[Clinical Analysis of Voriconazole Concentrations in Cerebrospinal Fluid and Blood in Patients with Ryptococcal Meningitis].

Objective: To investigate the concentrations of voriconazole (VCZ) in the central nervous system (CNS) of patients with cryptococcal meningitis and the relationship thereof. Methods: We retrospectively analyzed the trough concentration of VCZ in the cerebrospinal fluid (CSF) and the blood of 25 adult patients who had cryptococcal meningitis, and who were not infected with HIV. We also examined patient-level characteristics that could contribute to the differences in CSF/plasma VCZ concentration ratio. Results: The trough concentration of VCZ in plasma ranged from 0.38 to 8.56 mg/L, and the median (P 25, P 75) was 1.81 (1.40, 3.84) mg/L. The trough concentration of VCZ in CSF ranged from 0.17 to 3.92 mg/L, and the median (P 25, P 75) was 1.02 (0.54, 1.84) mg/L. The CSF VCZ trough concentration showed a slight negative correlation with the nucleated cell counts in CSF, but the correlation was not statistically significant ( r=-0.377, P=0.063). There was a positive correlation between VCZ concentrations in CSF and that in the plasma ( r=0.736, P<0.001), and the median (P 25, P 75) CSF/plasma ratio was 0.43 (0.34, 0.68). The CSF/plasma ratio did not statistically correlate with age, body surface area (BSA), radiology changes (hydrocephalus), or intracranial pressure. Conclusion: There is a positive correlation between VCZ concentration in CSF and VCZ concentration in the plasma, and no influencing factors of CSF/plasma ratio were found.

Correlation Between Smoking and Passive Smoking with Multiple Sclerosis and the Underlying Molecular Mechanisms.

Multiple sclerosis (MS) is a chronic immune-mediated disease of the spinal cord and brain. Many studies have shown that smoking and passive smoking are key environmental risk factors for MS. Here, we provide an overview of the human leukocyte antigen (HLA) gene studies on smoking and MS risk, and we discuss recent studies on between epigenetics and smoking-induced MS. In addition, in this review we also summarize current research advances in biological pathways and smoking-induced MS. This review provides an overview of studies on the association between smoking, passive smoking, and MS susceptibility, and the underlying molecular mechanism.

[Genotype Distribution of 1 998 Strains of Hepatitis C Virus in West China Hospital of Sichuan University from 2009 to 2013].

OBJECTIVES: To investigate hepatitis C virus (HCV) genotype distribution detected in West China Hospital of Sichuan University. METHODS: We analyzed genotype distribution data on HCV infected patients who had information of HCV genotypes from January 2009 to December 2013 diagnosed in West China Hospital of Sichuan University. RESULTS: Five genotypes and 15 genetic subtypes of HCV were found among the 1 998 cases, and 4 of the patients were infected with mixed HCV subtype. Among those genotypes and genetic subtypes, genotype 1a was detected in 8 cases (0.40%), genotype 1b in 1 368 cases (68.47%), genotype 1c in 18 cases (0.90%), genotype 2a in 78 cases (3.90%), genotype 2b in 1 case (0.05%), genotype 2i in 16 cases (0.80%), genotype 3a in 291 cases (14.56%), genotype 3b in 154 cases (7.71%), genotype 3k in 4 cases (0.20%), genotype 5a in 1 case (0.05%), genotype 6a in 50 cases (2.50%), genotype 6b in 3 cases (0.15%), genotype 6h in 1 case (0.05%), genotype 6n in 1 case (0.05%), mixed-genotype 1b/1c in 1 case (0.05%), mixed-genotype 1b/6h in 1 case (0.05%), mixed-genotype 2c/2a in 1 case (0.05%), and mixed-genotype 3b/3k in 1 case (0.05%). The distribution of five main HCV genetic subtypes on gender had no statistical significance (P>0.05), and its distribution on people with different ages had statistical significance ( P<0.05). CONCLUSIONS: The major genotypes of HCV were 1b (predominant), 3a, 3b, 2a, 6a in patients diagnosed in West China Hospital of Sichuan University, with the existence of single-genotype 1a, 1c, 2b, 2i, 3k, 5a, 6b, 6h, 6n and mixed-genotype 1b/1c, 1b/6h, 2c/2a, 3b/3k, indicating the diversity of HCV genotype.

Review on pharmacological effects of gastrodin.

