Interpretation and reflection on the Measures for the Administration of Standards for Medicinal Products / 中国药房

In July 2023， the National Medical Products Administration issued the Measures for the Administration of Standards for Medicinal Products （hereinafter referred to as the Measures）. This article interprets the main content of the Measures， and analyzes its shortcomings as unclear definition of the drug standard code and the goals of drug standard information construction. It is recommended that the national drug regulatory department promptly apply to the standardization authority for the confirmation of the drug standard code “YB” letter， and the drug standard code and numbering rules would be included in the next round of amendments to the Measures. It is necessary to clarify the construction goals of the information system for drug standards at the same time， and build a national drug standard data-sharing platform based on the basic framework of user interface layer， computing processing layer， and data storage layer. Digital drug standards will be free， and access and download services for the public will be provided.

Haploinsufficiency of A20 caused by a novel pathogenic missense variant of TNFAIP3 and successfully treated with anti-TNF and immunosuppressive therapies.

Loss-of-function of protein A20, encoded by TNFAIP3, leads to an early-onset haploinsufficiency of A20 (HA20). This study reports one Chinese child with HA20 and explores the genetic etiology of TNFAIP3 variant. The patient exhibited transient recurrent episodes of fever, intermittent signs of arthritis, gastrointestinal symptoms and multiple colonic ulcers. Laboratory tests revealed elevated inflammatory indicators and mild to moderate anemia. Genetic analysis identified a heterozygous de novo variant in his TNFAIP3 gene (c.740C＞T, p. P247L), which had never been reported before. The novel missense variation was validated to be pathogenic through causing insufficient expression of A20, over-activation of NF-κB signaling pathway and elevated levels of proinflammatory cytokines in response to stimulation by lipopolysaccharide. A combination of oral corticosteroids, TNF-α inhibitors and thalidomide freed him from symptoms and abnormal inflammatory indicators. Furthermore, continual improvement of the patient's condition was observed during a follow-up period of five months. We demonstrate a case with a de novo missense variant resulting in a loss-of-function of TNFAIP3, which expands the clinical spectrum of HA20. Cytokine antagonists and immunosuppressants may be effective drugs.

Qizhi Jiangtang capsule activates podocyte autophagy in diabetic kidney disease by inhibiting phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathways.

OBJECTIVE: To investigate the therapeutic action and mechanism of the Qizhi Jiangtang capsule (, QZJT) on diabetic kidney disease (DKD) treatment. METHODS: This experiment used db/db mice and podocytes (MPC5) to develop DKD model. Evaluation of the effect of the QZJT on db/db mice by testing urine and blood biochemical parameters (24-h urinary albumin, serum creatinine, blood urine nitrogen), pathological kidney injury, and podocyte integrity. Moreover, autophagosomes in podocytes of DKD mice and cultured podocytes were detected using electron microscopy. Additionally, Western blotting was applied to detect the expression of podocyte marker protein (podocin), autophagy-associated proteins, and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway changes and . RESULTS: QZJT significantly reduced urine protein, blood nitrogen urea, and serum creatinine and showed histological restoration of renal tissues. QZJT also significantly improved the down-regulation of podocin and foot fusion and effacement in db/db mice. QZJT increased autophagic vesicles in mice and cultured podocytes. QZJT also upregulated microtubule-associated protein 1 light chain 3-II (LC3-II) / (LC3-I) and Beclin-1 and downregulated phosphorylated-PI3K (p-PI3K), p-AKT, and p-mTOR in db/db mice and MPC5 cells. However, autophagy inhibitor 3-methyladenine partially alleviated the above effects in MPC5 cells. CONCLUSIONS: These results showed that the QZJT can enhance podocyte autophagy and ameliorate podocyte injury in DKD by inhibiting the PI3K/AKT/mTOR signaling pathway.

Prediction of Responses of Patients with Hepatocellular Carcinoma to Anti-PD-1 Immunotherapy by T-cell Invigoration to Tumour Burden Ratio / 肿瘤防治研究

Objective To explore the predictive value of T cell activation in peripheral blood of patients with hepatocellular carcinoma(HCC) after anti PD-1 therapy and its ratio to tumor burden on the efficacy of immunotherapy. Methods Serum specimens were obtained before and after treatment from 85 patients with HCC who received anti-PD-1 treatment. Indicators such as cell subpopulations and T cell activation were detected by flow cytometry. Combined with imaging analysis, cutoff value was obtained by X-tile software. Survival analysis was used to evaluate patients' outcomes. Results The maximum fold change of Ki-67+/PD-1+/CD8+ T cells in treatment cycles and the tumor burden determined by imaging were associated with prognoses. The ratio of T cell Ki-67+/PD-1+/CD8+ expression to tumor burden ratio greater than 0.6 at the first cycle of anti-PD-1 immunotherapy was associated with improvements in progression-free survival and overall survival (P < 0.05). Conclusion The ratio of activationa in T cells in peripheral blood after immunotherapy to the tumor burden may be related to the clinical efficacy of anti-PD-1 immunotherapy for HCC.

