blood pressure, heart rate and Ang- Ⅱ before and after cold pressor test.RESULTS: A total of 60 patients with primary hypertension were involved into the final analysis.① Totally effective rate of clinical symptoms of patients in mediodespidine group was higher than that of patients in verapamil group, but the effect of decompression was not significant between the two groups (P ＞ 0.05). ② There was remarkably significant difference of heart rate in both groups before and after treatment (P ＜ 0.01), especially the decrease in verapamil group was great, and there was significant difference (P ＜ 0.05). ③ Values of systolic pressure and diastolic pressure were decreased in both groups after cold pressor test (P ＜ 0.01), but there was no significant difference between the two groups (P ＞ 0.05). ④ There was no significant difference in clinical effect between the twogroups (P ＞ 0.05).⑤ After treatment, concentration of Ang- Ⅱ at basic level in both groups was decreased, and there was significant difference between them (P ＜ 0.01);concentration of Aug-Ⅱ was decreased in both groups after cold pressor test as compared with that before treatment, but there was no significant difference between them (P ＞ 0.05).CONCLUSION: Mediodespidine capsule can decrease blood pressure stably, and the effect is stronger than that of verapamil at the aspect of decompression and improving symptoms. Blood pressure of patients with primary hypertension in the types of yin deficiency and yang excess or liver fire can be decreased by decreasing the level of plasma Ang-Ⅱ to a certain degree.

Objective:To investigate the clinicopathological and genetic features of confined placental mosaicism (CPM) and its effect on fetal intrauterine growth.Methods:Fourteen CPM cases of Haidian Maternal and Children Health Hospital were collected from May 2018 to March 2022. Clinicopathological examination on placental specimens and molecular genetic analysis were performed.Results:The age of the parturient women ranged from 27 to 34 years, with an average age of (30.0±3.54) years. The gestational weeks ranged from 35 +1 to 41 +2 weeks. There were 4 premature births and 10 term births, among which 6 were female and 8 were male fetuses. Nine cases (9/14) had adverse pregnancy outcomes, including 7 cases of fetal growth restriction. The weight of CPM placenta decreased, with 6 cases below the 10th percentile of weight standards and 5 cases between the 10th and 25th percentile. All 14 CPM placental specimens showed morphological changes of perfusion dysfunction to varying degrees, with mainly placental-maternal vascular malperfusion followed by placental-fetal vascular malperfusion. The mosaic chromosomes in different CPM cases varied, with 16-trisomy/monosomy mosaicism being the most common followed by 7-trisomy and 21-trisomy/monosomy mosaicism. The mosaic proportion was unequal in different parts of the same CPM placenta, with the mosaic proportion of umbilical cord, fetal membranes, fetal surface, maternal surface, and edge ranging from 1% to 70%. Conclusions:The mosaic chromosomes in different CPM cases vary, and the mosaic proportion is unequal in different parts of the same CPM placenta. The pathological morphology is mainly manifested as perfusion dysfunction, which can lead to adverse pregnancy outcomes such as fetal growth restriction and preterm birth.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective To investigate the antimicrobial resistance profile of the clinical isolates collected from selected hospitals across China. Methods Twenty-nine general hospitals and five children's hospitals were involved in this program. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems. Results were interpreted according to CLSI 2017 breakpoints. Results A total of 190 610 clinical isolates were collected from January to December 2017, of which gram negative organisms accounted for 70.8％ (134 951/190 610) and gram positive cocci 29.2％ (55 649/190 610). The prevalence of methicillin-resistant strains was 35.3％ in S. aureus (MRSA) and 80.3％ in coagulase negative Staphylococcus (MRCNS) on average. MR strains showed much higher resistance rates to most of the other antimicrobial agents than MS strains. However, 91.6％ of MRSA strains were still susceptible to trimethoprim-sulfamethoxazole, while 86.2％ of MRCNS strains were susceptible to rifampin. No staphylococcal strains were found resistant to vancomycin. E. faecalis strains showed much lower resistance rates to most of the drugs tested (except chloramphenicol) than E. faecium. Vancomycin-resistant Enterococcus (VRE) was identified in both E. faecalis and E. faecium. The identified VRE strains were mainly vanA, vanB or vanM type based on phenotype or genotype. The proportion of PSSP or PRSP strains in the non-meningitis S.pneumoniae strains isolated from children decreased but the proportion of PISP strains increased when compared to the data of 2016. Enterobacteriaceae strains were still highly susceptible to carbapenems. Overall, less than 10％ of these strains (excluding Klebsiella spp.) were resistant to carbapenems. The prevalence of imipenem-resistant K. pneumoniae increased from 3.0％ in 2005 to 20.9％ in 2017, and meropenem-resistant K. pneumoniae increased from 2.9％ in 2005 to 24.0％ in 2017, more than 8-fold increase. About 66.7％ and 69.3％ of Acinetobacter (A. baumannii accounts for 91.5％) strains were resistant to imipenem and meropenem, respectively. Compared with the data of year 2016, P. aeruginosa strains showed decreasing resistance rate to carbapenems. Conclusions Bacterial resistance is still on the rise. It is necessary to strengthen hospital infection control and stewardship of antimicrobial agents. The communication between laboratorians and clinicians should be further improved in addition to surveillance of bacterial resistance.

