Interaction between handgrip strength and vitamin D deficiency on all-cause mortality in community-dwelling older adults: a prospective cohort study.

OBJECTIVE: Muscle strength decline and vitamin D deficiency are coexisting conditions associated with multiple adverse health outcomes. This prospective study aimed to investigate the multiplicative and additive interactions between handgrip strength (HS) and serum 25-hydroxyvitamin D [25(OH)D] on all-cause mortality in Chinese community-dwelling older adults. STUDY DESIGN: This is a population-based cohort study. METHODS: 2635 older adults (85.15 ± 12.01 years) were recruited from the Chinese Longitudinal Healthy Longevity Survey (2012-2018). Low HS was defined according to the Asian Working Group for Sarcopenia 2019 updated consensus (<28 kg for men and <18 kg for women). Serum 25(OH)D < 50 nmol/L were defined as vitamin D deficiency. Cox proportional hazard models were used to examine the association of HS and 25(OH)D with all-cause mortality. Socio-demographics, health status, and clinical characteristics were included as covariates. RESULTS: 1715 (65.09 %) and 1885 (71.54 %) participants had low HS and vitamin D deficiency, respectively. During a median follow-up of 3.52 years, 1107 older people died. After multivariable adjustment, both HS and 25(OH)D levels were inversely associated with all-cause mortality risk (Ps < 0.001). The hazard ratios (HRs) of low HS and vitamin D deficiency for all-cause mortality were 1.73 (95 % CI: 1.41-2.13) and 1.61 (95 % CI: 1.32-1.93), respectively. Although significant multiplicative interactions were not found, the association between low HS and all-cause mortality was attenuated in the higher 25(OH)D subgroup than in the lower 25(OH)D subgroup (stratified by 50 nmol/L). The multiple-adjusted HR of mortality for combined low HS and vitamin D deficiency was 2.18 (95 % CI: 1.73-2.56), which was higher than that for these two conditions alone. Significant additive interactions between low HS and vitamin D deficiency on mortality were observed (relative excess risk due to interaction: 0.71, 95 % CI: 0.37-1.05). CONCLUSIONS: Low HS and low 25(OH)D levels synergistically increased the risk of all-cause mortality. Our results added new insights to the priority of early detection for older adults with comorbid muscle strength decline and vitamin D deficiency.

[Clinicopathological analysis of gastric adenocarcinoma with elevated serum alpha-fetoprotein and enteroblastic differentiation].

Objective: To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED). Methods: The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis. Results: Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177-GNAS, AIM1-FGFR3, and EPHA6-ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis (P＜0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone (P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone (P＜0.05). Conclusions: Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement.

[Effect of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer and chronic obstructive pulmonary disease].