Gastrodia elata Blume is a well-known traditional Chinese medicine that is mainly used to treat diseases related to the nervous system, such as stroke, epilepsy, and headache. Gastrodin is the main bioactive component of Gastrodia elata Blume, and studies have shown that it has extensive pharmacological activity. This narrative review aims to systematically review relevant studies on the pharmacological effects of gastrodin to provide researchers with the latest and most useful information. Studies have shown that gastrodin has prominent neuroprotective effects and can treat or improve epilepsy, Tourette syndrome, Alzheimer's disease, Parkinson's disease, emotional disorders, cerebral ischemia-reperfusion injury, cognitive impairment, and neuropathic pain. Gastrodin can also improve myocardial hypertrophy, hypertension, and myocardial ischemia-reperfusion injury. In addition, gastrodin can mitigate liver, kidney, and bone tissue damage caused by oxidative stress and inflammation. In short, gastrodin is expected to treat many diseases, and it is worth investing more effort in research on this compound.

The Development and Validation of a Predictive Model for Voriconazole-Related Liver Injury in Hospitalized Patients in China.

Voriconazole is widely used in the treatment and prevention of invasive fungal diseases. Common drug-induced liver injuries increase the economic burdens and the risks of premature drug withdrawal and disease recurrence. This study estimated the disposal cost of voriconazole-related liver injury, explored the risk factors of voriconazole-related liver injury in hospitalized patients, and established a predictive model of liver injury to assist clinicians and pharmacists in estimating the probability or risk of liver injury after voriconazole administration to allow for early identification and intervention in patients at high risk of liver injury. A retrospective study was conducted on the selected inpatients whose blood concentration of voriconazole was measured in the West China Hospital of Sichuan University from September 2016 to June 2020. The incidence and disposal cost of voriconazole-related liver injuries were calculated. The incidence of voriconazole-related liver injury was 15.82% (217/1372). The disposal cost has been converted to 2023 at a discount rate of 5%. The median (P25, P75) disposal cost of severe liver injury (n = 42), general liver injury (n = 175), and non-liver injury (n = 1155) was 993.59 (361.70, 1451.76) Chinese yuan, 0.00 (0.00, 410.48) yuan, and 0.00 (0.00, 0.00) yuan, respectively, with a statistically significant difference (p < 0.001). Single factor analysis and multiple factor logistic regression were used to analyze the risk factors of voriconazole-related liver injury. The voriconazole-related liver injury was related to the trough concentration (Cmin, OR 1.099, 95% CI 1.058-1.140), hypoproteinemia (OR 1.723, 95% CI 1.126-2.636), and transplantation status (OR 0.555, 95% CI 0.325-0.948). The prediction model of liver injury was Logit (P)= -2.219 + 0.094 × Cmin + 0.544 × Hydroproteinemia - 0.589 × Transplantation, and the prediction model nomogram was established. The model validation results showed that the C-index of the derivation set and validation set was 0.706 and 0.733, respectively. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.705 and 0.733, respectively, indicating that the model had good prediction ability. The prediction model will be helpful to develop clinical individualized medication of voriconazole and to identify and intervene in the cases of patients at high risk of voriconazole-related liver injury early on, in order to reduce the incidence of voriconazole-related liver injuries and the cost of treatment.

HAGLR promotes neuron differentiation through the miR-130a-3p-MeCP2 axis.

Parkinson's disease (PD) is a prevalent neurodegenerative disease. Currently, the molecular mechanisms underlying the progressions of PD are not fully understood. The human neuroblastoma cell line SH-SY5Y has been widely used as an in vitro model for PD. This study aims to investigate the molecular mechanisms of the non-coding RNA-mediated SH-SY5Y differentiation induced by retinoic acid (RA). By microArray analysis, lncRNA HAGLR was observed to be significantly upregulated during the RA-induced SH-SY5Y differentiation. Silencing HAGLR blocked the RA-induced SH-SY5Y differentiation. Moreover, bioinformatical analysis illustrated that miR-130a-3p contains binding sites for HAGLR. The RNA-pull down assay and luciferase assay demonstrated that HAGLR functioned as a ceRNA of miR-130a-3p in SH-SY5Y cells. Overexpression of miR-130a-3p effectively inhibited SH-SY5Y differentiation. We identified MeCP2, a vital molecule in neuronal diseases, to be a direct target of miR-130a-3p in SH-SY5Y cells by western blot and luciferase assays. The rescue experiments verified that recovery of miR-130a-3p in HAGLR-overexpressing SH-SY5Y cells could successfully overcome the RA-induced SH-SY5Y differentiation by targeting MeCP2. In summary, this study reveals a potential molecular mechanism for the lncRNA-HAGLR-promoted in vitro neuron differentiation by targeting the miR-130a-3p-MeCP2 axis, contributing to the understanding of the pathogenesis and progression of PD.

