Advances of immunotherapy-related biomarker in esophageal carcinoma / 中华胃肠外科杂志

Esophageal carcinoma is one of the most common malignant tumors in the world, with incidence and mortality rankings of 7th and 6th, respectively. In recent years, immunotherapy represented by immune checkpoint inhibitors of programmed death-1 and programmed death ligand 1 (PD-L1) has been introduced into clinical practice and has changed the treatment status of esophageal cancer. Although immunotherapy has provided long-term survival benefits for patients with advanced esophageal cancer and high pathological response rates in the neoadjuvant therapy, only a few of the patients have satisfactory therapeutic outcomes. Therefore, effective biomarkers for predicting immunotherapeutic effects are urgently needed to identify those patients who could benefit from immunotherapy. In this paper, we mainly discuss recent research advances of biomarkers related to the immunotherapy of esophageal cancer and the clinical application prospects of these biomarkers.

A Spacetime Odyssey of Neural Progenitors to Generate Neuronal Diversity / 神经科学通报·英文版

To understand how the nervous system develops from a small pool of progenitors during early embryonic development, it is fundamentally important to identify the diversity of neuronal subtypes, decode the origin of neuronal diversity, and uncover the principles governing neuronal specification across different regions. Recent single-cell analyses have systematically identified neuronal diversity at unprecedented scale and speed, leaving the deconstruction of spatiotemporal mechanisms for generating neuronal diversity an imperative and paramount challenge. In this review, we highlight three distinct strategies deployed by neural progenitors to produce diverse neuronal subtypes, including predetermined, stochastic, and cascade diversifying models, and elaborate how these strategies are implemented in distinct regions such as the neocortex, spinal cord, retina, and hypothalamus. Importantly, the identity of neural progenitors is defined by their spatial position and temporal patterning factors, and each type of progenitor cell gives rise to distinguishable cohorts of neuronal subtypes. Microenvironmental cues, spontaneous activity, and connectional pattern further reshape and diversify the fate of unspecialized neurons in particular regions. The illumination of how neuronal diversity is generated will pave the way for producing specific brain organoids to model human disease and desired neuronal subtypes for cell therapy, as well as understanding the organization of functional neural circuits and the evolution of the nervous system.

Treatment and prognosis analysis of perineural invasion on sinonasal adenoid cystic carcinoma / 中华肿瘤杂志

Objective: To analyze the efficacy of sinonasal adenoid cystic carcinoma (ACC) with perineural invasion (PNI), and explore the prognostic value of PNI on sinonasal adenoid cystic carcinoma. Methods: The clinical data of 105 patients with sinonasal ACC admitted to Cancer Hospital, Chinese Academy of Medical Sciences from January 2000 to December 2016 were retrospectively reviewed. All patients were restaged according to American Joint Committee on Cancer 8th edition. Follow-up visits were conducted to obtain information of treatment failure and survival outcome. The Log rank test was used for univariate analysis of prognostic factors, and Cox regression model was used for multivariate prognostic analysis. Results: The maxillary sinus (n=59) was the most common primary site, followed by the nasal cavity (n=38). There were 93 patients with stage Ⅲ-Ⅳ. The treatment modalities included surgery alone (n=14), radiotherapy alone (n=13), preoperative radiotherapy plus surgery (n=10), and surgery plus postoperative radiotherapy (n=68). The median follow-up time was 91.8 months, the 5-year local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 72.6%, 73.0%, 52.9% and 78.0%, respectively. There were 33 patients (31.4%) with PNI-positive. The 5-year DMFS, PFS, and OS rates of PNI-positive group were 53.7%, 29.4% and 56.5%, respectively, which were significantly inferior to those of PNI-negative group (80.8%, 63.0% and 86.8%, respectively, P<0.05), while there was no significant difference in the 5-year LC rate between both groups (64.5% vs 76.5%, P=0.273). The multivariate Cox regression analysis showed PNI was one of the poor prognostic factors of DMFS (HR=3.514, 95%CI: 1.557-7.932), PFS (HR=2.562, 95%CI: 1.349-4.866) and OS (HR=2.605, 95%CI: 1.169-5.806). Among patients with PNI-positive, the 5-year LC, PFS and OS rates of patients received surgery combined with radiotherapy were 84.9%, 41.3% and 72.7%, respectively, which were significantly higher than 23.3%, 10.0% and 26.7% of patients receiving surgery or radiotherapy alone (P<0.05). Conclusion: The presence of PNI increases the risk of distant metastasis in patients with sinonasal ACC. Compared with patients with PNI-negative, the prognosis of patients with PNI-positive is relatively poor, and surgery combined with radiotherapy for PNI-positive sinonasal ACC results in good clinical outcomes.

