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.

Objective: To assess the relationship between hemoglobin A₁c (HbA₁c) and hemorrhagic cerebral infarction (HI) in patients with acute cerebral infarction. Methods: From January 2014 to June 2016, in the Lianyungang Hospital Affiliated to Xuzhou Medical University, 426 patients with acute anterior circulation infarction were included. The blood sugar status before stroke was expressed by HbA₁c. HbA₁c and fasting blood glucose (FBG) were measured on the second day after admission. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the severity of neurological function at admission. The modified Rankin scale (mRS) was used to evaluate the prognosis at discharge. CT or MRI/SWI examination was performed to determine whether there was HT. Logistic regression was used to evaluate the risk factors for HT and short-term prognosis after cerebral infarction. Results: Of the 426 patients enrolled, 93 (21.8%) appeared HT, 60 (14.1%) had hemorrhagic cerebral infarction (HI) and 33 (7.7%) had parenchymal hemorrhage (PH). Multivariate analysis showed that HbA₁c and infarct volume were independent predictor of HT. When patients were grouped according to fasting blood glucose (FBG<7.8 mmol/L or ≥ 7.8 mmol/L), the predictive effect of HbA₁c on HT was found in both groups. In multiple Logistic regression analysis, HbA₁c was also a predictor of poor prognosis after stroke (OR=1.482, 95% CI 1.228 -1.788). Conclusions In patients with ischemic stroke, elevated HbA₁c is independently associated with post-infarction HT, and this result doesn′t change even in patients with well-controlled blood glucose. HbA₁c is also a predictor of poor prognosis after stroke. These findings are important for blood glucose management in patients with diabetes and acute anterior circulation infarction.

Objective To investigate the effects of cholinergic pathway on acute renal tubular cell injury induced by acute oxygen and glucose deprivation. Methods Rat kidney macrophages were isolated and cultured for constructing macrophages and renal epithelial cells co-cultivating model of oxygen-glucose deprivation (OGD), and the model cells were divided into three groups: OGD alone group, acetylcholine (ACh 100μmol/L)+OGD group and ACh + galantamine (Gal 10μmol/L)+OGD group. The cells underwent OGD treatment for 1 hour, and normally cultured for 24 hours. The expressions of TNF alpha, IL-1 beta, and IL-10 in supernatant fluid were detected by ELISA, the renal tubular cell viability was determined by MTT assay, the expression of acetylcholine esterase (AChE) mRNA and protein were determined by RT-qPCR and Western blotting. The activity of AChE was determined by colorimetric method. Results The expressions of TNF alpha (pg/ml) in OGD, Ach+OGD group, Ach+Gal+OGD groups were 140.2±44.81, 119.46±4.42 and 103.31±1.62 respectively (P<0.05), those of IL-1β (pg/ml) were 172.26±13.51,144.34±5.53 and 119.37±11.42 respectively (P<0.05), and those of IL-10 (pg/ml) were 181.47±16.01, 173.62±10.12 and 188.36±8.73 respectively (P>0.05); The values of renal tubular cell proliferation were 55.02%±6.28%, 66.65%±6.47%, and 79.75%±4.22% respectively (P<0.01); the expressions of AChE mRNA in macrophages were 4.07±0.03, 4.22±0.15 and 3.98±0.29 respectively in the three groups (P>0.05); those of AchE protein were 0.66±0.07, 0.74±0.04 and 0.67±0.06 respectively (P>0.05); The activity of AChE (kU/L) was 0.51±0.02, 0.35±0.05 and 0.32±0.04 respectively (P=0.001, 0.001 and 0.368). Conclusions ACh and Gal could inhibit the secretion of inflammatory mediators and cholinesterase activity and can reduce the acute hypoxic renal tubular cell injury. The modulation of the cholinergic pathway in macrophages may be the important treatment method for acute renal injury in the future.

ObjectiveToinvestigatethecorrelationbetweenbloodpressurevariabilityandcognitive impairment in ischemic stroke. Methods The inpatients with acute ischemic stroke were enroled. The demographic and clinical data were colected. The coefficient of variation of blood pressure within 7 days after onset w as calculated. Montreal Cognitive Assessment w as used to evaluate the cognitive function at three month after onset. Multivariate logistic regression analysis w as used to identify the relationship betw een the coefficient of variation of blood pressure w ithin 7 days and the cognitive impairment at 3 months after onset. Results A total of 708 patients w ith acute ischemic stroke w ere enrol ed in the study. At 3-month folow-up, 510 patients (72.0%) had cognitive impairment and 198 (28.0%) had normal cognitive function. The coefficient of variation for systolic blood pressure ( 8.3 ±1.2 vs.8.7 ±1.4; t= -3.299, P=0.001) and coefficient of variation for diastolic blood pressure ( 7.8 ±1.3 vs.8.0 ±1.5; t= -2.529, P=0.012) in the cognitive impairment group w ere significantly higher than those in the normal cognitive function group. With the first quintile as a reference, after adjusting other confounding factors, multivariate logistic regression analysis show ed that cognitive impairment at 3 months after onset w as significantly associated w ith coefficient of variation for systolic blood pressure. The odds ratios and 95 % confidence intervals for the 2-5 quantile groups w ere 2.33 (1.18-4.6), 2.31 (1.15-4.66), 2.70 (1.29-5.65), and 4.82 (1.92-12.1), respectively ( al P<0.05 ). Conclusion Systolic blood pressure variability in the acute phase of ischemic stroke is associated w ith cognitive impairment.