Value of biliopancreatic-duct-imaging-system-assisted endoscopic retrograde appendicitis therapy for children with acute appendicitis (with video) / 中华消化内镜杂志

Objective:To investigate the diagnostic and therapeutic value of one-time biliopancreatic-duct-imaging-system (eyeMax)-assisted endoscopic retrograde appendicitis therapy (ERAT) for children.Methods:A total of 11 children who were diagnosed as having uncomplicated acute appendicitis by imaging in Xi′an Children′s Hospital from August to November 2022 were enrolled. All patients received subscope-assisted ERAT. Subscope was intubated into the appendix cavity to observe the mucosa directly. Appendicitis was treated through cleansing, fecalith extraction, stent drainage. The clinical manifestations under subscope were recorded, as well as the treatment success rate, intubation success rate, the effective rate, complication incidence during and after the operation.Results:The age of 11 children was 7.93±2.67 years old. Appendix intubation was successful in all patients. Congestion and swelling of the mucosa in appendiceal orifice and appendix cavity were seen under the subscope in 11 children. There were 6 cases with appendiceal fecaliths, 8 cases with pus and 6 cases with luminal distortion or stenosis. Perforation was observed in 1 case during the operation and no other complication occurred. All patients were treated under subscope, including flushing appendiceal cavity (11 cases), fecalith extraction with extraction basket (3 cases), and appendiceal drainage with stenting (2 cases). The symptoms and signs were relieved after the operation, and the effective rate within 48 hours was 10/11. There were no procedure-related complications or recurrence during postoperative follow-up for 1 week to 4 months.Conclusion:Acute appendicitis could be diagnosed by observing the appendix cavity directly under one-time biliopancreatic-duct-imaging-system-assisted ERAT, and also could be treated with the system, where appendix could be preserved and radiation damage could be avoided with safety and effectiveness.

Influence of airway mucus plugs on patients with bronchial asthma and its management / 中华健康管理学杂志

Objective:To explore the influence of airway mucus plugs on patients with bronchial asthma and its management.Methods:In this cross-sectional study, from January 2020 to June 2022, 100 patients who were diagnosed with asthma and underwent chest CT examination in the Outpatient Department of Peking University Third Hospital were included. The chest CT results and medical history, pulmonary function, fractional exhaled nitric oxide (FeNO), blood routine, total allergen IgE, Aspergillus fumigatus M3 allergen-specific IgE antibody test results were collected. According to the results of chest CT, the asthma patients were divided into group with mucus plugs and those without mucus plugs. Distribution of airway mucus plugs and the mucus plug scores based on lung segments were calculated. The relationships of mucus plugs with medical history, pulmonary function [These included before and after the bronchodilation test, forced vital capacity percent of predicted value (FVC%pred), forced expiratory volume in one second percent of predicted value (FEV 1%pred), FEV 1/FVC, peak expiratory flow percent of predicted value (PEF%pred), maximal mid-expiratory flow percent of predicted value (MMEF%pred), maximal expiratory flow at 25%, 50%, 75% of vital capacity remaining percent of predicted value (MEF 25%pred, MEF 50%pred, MEF 75%pred)], FeNO, and peripheral blood eosinophil (Eos) counts were analyzed. The logistic regression model was used to analyze whether airway mucus plug was a risk factor for asthma exacerbation, and the corresponding intervention strategies were explored. Results:Among the 100 patients with asthma, 24 cases were in the mucus plug group and 76 cases were in the non-mucus plug group. The distribution of mucus plug was more common in the lower lungs (30.53% and 9.16% in the lower and upper lobe of left lung, respectively; 29.01%, 14.50% and 16.80% in the lower, middle and upper lobe of right lung, respectively). The average score of mucus plug was (4.42±3.12) points. The body mass index (BMI), the number of visits to a doctor due to asthma exacerbations, FeNO, peripheral blood Eos counts in the mucus plug group were higher than those in the non-mucus plug group [(24.95±4.34) vs (23.22±2.91) kg/m 2, 0(0, 1) vs 0(0, 0), 97(37, 169) vs 31(18, 59) ppb (1 ppb=1×10 -9), 0.41(0.15, 0.70) vs 0.18(0.09, 0.37)×10 9/L](all P<0.05), and FVC%pred, FEV 1%pred, FEV 1/FVC, PEF%pred, MEF 50%pred, MEF 25%pred, MMEF%pred, MEF 75%pred were lower than those in the non-mucus plug group [(87.49±19.32)% vs (97.34±14.24)%, (76.49±19.58)% vs (91.07±18.33)%, (72.44±10.91)% vs (79.48±8.13)%, (82.36±24.46)% vs (93.83±18.27)%, (53.03±24.81)% vs (75.75±27.15)%, (46.47±22.92)% vs (64.09±25.90)%, (50.28±23.73)% vs (74.53±26.80)%, (71.30±27.55)% vs (89.92±26.82)%] (all P<0.05). In the group with mucus plug, the airway mucus plug score was positively correlated with the patient′s body weight and the number of peripheral blood Eos counts at enrollment ( r=0.413, 0.478; all P<0.05), and negatively correlated with FVC%pred and FEV 1%pred ( r=-0.576, -0.465; all P<0.05). Logistic regression analysis showed that airway mucus plug score was a risk factor for acute asthma attack ( OR=1.269, 95% CI: 1.031-1.562; P=0.024). Conclusions:Asthma patients have a high incidence of airway mucus plug, which is related to the level of Eos inflammation and body size. Airway mucus plugs can promote airflow obstruction and acute exacerbation of asthma. In clinical practice, appropriate asthma management policies can be formulated for airway mucus plugs to delay the progression of asthma and reduce the number of acute attacks.