Objective: To investigate the impact of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) complicated with chronic obstructive pulmonary disease (COPD). Methods: A retrospective cohort study was performed to include 178 patients with Ⅲ-Ⅳ NSCLC complicated with COPD who received at least 2 times of immunotherapy in Xinqiao Hospital of the Army Medical University from January 2019 to August 2021. Baseline peripheral blood inflammatory indicators such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) were collected within 2 weeks before the first treatment, with the last one being on or before February 7, 2022. X-tile software was used to determine the optimal cut-off value of peripheral blood inflammatory indicators. The Cox multivariate regression models were used to analyze the factors affecting progression free survival (PFS) and overall survival (OS). Results: Among the 178 patients, there were 174 males (97.8%) and 4 females (2.2%); the age ranged from 42 to 86 (64.3±8.3) years old.There were 30 cases (16.9%) of immunotherapy monotherapy, 114 cases (64.0%) of immunotherapy combined with chemotherapy, 21 cases (11.8%) of immunotherapy combined with antivascular therapy, and 13 cases (7.3%) of immunotherapy combined with radiotherapy. The median follow-up period was 14.5 months (95%CI: 13.6-15.3 months). The objective response rate (ORR) and disease control rate (DCR) were 44.9% (80/178) and 90.4% (161/178) for the whole group, the median PFS was 14.6 months (95%CI: 11.6-17.6 months), and the median OS was 25.7 months (95%CI: 18.0-33.4 months). The results of Cox multivariate analysis showed that IL-6>9.9 ng/L (HR=5.885, 95%CI: 2.558-13.543, P<0.01), TNF-α>8.8 ng/L (HR=3.213, 95%CI: 1.468-7.032, P=0.003), IL-8>202 ng/L (HR=2.614, 95%CI: 1.054-6.482, P=0.038), systemic immune inflammatory index (SII)>2 003.95 (HR=2.976, 95%CI: 1.647-5.379, P<0.001) were risk factors for PFS, and advanced lung cancer inflammation index (ALI)>171.15 was protective factor for PFS (HR=0.545, 95%CI: 0.344-0.863, P=0.010). IL-6>9.9 ng/L(HR=6.124, 95%CI: 1.950-19.228, P<0.002), lactate dehydrogenase (LDH)>190.7 U/L (HR=2.776, 95%CI: 1.020-7.556, P=0.046), SII>2 003.95 (HR=4.521, 95%CI: 2.241-9.120, P<0.001) were risk factors for OS, and ALI>171.15 was a protective factor for OS (HR=0.434, 95%CI: 0.243-0.778, P=0.005). Conclusion: Baseline high levels of IL-6, TNF-α, IL-8, SII, LDH, and low levels of ALI are risk factors for poor prognosis in patients with advanced NSCLC-COPD receiving immunotherapy.

[Epidemiological investigation on the local epidemic situation in Zhengzhou High-Tech Zone caused by SARS-CoV-2 Delta variant].

This study collected epidemic data of COVID-19 in Zhengzhou from January 1 to January 20 in 2022. The epidemiological characteristics of the local epidemic in Zhengzhou High-tech Zone caused by the SARS-CoV-2 Delta variant were analyzed through epidemiological survey and big data analysis, which could provide a scientific basis for the prevention and control of the Delta variant. In detail, a total of 276 close contacts and 599 secondary close contacts were found in this study. The attack rate of close contacts and secondary close contacts was 5.43% (15/276) and 0.17% (1/599), respectively. There were 10 confirmed cases associated with the chain of transmission. Among them, the attack rates in close contacts of the first, second, third, fourth and fifth generation cases were 20.00% (5/25), 17.86% (5/28), 0.72% (1/139) and 14.81% (4/27), 0 (0/57), respectively. The attack rates in close contacts after sharing rooms/beds, having meals, having neighbor contacts, sharing vehicles with the patients, having same space contacts, and having work contacts were 26.67%, 9.10%, 8.33%, 4.55%, 1.43%, and 0 respectively. Collectively, the local epidemic situation in Zhengzhou High-tech Zone has an obvious family cluster. Prevention and control work should focus on decreasing family clusters of cases and community transmission.

[Clinical value of mesh prophylaxis for parastomal hernia based on evidence-based medicine].

The incidence of parastomal hernia is substantially high, significantly affecting the quality of life of patients with stoma. How to effectively solve the problem of parastomal hernia is a long-term focus of hernia and abdominal wall surgery and colorectal surgery. The European Hernia Society guidelines on prevention and treatment of parastomal hernia published in 2018 has recommended the use of a prophylactic mesh to prevent parastomal hernia for the first time. In the following 5 years, more randomized controlled trials of multi-center, large-sample, double-blind, long-term follow-up have been published, and no significant effect of mesh prophylaxis has been observed on the incidence of parastomal hernia. However, whether mesh could decrease surgical intervention by limiting the symptoms of parastomal hernias would become a potential value of prophylaxis, which requires further research to elucidate.

[Analysis of the etiology and clinical characteristics of patients with hemophagocytic lymphohistiocytosis].

