Objective To investigate the efficacy of voriconazole in the treatment of pulmonary tuberculosis complicated with chronic pulmonary aspergillosis(CPA)based on CYP2C19 gene polymorphism detection and examine the factors affecting the efficacy for improving targeted therapy in clinical practice.Methods A total of 207 patients with pulmonary tuberculosis complicated with CPA treated in the Third People's Hospital of Kunming from December 2018 to November 2022 were randomly assigned to an observation group(105 cases)or a control group(102 cases).The patients in the control group received standard voriconazole treatment,while the patients in the observation group had their voriconazole regimen tailored based on CYP2C19 genotyping results.Plasma drug concentration levels,efficacy,and safety were compared between the two groups and in terms of CYP2C19 genotypes.Logistic regression analysis was used to identify the factors affecting treatment efficacy.Results The observation group showed significantly higher plasma voriconazole concentrations and overall antifungal efficacy compared to the control group(P＜0.05).In the observation group,CYP2C19 genotyping identified 37 extensive metabolizers(EM),47 intermediate metabolizers(IM),and 21 poor metabolizers(PM).Plasma concentration of voriconazole did not show significant difference between EM and IM(P＞0.05),but both PM and IM were associated with significantly lower plasma concentration of voriconazole than PM(P＜0.05).The clinical efficacy rate was 100％for PM,91.5％for IM,and 83.8％for EM(P＜0.05).The incidence of adverse events did not show significant difference among the three genotypes(P＞0.05).Logistic regression analysis revealed that lung cavitation,hypoalbuminemia,and agranulosis were significantly correlated with therapeutic efficacy(P＜0.05).Conclusions CYP2C19 gene polymorphism detection is valuable in clinical practice.It can inform anti-aspergillus therapy with voriconazole to effectively improve symptoms and clinical efficacy in patients with pulmonary tuberculosis complicated with CPA.Meanwhile,clinicians should be aware of the factors such as hypoproteinemia,agranulocytosis,and lung cavitation that may affect the efficacy of voriconazole.

Objective To investigate the efficacy of voriconazole in the treatment of pulmonary tuberculosis complicated with chronic pulmonary aspergillosis(CPA)based on CYP2C19 gene polymorphism detection and examine the factors affecting the efficacy for improving targeted therapy in clinical practice.Methods A total of 207 patients with pulmonary tuberculosis complicated with CPA treated in the Third People's Hospital of Kunming from December 2018 to November 2022 were randomly assigned to an observation group(105 cases)or a control group(102 cases).The patients in the control group received standard voriconazole treatment,while the patients in the observation group had their voriconazole regimen tailored based on CYP2C19 genotyping results.Plasma drug concentration levels,efficacy,and safety were compared between the two groups and in terms of CYP2C19 genotypes.Logistic regression analysis was used to identify the factors affecting treatment efficacy.Results The observation group showed significantly higher plasma voriconazole concentrations and overall antifungal efficacy compared to the control group(P＜0.05).In the observation group,CYP2C19 genotyping identified 37 extensive metabolizers(EM),47 intermediate metabolizers(IM),and 21 poor metabolizers(PM).Plasma concentration of voriconazole did not show significant difference between EM and IM(P＞0.05),but both PM and IM were associated with significantly lower plasma concentration of voriconazole than PM(P＜0.05).The clinical efficacy rate was 100％for PM,91.5％for IM,and 83.8％for EM(P＜0.05).The incidence of adverse events did not show significant difference among the three genotypes(P＞0.05).Logistic regression analysis revealed that lung cavitation,hypoalbuminemia,and agranulosis were significantly correlated with therapeutic efficacy(P＜0.05).Conclusions CYP2C19 gene polymorphism detection is valuable in clinical practice.It can inform anti-aspergillus therapy with voriconazole to effectively improve symptoms and clinical efficacy in patients with pulmonary tuberculosis complicated with CPA.Meanwhile,clinicians should be aware of the factors such as hypoproteinemia,agranulocytosis,and lung cavitation that may affect the efficacy of voriconazole.

Insertion/deletion polymorphism(InDel)markers are a class of length polymorphic genetic markers widely distributed in genomes,which have the characteristics of both STR and SNP.InDel markers can be applied to the work like individual identification of degraded materials and the identification of complex relationship.It can narrow the scope of investigation by ancestral inference,which have important practical value in forensic genetics inspection and analysis.With the development of research on Multi-InDel and Multi-allelic InDel markers,the identification efficiency of InDel markers continues to improve,and their forensic application scenarios are also expanded.This review summarized the application and development of InDel markers in forensic genetics,and explored the development in the future.

