[Clinical characteristics and their influences on the survival of leptomeningeal metastasis derived from lung adenocarcinoma harboring epithelial growth factor receptor mutation].

Objective: To analyze the clinical characteristics of leptomeningeal metastasis (LM) patients from epithelial growth factor receptor (EGFR)-mutated lung adenocarcinoma, and their impacts on the survival of the patients. Methods: From July 2018 to July 2022, the clinicopathological data of 81 patients diagnosed as EGFR-mutated lung adenocarcinoma LM by cytopathology who admitted to the Department of Oncology of Xiangya Hospital of Central South University were retrospectively analyzed, including 33 males and 48 females. The age ranged from 31 to 76 years, with a median age of 54 years. All the 81 patients were followed up, with a median follow-up of 21.0 months (95%CI: 12.5 to 29.5 months). The Kaplan Meier method was used to draw survival curve. Cox proportional hazards regression model was used to analyze the impact of the factors on the survival of patients. Results: Among the 81 patients, the interval between the initial diagnosis of lung cancer and the pathological diagnosis of LM in cerebrospinal fluid (CSF) was 0-108 months, with a median interval of 14 months. Fifty-two patients (64.2%) used the third-generation epithelial growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs), while 17 patients (21.0%) used EGFR-TKIs in combination with other drugs, and 12 patients (14.8%) were treated with best supportive care (BSC). Sixty patients (74.1%) had a Kanofsky performance status (KPS) score of less than 60 points, and 71 patients (87.7%) had brain parenchymal metastasis and/or spinal metastasis. Twenty-two patients (27.2%) used pemetrexed through intrathecal CSF, and 17 patients (21.0%) used pemetrexed through the Ommaya sac to the CSF of the ventricle. The incidence of adverse event related to the administration of pemetrexed through CSF was 64.1% (25/39), mainly manifested as myelosuppression, including 22 patients of leukocyte reduction, 25 patients of hemoglobin reduction, and 14 patients of platelet reduction. The median post-leptomeningeal metastasis overall survival (pLM-OS) in 81 patients was 11.0 (95%CI: 7.7-14.3) months. KPS score≥60 points (HR=0.407, 95%CI: 0.170-0.973, P=0.043), CSF cytology negative after treatment (vs persistent positive, HR=0.351, 95%CI: 0.155-0.792, P=0.012), intraventricular administration of pemetrexed (vs non intraventricular administration of pemetrexed, HR=0.319, 95%CI: 0.137-0.745, P=0.008) and the treatment with third-generation EGFR-TKIs after LM (vs EGFR-TKIs in combination with other drugs, HR=0.486, 95%CI: 0.237-0.998, P=0.049) were a factor affecting pLM-OS of patients. Conclusions: Brain parenchyma, or/and spine are the most sites where the LM patients concurrently metastasize. KPS score≥60 points and CSF cytology negative after treatment, intraventricular administration of pemetrexed and the treatment with third-generation EGFR-TKIs are indictors affecting pLM-OS of the patients.

[Molecular epidemiological study on rubella virus circulating in Yunnan Province during 2011-2021].

Objective: To understand the genotype distribution and transmission pattern of rubella virus (RuV) circulating in Yunnan Province. Methods: Throat swab samples were collected from rubella outbreaks and sporadic cases in nine prefectures/cities of Yunnan Province from 2011 to 2021. Virus isolation, amplification of target genes and sequence determination were performed on the RuV-positive samples. The genotypes and lineages of Yunnan strains were determined by comparing them with the reference strains, and further phylogenetic analysis was performed with Yunnan strains and strains circulating in other provinces of China during the same period. Results: RuV circulating in Yunnan province during 2011-2021 showed significant genetic diversity, and three lineages, 1E-L1, 2B-L1 and 1E-L2, were detected. Two lineage-switches were also identified, including the conversion of 1E-L1 to 2B-L1 between 2012 and 2013, and the replacement of 2B-L1 to 1E-L2 after 2018. The time of the switches was basically consistent with the outbreak in Yunnan province in 2012 and the time of the rubella reemergence and epidemic between 2018 and 2019. The amino acid sequence of RuV virus strains in Yunnan province was highly conserved, and no important functional regions were changed. Conclusions: The transmission pattern of RuV in Yunnan province is generally consistent with the epidemic trend of RuV in other provinces of China.