Objective: To explore the etiology of hemophagocytic lymphohistiocytosis (HLH) and analyze the clinical features, treatment options and outcomes of patients with HLH induced by infectious and non-infectious factors. Methods: The clinical data of 97 patients aged ≥14 years who were diagnosed or suspected of HLH during their hospitalization at Peking University First Hospital from January 1, 2006 to December 4, 2021 were retrospectively analyzed, and 80 patients with HLH were further screened for inclusion. The general condition and etiological composition of the patients were analyzed, and the laboratory tests, treatment and outcome of patients in the infection, tumor and autoimmune disease groups were compared. Results: The age[M(Q1,Q3)] of the 80 patients with HLH was 53.5 (32.0, 64.0) years, with a male-to-female ratio of 1∶1. Of the 80 HLH patients with HLH, 23.8% (19/80)、37.5% (30/80)、15.0% (12/80)、10.0% (8/80) were secondary to infection, neoplasm, autoimmune disease, and mixed factors, respectively, with EBV infection (n=15) and hematologic neoplasm (n=28) being the most common etiologies in infection or non-infection-related HLH. The incidence of peripheral blood secondary or tertiary lineage reduction was significantly higher in patients in the infection group than in the autoimmune disease group [68.4% (13/19), 33.3% (4/12), P=0.002]. Serum ferritin (SF) ≥500 µg/L and ≥1 500 µg/L were 93.1% (54/58) and 72.4% (42/58), respectively; among them, 29 patients had significantly lower SF after treatment than before treatment, 1 049 (362, 1 769)µg/L and 2010 (1 231, 7 323) µg/L (P<0.001). Phagocytosis was seen in 68.75% (55/80) and HLH-related gene mutations were detectable in 5 cases. In the three groups, 13.1% (8/61) of patients died of disease, 47.5% (29/61) improved and 9.8% (6/61) relapsed. Conclusions: HLH has no specific symptoms and progresses rapidly, mainly due to infections, neoplastic diseases, autoimmune diseases. The prognosis may be improved with early treatment.

[Study on the reliability and validity of the Chinese Criteria of Health Scale for the elderly people].

Objective: To evaluate the reliability and validity of the Chinese Criteria of Health Scale for the elderly people. Methods: A cross-sectional study was performed among older adults of Meiyuan Community in Haidian District, Beijing and Nanwangkong Village in Qingzhou City,Shandong Province during July 2021. Using a cluster sampling method, totally 667 elderly people were investigated by face-to-face interview, using the scale which was formulated after two rounds of the Delphi method and pilot study. The overall scale includes physical health, mental health and social health subscales, including 9, 52 and 15 items, respectively. Four weeks after the survey, 56 elderly people were randomly selected and repeated the survey with the same method. The test-retest reliability, split-half reliability and internal consistency reliability of the scale were evaluated, and the validity was evaluated at the same time, including construct validity and content validity. Results: A total of 710 questionnaires were distributed and 667 valid questionnaires were obtained, with a total effective rate of 93.94%. The score of the overall scale was 79.79±16.22, the scores of the physical health, mental health, social health sub-scores were 41.64±9.76, 26.82±3.92 and 11.34±5.19, respectively. The scale had excellent reliability. In the test-retest reliability, the intraclass correlation coefficient (ICC) of the overall scale and each subscale were 0.766-0.861, and the weighted Kappa values were 0.762-0.817. The Spearman-Brown coefficient of the overall scale and each subscale in the split-half reliability were 0.722-0.855 (all P<0.001). The Cronbach's α coefficients of the overall scale of internal consistency reliability and each subscale were 0.748-0.899, and the Cronbach's α coefficients of each dimension were from 0.709 to 0.963(all P<0.001). At the same time, the scale had good construct validity and content validity. The correlation coefficients between the score of each dimension and its sub-scale were larger, from 0.641 to 0.873 (all P<0.05). The cumulative variance contribution rates of the scale and three subscales were all more than 50% of the approved standard. A total of 11 common factors were extracted, and all the load values of each item on the corresponding factors were ≥0.04. Conclusion: The Chinese Criteria of Health Scale for the elderly people has good validity and excellent reliability. It can be used as a basis for the scientific division of the health status of the elderly, the formulation of relevant policies by the government and the provision of appropriate health services for the elderly.

