Objective We aimed to investigate(i)the preventive and therapeutic effects of Huogu Muli Prescription(HGMLP),a Chinese medical compound consisting of epimedii folium,drynariae rhizoma,and ostreae concha,on postmenopausal osteoporosis(PMOP)rats and(ii)whether it exerts its effects by regulating the osteoclast-osteogenesis balance.Methods Forty-eight female Sprague-Dawley rats were randomly divided into the following six groups:(i)the sham-operated group,(ii)the model group,(iii)the Qianggu Capsule group,(iv)the calcium carbonate group,and(v,vi)the HGMLP low-dose and high-dose groups(n = 8 rats per group).After adaptive feeding,rats in all groups except the sham-operated group were treated with bilateral ovarian castration to establish the PMOP model.Each day,rats in the Qianggu Capsule group received 0.054 g/kg Qianggu Capsule suspension intragastrically,rats in the calcium carbonate group received 1.670 g/kg calcium carbonate suspension intragastrically,and rats in the HGMLP low-dose and high-dose groups received 0.188 g/kg and 0.375 g/kg HGMLP intragastrically.Rats in the sham-operated group and the model group received an equal volume of normal saline intragastrically.After 90 consecutive days,serum estradiol(E2),estrogen receptor α(ERα),procollagen typeⅠN propeptide(PINP),and tartrate-resistant acid phosphatase 5b(TRACP-5b)were detected by ELISA.Total antioxidant capacity(T-AOC),superoxide dismutase(SOD),catalase(CAT),and malondialdehyde(MDA)levels were measured by colorimetry.Bone mineral density(BMD),trabecular number(Tb.N),trabecular separation/spacing(Tb.Sp),trabecular thickness(Tb.Th),and structure model index(SMI)were measured by Micro-CT,and the microstructure of cancellous bone was observed.The expressions of osteoprotegerin(OPG),receptor activator of nuclear factor-κB(RANK),RANK ligand(RANKL),phosphorylation of forkhead box O3(FoxO3α),Wnt2,β-catenin,and peroxisome proliferator-activated receptor γ(PPARγ)in rat femur tissue were detected by Western blotting.Results(i)The serum levels of E2 and ERα increased in the Qianggu Capsule group and HGMLP groups,compared with the model group(all P<0.05).(ii)Compared with the model group,the serum levels of PINP,TRACP-5b decreased and PINP/TRACP-5b increased in both the Qianggu Capsule group and HGMLP high-dose group(all P<0.05).(iii)The activities of T-AOC,AOD,and CAT in the Qianggu Capsule group and HGMLP groups were higher than those in the model group,while the content of MDA lower(all P<0.05).(iv)Compared with the model group,the femoral BMD,Tb.Th,and Tb.N increased in the Qianggu Capsule group and HGMLP groups,while the femoral Tb.Sp and SMI decreased(all P<0.05);the femoral BMD increased and the Tb.Sp decreased in the calcium carbonate group(all P<0.05).(v)The protein expressions of RANKL,RANK,FoxO3α,and PPARγ in the Qianggu Capsule group and HGMLP groups were lower than those in the model group,while the protein expressions of OPG,Wnt2,and β-catenin were higher(all P<0.05).Conclusion HGMLP can significantly increase estrogen levels,inhibit osteoclast differentiation,and inhibit bone resorption in the PMOP rats.It also alleviates oxidative stress,promotes osteogenic differentiation,inhibits lipogenic differentiation,improves bone formation,and recovers the balance between osteoclasts and osteoblasts,thus achieving prevention and treatment of PMOP.The potential mechanism of HGMLP may be related to regulation via the OPG/RANKL/RANK or FoxO3α/Wnt2/β-catenin/PPARγ pathways.