[Clinical features of vestibular syncope associated with tumarkin attacks in delayed endolymphatic hydrops].

Objective: To analyze the clinical characteristics of vestibular syncope (VS) associated with drop attacks (DA) in delayed endolymphatic hydrops (DEH). Methods: DEH cases with complete data were retrospectively analyzed, including three DEH cases with DA and VS (VS group), and six DEH cases without DA or VS (control group). The clinical profile, the results of neurotological examinations [such as pure tone audiometry, electrocochleography (EcochG), caloric test, vestibular evoked myogenic potentials (VEMP), and video head impulse test (vHIT)] and treatment outcomes were analyzed. Results: (1) In the VS group, there were three cases of ipsilateral DEH; in the control group, there were six cases of ipsilateral type. One case in each group had a history of migraine. (2) The prevalence of abnormal results in caloric test, vHIT, cervical VEMP, and ocular VEMP in the VS group was 3/3, 1/3, 2/2, and 2/2, respectively, and in the control group was 3/6, 0/3, 1/6, and 4/6, respectively. Two cases in each group underwent EcochG, and no identifiable waveform was elicited on the affected side, and-SP/AP ratio of unaffected side was less than 0.4. (3) Patients in both groups were initially treated with conservative medication. Two cases in the VS group subsequently received intratympanic injections of dexamethasone. No DA or VS occurred during a follow-up period lasting over one year. All patients achieved good control of vertigo during the follow-up period. Conclusions: VS may occur in the patients with DEH. The differential diagnosis of syncope in patients with otogenic vertiginous disease can help improve clinical diagnosis and treatment.

[Exogenous CRX gene induces Müller cell-derived progenitors to differentiate into photoreceptors].

Objective: To investigate whether exogenous CRX gene would be able to induce Müller cells-derived progenitors to differentiate into photoreceptors. Methods: Experimental study. Müller cells-derived progenitors resulted from primary Müller cells isolated from KunMing mice(5-7 days old) and cultured in free-serum media. Markers of Müller cells(glutamine synthetase, GS and Vimentin) and stem cells (Nestin and Sox2) were analysed by immnocytochemical assays. The secondary passage progenitors were divided into three groups: (1)the control group; (2)the empty vector group was transfected with lentivirus GFP; (3)the treated group was transfected with lentivirus GFP-CRX. After differentiation for 7 days, 7 days after differentiation, the expression of markers of photoreceptors were analyzed by q-PCR and Western blot assay. Results: There were 96.03%±1.21% of Müllerz cells cultured in vitro were immunoreactive to both GS and Vimentin. The dedifferentiation cells expressed Nestin and Sox2. After 7 days of induction, Exogenous CRX induced Müller cell-derived progenitors to differentiate into rod-like cells showed appearance like neuron morphology. q-PCR demonstrated that mRNAs of CRX and Rhodopsin were upregulated greatly. CRX mRNA were 9 times (P<0.05) and Rhodopsin mRNA were 20 times (P<0.05). The difference between the control group and the empty vector group was not statistically significant. Western blot showed that the expression of CRX was upregulated significantly, and was 2.7 times(P<0.05). But expression of Rhodopsin was weak and was nearly not detected in the control group and empty vector group. The expression of S-opsin was not detected. Conclusion: CRX gene could induce the differentiation of Müller cell-derived progenitor into rod photoreceptors, indicating a new avenue to study müller cells as endogenous seed cells for retinal photoreceptor. (Chin J Ophthalmol, 2018, 54: 923-928).