[Advances in the diagnosis and treatment of porphyria-related hepatic manifestations].

Porphyria is a disease caused by defects in the activity of any of the eight enzymes required for the heme synthesis pathway. Most of these are genetic diseases, and the main clinical symptoms are abdominal pain, neuropsychiatric symptoms and skin lesions. Detection of high levels of porphyrin and/or its precursors in blood, urine and feces can be used as diagnostic clues, and known genetic mutations can confirm the diagnosis. Porphyria is rare in clinical practice. However, in recent years, the number of porphyria patients with hepatic disease as the initial symptom has been increasing. Here, we focus on porphyria-related hepatic manifestations and their diagnosis and treatment, so as to provide recommendations for clinicians to reduce the misdiagnosis and missed diagnosis incidence rate.

[Clinical features and risk factors of metabolic syndrome in adult hypopituitary patients].

Objective: To investigate the clinical features and risk factors of metabolic syndrome (MS) in adult hypopituitary patients (HP). Methods: Patients diagnosed with HP in the outpatient or inpatient department of the endocrinology department in West China Hospital from January,2012 to December,2019 were selected as the experimental group (HP group), and patients with normal pituitary function treated for saddle lesions were selected as the control group. HP patients with or without MS were divided into MS group and non-MS group HP patients were divided into four groups according to the level of growth hormone by the quartile method (GH>0.35 µg/L、0.13 µg/L0.35 µg/L、0.13 µg/L

[Effect of platelet reactivity on clinical events in patients using bivalirudin in selective percutaneous coronary intervention].

Objective: To investigate the effect of platelet reactivity and other clinical factors on the postoperative 1-year adverse clinical events in patients who underwent selective percutaneous coronary intervention (PCI) anticoagulated with bivalirudin. Methods: This is a multicenter, retrospective and observational study, enrolling 632 patients at high risk of bleeding adjudicated by operators who underwent selective PCI anticoagulated with bivalirudin and had preoperative thrombelastography (TEG) test results in Fuwai Hospital, Northern Theater General Hospital and Xinxiang Central Hospital between January 2017 and August 2018. Platelet reactivity was tested by TEG and adenosine-induced maximal amplitude (MAADP) was recorded. According to MAADP patients were divided into three groups: low on-treatment platelet reactivity (LTPR) group (MAADP<31 mm, n=229), normal on-treatment platelet reactivity (NTPR) group (31 mm≤MAADP≤47 mm, n=207) and high on-treatment platelet reactivity (HTPR) group (MAADP>47 mm, n=196). The endpoints consisted of major adverse cardiovascular and cerebrovascular events (MACCE) and bleeding events. The definition of MACCE was the composite of all-cause mortality, myocardial infarction, intrastent thrombosis, stroke and revascularization. Bleeding events were defined by bleeding academic research consortium (BARC) type 2, 3 and 5 bleeding. Using multivariate Cox regression to analyze the factors of MACCE and bleeding events in patients underwent selective PCI anticoagulated with bivalirudin. Results: A total of 632 patients were finally enrolled in the study with age of (68.3±10.0) years and there were 423 (66.9%) males. All of 632 patients finished one-year follow-up, and 48 (7.6%) patients occurred MACCE and 11 (1.7%) patients occurred bleeding events. There was not statistically significant difference in the incidence of MACCE (8.3% (19/229) vs. 6.3% (13/207) vs.8.2% (16/196), P=0.68) and bleeding events (1.8% (4/229) vs. 2.9% (6/207) vs. 0.5% (1/196), P=0.17) in LTPR, NTPR and HTPR group. Multivariate Cox regression showed that HTPR was not the independent factor of MACCE (HR=1.25, 95%CI 0.67-2.30, P=0.49), and the history of peripheral vessel disease was the independent risk factor of MACCE (HR=2.47, 95%CI 1.19-5.11, P=0.02). LTPR was not the independent factor of bleeding events (HR=1.35, 95%CI 0.39-4.66, P=0.64), and the independent factors of bleeding events were history of peripheral vessel disease (HR=3.95, 95%CI 1.03-15.22, P=0.05) and hemoglobin (HR=0.96, 95%CI 0.93-0.99, P=0.01). Conclusions: In patients undergoing selective PCI anticoagulated with bivalirudin, there is no significant association between platelet reactivity and postoperative 1-year MACCE or bleeding events. History of peripheral vessel disease is an independent risk factor of MACCE, and history of peripheral vessel disease and decreased hemoglobin are independent risk factors of bleeding events.