Structural basis of a two-antibody cocktail exhibiting highly potent and broadly neutralizing activities against SARS-CoV-2 variants including diverse Omicron sublineages

SARS-CoV-2 variants of concern (VOCs), especially the latest Omicron, have exhibited severe antibody evasion. Broadly neutralizing antibodies with high potency against Omicron are urgently needed for understanding working mechanisms and developing therapeutic agents. In this study, we characterized previously reported F61, which was isolated from convalescent patients infected with prototype SARS-CoV-2, as a broadly neutralizing antibody against all VOCs including Omicron BA.1, BA.1.1, BA.2, BA.3 and BA.4 sublineages by utilizing antigen binding and cell infection assays. We also identified and characterized another broadly neutralizing antibody D2 with epitope distinct from that of F61. More importantly, we showed that a combination of F61 with D2 exhibited synergy in neutralization and protecting mice from SARS-CoV-2 Delta and Omicron BA.1 variants. Cryo-EM structures of the spike-F61 and spike-D2 binary complexes revealed the distinct epitopes of F61 and D2 at atomic level and the structural basis for neutralization. Cryo-EM structure of the Omicron-spike-F61-D2 ternary complex provides further structural insights into the synergy between F61 and D2. These results collectively indicated F61 and F61-D2 cocktail as promising therapeutic antibodies for combating SARS-CoV-2 variants including diverse Omicron sublineages.

Health survey among patients with coronary heart disease under standardized management in Beijing Yuetan community / 中华全科医师杂志

Objective:To survey the current health status, and awareness and participation rate of cardiac rehabilitation in patients with coronary heart disease of Beijing Yuetan community.Methods:From June to December 2020, a purposeful sampling method was used to select 983 patients with coronary heart disease under standardized management at Yuetan Community Health Service Center and its 8 community health service stations in Xicheng District of Beijing, and a health questionnaire survey was conducted. The questionnaire included the general condition of the patient, the type of coronary heart disease, the comorbidities, the current secondary preventive medication and disease control, the exercise method and the patient′s awareness and participation rate of cardiac rehabilitation.Results:Among 983 participants, 541 (55.0%) were male, 578 (58.8%) were aged 65-<75 years; 591 (60.1%) were overweight or obese (BMI≥24.0 kg/m 2) (60.1%). The top three complications were hypertension (790 cases, 80.4%), dyslipidemia (646 cases, 65.7%) and diabetes (451 cases, 45.9%). The control rate of blood pressure, blood sugar and blood lipids in patients after percutaneous coronary intervention and coronary artery bypass grafting was the lowest. There were 733 (74.6%) regular exercisers; while only 8 cases, 4 cases, and 6 cases received professional exercise risk assessment, professional exercise ability evaluation, and professional exercise guidance evaluation, respectively; and only 8 cases received cardiac rehabilitation. Most participants (88.9%, 867/975) responded that they “never heard of” cardiac rehabilitation. Conclusions:Community patients with coronary heart disease mostly have comorbidities such as hypertension, dyslipidemia and diabetes. The control rate of blood lipids and blood sugar needs to be improved. Patients with coronary heart disease have a low awareness and participation rate of cardiac rehabilitation. It is recommended that community doctors should promote cardiac rehabilitation and the community cardiac rehabilitation team should be constructed.