Application of acellular bovine pericardium patch in implant based immediate breast reconstruction / 中华外科杂志

Objective: To examine the clinical effect of acellular bovine pericardium patch in implant based immediate breast reconstruction. Methods: The clinicopathological information of 141 breast cancer patients, who admitted to Department of Breast Reconstruction and Oncoplastic Surgery, Tianjin Medical University Cancer Hospital, underwent immediate mammoplasty with implants combined with acellular bovine pericardium patches were analyzed from June 2016 to October 2019. All patients were female, with the age of (38.8±8.5) years (range: 13 to 60 years). The body mass index was (21.9±2.5) kg/m2 (range: 16.0 to 32.3 kg/m2). There were 39 cases of duct carcinoma in situ, 46 cases of stage Ⅰ, 40 cases of stage Ⅱ and 16 cases of stage Ⅲ. All patients received nipple-areola-sparing mastectomy or skin-sparing mastectomy with sentinel lymph node biopsy or axillary lymph node dissection, and prosthesis implantation with sub-pectoralis combined with breast patch. The correlation of clinicopathological characters and complications was assessed by t test, χ2 test, Fisher's exact probability method and Logistic regression. Pre-and post-operative aesthetic, quality of life scores were recorded. Results: The operation time (M(IQR)) was 3.6(1.5) hours (range: 3.0 to 6.5 hours). The early postoperative complication rate was 22.0% (31/141), prosthesis removal was the main postoperative complication, accounting for 64.5% (20/31) of the total complications, of which 15 cases occurred in the first 30 patients. The follow-up time was 28(8) months (range: 20 to 53 months), The most frequent long-term complications were capsular contracture and implant displacement, with the incidence of 11.2% (14/125) and 10.4% (13/125), respectively. Multivariate analysis showed that prosthesis volume ≥300 ml (OR=8.173, 95%CI: 1.302 to 51.315, P=0.021) and peri-areolar incision (OR=7.809, 95%CI: 2.162 to 28.211, P<0.01) were independent relative factors for the occurrence of short-term postoperative local complications. After 2 years of operation, the score of breast appearance satisfaction was 71.7±15.5, postoperative effect satisfaction was 90.4±9.5, psychological satisfaction was 90.7±17.1, sexual satisfaction was 70.1±25.1. The immediate postoperative satisfaction rate at discharge was 95.4% (134/141), and 17.6% (22/125) of patients had the intention to received revision surgery. Conclusions: Prosthesis volume ≥300 ml and peri-areolar incision were independent realtive factors for short-term local complications after bovine pericardium patch combined with prosthesis implantation in the immediate breast reconstruction. After completing the learning curve, the postoperative complications of the procedure could be decreased.

Oligometastatic and oligoprogressive esophageal squamous cell carcinoma:clarifying conceptions and surgery perspectives / 中华外科杂志

The oligometastatic and oligoprogressive state has been a hot issue in cancer research. Its indolent tumor behavior, representing a novel therapeutic opportunity, has been identified as a clinical subtype in several malignancies. However, the clinical implications of the oligometastatic and oligoprogressive state in esophageal squamous cell carcinoma (ESCC) have not been thoroughly elucidated. There are still controversies regarding the existence of the oligometastatic state in ESCC, if the solitary regional lymph node metastasis should be viewed as oligoprogressive disease after esophagectomy, and the role of surgery and radiotherapy in ESCC oligometastatic disease. Despite many exciting contributions to the literature on these, further exploration is warranted. Thus, fostering the advance of research and scientific knowledge on the biological and prognostic characteristics scrupulously would facilitate personalizing treatment strategy for better outcomes.