OBJECTIVE To provide certain therapeutic ideas and references for the pharmaceutical care of severe Legionella pneumonia in anti-infection treatment. METHODS Clinical pharmacists participated in the entire treatment process of a patient with severe Legionella pneumonia， and assisted clinical physicians in evaluating the infecting pathogens using the WUH （Winthrop- University Hospital criteria） scoring system， based on the patient’s clinical symptoms， physical signs， and changes in pulmonary imaging. Leveraging their pharmaceutical expertise， clinical pharmacists recommended a combination of piperacillin sodium and tazobactam with moxifloxacin hydrochloride for anti-infection treatment， and closely monitored the patient’s clinical manifestations. They promptly identified delirium and abnormally elevated levels of lipase， amylase and liver enzymes， and successively suggested adjusting the treatment plan to a combination of piperacillin sodium and tazobactam with doxycycline or azithromycin for anti- infection after analyzing the causes， along with liver protection treatment， enteral nutrition， and parenteral nutrition. Additionally， clinical pharmacists closely monitor the patient’s medication adherence and provide her with medication education. RESULTS The clinical physicians accepted the recommendations of the clinical pharmacists， and the patient improved after treatment and was discharged. A follow-up examination one month later showed no recurrence. CONCLUSIONS Clinical pharmacists， when assisting clinicians in treating severe Legionella pneumonia， not only pay attention to changes in the patient’s clinical symptoms and physical signs， but also closely monitor the adverse reactions of fluoroquinolone， tetracycline， and macrolide antibiotics. They should promptly recognize adverse reactions and provide recommendations for adjusting treatment plans， as well as offer comprehensive pharmaceutical care throughout the patient’s treatment， to ensure the effectiveness and safety of clinical therapy.

Danggui Buxuetang， derived from Clarifying Doubts about Damage from Internal and External Causes （Volume 2）： Treatise on Heat Injury to Stomach Qi（《内外伤辨惑论卷中·暑伤胃气论》） by LI Dongyuan in the Jin and Yuan dynasties， is a classic and famous formula for tonifying qi and generating blood that has been inherited and promoted by successive generations of medical practitioners and has been included in the "Catalogue of Ancient Classical Prescriptions （First Batch）" published by the National Administration of Traditional Chinese Medicine in 2018. The paper analyzed the historical origin， composition， dosage， processing， preparation， decocting， and taking methods， efficacy， and application of the classic formula Danggui Buxuetang by consulting ancient and modern literature and combining the key information examination principles of ancient classic prescriptions. A total of 604 pieces of information on relevant ancient literature were collected， including 186 ancient Chinese medical books， of which 40 （five in the Jin and Yuan dynasties， 19 in the Ming Dynasty， and 16 in the Qing Dynasty） had detailed records of composition， processing， and dosage. Danggui Buxuetang is mainly comprised of Astragali Radix and Angelicae Sinensis Radix. According to the ancient and modern dose conversion， there are 37.3-38.1 g of Astragali Radix and 7.5-7.6 g of Angelicae Sinensis Radix in the formula. Astragali Radix is preferably fried with honey and Angelicae Sinensis Radix with wine. Astragali Radix and Angelicae Sinensis Radix are decocted with 600 mL of water to 300 mL， and taken warm before meals. The main effect of this formula are described in ancient books as blood deficiency and fever， with symptoms of muscle fever， dryness and heat， irritability and thirst， red eyes and face， sleeplessness in daytime and night， and surging and feeble pulse which is weak under hard pressing， and it is a famous formula for replenishing qi and generating blood. Modern research shows that Danggui Buxuetang is commonly used in the treatment of various kinds of anemia， diabetic nephropathy， tumors， and cardiovascular and cerebrovascular diseases. The above research results can provide a reference for the subsequent development and research on the classic formula Danggui Buxuetang.