Relationship between peripheral blood eosinophils levels and clinical characteristics of patients with acute exacerbation of chronic obstructive pulmonary disease / 中华健康管理学杂志

Objective:To study the correlation between peripheral blood eosinophils levels and clinical characteristics of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods:A retrospective study was conducted in 79 AECOPD patients admitted to the Department of Respiratory and Critical Care Medicine of Peking University Third Hospital from January 2015 to December 2016. Peripheral blood EOS level 100/μl, 300/μl, 2%, 3%, and sputum EOS level 3% were the cut-off values. Patients were divided into EOS≥100/μl group ( n=33), EOS<100/μl group ( n=46); EOS≥300/μl group ( n=10), EOS<300/μl group ( n=69); EOS%≥2% group ( n=27), EOS<2% group ( n=52); blood EOS≥3% group ( n=16), blood EOS<3% group ( n=63); sputum EOS≥3% group ( n=7), sputum EOS<3% group ( n=15) respectively. The study analyzed the differences of clinical features between each two groups of patients; According to the blood EOS level in the acute phase and the recovery phase, ≥100/μl was high and<100/μl was low, they were divided into high EOS in both acute and recovery phase group ( n=21), high EOS in the acute phase and low EOS in the recovery phase group ( n=4), low EOS in the acute phase and high EOS in the recovery phase group ( n=20) and low EOS in both acute and recovery phase group ( n=12). The differences of clinical characteristics in each group were analyzed. Results:The median duration of COPD, proportion of patients with forced expiratory volume in the first second (FEV 1) percentage of predicted value (FEV 1% predicted value)<50%, proportion of complicated with respiratory failure, median level of procalcitonin, proportion of systemic glucocorticoid therapy and median length of stay in the EOS≥100/μl group were all significantly lower than EOS<100/μl group (5 vs 13 years, 48.0% vs 81.8%, 21.9% vs 50.0%, 0.04 vs 0.09 μg/L, 21.2% vs 56.5%, 11 vs 14 d, all P<0.05). The proportion of re-acute exacerbation in the EOS≥300/μl group was significantly higher than EOS<300/μl group (60.0% vs 23.2%), while the median fibrinogen level and median procalcitonin level were significantly lower than EOS<300/μl group (3.38 vs 3.85 g/L, 0.03 vs 0.07 μg/L, all P<0.05). The median duration of COPD, proportion of FEV 1% predicted value<50%, proportion of complicated with respiratory failure, the modified British Medical Research Council′s dyspnea scale (mMRC) score, median fibrinogen level, median C-reactive protein level, median procalcitonin level, proportion of systemic glucocorticoid therapy, proportion of non-invasive ventilation during hospitalization and median length of stay in the EOS≥2% group were all significantly lower than EOS<2% group [5 vs 13 years, 40.9% vs 83.3%, 12.0% vs 51.0%, 3 (2, 3) vs 3 (3, 4) points, 3.37 vs 3.97 g/L, 3.6 vs 16.8 mg/L, 0.04 vs 0.09 μg/L, 14.8% vs 55.8%, 0 vs 19.2%, 9 vs 14 d] (all P<0.05). The median duration of COPD, proportion of complicated with respiratory failure, median level of C-reactive protein and proportion of systemic glucocorticoid therapy in the blood EOS≥3% group were significantly lower than blood EOS<3% group (5 vs 10 years, 6.7% vs 45.8%, 4.4 vs 12.9 mg/L, 12.5% vs 49.2%) (all P<0.05). The median duration of COPD and median length of stay in the sputum EOS≥3% group were significantly shorter than sputum EOS<3% group (2 vs 15 years, 10 vs 21 d), while the median blood EOS count and median blood EOS ratio were significantly higher than sputum EOS<3% group (0.20 vs 0.01×10 9/L, 2.4% vs 0.1%) (all P<0.05). The proportion of complicated with respiratory failure and received systemic glucocorticoid therapy in the high EOS in both acute and recovery phase group were significantly lower than the low EOS in the acute phase and high EOS in the recovery phase group (14.3% vs 75.0%, 14.3% vs 55.0%) (all P<0.05). The proportion of FEV 1% predicted value <50% in the high EOS in the acute phase and low EOS in the recovery phase group was significantly lower than the low EOS in the acute phase and high EOS in the recovery phase group (0 vs 82.4%) ( P<0.05). The median FEV1% predicted value level in the high EOS in the acute phase and low EOS in the recovery phase group was significantly higher than the low EOS in both acute and recovery phase group (59.5% vs 36.0%) ( P<0.05). Conclusions:High EOS AECOPD patients have a shorter duration of disease and fewer days of hospitalization. The proportion of patients complicated with respiratory failure is lower. It is easier to distinguish the differences in clinical characteristics of AECOPD patients with a blood EOS count of 100/μl as a cut-off value. EOS levels in the acute phase and the recovery phase are helpful to distinguish the clinical characteristics of AECOPD patients.