A new quinoline alkaloid from Scolopendra subspinipes mutilans / 中国中药杂志

Three compounds, including scolosprine C(1), uracil(2) and hypoxanthine(3), were isolated and purified from the ethyl acetate fraction of centipede by silica gel normal-phase column chromatography, reversed-phase medium pressure preparation chromatography, and high-pressure semi-preparative HPLC. The structure was elucidated through a combination of spectroscopic analyses [such as nuclear magnetic resonance(NMR) and mass spectrometry(MS)] and literature review. Among them, compound 1 was a new quinoline alkaloid. In previous reports, we have described the isolation and structure elucidation of one new and two known quinoline alkaloids. In this paper, we would report the isolation and structure elucidation of scolosprine C in detail.

Physiologically-based pharmacokinetic modeling for predicting drug-drug interactions induced by acid-reducing agents / 药学学报

Gastric pH is an important factor that affects drug absorption, as gastric pH may lead to lower bioavailability, especially for weak-base drugs. Acid-reducing agents (ARAs) such as antacids, histamine-2 receptor antagonists, and proton pump inhibitors, are susceptible to drug-drug interactions (DDIs), potentially resulting in the loss of efficacy. Physiologically based pharmacokinetic (PBPK) modeling is an important tool for the evaluation of oral drug-drug interactions and the most commonly used models include the advanced comparative absorption and transport (ACAT) model and the advanced dissolution, absorption and metabolism (ADAM) model. These models can be used for adjustment of the dosage regimen and the screening of candidate drugs in drug development by simulating the change of gastric pH to predict the change in drug absorption. This review summarizes the theoretical basis, the most common PBPK models used to predict drug absorption, and the effects of different kinds of ARAs drugs on gastric pH. Some successful applications of PBPK modeling in predicting the effects of gastric pH on drug absorption are also presented.

Advances in Research on Pharmacological Effect of Astragaloside Ⅳ on Cardiovascular and Cerebrovascular Diseases / 中国实验方剂学杂志

Astragalus membranaceus has the effect of tonifying Qi and solid surface， diuretic support poison， discharging pus and astringent sores to produce muscle. It is not only used for syndromes such as deficiency of lung and temper， deficiency of spleen and diarrhea， but also for stroke， chest obstruction and other diseases. Due to the complex chemical composition and diverse pharmacological effect of Astragalus membranaceus， and the main role in invigorating qi and activating blood circulation has not been clarified. Astragaloside Ⅳ is one of its main active ingredients. In recent years， more and more studies on Astragaloside Ⅳ have been conducted at home and abroad. It has been reported that it has the medicinal value of enhancing immune function， strengthening heart and lowerin blood glucose， diuresis， anti-aging and anti-fatigue， et al， and has extensive pharmacological activity. Among them， the role of cardiovascular and cerebrovascular diseases in particular has attracted increasing attention. Cardiovascular and cerebrovascular diseases are ischemic or hemorrhagic diseases occurring in the heart， brain and systemic tissues due to blood viscosity， atherosclerosis， hypertension， hyperlipidemia， etc.， including cardiovascular and cerebrovascular diseases. Such diseases are a serious threat to mankind and are the leading cause of death worldwide. At present， western medicine is the main treatment， with many adverse reactions and poor long-term prognosis. TCM believes that the imbalance of qi and blood is the basic pathogenesis of this kind of disease. Qi deficiency and blood stasis are more common.At present， Astragaloside Ⅳ in the treatment of cardiovascular and cerebrovascular diseases in a number of studies， and achieved some results， but this review in recent years， Astragaloside Ⅳ in the treatment of cardiovascular and cerebrovascular diseases play the pharmacological activity， in order to explore whether Astragaloside Ⅳ is the main role of astragalus qi to find a theoretical basis for material basis， but also for the innovation of traditional Chinese medicine drug research and development of theoretical basis and practical guidance.