Objective:To investigate the effect of miR-214 targeting sex determining region Y-box 4 (SOX4) on the proliferation and apoptosis of rheumatoid arthritis (RA) synovial fibroblasts.Methods:Synovial tissue samples from 45 patients with rheumatoid arthritis and 30 patients with joint trauma who underwent joint replacement surgery from 2017 to 2019 in Shangqiu First People's Hospital samples were collected. The expression levels of miR-214 and SOX4 in synovial tissues were detected by real time quantitative polymerase chain reaction (RT-qPCR); The expression levels of serum rheumatoid factor (RF) and C-reactive protein (CRP) were detected by enzyme-linked immunosorbent assay (ELISA) test. The correlation between miR-214 or SOX4 and RF, CRP, erythrocyte sedimentation rate (ESR) was tested by Pearson's analysis. Human fibroblast-like synoviocytes (HFLS)-RA cells were derived from the control group, miR-214 mimic group, mimic-NC group and miR-214 mimic+pcDNA3.1-SOX4 group and se-parated by Lipofectamine 3 000. The cell viability of each group was detected by CCK8, the apoptosis of each group was detected by flow cytometry, the target relationship was verified by dual luciferase experiment, Western-blot was used to detect the protein expression levels of related indicators. Independent sample t test was used for the comparison between the two groups, one-way nalysis of variance (ANOVA) was used for multi-group comparison, and LSD- t test was used for the comparison between the two groups. Results:Compared with the control group (4.6±0.7, 1.9±0.7) and HFLS cells (1.00±0.06, 1.00±0.09), miR-214 was expressed lower in RA tissues (2.6±0.9) and HFLS-RA (0.30±0.05) ( t=10.026, P<0.05; t=15.815, P<0.05). Compared with SOX4 was highly expressed in RA tissues (4.6±0.9) and HFLS-RA cells (3.89±0.41) ( t=14.772, P<0.05; t=12.020, P<0.05). Serum RF, ESR and CRP expression levels in RA group [(46±7) U/ml, (46.4±9.6) mm/1 h, (34.8±9.8) mg/ml] were signifi-cantly higherthan those in the control group [(16±4) U/ml, (9.2±2.0) mm/1 h, (2.1±0.7) mg/ml] ( t=22.906, P<0.05; t=25.338, P<0.05; t=22.314, P<0.05). miR-214 was negatively correlated with serum RF, CRP and ESR was negatively correlated with miRNA( r=-0.574, P<0.05; r=-0.448, P<0.05; r=-0.549, P<0.05), while was positively correlated with SOX4 ( r=0.492, P<0.05; r=0.369, P<0.05; r=0.325, P<0.05). Compared with the control group and the mimic-NC group, cell viability, Ki-67 and p-p65 protein expression decreased significantly after miR-214 mimic transfection for 24 h ( F24 h=16.980, P<0.05;, F48 h=42.735, P<0.05; F72 h=164.448, P<0.05; FKi-67=290.112, P<0.05; Fp-p65/p65=223.548, P<0.05), while the apoptosis rate and Bax protein expression increased significantly ( F=344.360, P<0.05; F=106.376, P<0.05). Overexpression of SOX4, reverses the effect of miR-214. Conclusion:miR-214 targets SOX4 to inhibit the proliferation of synovial fibroblasts and promote apoptosis in rheumatoid arthritis. This may relate to the inhibition of NF-κB signaling pathway by miR-214.