Antibody Cocktail Exhibits Broad Neutralization against SARS-CoV-2 and SARS-CoV-2 variants

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated multiple variants resistant to therapeutic antibodies. In this study, 12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries. Of them, two RBD-binding antibodies (F61 and H121) showed high affinity neutralization against SARS-CoV-2, whereas three S2-target antibodies failed to neutralize SARS-CoV-2. Following structure analysis, F61 identified a linear epitope located in residues G446 -S494, which overlapped with angiotensin-converting enzyme 2 (ACE2) binding sites, while H121 recognized a conformational epitope located on the side face of RBD, outside from ACE2 binding domain. Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-CoV-2. Importantly, F61 and H121 exhibited efficient neutralizing activity against variants B.1.1.7 and B.1.351, those showed immune escape. Efficient neutralization of F61 and H121 against multiple mutations within RBD revealed a broad neutralizing activity against SARS-CoV-2 variants, which mitigated the risk of viral escape. Our findings defined the basis of therapeutic cocktails of F61 and H121 with broad neutralization and delivered a guideline for the current and future vaccine design, therapeutic antibody development, and antigen diagnosis of SARS-CoV-2 and its novel variants.

Effects of adjuvant therapy with low molecular weight heparin on nephrotic syndrome in 32 cases / 中国基层医药

Objective:To investigate the clinical efficacy of adjuvant therapy with low molecular weight heparin on nephrotic syndrome.Methods:Sixty-four patients with nephrotic syndrome who received treatment in Linyi People's Hospital between January 2018 and January 2020 were included in this study. They were randomly assigned to receive either conventional treatment combined with low molecular weight heparin treatment (observation group, n = 32) or conventional treatment (control group, n = 32) for 28 successive days. Before and after treatment, renal function indexes, blood lipid, coagulation function indexes, clinical efficacy, and adverse reactions were compared between the two groups. Results:After treatment, serum creatinine, urea nitrogen, 24-hour urinary protein, total cholesterol and triacylglycerol levels in the observation group were (109.21 ± 9.81) μmol/L, (5.35 ± 1.01) mmol/L, (1.12 ± 0.25) g/L, (5.12 ± 1.09) mmol/L, (1.52 ± 0.18) mmol/L, respectively, which were significantly lower than those in the control group [(120.54 ± 9.72) μmol/L, (6.05 ± 0.95) mmol/L, (1.42 ± 0.28) g/L, (6.92 ± 1.15) mmol/L, (1.96 ± 0.22) mmol/L, t = 4.641, 2.855, 4.521, 6.426, 8.756, all P < 0.05]. The activated partial thromboplastin time and prothrombin time in the observation group were (1.52 ± 0.18) seconds and (14.57 ± 1.70) seconds, respectively, which were significantly longer than those in the control group [(31.02 ± 4.59) seconds, (12.62 ± 1.67) seconds, t = -4.388, -4.628, both P < 0.05]. Total effective rate in the observation group was significantly higher than that in the control group [96.88% (31/32) vs. 75.00% (24/32), χ2 = 6.335, P < 0.05]. The time to relief of symptom in the observation group was significantly shorter than that in the control group [(3.12 ± 1.42) weeks vs. (5.04 ± 1.24) weeks, t = -5.761, P < 0.05). The incidence of adverse reactions in the observation group was significantly lower than that in the control group [3.13% (1/32) vs. 21.88% (7/32), χ2 = 5.143, P < 0.05]. Conclusion:Based on conventional treatment, adjuvant therapy with low molecular weight heparin for nephrotic syndrome can greatly improve clinical symptoms, increase clinical efficacy, and decrease the incidence of adverse reactions.