Delayed seroreversion of specifical antibody against HIV in HIV-exposed infants: A retrospective cohort study.

OBJECTIVES: To investigate the seroreversion time in HIV-1-exposed but uninfected infants from two tertiary hospitals in China. METHODS: This study retrospectively investigated the data of perinatal, HIV-1-exposed infants from hospitals in Beijing and Shenzhen. Maternal and infant medical records from both hospitals from January 2009 to December 2019 were reviewed, and the HIV antibody seroreversion times of infants were determined. From 2009 to 2019, a total of 485 HIV-1-exposed but uninfected infants were enrolled. The majority of infants were born at term with normal birth weight. RESULTS: The seroreversion rates were 89.3%, 94.2% and 100% at 12, 18 and 24 months of age, respectively. There were no significant associations between seroreversion and several risk factors, such as gender, birth weight, gestational age, mode of delivery, postpartum prophylaxis and antiretroviral treatment duration. The mean value of HIV-specific immunoglobulin G concentration decreased from 15.4 at day 42 to 0.03 after 24 months in HIV-exposed, uninfected infants. CONCLUSIONS: Clearance of HIV antibodies could take more than 18 months in a small number of perinatally exposed infants. Caution should be used in excluding or diagnosing perinatal HIV infection in children with long persistence of HIV antibodies.

[Clinical features of anti-myelin oligodendrocyte glycoprotein antibody-associated diseases in children with cortical encephalitis].

Objective: To describe the clinical features of anti-myelin oligodendrocyte glycoprotein (MOG) antibody-positive cortical encephalitis in children. Methods: Patients who were hospitalized in Beijing Children's Hospital from June 2018 to October 2019, with positive MOG antibodies and phenotype of cortical encephalitis were retrospectively analyzed. Cell-based assays (CBAs) were used to test MOG antibodies. Results: Five patients had the phenotype of cortical encephalitis during follow-up, with 3 females and 2 males. The age of onset ranged from 8 years to 12 years and 1 month. At the last follow-up, 3 cases exhibited a monophasic course and 2 cases were with relapse and remission courses. Six out of 8 episodes which had the phenotype of cortical encephalitis presented with seizures, among which 3 episodes had status epilepticus. None had recurrent seizures during remission. Other symptoms included fever (7/8), headache and vomiting (4/8), somnolence (3/8) and hemiplegia (1/8). Unilateral cortical swelling was observed in cerebral magnetic resonance imaging (MRI) of all patients, without any hemorrhage and necrosis. White blood cell (WBC) counts of cerebrospinal fluid increased, ranging from8×10(6)/L to 186×10(6)/L. All patients recovered well after treatment with intravenous immunogloblin and glucocorticoid. Two patients had relapses during follow-up and were additionally treated with mycophenolate mofetil. Conclusions: Anti-MOG antibodies can induce cortical encephalitis. In clinical setting, fever, headache and seizures are common, however, severe consciousness disturbance and local neurological deficits are rare in these patients. Cerebral MRI shows unilateral cortical swelling without any hemorrhage and necrosis. Usually, immunotherapy works well. No patients exist repeated seizures in remission, but some patients may have relapses.