OBJECTIVE：To systematically evaluate the effectiveness and safety of Shenfu qiangxin pills combined with chemical medicine conventional therapy in the treatment of chronic heart failure ，and to provide evidence-based reference for clinical drug use. METHODS ：Retrieved from CNKI ，Wanfang database ，VIP，Google Scholar ，PubMed，the Cochrane Library and Embase database ，RCTs about Shengfu qiangxin pills combined with chemical medicine conventional therapy （trial group ） versus chemical medicine conventional treatment （control group ）were collected during the inception to May 12th，2020. After literature screening and data extraction ，the quality of the literatures was evaluated with risk bias assessment tool recommended by Cochrane 5.1.0 system evaluator manual. Meta-analysis and sensitivity analysis were performed by using Stata 14.0 software. RESULTS：A total of 7 RCTs were included ，involving 596 patients. Meta-analysis results showed that the total response rate of trial group was significantly higher than that of control group [OR ＝4.14，95％CI（2.15，7.97），P＜0.000 01]；the results of sub-group analysis according to the different criteria for determining the efficacy showed that the total response rates of trial group determined by Lee integral method and cardiac function grading method were sig nificantly higher than that of the control group （P＜0.05）. After treatment ，N-terminal pro-B-type natriuretic peptide （NT-proBNP） level of trial group was significantly lower than that of control group [OR ＝－1.33，95％CI（－1.55， qq.com －1.11），P＜0.000 01]. Results of sub-group analysis accor- ding to cardiac failure type showed that NT-proBNP level of patients with chronic heart failure in trial group was lower than control group （P＜0.001）. The level of left ventricular ejection fraction （LVEF）in trial group after treatment [WMD ＝5.76，95％CI （5.05，6.47），P＜0.000 01] was significantly higher than control group ；after treatment ，the level of B-type natriuretic peptide [SMD＝－1.61，95％CI（－2.58，－0.54），P＜0.000 01]，left ventricular end-diastolic diameter （LVEDD）level [WMD ＝ －6.06，95％CI（－6.84，－5.27），P＜0.000 01]，left ventricular end-systolic diameter level [WMD ＝－0.52，95％CI（－5.70，－4.33）， P＜0.000 01] were significantly lower than control group. There was no statistically significant difference in the incidence of ADR between 2 groups（P＞0.05）. Results of sensitivity analysis showed that when NT-proBNP ，LVEF level ，LVEDD level after treatment were used as indicators ，there was no significant difference in the analysis results after eliminating heterogeneity source ， compared with before elimination. CONCLUSIONS ：Shenfu qiangxin pills combined with chemical medicine conventional treatment has good efficacy and safety.

Objective:To evaluate the immunogenicity and immune persistence of purified Vero cells rabies vaccine (PVRV) with Zagreb and Essen regimen.Methods:Prospective study: Patients with first Class II exposure to rabies were recruited from the Dog Injury Cinic of Guangxi Center for Disease Control and Prevention (Guangxi CDC) and randomly divided into the Zagreb (2-1-1) and Essen (1-1-1-1-1) regimen group. All patients were inoculated with the vaccines from the same manufacturer and batch, and 3 ml serum was collected at the 45th day and in 1-year, 2-year and 3-year after immunization. Rapid fluorescent inhibition test (RFFIT) was used to detect rabies virus neutralizing antibody (RVNA). The attenuation of RVNA positive rate and geometric mean titer (GMT) with time was analyzed. Retrospective study: The informed consents for rabies vaccine in the Dog Injury Clinic of Guangxi CDC were checked out. The patients who were injected with PVRV (same manufacturer but unlimited batch) but without passive immune agents for the first time within 3 years were selected and divided into 1-year, 2-year and 3-year group. Each group was further divided into Zagreb and Essen regimen group. The serum (3 ml) was collected at 1 year, 2 years and 3 years after immunization and detected the RVNA by RFFIT.Results:Prospective study: The RVNA positive rates on the 45th day and in 1-year, 2-year and 3-year after immunizationin in the Zagreb and Essen regimen group were 100%, 95%, 85%, 80% and 98.25%, 89.47%, 89.47%, 85.96%, respectively. There was no statistically significant difference in the RVNA positive rates at the same time point between the two regimen groups ( P>0.05). The RVNA GMT on the 45th day and in 1-year, 2-year, and 3-year in the Zagreb and Essen regimen group were 11.32 IU/ml, 1.69 IU/ml, 1.30 IU/ml, 1.30 IU/m and 13.18 IU/ml, 2.13 IU/ml, 1.87 IU/ml, 1.84 IU/m, respectively. There was no significant difference in the RVNA GMT levels at the same time point between the two regimen groups ( F=1.971, P=0.164). The RVNA GMT levels in the two regimen groups had the same trend of attenuation over time (time*group F=0.702, P=0.435). Retrospective study: The RVNA positive rates in 1-year, 2-year and 3-year after immunization in the Zagreb and Essen regimen group were 100%, 95%, 91.43%和94.73%, 86.21%, 87.5%, respectively. There was no statistically significant difference in the RVNA positive rates at the same time point between the two regimen groups ( P>0.05). The RVNA GMT in 1-year, 2-year, and 3-year groups after immunization in the Zagreb and Essen regimen group were 2.65 IU/ml, 2.03 IU/ml, 1.57 IU/ml和3.2 IU/ml, 2.58 IU/ml, 2.45 IU/ml, respectively. There was no significant difference in the RVNA GMT levels at the same time point between the two regimen groups ( P>0.05). Conclusions:The PVRV showed the same excellent immunogenicity and immune persistence after the vaccination with the Zagreb and Essen regimens.