Research progress in characteristics of B cells in high-, low- and non-responsive individuals after HBV vaccination / 中华微生物学和免疫学杂志

Hepatitis B virus (HBV) infection remains a serious global health problem, which can lead to acute and chronic liver diseases and a variety of complications. HBV vaccination, which induces B cells to secrete protective hepatitis B surface antibody (HBsAb), is an important measure to prevent HBV infection. Some studies have shown that different individuals have different responses to HBV vaccine, which can be divided into ultra-high/high, normal/medium and low/non-response. Research on the potential mechanisms can provide reference for the preparation of high-titer HBsAb and the prevention and treatment of HBV infection. This paper reviewed the research situation and progress in the characteristics and mechanism of B cells in different responders after HBV vaccination.

Study on the relationship between vitamin D, grip strength and muscle mass in elderly diabetic patients / 中国综合临床

Objective:To study the relationship between vitamin D level and muscle mass and grip strength in elderly patients with type 2 diabetes mellitus (T2DM).Methods:From May 2016 to January 2018, 201 patients with type 2 diabetes mellitus aged ≥ 60 who were admitted to the Department of endocrinology of Xuanwu Hospital were selected for prospective study. According to 25-hydroxyvitamin D level(25(OH)D), the patients were divided into the vitamin D deficiency group (25(OH)D<20 μg/L, 140 cases) and the non-deficiency group (20 μg/L≤25(OH)D<70 μg/L, 61 cases). The grip strength, walking speed and muscle mass of upper and lower limbs were measured.Physical examination and laboratory examination were carried out.Results:There was no significant difference between the two groups ( P>0.05). The grip strength, upper limb and lower limb muscle contents in the non deficiency group were significantly higher than those in the deficiency group ((33.49±9.43) kg vs.(29.59±10.30) kg, (4.99±1.09) kg vs.(4.57±1.11) kg, (15.69±3.10) kg vs.(14.54±3.03) kg, P=0.01, 0.015, 0.017). Multivariate logistic regression analysis showed that vitamin D deficiency was independently related to grip strength and lower limb muscle mass( OR=1.286, 95% CI: 1.197-1.346, P<0.01; OR=1.231, 95% CI: 1.102-1.283, P<0.05). Conclusion:Vitamin D deficiency is a risk factor for the decrease of grip strength and lower extremity muscle mass in elderly patients with type 2 diabetes.

Development of a triplex real-time RT-PCR assay to detect Zika, Chikungunya and Mayaro viruses / 中华实验和临床病毒学杂志

Objective@#To establish a method for the simultaneous identification of Zika, Chikungunya and Mayaro viruses.@*Methods@#The complete genome sequences of Zika, Chikungunya and Mayaro virus were retrieved from Global Shared Database for comparative analysis, estimate its conservative region and determine the target gene location, specific primers and probes were designed, then a triplex real-time RT-PCR assay was developed. The specificity, sensitivity and repeatability of the assay were assessed by viral nucleic acid of Zika virus, Chikungunya virus a, in vitro transcriptional RNA of Mayaro virus, normal human serum and related virus simulation sample.@*Results@#The result showed that the established method could detect Zika virus, Chikungunya virus, as well as simulated Mayaro virus samples, the limit of detection (LOD) of Zika and Chikungunya virus was 16.22 Copy/PCR and 12.02 Copy/PCR, respectively, the LOD for simulated Mayaro virus RNA was 2.82 Copy/PCR, no significant difference was detected between the triplex and monoplex assays. No cross reaction was found in the detection of dengue virus, Hantavirus, severe fever with thrombocytopenia syndrome (SFTS) virus, yellow fever virus and influenza virus, and 100 healthy adults blood samples, the specificity of the method was 100%. The repeatability result showed that the standard deviation of all three detections were blow 0.5 and the coefficient of variation was less than 2% by selecting viral nucleic acids or transcribed RNA with high, medium and low concentration gradients.@*Conclusions@#A triplex real-time RT-PCR assay for detection of Zika, Chikungunya and Mayaro virus has been established with an acceptable specificity, sensitivity and repeatability.

