Based on the natures and flavors of herbal medicinals recorded in Shen Nong's Classic of the Materia Medica （《神农本草经》）； Miscellaneous Records of Famous Physicians （《名医别录》）， this study analyzed the characte-ristics of the natures， flavors and combination of medicinals of the two-herb compound formulas in Treatise on Cold Damage and Miscellaneous Diseases （《伤寒杂病论》）.Finally， 31 compound formulas were included， and it was found that the nature and flavor of the herbs in these two-herb compound formulas are closely related to the functions of the compound formulas， such as the common pairing of the acrid and the sweet herbs to warm yang and transform qi， the acrid and the bitter herbs in pairs to regulate and harmonize cold and heat， the sweet and the bitter in pairs to remove dampness and clear heat， the acrid and the acrid in pairs to arrest vomiting and direct qi downward， and the sour and the sweet in pairs to slow the urgent and relieve pain. Regardless of the deficiency or excess nature of the disease， the corresponding two-herb compound formulas often aim to reinforce healthy qi while eliminating pathogenic factors， with some formulas showcasing a unique correspondence between the disease pattern and the symptoms addressed.

Objective To explore the significance of serum β-nerve growth factor(β-NGF)and tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)testing in clinical diagnosis and prognosis assessment in patients with pulmonary heart disease(PHD)complicated with pulmonary artery hypertension(PAH).Methods A 1:1 case-control study was conducted in Daxing District People's Hospital of Beijing from January 2019 to June 2022,in which 86 patients with PHD complicated with PAH and 86 patients with isolated PHD were selected as case group and control group.Retrospective analysis was conducted.The case group was divided into mild PAH group(n=39),moderate PAH group(n=25)and severe PAH group(n=22)according to pulmonary artery systolic pressure(PASP).Meanwhile,the case group was divided into good prognosis group(n=75)and poor prognosis group(n=11)based on the outcomes after one year of discharge.Demographic data and laboratory examination indicators of study subjects were collected,and serum β-NGF and TRAIL levels were measured using enzyme-linked immunosorbent assay(ELISA).Pearson product-moment correlation analysis was used to assess the relationship among β-NGF,TRAIL and PASP.Logistic regression analysis was performed to identify factors influencing PAH in patients with PHD.ROC curve was used to evaluate the diagnostic value of β-NGF and TRAIL for PAH.Cox proportional hazards regression analysis was carried out to assess the relationship among β-NGF,TRAIL and poor prognosis in patients with PHD complicated with PAH,and ROC curve was used to evaluate its predictive value for poor prognosis.Result Compared with control group,the duration of PHD in case group was longer(8.63±1.27 years vs 5.49±1.15 years),and serum β-NGF level(26.97±8.25 ng/ml vs 22.14±7.32 ng/ml)and TRAIL level(2.83±0.76 ng/ml vs 1.71±0.68 ng/ml)were increased,with significant differences(t=17.006,4.064,10.183,all P＜0.05).Serum β-NGF and TRAIL had certain diagnostic values for PAH in PHD patients,with AUC of 0.842 and 0.838,respectively.And the combined diagnostic AUC was 0.920,which was higher than that of single indicators(Z=3.416,3.508,all P＜0.05).Serum β-NGF(23.26±5.13 ng/ml,27.83±5.57 ng/ml,32.57±6.02 ng/ml)and TRAIL(2.24±0.65 ng/ml,2.89±0.71 ng/ml,3.81±0.90 ng/ml)levels among patients with mild PAH,moderate PAH,severe PAH were sequentially elevated,and the differences were significant(F=20.624,31.972,all P＜0.05).Serum β-NGF and TRAIL were positively associated with PASP(r=0.673,0.659,P＜0.05).Serum β-NGF(36.34±8.05 ng/ml)and TRAIL(3.49±1.01 ng/ml)levels in poor prognosis group were higher compared to good prognosis group(25.59±7.28 ng/ml,2.73±0.89 ng/ml),and the differences were significant(t=4.516,2.604,all P＜0.05).Logistic regression analysis showed that,the PHD duration[OR(95％CI):1.784(1.135～2.806)],β-NGF[OR(95％CI):1.976(1.108～3.523)]and TRAIL[OR(95％CI):1.866(1.123～3.101)]were independent risk factors for occurrence of PAH in patients with PHD(all P＜0.05).Multivariate COX proportional risk regression results showed that PHD duration[OR(95％CI):1.167(1.082～1.364)],β-NGF[OR(95％CI):1.322(1.134～1.649)],TRA-IL[OR(95％CI):1.259(1.087～1.590)]were independent risk factors for poor prognosis in patients with PHD complicated with PAH(all P＜0.05).Serum β-NGF and TRAIL could predict the poor prognosis in patients with PHD complicated with PAH,with AUC of 0.863 and 0.881,respectively.The combined diagnostic AUC was 0.907,which was higher than that of single indicators(Z=2.905,3.128,all P＜0.05).Conclusion Elevated serum β-NGF and TRAIL were independent risk factors for PAH and were associated with severity of PAH.Early combined detection of β-NGF and TRAIL can improve the diagnostic value for PAH and predict poor prognosis of patients.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

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.