The purpose of this study is to explore the smoking-related behaviors of people ≥60 years of age with respiratory diseases in Shangqiu area. A total of 550 patients with respiratory diseases ≥60 years old who were treated at the First People′s Hospital of Shangqiu from April 2015 to April 2017 were selected as the survey subjects through random sampling. Among them, there were 351 males and 199 females; the age ranged from 60 to 86 (72.85±5.71) years old. Follow-up until April 2020, and the follow-up was 3 years or more and related information and death information were also collected. The multivariate Cox proportional hazard regression model was used to analyze the influence of smoking behavior in the survey subjects on the death risk of people with respiratory diseases ≥ 60 years old. A total of 550 cases were included in the survey, and 25 cases were lost to follow-up. The effective number was 525, and the survey effective rate was 95.45%. Among the 525 patients, 336 (64.00%) were males and 189 (36.00%) were females. The age ranged from 60 to 86 (72.69±5.64) years old. The education level was mainly high school and technical secondary school, accounting for 39.24% of the total population. The primary diseases included tracheitis/bronchitis, asthma, pneumonia, COPD and lung cancer. Among 525 patients with respiratory diseases ≥60 years old, non-smokers accounted for 11.05% (58/525), smokers accounted for 68.00% (357/525), and quitters accounted for 20.95% (110/525). The duration of smoking was more than 20 years, accounting for 33.33% (175/525). The smoking intensity was mainly moderate, accounting for 33.90% (178/525). The duration of smoking cessation was mainly<5 years, accounting for 8.76% (46/525). Follow-up until April 2020, the mortality rate of 525 patients with respiratory diseases ≥60 years old was 14.10% (74/525). Cox regression analysis showed that smoking duration, smoking intensity, cumulative smoking amount, and duration of smoking cessation were the influencing factors of death in patients with respiratory diseases ≥60 years old in Shangqiu area ( P<0.05). It can be seen that smoking duration, smoking intensity, cumulative smoking amount, and smoking cessation duration may be independent risk factors for death in patients with respiratory diseases ≥ 60 years old in Shangqiu area, and may increase the relative risk of death.

The purpose of this study is to explore the smoking-related behaviors of people ≥60 years of age with respiratory diseases in Shangqiu area. A total of 550 patients with respiratory diseases ≥60 years old who were treated at the First People′s Hospital of Shangqiu from April 2015 to April 2017 were selected as the survey subjects through random sampling. Among them, there were 351 males and 199 females; the age ranged from 60 to 86 (72.85±5.71) years old. Follow-up until April 2020, and the follow-up was 3 years or more and related information and death information were also collected. The multivariate Cox proportional hazard regression model was used to analyze the influence of smoking behavior in the survey subjects on the death risk of people with respiratory diseases ≥ 60 years old. A total of 550 cases were included in the survey, and 25 cases were lost to follow-up. The effective number was 525, and the survey effective rate was 95.45%. Among the 525 patients, 336 (64.00%) were males and 189 (36.00%) were females. The age ranged from 60 to 86 (72.69±5.64) years old. The education level was mainly high school and technical secondary school, accounting for 39.24% of the total population. The primary diseases included tracheitis/bronchitis, asthma, pneumonia, COPD and lung cancer. Among 525 patients with respiratory diseases ≥60 years old, non-smokers accounted for 11.05% (58/525), smokers accounted for 68.00% (357/525), and quitters accounted for 20.95% (110/525). The duration of smoking was more than 20 years, accounting for 33.33% (175/525). The smoking intensity was mainly moderate, accounting for 33.90% (178/525). The duration of smoking cessation was mainly<5 years, accounting for 8.76% (46/525). Follow-up until April 2020, the mortality rate of 525 patients with respiratory diseases ≥60 years old was 14.10% (74/525). Cox regression analysis showed that smoking duration, smoking intensity, cumulative smoking amount, and duration of smoking cessation were the influencing factors of death in patients with respiratory diseases ≥60 years old in Shangqiu area ( P<0.05). It can be seen that smoking duration, smoking intensity, cumulative smoking amount, and smoking cessation duration may be independent risk factors for death in patients with respiratory diseases ≥ 60 years old in Shangqiu area, and may increase the relative risk of death.