AIM:To identify transcriptional differences between the ocular surface ectoderm(OSE)and surface ectoderm(SE)using RNA-seq, and elucidate the OSE transcriptome landscape and the regulatory networks involved in its development.METHODS:OSE and SE cells were differentiated from human embryonic stem(hES)cells. Differentially expressed genes(DEGs)between OSE and SE were analyzed using RNA-seq. Based on the DEGs, we performed gene ontology(GO)analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis, and protein-protein interaction(PPI)network analysis. Transcription factors(TFs)and hub genes were screened. Subsequently, TF-gene and TF-miRNA regulatory networks were constructed using the NetworkAnalyst platform.RESULTS:A total of 4 182 DEGs were detected between OSE and SE cells, with 2 771 up-regulated and 1 411 down-regulated genes in OSE cells. GO-BP analysis revealed that up-regulated genes in OSE were enriched in the regulation of ion transmembrane transport, axon development, and modulation of chemical synaptic transmission. Down-regulated genes were primarily involved in nuclear division, chromosome segregation, and regulation of cell cycle phase transition. KEGG analysis indicated that up-regulated genes in OSE cells were enriched in signaling pathways such as cocaine addiction, axon guidance, and amphetamine addiction, while down-regulated genes were enriched in proteoglycans in cancer, ECM-receptor interaction, protein digestion and absorption, and cytokine-cytokine receptor interaction. Additionally, compared with SE, 204 TFs(including FOS, EGR1, POU5F1, SOX2, and PAX6)were up-regulated, and 80 TFs(including HAND2, HOXB6, HOXB5, HOXA5, and HOXB8)were down-regulated in OSE cells. Furthermore, we identified 6 up-regulated and 9 down-regulated hub genes in OSE cells, and constructed TF-gene and TF-miRNA regulatory networks based on these hub genes.CONCLUSIONS:The transcriptome characteristics of OSE and SE cells were elucidated through RNA-seq analysis. These findings may provide a novel insight for studies on the development and in vitro directed induction of OSE and corneal epithelial cells.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.

Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.

Objective To understand the changing distribution and antimicrobial resistance profiles of Proteus,Morganella and Providencia in hospitals across China from January 1,2015 to December 31,2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods Antimicrobial susceptibility testing was carried out following the unified CHINET protocol.The results were interpreted in accordance with the breakpoints in the 2021 Clinical & Laboratory Standards Institute(CLSI)M100(31 st Edition).Results A total of 32 433 Enterobacterales strains were isolated during the 7-year period,including 24 160 strains of Proteus,6 704 strains of Morganella,and 1 569 strains of Providencia.The overall number of these Enterobacterales isolates increased significantly over the 7-year period.The top 3 specimen source of these strains were urine,lower respiratory tract specimens,and wound secretions.Proteus,Morganella,and Providencia isolates showed lower resistance rates to amikacin,meropenem,cefoxitin,cefepime,cefoperazone-sulbactam,and piperacillin-tazobactam.For most of the antibiotics tested,less than 10％of the Proteus and Morganella strains were resistant,while less than 20％of the Providencia strains were resistant.The prevalence of carbapenem-resistant Enterobacterales(CRE)was 1.4％in Proteus isolates,1.9％in Morganella isolates,and 15.6％in Providencia isolates.Conclusions The overall number of clinical isolates of Proteus,Morganella and Providencia increased significantly in the 7-year period from 2015 to 2021.The prevalence of CRE strains also increased.More attention should be paid to antimicrobial resistance surveillance and rational antibiotic use so as to prevent the emergence and increase of antimicrobial resistance.

Objective To understand the changing distribution and antimicrobial resistance profiles of Klebsiella strains in 52 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Antimicrobial susceptibility testing was carried out according to the unified CHINET protocol.The susceptibility results were interpreted according to the breakpoints in the Clinical & Laboratory Standards Institute(CLSI)M100 document.Results A total of 241,549 nonduplicate Klebsiella strains were isolated from 2015 to 2021,including Klebsiella pneumoniae(88.0％),Klebsiella aerogenes(5.8％),Klebsiella oxytoca(5.7％),and other Klebsiella species(0.6％).Klebsiella strains were mainly isolated from respiratory tract(48.49±5.32)％.Internal medicine(22.79±3.28)％,surgery(17.98±3.10)％,and ICU(14.03±1.39)％were the top 3 departments where Klebsiella strains were most frequently isolated.K.pneumoniae isolates showed higher resistance rate to most antimicrobial agents compared to other Klebsiella species.Klebsiella isolates maintained low resistance rates to tigecycline and polymyxin B.ESBLs-producing K.pneumoniae and K.oxytoca strains showed higher resistance rates to all the antimicrobial agents tested compared to the corresponding ESBLs-nonproducing strains.The K.pneumoniae and carbapenem-resistant K.pneumoniae(CRKP)strains isolated from ICU patients demonstrated higher resistance rates to majority of the antimicrobial agents tested than the strains isolated from non-ICU patients.The CRKP strains isolated from adult patients had higher resistance rates to most of the antimicrobial agents tested than the corresponding CRKP strains isolated from paediatric patients.Conclusions The prevalence of carbapenem-resistant strains in Klebsiella isolates increased greatly from 2015 to 2021.However,the Klebsiella isolates remained highly susceptible to tigecycline and polymyxin B.Antimicrobial resistance surveillance should still be strengthened for Klebsiella strains.