Insertion/deletion polymorphism(InDel)markers are a class of length polymorphic genetic markers widely distributed in genomes,which have the characteristics of both STR and SNP.InDel markers can be applied to the work like individual identification of degraded materials and the identification of complex relationship.It can narrow the scope of investigation by ancestral inference,which have important practical value in forensic genetics inspection and analysis.With the development of research on Multi-InDel and Multi-allelic InDel markers,the identification efficiency of InDel markers continues to improve,and their forensic application scenarios are also expanded.This review summarized the application and development of InDel markers in forensic genetics,and explored the development in the future.

Objective:To investigate the related factors of vertebral body height reloss after pedicle screw fixation of thoracolumbar fracture and to determe the optimum prediction point.Methods:A retrospective case control study was made on 215 patients with thoracolumbar fracture admitted to Second Affiliated Hospital of Soochow University from January 2010 to December 2017. There were 155 males and 60 females，aged 21-80 years［（48.6±10.4）years］. According to Denis fracture classification，there were 73 patients with compression fractures（type A in 15 patients，type B in 51，type C in 7），135 burst fractures（type A in 28 patients，type B in 87，type C in 20）and flexion distraction fractures（type A in 4，type B in 2，type C in 1）. All patients were treated by pedicle screw fixation. Follow-up lasted for 12- 48 months［（23.8±8.2）months］. Vertebral body height loss occurred in 86 patients（loss group），but did not in 129 patients（non-loss group）. The two groups were compared concerning sex，age，osteoporosis self-assessment tool for Asians（OSTA），body mass index（BMI），fracture types，number of fractured vertebrae，preoperative sagittal Cobb angle，preoperative degree of vertebral compression，number of screws placed in injured vertebrae，extent of vertebral reset and other related factors. Univariate analysis was used to identify the correlation of those factors with vertebral body height reloss. Multivariate Logistic regression analysis was performed to identify the independent factors for the height reloss with the receiver operating characteristic curve（ROC）and area under the curve（AUC）calculated to evaluate the optimum point in prediction of vertebral height reloss.Results:The two groups showed no significant differences in sex，age，BMI，fracture types，number of injured vertebrae，preoperative sagittal Cobb angle and number of screws placed in injured vertebrae（ P>0.05），but the differences were statistically significant in OSTA，preoperative degree of vertebral compression and extent of vertebral reset（ P<0.05）. According to the univariate analysis，OSTA，preoperative degree of vertebral compression and extent of vertebral reset were significantly correlated with the occurrence of vertebral body height reloss（ P<0.05）. According to the multivariate Logistic regression，OSTA（ OR=1.109，95% CI 0.527-0.685， P<0.05）and preoperative degree of vertebral compression（ OR =0.038，95% CI 0.539-0.689， P<0.05）were significantly related to vertebral body height reloss. The AUC relating OSTA and preoperative degree of vertebral compression to vertebral body height reloss was 0.604 and 0.614，respectively. The optimum prediction point of OSTA and preoperative degree of vertebral compression for vertebral body height reloss was 1.9 and 31.3%，respectively. Conclusions:OSTA and the preoperative degree of vertebral compression are independent risk factors for vertebral body height reloss. OSTA≤1.9 or preoperative degree of vertebral compression ≥31.3% indicates a significantly higher risk of postoperative vertebral body height reloss.

Objective To assess the quantitative impact of the application of high-throughput sequencing worldwide on clinical virology.Methods The following records from 2000 to 2018 were collected from National Center for Biotechnology Information:The number of complete genome of virus records per year;the number of virus discovery articles per year;the number of virus quasi-species articles per year;the number of viral infection gene signature articles per year.The method of interrupted time series was applied to analyze the trends of those records.Results Since the sequencing centers worldwide began to transit from the Sanger sequencing to the high-throughput sequencing technology in 2008,the annual value of records mentioned above increased by 3.755,2.760,6.195 and 3.885 times respectively.The long-term trends of change of each record are as follows:the number of complete genome of virus records increased by 1639.991 per year (P＜0.001);the number of virus discovery articles increased by 83.091 per year (P＜0.001);the number of virus quasi-species articles increased by 2.509 per year (P＜ 0.001);the number of viral infection gene signature articles increased by 30.836 per year (P＜ 0.001).Conclusions In 2008,the sequencing centers worldwide began to apply high-throughput sequencing technology which led to continuous decrease of the cost for sequencing.It result ed in not only increasingly enriched applications in clinical virology but also a long-term positive impact on the advance of clinical virology.