Generation of human monoclonal antibody Fab fragment to Zika Virus by Phage Display Technology / 中华实验和临床病毒学杂志

Objective@#In this study, phage display technology was used to construct the human anti-Zika virus(ZIKV), phage antibody library and to obtain and express the monoclonal antibody. The aim was to master the preparation and expression of human phage antibody library screening method for highly specific antibodies.@*Methods@#The whole blood samples of Zika patients were collected and the lymphocytes were isolated. The RT-PCR method was used to amplify the antibody light chain and heavy chain Fab gene from lymphocyte Ig mRNA. The pComb3H system was used to construct the gene with genetic diversity Preparation of human anti-ZIKV phage antibody library. The purified antibody library was screened by using the purified ZIKV and the obtained ZIKV E protein antigen.@*Results@#The monoclonal antibody Fab fragment gene was successfully obtained for the ZIKV E protein antigen. The gene can be efficiently expressed in Escherichia coli.@*Conclusions@#According to the sequence analysis, this study showed that the monoclonal antibody was a new human genetically engineered antibody against ZIKV, which laid the foundation for the early diagnosis of ZIKV, and obtain a specific monoclonal antibody to ZIKV for human treatment of ZIKV infection.

Implementation of cardiac rehabilitation for patients with acute coronary syndrome in community hospital / 中华全科医师杂志

Acute coronary syndrome (ACS) is a serious type of coronary disease with high morbidity and mortality rates,being one of leading causes of death in both developed and developing countries.Studies abroad have shown that,the cardiac rehabilitation in community hospitals carried out by general practitioners with the guidance of cardiac specialists and the establishment of a continuous,longterm exercise rehabilitation and drug therapy can effectively reduce the mortality of ACS patients.In order to complete the health care chain from prevention,treatment to rehabilitation for ACS patients in China,it is imperative for community hospitals to provide cardiac rehabilitation service.

A case of liver cirrhosis due to hypopituitarism in adolescence after nasopharyngeal carcinoma radiotherapy / 中华内分泌代谢杂志

Nonalcoholic fatty liver disease is a metabolic stress liver injury, including simple hepatic steatosis, nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC). Liver fibrosis in NASH patients progressed by an average of 7 to 10 years, and the incidence of cirrhosis in NAH patients was only 0.6％to 3.0％after 10 to 20 years of follow-up. This case reports a 21-year-old man with pituitary dysfunction and cirrhosis, whose condition develops rapidly. The mechanism may be that growth hormone deficiency affects liver signaling transduction pathways to make the liver metabolism disordered, causing nonalcoholic fatty liver disease. In this report, the pathogenesis, diagnosis and treatment of this case of cirrhosis duo to hypopituitarism in adolescence are reviewed retrospectively to improve the understanding of the diagnosis and therapy of this disease.

Construction of a mutant strain of Nocardia farcinica with mce4A gene deletion and analysis of the role of mce4A gene / 中华微生物学和免疫学杂志

Objective To construct a mutant strain of Nocardia farcinica ( N. farcinica ) IFM10152 with mammalian cell entry 4A gene (mce4A) deletion and to analyze the function of that gene dur-ing infection. -ethods The mutant strain of N. farcinica was constructed through in-frame deletion without antibiotic labeling and verified by PCR and sequencing analysis. To analyze the function of mce4A gene in the interaction between N. farcinica and host cells, in vitro growth experiment, macrophage killing experi-ment using THP-1 ( a human leukemia mononuclear cell line) as the model and adhesion and invasion exper-iments using HeLa cells ( cervical cancer epithelial cells) were carried out. Results The mutant strain with mce4A gene deletion was successfully constructed and named △mce4A. No significant difference in growth rate was observed between the mutant and the wild-type strains. After knocking out the mce4A gene, the ability of N. farcinica to resist macrophage killing was obviously weakened as well as its ability to adhere and invade. Conclusions The mutant strain of N. farcinica with mce4A gene deletion was successfully construc-ted. The mce4A gene might play an important role in the adhesion and invasion of N. farcinica to host cells and its survival in macrophages.