Optical quantum weak measurement coupled with UV spectrophotometry for sensitively and non-separatedly detecting enantiopurity.

Based on the theories of quantum weak measurement, we built a set of linear common-path optical weak measurement systems in frequency domain for detecting chiral molecules. The polarization resolution with this system to detect the optical rotation of chirality molecules is nearly two orders of magnitude higher than that of conventional polarizers. Combined with ultraviolet spectroscopy, the purity of the proline enantiomers mixture was detected. The purity resolution can reach to 0.14%, which is comparable to the liquid chromatography. Weak measurement combined with ultraviolet spectroscopy to non-separatedly detect the purity of chiral enantiomers has great application potential in the pharmaceutical industry.

Association between remote diffusion-weighted imaging lesions and cerebral small vessel disease in primary intracerebral hemorrhage.

BACKGROUND AND PURPOSE: The aim of this study was to examine the association amongst remote diffusion-weighted imaging lesions (R-DWILs), imaging markers of cerebral small vessel disease (cSVD) and total cSVD burden in patients with primary intracerebral haemorrhage (ICH). METHODS: In total, 344 consecutive primary ICH patients were enrolled prospectively. R-DWILs on magnetic resonance imaging as well as four imaging markers of cSVD, including cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), lacunes and enlarged perivascular spaces, were rated with validated scales. The total cSVD score was calculated by adding up these four markers. Univariate and multivariate analyses were performed. RESULTS: Remote DWI lesions were detected in 57 (16.6%) primary ICH patients. On multivariate logistic regression analysis, the presence of CMBs [odds ratio (OR) 5.26, 95% confidence interval (CI) 1.72-16.12], of high-grade WMHs (OR 4.68, 95% CI 2.01-10.90), the presence of lacunes (OR 2.69, 95% CI 1.20-6.06), mixed CMBs (OR 2.93, 95% CI 1.35-6.36), mixed lacunes (OR 3.60, 95% CI 1.25-10.37), periventricular WMHs (OR 2.19, 95% CI 1.40-3.44), deep WMHs (OR 1.92, 95% CI 1.24-2.97) and total WMHs (OR 1.52, 95% CI 1.20-1.94) were associated with the presence of R-DWILs. A significant association was also found between high-grade total cSVD score and R-DWILs (OR 1.97, 95% CI 1.36-2.84). This association remained significant in patients stratified by an age of 60 years or more than 60 years. CONCLUSIONS: Remote DWI lesions are correlated with the severity of each imaging marker of cSVD and with the total burden of cSVD.

[Spectrometric analyses of larotaxel and larotaxel liposomes quantification by high performance liquid chromatography].

OBJECTIVE: Larotaxel is a new chemical structure drug, which has not been marketed worldwide. Accordingly, the standard identification and quantification methods for larotaxel remain unclear. The spectrometric analyses were performed for verifying weight molecular formula, molecular weight and chemical structure of larotaxel. Besides, a quantification method was developed for measuring larotaxel in the liposomes. METHODS: The molecular formula, molecular weight and chemical structure of larotaxel were studied by using mass spectrometry (MS), infra-red (IR), nuclear magnetic resonance (NMR) and ultraviolet-visible (UV-vis) spectrometric techniques. The absorption wavelength of larotaxel was investigated by UV-vis spectrophotometry full-wavelength scanning. Besides, a quantification method was developed by high performance liquid chromatography (HPLC), and then validated by measuring the encapsulation efficacy of larotaxel liposomes. RESULTS: The four spectral characteristics of larotaxel were revealed and the corresponding standard spectra were defined. It was confirmed that larotaxel had the structure of tricyclic diterpenoids, with the molecular formula of C45H53NO14, the molecular weight of 831.900 1, and the maximum absorption wavelength of 230 nm. The quantitative method of larotaxel was established by using HPLC with a reversed phase C18 column (5 µm, 250 mm×4.6 mm), a mobile phase of acetonitrile-water (75:25, volume/volume), and a detection wavelength of 230 nm. The validation study exhibited that the established HPLC method was stable, and had a high recovery and precision in the quantitative measurement of larotaxel in liposomes. In addition, a new kind of larotaxel liposomes was also successfully prepared. The particle size of the liposomes was about 105 nm, with an even size distribution. And the encapsulation efficiency of larotaxel in the liposomes was above 80%. CONCLUSION: The present study offers reference standard spectra of larotaxel, including MS, IR, NMR, and UV-vis, and confirms the molecular formula, molecular weight and chemical structure of larotaxel. Besides, the study develops a rapid HPLC method for quality control of larotaxel liposomes.