Objective To systematically review the clinical efficacy and safety of early use of recombinant human erythropoietin (rHu-EPO) for neuroprotection in premature infants.Method From establishment of the databases to November 2017,clinical randomized controlled trials (RCTs) of early use of rHu-EPO in premature infants were searched on English databases (PubMed,Embase,Cochrane Collaboration) and Chinese databases (CNKI,SinoMed,Wanfang,and VIP Database).Patients receiving conventional therapy were assigned into control group,and patients receiving both conventional therapy and rHu-EPO were assigned into rHu-EPO group.rHu-EPO group was subdivided into high-dose continuous group and low-dose intermittent group.We retrieved the related literatures,evaluated the quality,and then performed Meta-analysis using RevMan 5.3 software.Result A total of 2 588 patients in 17 studies were included and analyzed.Compared with the control group,Meta-analysis showed that early use of rHu-EPO was more effective in improving NBNA scores at 40 weeks of corrected gestational age (cGA) (MD=2.46,95％CI 1.58～3.33,P＜0.001),and high-dose continuous group was better than low-dose intermittent group (MD=3.19,95％CI 0.45～5.93,P=0.002;MD=2.22,95％CI 1.29～3.16,P＜0.001).Low-dose intermittent use of rHu-EPO significantly increased mental development index (MDI) (MD=6.66,95％CI 0.80～12.51,P=0.010) and psychomotor development index (PDI) (MD=5.77,95％CI 4.00～7.55,P＜0.001),and reduced the incidence of MDI＜70 at cGA 18～22 months (OR=0.42,95％CI 0.27～0.67,P＜0.001).As to the safety and side effects,treatment with rHu-EPO reduced the risk of necrotizing enterocolitis (OR=0.48,95％CI 0.31 ～0.72,P＜0.001) and periventricular leukomalacia (OR=0.52,95％CI 0.35～0.75,P＜0.001)without increasing the risk of bronchial dysplasia,patent ductus arteriosus,retinopathy in prematurity and intraventricular hemorrhage.Conclusion Current evidence shows that the early use of rHu-EPO in premature infants is relatively effective and safe,but multi-center RCTs are still needed.

Clinical data of a 33-year-old rheumatoid arthritis patient accompanied with pregnancy and lactation-associated osteoporosis(PLO) was retrospectively reviewed.The patient had two pregnancies within three years,and bone pain occurred during lactation of the second pregnancy after 2 months of delivery.Dual-energy X-ray (DEXA) showed decreased bone density,while thoracolumbar spine and pelvic X-ray film suggested osteoporosis.Her rheumatoid arthritis was stable and previous treatment did not include glucocorticoids.Other causes of metabolic bone diseases were excluded and the diagnosis of PLO was confirmed.The breastfeeding was stopped;calcium,active vitamin D,alendronate sodium were administrated,and the treatment was effective.Domestic and international literature from January 2000 to January 2019 was searched and no cases of PLO accompanied with rheumatoid arthritis were reported.There were only 100 cases of PLO retrieved in the literature,including 19 cases of PLO in China reported by four articles.It is suggested that PLO should be considered in RA patients presenting with arthragia during the lactation,in addition to relapse of disease.Awareness of PLO should be increased in physicians,especially rheumatologists,and anti-osteoporosis therapy is effective in patients with PLO.

Objective: To develop a micro-neutralization test for determination of neutralizing antibody against ZIKA virus (ZIKV) in human sera and to verify the acute and convalescent serum samples of 10 ZIKA virus-infected cases diagnosed by nucleic acid detection and/or virus isolation. Methods: ZIKV isolated from ZIKA cases was used to determine micro-neutralization antibody. The virus solution was prepared by infecting BHK21, VERO and VERO-E6 cell lines and viral titer was tested; 100 TCID₅₀ viral solution and 4 times diluted sera which were inactivated at 56 ℃ for 30 min were neutralized, then added the cell suspension and incubated in 5% CO₂ incubator at 37 ℃ for 7 d. The CPE was observed every day. Results: The sensitivity of BHK21, VERO and VERO-E6 was different after infection with ZIKA virus. VERO cell line was the most sensitive and showed typical CPE. VERO cell line was used to establish a micro-neutralization test for determination of neutralizing antibody against ZIKA virus in sera. Conclusions The neutralizing antibody test for zika virus in sera is a special and usefulmethod to diagnose human infection of ZIKV and to conduct population based epidemiological investigation.

Objective To report two cases of familial Gitelman syndrome and literature review regarding the updates of relevant genes,classification,treatment,and prognosis.Methods The clinical data of two sisters with Gitelman syndrome were retrospectively analyzed.Results Their blood pressures were within normal range.Hypokalaemic alkalosis,hypomagnesemia,and hypocalciuria were corrected almost completely after three days of intravenous magnesium and potassium infusion,spirolactone and indometacin.However,the maintenance of normal potassium was unsuccessful over one year.Conclusion Hypokalaemic alkalosis,hypomagnesemia,and hypocalciuria were normalized in Gitelman syndrome.There was some debate in regard to using PGE2 synthetase inhibitors.Tolerance of long-term medication will be the big challenge for curative effect.