Statin therapy on glycemic control in type 2 diabetic patients: A network meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Statins are the cornerstone of primary and secondary prevention of cardiovascular diseases (CVDs) and are effective for the prevention of vascular events in diabetic patients. Diabetes mellitus is an important risk factor for CVDs .The majority of patients with diabetes mellitus benefits from statin therapy. According to the recent clinical guidelines of the American College of Cardiology and the American Heart Association, moderate-intensity or high-intensity statin therapy should be used as the primary prevention for individuals with diabetes mellitus, aged between 40 and 75 years and with low-density lipoprotein cholesterol (LDL-C) from 70 to 189 mg/dL. The objective of this review was to compare the associations of individual statins with their adverse effects on glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS: MEDLINE, EMBASE and CENTRAL were searched from inception through March 2017. There were included randomized controlled trials comparing statins with placebo or active comparators in patients with T2DM. The endpoints of interest were glycated haemoglobin A1C (HbA1C ) and fasting plasma glucose (FPG). We performed a pairwise meta-analysis and a network meta-analysis within a frequentist framework. The standard mean differences (SMD) and 95% confidence intervals (CI) were calculated. RESULTS: Twenty-three trials were included. A significant increase in HbA1c was detected in the pairwise meta-analysis when statins as a class were compared with placebo (SMD: 0.11). Moderate-intensity pitavastatin lowered HbA1c compared with moderate-intensity atorvastatin (SMD: -0.16), high-intensity atorvastatin (SMD: -0.77), moderate-intensity rosuvastatin (SMD: -0.16) and low-intensity pravastatin (SMD: -0.15). Moderate-intensity simvastatin lowered HbA1c compared with high-intensity rosuvastatin (SMD: -0.45) and high-intensity atorvastatin (SMD: -0.77). High-intensity atorvastatin elevated HbA1c compared with placebo (SMD: 0.63), moderate-intensity rosuvastatin (SMD: 0.50), low-intensity pravastatin (SMD: 0.51) and moderate-intensity atorvastatin (SMD: 0.50). Moderate-intensity pitavastatin has lowered FPG compared with placebo (SMD: -0.55), moderate-intensity rosuvastatin (SMD: -0.65), moderate-intensity atorvastatin (SMD: -0.65) and high-intensity atorvastatin (SMD: -1.25). High-intensity atorvastatin has elevated FPG compared with placebo (SMD: 0.70), moderate-intensity atorvastatin (SMD: 0.60), moderate-intensity rosuvastatin (SMD: 0.60) and moderate-intensity simvastatin (SMD: 0.90). WHAT IS NEW AND CONCLUSION: Statins were associated with an increase in HbA1c compared with placebo. In patients with T2DM, moderate-intensity pitavastatin improved the glycemic control whereas high-intensity atorvastatin worsened it. Appropriate statins should be administered for patients with diabetes mellitus.

[Analysis of measles immunity level and serological susceptibility among Yunnan residents aged ≥20 years].

Objective: To evaluate the population immunity to measles and explore the factors associated with measles susceptibility in Yunnan residents aged ≥20 years. Methods: 2 689 residents aged ≥20 years were selected by multistage stratified systematic randomized sampling in 252 villages of 42 counties in Yunnan Province between June and September in 2015. Each subject was surveyed by the same questionnaire, including general information, measles contained vaccine history, measles history, and 5 ml blood sample of each subject was collected. Serum IgG antibodies against measles virus were measured by ELISA. Positive was defined as the antibody concentration ≥250 mU/ml, and negative as <250 mU/ml. Non-conditional logistic regression model was used analyze the factors associated with measles susceptibility in adults. Results: Among 2 689 subjects, 1 214 were males (45.15%), and the overall positive rate of measles IgG antibody was 89.77%. Compared with subjects from the region where economic development was low, subjects from the region where economic development was moderate were likely to be susceptible to measles virus (OR=1.81, 95%CI: 1.33-2.47). Four age groups had higher risk of being susceptible to measles virus (compared with ≥40 years: 20-24 years old, OR=2.04, 95%CI: 1.26-3.31; 25-29 years old, OR=3.72, 95%CI: 2.37-5.86; 30-34 years old, OR=1.94, 95%CI: 1.22-3.09; 35-39 years old, OR=1.81, 95%CI: 1.07-3.05). Conclusion: Our results suggest that the serological susceptibility in adults (20-39 years), especially adults from the regions where the economic development was moderate, should be concerned. The additional vaccination strategy targeting young adults is important for reducing the risk of measles infection.