Comparison of efficacy and safety between percutaneous drainage and endoscopic drainage in 153 cases of pancreatic pseudocysts / 中华消化杂志

Objective To investigate the clinical outcome of pancreatic pseudocyst(PPC)treated with non-surgical methods,and to compare the efficacy and safety between percutaneous drainage and endoscopic drainage in the management of PPC.Methods From February 2010 to July 2017,clinical data of patients with PPC,who received percutaneous drainage or endoscopic drainage,were retrospectively analyzed.The symptom relief rate,short-term and long-term radiologic remission rate,complication rate, recurrence rate and length of hospital stay were compared between patients treated by ultrasound guided percutaneous drainage(percutaneous group),by endoscopic ultrasonography-guided drainage(EUS group)and by endoscopic retrograde pancreatography guided transpapillary drainage(ERP group).Two independent samples t test,one-way analysis of variance,non-parametric test and Fisher′s exact test were performed for statistical analysis.Results A total of 153 patients were treated and the operation was successfully conducted in 148 patients(96.7%),of whom 39 were in percutaneous group,73 in EUS group and 36 in ERP group.The median follow-up time was 26 weeks(two weeks to 358 weeks).The symptom relief rate,long-term radiographic remission rate,complication rate,recurrence rate and retreatment rate of percutaneous group,EUS group and ERP group were 87.2%(34/39),79.5%(58/73),80.6%(29/36);81.5%(22/27),88.6%(39/44),66.7%(16/24);17.9%(7/39),28.8%(21/73),16.7%(6/36);15.0%(3/20),13.8%(8/58),10.0%(2/20);and 10.3%(4/39),8.2%(6/73),2.8%(1/36),respectively.There was no statistically significant difference among three groups (all P> 0.05).The short-term radiographic remission rate of ERP group was significantly lower than those of percutaneous group and EUS group(46.7%,14/30 vs 77.1%,27/35 and 87.7%,64/73),and the differences were statistically significant(χ2 =6.442 and 19.450,both P<0.01).The median hospital stay of percutaneous group was longer than those of EUS group and ERP group(14.0 days vs 9.0 days and 8.0 days),and the differences were statistically significant(Z= -3.687 and -2.630,both P<0.01).Conclusions The efficacies of percutaneous drainage and EUS-guided drainage are both better than ERP,and they are effective and safe methods especially for the patients with complication of pseudocysts and necrosis debris in pseudocysts.However,the hospitalization time of percutaneous drainage is longer. In addition,percutaneous drainage can be an alternative method after failed endoscopic drainage.

Effects of high glucose and lysophosphatidylcholine (LPC) on RAW264.7 macrophages during No-cardia farcinica infection / 中华微生物学和免疫学杂志

Objective To investigate the effects of high glucose and lysophosphatidylcholine (LPC) on the immune function of in vitro cultured macrophages during Nocardia farcinica infection. Meth-ods RAW264.7 macrophages were cultured in vitro under different conditions as follows: routine culture (control group),50 mmol/L glucose (high glucose group),10 mg/L LPC(LPC groupⅠ),25 mg/L LPC (LPC groupⅡ) and 50 mmol/L glucose+25 mg/L LPC(high glucose and LPC group). The activity of mac-rophages in each group was tested after 6,12,24 and 36 h of culture. After 24 h of culture, macrophages were collected from every group and co-cultured with Nocardia farcinica. Dynamic phagocytosis rates were detected at 1,2,3,4,5 and 6 h after co-culture. Toxic effects of Nocardia farcinica on macrophages and concentrations of IL-10 and TNF-α were measured at 1,3 and 6 h after co-culture. Results Macrophages in all four experimental groups showed decreased activity as compared with those in the control group (P<0.01). Phagocytosis of Nocardia farcinica by macrophages was also reduced by high glucose and LPC. Phagocytosis rates of high glucose group and LPC groupⅡ at 1 and 2 h,LPC groupⅠat 1,2 and 3 h,and high glucose and LPC group at 1,2,3 and 4 h after co-culture were significantly lower than that of the con-trol group (P<0.05 or P<0.01). Compared with the control group, significantly reduced toxic effects on macrophages caused by Nocardia farcinica was observed in the experimental groups (P<0.05 or P<0.01). Compared with the control group,LPC groupsⅠand Ⅱ and high glucose and LPC group had decreased se-cretion of IL-10 at 3 h,and high glucose group and LPC groupⅠhad decreased secretion of TNF-α at 1 h(P<0.05). Conclusion Culture macrophages under the conditions of high glucose and LPC would reduce their activity and impair their ability to phagocytose Nocardia farcinica. Moreover, high glucose and LPC might have impacts on the toxic effects of Nocardia farcinica on macrophages and the secretion of IL-10 and TNF-α.