Sudden rhabdomyolysis in an elderly patient after single atorvastatin dose: The need for early and frequent creatine kinase monitoring in high-risk patients.

An 80-year-old patient with diabetes mellitus, chronic bronchitis, and chronic heart failure presented with pain in the right calf after one dose of atorvastatin. Significant increases in creatine kinase, myoglobin, and potassium levels were also observed. Based on the symptoms and laboratory results, the patient was diagnosed with rhabdomyolysis. Older patients with co-morbidities may have a higher risk of statin-associated myopathy. However, there is currently no recommendation for creatine kinase monitoring in this population. This case emphasizes the need to identify high-risk populations and provide early and more frequent creatine kinase measurements to help avoid statin-associated myopathy.

[Comparison of three types of self-treatments for posterior canal benign paroxysmal positional vertigo: modified Epley maneuver, modified Semont maneuver and Brandt-Daroff maneuver].

OBJECTIVE: To compare the efficacy and recurrence rates of modified Epley maneuver, modified Semont maneuver and Brandt-Daroff maneuver in patients with posterior canal benign paroxysmal positional vertigo (PC-BPPV). METHODS: One hundred and sixty-eight patients with unilateral PC-BPPV were included in the study, which were divided into four groups randomly, 45 with modified Epley maneuver (group 1), 43 with modified Semont maneuver (group 2), and 40 with Brandt-Daroff maneuver (group 3). There were 40 controls without physical therapy technique (group 4) included. The efficacy after one week and one month, the time to recovery, the frequency of side effects and recurrence rates among the four groups were evaluated. RESULTS: The efficacy of modified Epley maneuver was superior to the other three groups after one week (χ(2)(1, 2) = 8.55, P < 0.05; χ(2)(1, 3) = 23.23, P < 0.01;χ(2)(1, 4) = 44.00, P < 0.01) and to the Brandt-Daroff maneuver at follow-up evaluation after one month (χ(2) = 8.42, P < 0.05). The efficacy of modified Semont maneuver was superior to the control groups after one week (χ(2) = 14.49, P < 0.01), but there was no difference between the two groups after one month (χ(2) = 0.01, P > 0.05). The efficacy of Brandt-Daroff maneuver was not different with the control group at one week and one month follow-up evaluation (χ(2) = 3.35, P > 0.05;χ(2) = 0.18, P > 0.05). Kaplan-Meier testing showed that the time to recovery was significantly shorter in the modified Epley group. The frequency of side effects was not significantly different among the three physical therapy groups. There was no difference in the frequency of recurrence among the four groups (χ(2) = 4.076, P = 0.253). Duration of illness before self-treatment and age were the independent predictors of recurrence. CONCLUSIONS: The modified Epley maneuver is more effective for self treatment of PC-BPPV than modified Semont maneuver and Brandt-Daroff maneuver. Daily routine of self-treatment does not prevent the recurrence of PC-BPPV.

[Observation on therapeutic effect of electroacupuncture combined with functional training for treatment of peripheral nerve incomplete injury of upper limbs].

OBJECTIVE: To search for the best program for treatment of peripheral nerve incomplete injury. METHODS: Ninety cases were randomly divided into a treatment group, a control group I and a control group II, 30 cases in each group. The treatment group were treated with electroacupuncture at Jianyu (LI 15), Hegu (LI 4), Quchi (LI 11), etc. plus functional training, and the control group I with electroacupuncture and the control group H with functional training. After treatment for 3 months, basic function, practical function, EMG, nerve conduction velocity were compared among the 3 groups. RESULTS: The good rate of basic function of 50.0%, the curemarkedly effective rate of practical function of 50.0% and the total effective rate of neurophysiology of 64.3% in the treatment group were better than 20.7%, 17.2%, 41.4% in the control group I (P < 0.05) and 23.3%, 20.0% and 36.O7% in the control group II (P 0.05). CONCLUSION: Electroacupuncture combined with functional training can accelerate nervous repair, promote functional recovery of the denervated muscles, so as to shorten the restoring time of nerve-muscle and increase life quality of the patient.