Pharmacokinetics of tablet huperzine A in six volunteers.

AIM: To study pharmacokinetics of tablet huperzine A (Hup-A) in Chinese volunteers to help establishing its drug administration schedule. METHODS: For 6 volunteers after a single oral dose of 0.99 mg, drug concentrations in plasma were assayed by reverse phase high pressure liquid chromatography (HPLC) at 0.5, 0.75, 1.0, 1.25, 1.5, 2, 4, 6, 8, and 10 h. The pharmacokinetic parameters were calculated with a 3P87 program by computer. RESULTS: The time course of plasma concentrations conformed to a one-compartment open model with a first order absorption. The pharmacokinetic parameters were as follows: T 1/2ka = 12.6 min, T 1/2ke = 288.5 min, Tmax = 79.6 min, Cmax = 8.4 micrograms L-1, AUC = 4.1 mg L-1 min. CONCLUSION: Hup-A was absorbed rapidly, distributed widely in the body, and eliminated at a moderate rate.

[Transdermal permeability of l- and dl-norgestrel through human skin in vitro].

Transdermal permeability of l-norgestrel (l-NG) and dl-norgestrel (dl-NG) at 6 skin regions with and without stratum corneum was investigated by using Valia-Chien double-compartment permeation cells. The permeation rates and accumulative amounts within 72 h in vitro were measured by HPLC. The results showed that the permeation rates of dl-NG through intact skin were significantly higher than those of l-NG (P less than 0.01). For the skins without stratum corneum, the permeation rates and permeation amounts of l-NG and dl-NG were higher than those for the intact skin (P less than 0.01), but no significant difference was seen between l-NG and dl-NG. Hence the stratum corneum played an important role of rate-limiting barrier in the skin permeation of l-NG and dl-NG. It is possible that the difference in permeability between l-NG and dl-NG is related to their partition coefficients.

[Influence of vehicles on human skin permeation of norgestrel and levonorgestrel in vitro].

In the experiment Valia-Chien skin permeation cell and methods were constructed for investigating the influence of various vehicles on the transdermal absorption of norgestrel (NG) and levonorgestrel (LNG). All of the vehicles were saturated with NG or LNG at 37 degrees C, so variations in permeation were mainly attributable to the vehicle effects. The results showed that the transdermal fluxes of NG and LNG were increased about 5-6 fold using an optimal concentration range of aqueous ethanol as a vehicle relative to that when normal saline was used as a vehicle. The NG permeation rate was about 1-2 fold greater than that of LNG in the above--mentioned saline aqueous ethanol and neat ethanol. Oleic acid (OA) and aqueous ethanol both enhanced synergistically the permeation of LNG through the human cadaver skin. When OA--80% ethanol (0.75:9.25 v/v) was used as a co--vehicle, the flux of LNG was 0.53 micrograms/cm2.h, which was 3 fold and 29 fold respectively greater than that when 80% ethanol and neat OA were used as the vehicle.

[Transdermal permeability of estradiol through human skin of different body regions in vitro].

Transdermal permeability of estradiol was carried out by using Valia-Chien double-compartment permeation cell for the following 6 skin regions with intact and without stratum corneum: chest, abdomen, hip, upper arm, thigh and back. The estradiol permeation rates and accumulative amounts within 72 h in vitro were examined by HPLC. The results showed that the permeation rates of intact skin from different regions of the body were significantly different (P less than 0.01), and for the skins without stratum corneum over different regions, the permeation rates or the permeation amounts were about 18-55 times higher than that for the intact skin. The results demonstrated that the stratum corneum acts as the rate-limiting barrier in the skin permeation of estradiol, and that the difference in estradiol permeation rates for different skin regions was mainly caused by the different extents of the barrier.