Objective To investigate the changing distribution and antibiotic resistance profiles of clinical isolates of Staphylococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Staphylococcus according to the unified protocol of CHINET(China Antimicrobial Surveillance Network)using disk diffusion method and commercial automated systems.The CHINET antimicrobial resistance surveillance data from 2015 to 2021 were interpreted according to the 2021 CLSI breakpoints and analyzed using WHONET 5.6.Results During the period from 2015 to 2021,a total of 204,771 nonduplicate strains of Staphylococcus were isolated,including 136,731(66.8％)strains of Staphylococcus aureus and 68,040(33.2％)strains of coagulase-negative Staphylococcus(CNS).The proportions of S.aureus isolates and CNS isolates did not show significant change.S.aureus strains were mainly isolated from respiratory specimens(38.9±5.1)％,wound,pus and secretions(33.6±4.2)％,and blood(11.9±1.5)％.The CNS strains were predominantly isolated from blood(73.6±4.2)％,cerebrospinal fluid(12.1±2.5)％,and pleural effusion and ascites(8.4±2.1)％.S.aureus strains were mainly isolated from the patients in ICU(17.0±7.3)％,outpatient and emergency(11.6±1.7)％,and department of surgery(11.2±0.9)％,whereas CNS strains were primarily isolated from the patients in ICU(32.2±9.7)％,outpatient and emergency(12.8±4.7)％,and department of internal medicine(11.2±1.9)％.The prevalence of methicillin-resistant strains was 32.9％in S.aureus(MRSA)and 74.1％in CNS(MRCNS).Over the 7-year period,the prevalence of MRSA decreased from 42.1％to 29.2％,and the prevalence of MRCNS decreased from 82.1％to 68.2％.MRSA showed higher resistance rates to all the antimicrobial agents tested except trimethoprim-sulfamethoxazole than methicillin-susceptible S.aureus(MSSA).Over the 7-year period,MRSA strains showed decreasing resistance rates to gentamicin,rifampicin,and levofloxacin,MRCNS showed decreasing resistance rates to gentamicin,erythromycin,rifampicin,and trimethoprim-sulfamethoxazole,but increasing resistance rate to levofloxacin.No vancomycin-resistant strains were detected.The prevalence of linezolid-resistant MRCNS increased from 0.2％to 2.3％over the 7-year period.Conclusions Staphylococcus remains the major pathogen among gram-positive bacteria.MRSA and MRCNS were still the principal antibiotic-resistant gram-positive bacteria.No S.aureus isolates were found resistant to vancomycin or linezolid,but linezolid-resistant strains have been detected in MRCNS isolates,which is an issue of concern.

Objective To investigate the safety and efficacy of camrelizumab added to second-line therapy after drug- eluting bead transarterial chemoembolization (DTACE) combined with apatinib for unresectable hepatocellular carcinoma (HCC). Methods A retrospective analysis was performed for 89 HCC patients with camrelizumab added to second-line therapy who attended The First Affiliated Hospital of Zhengzhou University from December 2019 to December 2020. The primary endpoints were overall survival (OS) and progression-free survival (PFS) after the application of camrelizumab, and the secondary endpoints were objective remission rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). The Kaplan-Meier method was used to plot survival curves, the Log-rank test was used for stratified analysis of subgroups based on baseline characteristics, and the influencing factors for prognosis were analyzed. Results A total of 89 patients were screened and followed up in this study. The patients were followed up to December 2021, with a median follow-up time of 16 months, a median OS time of 17.0 (95% confidence interval [ CI ]: 15.3-18.7) months, and a median PFS time of 7.0 (95% CI : 6.2-7.8) months. There were significant differences in OS and PFS between the patients with different ECOG-PS scores, liver function Child-Pugh classes, portal vein invasion, patterns of progression, times of DTACE treatment, durations of oral administration of apatinib, and durations of application of camrelizumab (all P < 0.05). At 3 and 6 months after the application of camrelizumab, ORR was 39.3% and 22.4%, respectively, and DCR was 80.9% and 54.1%, respectively. The univariate analysis using the Log-rank test showed that compared with the patients receiving 0 time of DTACE treatment, the patients receiving 3-4 or 1-2 times of DTACE treatment had significant improvements in median OS [22.0 (95% CI : 21.1-22.9) months and 17.0 (95% CI : 15.8-18.2) months vs 10.0 (95% CI : 7.0-13.0) months, χ 2 =31.423, P < 0.001] and PFS [10.0 (95% CI : 7.0-13.0) months and 7.0 (95% CI : 6.2-7.8) months vs 3.0 (95% CI : 1.9-4.1) months, χ 2 =20.741, P < 0.001]; compared with the patients using apatinib for ≤4 months, the patients using apatinib for > 4 months had significant improvements in median OS [21.0 (95% CI : 19.1-22.9) months vs 14.0 (95% CI : 10.4-17.6) months, χ 2 =19.399, P < 0.001] and PFS [9.0 (95% CI : 7.3-10.7) months vs 5.0 (95% CI : 4.0-6.0) months, χ 2 =27.733, P < 0.001]; compared with the patients using camrelizumab for ≤5 months, the patients using camrelizumab for > 5 months had significant improvements in median OS [22.0 (95% CI : 20.2-23.8) months vs 13.0 (95% CI : 9.3-16.7) months, χ 2 =22.336, P < 0.001] and PFS [9.0 (95% CI : 7.0-11.0) months vs 5.0 (95% CI : 4.1-5.9) months, χ 2 =26.141, P < 0.001]. Post-embolization syndrome was the adverse event after DTACE and resolved after symptomatic treatment. Adverse reactions related to targeted drugs and immunotherapy all resolved after symptomatic supportive treatment, with no grade ≥4 adverse reactions, and no patients withdrew from target-free therapy due to TRAEs. Conclusion As for DTACE combined with apatinib in the treatment of unresectable HCC, camrelizumab added after progression has a marked therapeutic efficacy with safe and controllable TRAEs.