Objective To investigate the effects of prenatal alcohol exposure on rhythmic respiratory discharge activity (RRDA) in the medullary slices of neonatal rats. Methods Ten pregnant female SD rats were exposed to 0, 4%, 6%, 8%, and 10%alcohol in drinking water from 1 week before till 3 days after delivery. The medullary slices of the neonatal rats containing the medial region of the nucleus retrofacialis (mNRF) with the hypoglossal nerve rootlets were prepared and perfused with modified Kreb's solution to record RRDA from the hypoglossal nerve rootlets using suction electrodes. Results No significant difference was found in RRDA in 50 min among the neonatal rats with prenatal exposure to 0, 4%, 6%, and 8%alcohol, but the RRDA in 10%alcohol exposure group became irregular. Prenatal exposure to increased alcohol concentrations caused attenuated RRDA attenuated in the neonatal rats, shown by shortened inspiratory time (TI), decreased respiratory frequency (RF), and reduced integral amplitude (IA) as compared with those in the control group. Conclusion Prenatal alcohol exposure inhibits RRDA in medullary slices of neonatal rats, which might be a mechanism by which maternal alcohol exposure causes suppressed offspring respiratory functions.

Objective To investigate the effects of prenatal alcohol exposure on rhythmic respiratory discharge activity (RRDA) in the medullary slices of neonatal rats. Methods Ten pregnant female SD rats were exposed to 0, 4%, 6%, 8%, and 10%alcohol in drinking water from 1 week before till 3 days after delivery. The medullary slices of the neonatal rats containing the medial region of the nucleus retrofacialis (mNRF) with the hypoglossal nerve rootlets were prepared and perfused with modified Kreb's solution to record RRDA from the hypoglossal nerve rootlets using suction electrodes. Results No significant difference was found in RRDA in 50 min among the neonatal rats with prenatal exposure to 0, 4%, 6%, and 8%alcohol, but the RRDA in 10%alcohol exposure group became irregular. Prenatal exposure to increased alcohol concentrations caused attenuated RRDA attenuated in the neonatal rats, shown by shortened inspiratory time (TI), decreased respiratory frequency (RF), and reduced integral amplitude (IA) as compared with those in the control group. Conclusion Prenatal alcohol exposure inhibits RRDA in medullary slices of neonatal rats, which might be a mechanism by which maternal alcohol exposure causes suppressed offspring respiratory functions.

Objective To explore the effect of body-weight support treadmill training(BWSTT)on lower extremity muscle atrophy and ambulatory capacity in complete spinal cord injured(SCI)patients.Methods 20 patients with complete SCI at the thoracic level were divided into control and BWSTT group.They all received comprehensive rehabilitation,and patients in BWSTT group also received BWSTT for 3 months when the physical condition was permitted.They were assessed before and after treatment with measurement of thigh girth,ambulatory capacity measure of Functional Independence Measure(FIM),10 meters ambulatory velocity and activity of daily living(ADL)evaluation.Patients in BWSTT group also received middle thigh MRI examination before and after BWSTT.Results The muscles at the mid-thigh of the BWSTT group looked larger after BWSTT than before.The scores of FIM ambulatory function,the 10 miters ambulatory velocity of BWSTT group improved significantly when compared with that of the control group(P<0.05).The thigh girth and the scores of ADL were no different between these two groups before and after treatment(P<0.05).Conclusion BWSTT may ameliorate lower extremities skeletal muscle atrophy and improve ambulatory capacity for SCI patients.

Objective To research the mechanism or pathway through which Substance P(SP) inhibits r-aminobutyric acid(GABA) activated currents in bullfrog dorsal root ganglion(DRG) neurons.Method The experiment was conducted on freshly isolated bullfrog dorsal root ganglion neurons using a whole-cell patch-clamp technique.Results SP could caused a slow inward current when SP was applied to DRG neurons;SP could inhibits GABA-activated currents;The inhibition could be reduced largely when protein kinase C(PKC) inhibiter,1-(5-isoquinolinesulphorry)-2-methylpiperazine(H-7), was dialyzed in cell body.Conclusion The SP ton inhibit GABA-activated currents through protein kinase C.