Prevalence of transmitted drug resistance among HIV-1 treatment-naive patients in Beijing.

To optimise patients' outcomes and gain insight into transmitted drug resistance (TDR) among human immunodeficiency virus (HIV)-1 treatment-naive patients in Beijing, the prevalence of TDR was assessed. Demographic and clinical data of 1241 treatment-naive patients diagnosed between April 2014 and February 2015 were collected. TDR was defined using the Stanford University HIV drug resistance mutations database. The risk factors were evaluated by multi-logistic regression analysis. Among 932 successfully amplified cases, most were male (96.78%) and infected through men having sex with men (91.74%). Genotype were CRF01_AE (56.44%), B (20.60%), CRF07_BC (19.96%), C (1.61%) and other genotypes (1.39%). The overall prevalence of TDR was 6.12%. Most frequent mutations occurred in non-nucleoside reverse transcriptase inhibitors (NNRTIs) (3.11%), followed by protease inhibitors (PIs) (2.25%) and nucleoside reverse transcriptase inhibitors (NRTIs) (1.32%). Furthermore, HIV-1 genotype was associated with high risk of resistance, in which genotype C and other genotype may have higher risk for resistance. The prevalence among treatment-naive patients in Beijing was low. Resistance to NNRTIs was higher than with PIs or NRTIs. Continuous monitoring of regional levels of HIV-1 TDRs would contribute to improve treatment outcomes and prevent failures.

[Logistic regression analysis of risk factors for primary graft dysfunction after lung transplantation].

Objective: To explore the risk factors of primary graft dysfunction (PGD) after lung transplantation and provide a new therapeutic strategy for PGD. Methods: A retrospective analysis of lung transplant patients from January 2014 to July 2017 in Henan Provincial People's Hospital.According to the PGD classification standard established by the International Society for Heart and Lung Transplantation, the association of potential risk factors with PGD was analyzed by using multivariable Logistic regression. Results: Fourteen of 30 patients (46.7%) developed grade 3 PGD.There was no significantly statistical difference in gender, etiology, duration of anesthesia, amount of blood transfusion, amount of blood transfusion and donor gender(all P>0.05). Body mass index (BMI), donor pulmonary cold ischemia time, duration of operation, extracorporeal membrane lung oxygenator (ECMO), systolic pulmonary arterial pressure and donor smoking history were all higher than those of non-PGD patients (all P<0.05). Independent risk factors for PGD were donor pulmonary cold ischemia time (OR 1.032, 95%CI 1.000-1.065, P=0.048); systolic pulmonary arterial pressure (OR 1.258, 95%CI 0.969-1.632, P=0.007); donor smoking (OR 8.879, 95%CI 1.096-71.913, P=0.041). Conclusion: Donor pulmonary ischemic time, systolic pulmonary arterial pressure and donor smoking history are PGD risk factors, which provide new ideas for PGD treatment.

[Effect of mesenchymal stem cells on expression of high mobility group box 1 protein in rats with ischemia reperfusion injury after lung transplantation].