OBJECTIVE： To explore potential mechanism of “Astragalus membranaceus-Draba nemorosa” couplet medicine for heart failure. METHODS： By network pharmacology， based on drug-like and oral bioavailability， the active components of “A. membranaceus-D. nemorosa” for chronic heart failure were screened and the targets of treating chronic heart failure were predicted by using TCMSP，GeneCards database， OMIM database and DRAR-CPI. The active component-chronic heart failure target network was established by Cytoscape 3.6.0 software. The protein-protein interaction network was constructed by utilizing STRING database. Then top 5 targets in the list of connectivity were screened and performed a molecular docking in molecular docking server. Finally， GO bioprocess analysis and KEGG pathway enrichment analysis were performed in DAVID database. RESULTS： The study predicted 28 active components in total， including 20 A. membranaceus and 12 D. nemorosa， such as kaempferol and quercetin， there were four components in common. Totally 92 target gene of active components were obtained， including heat shock protein 90α （HSP90AA1）， tyrosine protein kinase SRC gene， etc. Results of GO bioprocess analysis showed an association with mitochondrial electron transport， mitochondrial intima， cytoplasmic sol， extracellular body， mitochondrial matrix and drug response. KEGG pathway enrichment analysis showed a link with MAPK signal pathway， TGF signal pathway， PI3K signal pathway， cAMP signal pathway， protein kinase B signal pathway， EPK1 signal pathway and NF-κB signal pathway. CONCLUSIONS： “A. membranaceus-D. nemorosa” couplet medicine exerts therapeutic effects on heart failure from multiple targets as HSP90AA1， SRC and mitochondrial electron transport and MAPK signaling pathway. The study can provide reference for further researches on its material basis and mechanism.

Objective: To explore the application of asymmetrical sculpture in the ear reconstruction with autologous cartilage through comparing the difference of the balanced sculpture and asymmetrical sculpture. Methods: We used the method of retrospective survey and classified the patients who had undergone ear reconstruction because of microtia into two groups. Group A included the patients who had undergone operation with the application of balanced sculpture method. Group B included the patients who had undergone operation with the application of unsymmetrical sculpture method. We picked out 35 patients containing 19 patients of group A and 16 patients of group B according to our grouping criteria and exclusion criteria. The number of cases with complications was recorded, such as collapse of framework, exposure of cartilage, necrosis of skin flap and reconstructed ear infection. The clinical outcomes of two methods in refining the delicate structures of the reconstructed ear were evaluated (that is the definition, shape, size, color and projection). The time for sculpture was compared. Then we analysed the results and evaluated the effectiveness, safety and feasibility of asymmetrical sculpture′s application in the ear reconstruction. Results: Group A had 2 cases which suffered skin flap necrosis. One of them had cartilage exposure and then had secondary infection leading to local cartilage necrosis and absorption, but after active treatment and local skin flap transplantation it was cured. Group B had no skin flap necrosis, cartilage extrusion, framework deformation and distortion, framework collapse and necrosis or absorption. Group B had a higher score in definition, shape, size, color and projection, and the difference was significant in definition, shape, color and projection. In our clinical practice, the sculpture time in both group was similarly about 40 minutes after the surgery operator had skillfully mastered both techniques. Conclusions Both methods are safe and feasible. The method of asymmetrical sculpture does not require additional operative time, and the method of asymmetrical sculpture is a better one compared with the method of balanced sculpture in refining the reconstructed ear.