Objective To investigate the values of nucleoprotein transformation in sperm for predicting recurrent abortion.Methods A total of 521 infertile couples with complete test indicators on fertility were selected from the reproductive medical clinic of our hospital from 2019 to 2022,among which the ages of the male were from 23 to 56 years old.The following factors causing recurrent abortion were excluded,including the age of woman,body mass index,metabolic disease,antiphospholipid syndrome,uterine and accessory abnormalities,history of caesarean section and intrauterine myoma/cervical conectomy,peripheral blood chromosome abnormalities of both the couple,and adverse life history,such as smoking/alcohol abuse.According to the abortion situation,they were divided into the recurrent abortion group(≥two spontaneous abortions),one spontaneous abortion group and no abortion group.Tukey's multiple comparison was performed to compare the differences of nucleoprotein transformation of sperm in each group by using GraphPad6.0 sta-tistical software.The Pearson method was used to analyze the correlation between nucleoprotein transformation and recurrent abortion.The predictive values of nucleoprotein transformation in recurrent abortion were analyzed by the parameters of sensitivity,specificity,positive predictive value,negative predictive value,Youden index and odd ratio.Results The percentages of abnormal nucleoprotein transformation in recurrent abortion group[(33.31±13.83)％]were significantly higher than those in non-abortion group[(26.85± 15.38)％]and the one abortion group[(28.20±12.50)％,P＜0.05].Pearson correlation analysis showed that there was a significant positive correlation between abnormal nucleoprotein transformation and recurrent abortion.The sensitivity and specificity of nucleoprote-in transformation for predicting recurrent abortion were 45.24％and 73.64％,respectively.All of the data of positive predictive value(15.70％),negative predictive value(92.53％),Youden index(18.88％)and odd ratio(2.31)of nucleoprotein transformation in predicting recurrent abortion were higher than those of high DNA stainability(10.64％,90.31％,1.05％and 1.11).Conclusion In the spouses of patients with recurrent abortion,the immaturity of sperm nuclear protein is significantly increased and significantly posi-tively correlated with recurrent abortion.The abnormal nucleoprotein transformation of sperm may be the important factor of recurrent a-bortion in males,and it has high predictive value for recurrent spontaneous abortion in clinical practice.

Objective To investigate the cost-effect of transarterial chemoembolization (TACE) with CalliSpheres beads loaded with arsenic trioxide (ATO) (CBATO) versus ATO iodized oil emulsion (conventional TACE, cTACE) in the treatment of unresectable liver cancer. Methods A total of 100 patients with advanced liver cancer who attended The First Affiliated Hospital of Zhengzhou University from May 2017 to December 2018 were enrolled and divided into CBATO group( n =45) and cTACE group( n =55) according to the treatment regimen. Progression-free survival (PFS) was used to evaluate the efficacy of quality-adjusted life year (QALY), and European Quality of Life-5 Dimensions (EQ-5D) index was used to evaluate quality of life. The t -test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups; the number of surgeries, length of hospital stay, treatment cost, and incremental cost-effectiveness ratio (ICER) were calculated for the two groups, and then a cost-effect analysis was performed. Results Within the PFS time, the per capita hospital cost was 96 446 yuan in the CBATO group and 91 230.43 yuan in the cTACE group. There were significant differences between the two groups in the mean number of surgeries (2.5±0.7 vs 3.4±0.8, t =16.911, P < 0.01) and mean hospital stay (5.8±1.2 days vs 7.5±1.8 days, t =12.459, P < 0.01). The CBATO group had a significantly higher QALY than the cTACE group (0.804 vs 0.512). Compared with the cTACE group, the CBATO group had an ICER of 17 861.53 yuan/QALY for unresectable liver cancer. Conclusion Although CBATO has a higher surgery cost than cTACE, CBATO has a better clinical effect than cTACE and can reduce the number of surgeries and length of hospital stay, with a better postoperative quality of life than cTACE, suggesting that CBATO has marked cost-effect advantages.