Objective: To establish the ischemia reperfusion injury model in rat after lung transplantation(LT) and explore the expression of high mobility group box 1 protein(HMGB1) after intravenous injection with bone marrow mesenchymal stem cells(MSCs). Methods: Forty healthy 8-10 weeks male SD rats were randomly divided into four groups including the sham-operated group, ischemia-reperfusion (IR), Saline-IR and MSC-IR group. The sham-operated rats were only conducted thoracotomy without lung transplantation and the rest groups were respectively conducted with the left LT, left LT followed by 1 ml saline and left LT followed by 1 ml MSCs (1.0×10(7)/ml). Four groups of rats were killed at 24 h after reperfusion. The blood and left lung tissue were collected. Oxygenation index(OI) and the ratio of wet/dry in four groups were detected and histological sections stained with hematoxylin and eosin (HE) were made. HMGB1 levels in serum were detected with ELISA. Real-time PCR and Western blot were performed to detect the expression of HMGB1 in mRNA and protein levels. Results: The OI in four groups were respectively 383±15, 174±24, 170±30 and 217±21.OI in IR and Saline-IR group decreased compared with the sham-operated group , all P<0.01. The OI increased after injection with MSCs compared with IR group, P<0.01. The histological images showed the marked inflammatory infiltrates and interalveolar septal thickening in IR group. Treatment with MSCs reduced inflammatory injury.The ratio of wet/dry in IR group and Saline-IR group increased compared with the sham-operated group((5.38±0.19), (5.24±0.15) vs (4.16±0.12), all P<0.05). Ratio in MSC-IR group decreased compared with the IR group (4.47±0.14) vs (5.38±0.19), P<0.05. ELISA results showed that HMGB1 level increased significantly in IR group (287±37)ng/ml, Saline-IR group (260±24)ng/ml and MSC-IR group (101±14)ng/ml when compared with the sham-operated group (41±5) ng/ml. The serum HMGB1 level in IR group was positively correlated with the OI (r=0.759, P<0.05) and wet/dry ratio (r=0.725, P<0.05). RT-PCR showed that HMGB1 mRNA level in sham-operated group was the lowest and increased significantly in IR group, while decreased significantly in MSC-IR group compared with IR group and Saline-IR group(P<0.01). The results of HMGB1 expression at protein level by Western blot were consistent with the mRNA level. Conclusion: Lung transplantation can induce the expression of HMGB1 but HMGB1 level of lung tissue decreased significantly after the treatment with MSCs, which indicated that MSCs might play an important role in protecting transplanted lung via HMGB1.

[Personalized repeat Gamma Knife Radiosurgery treatment in patients with recurrent refractory trigeminal neuralgia].

Objective: To analyze the prognosis and untoward effect in recurrent refractory trigeminal neuralgia (RRTN) patients who underwent repeat Gamma Knife Radiosurgery treatment (GKRS) retrospectively, and to summarize the experience of repeat Gamma Knife Radiosurgery treatment of recurrent refractory trigeminal neuralgia. Methods: RRTN patients who treated with repeat GKRS during 1998.8.1 to 2014.10.1 in Gamma Knife treatment Center of the Fifth Affiliated Hospital of Zhengzhou University were involved. The factors influencing long-term prognosis and facial numbness adverse reactions were statistically analyzed. Results: Therapeutic dose was an independent factor that influence long-term prognosis of RRTN patients. Therapeutic dose was a dangerous factor that influence long-term facial numbness. Interval time between twice GKRS treatment was a favorable factor for facial numbness. Long-term prognosis of repeat GKRS treatment was positively correlated with therapeutic dose. Untoward effect of facial numbness after repeat GKRS treatment was positively correlated with therapeutic dose and negatively correlated with interval time between twice GKRS treatment. Conclusions: Repeat GKRS for RRTN patients is safe and effective, but personalized treatment plan should be given according to the patient's own condition.