Prevention and control of HIV/AIDS in China: lessons from the past three decades / 中华医学杂志(英文版)

In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.

Effect of warm needling therapy on nerve conduction in patients with occupational hand-arm vibration disease / 中国职业医学

OBJECTIVE: To investigate the effect of warm needling therapy on the conduction of hand-arm motor nerve and sensory nerve in patients with occupational hand-arm vibration disease(HAVD). METHODS: Male occupational HAVD patients were divided into control group(39 cases) and experimental group(36 cases) by random number table method. The control group received routine therapy, while the experimental group was treated with routine therapy plus warm needling therapy five times a week for four consecutive weeks. The changes on the conduction of motor nerve and sensory nerve in these two groups before and after treatment were compared. RESULTS: Before treatment, the motor nerve conduction velocity(MCV), distal motor latency(DML), compound muscle action potential amplitude(CMAP), sensory nerve conduction velocity(SCV) and sensory nerve action potential amplitude(SNAP) of the median nerve and ulnar nerve in the two groups were compared, and there was no statistically significant difference(all P>0.05). After treatment, the MCV and SCV of median nerve and ulnar nerve in the experimental group were accelerated(all P<0.05), the DML of median nerve and ulnar nerve were shortened(all P<0.01), and the CMAP of median nerve increased compared with the control group(P<0.01). However, there was no significant difference in the CMAP of ulnar nerve and SNAP of median nerve and ulnar nerve(all P>0.05). CONCLUSION: Warm needling therapy can improve the conduction of motor nerve and sensory nerve. Warm needling therapy might be able to promote the repair of injury in axons and myelin sheaths.

Application of the transosseous approach for computed tomography-guided radioactive 125-iodine seed implantation for the treatment of thoracic and abdominal lymph node metastases

Aim: This study aimed to investigate the technical procedure, safety, and clinical value of the transosseous approach for computed tomography (CT)-guided radioactive 125-iodine (125I) seed implantation for the treatment of thoracic and abdominal lymph node metastases. Subjects and Methods: This was a retrospective study that Nine lymph node metastases in nine patients were treated in our hospital between January 2010 and August 2018. Under CT guidance, at least one puncture path was made through the transosseous approach. The seeds were planted according to the TPS. CT/MRI scans were performed every 2 months after the treatment to evaluate local therapeutic efficacy according to the Response Evaluation Criteria in Solid Tumors. Results: The transosseous approach was successfully established in all patients. The median follow-up time was 11 months (6–36 months). At 2, 4, 6, 8, 10 and 12 months after operation, the objective effective rate and clinical benefit rate were 66.67%, 77.78%, 77.78%, 71.43%, 66.67% and 50.00%; and 88.89%, 88.89%, 88.89%, 71.43%, 66.67% and 50.00%, respectively. The survival rate of the patients at 6, 12, 18, 24, 30 and 36 months after operation was 53.00%, 26.00%, 26.00%, 13.00%, 13.00% and 13.00%, respectively. Conclusions: The transosseous approach for CT-guided radioactive 125I seed implantation was safe, effective, and minimally invasive for the treatment of thoracic and abdominal lymph node metastases

Identification of ezrin gene transcriptional regulatory region and its gRNA target site in pancreatic cancer cells / 医学研究生学报

Objectiveezrin gene is overexpressed in pancreatic cancer, and its upstream sequence plays an important role in gene expression. This study intends to knock out ezrin transcriptional regulatory region and identify its gRNA target sites for gene editing in pancreatic cancer cells.MethodsThe reporter gene expression vectors carrying the upstream segment of ezrin gene were transiently transfected into Panc-1 cells. The ezrin transcriptional regulatory regions were identified by double luciferase reporter gene detection system. Then, the online software was utilized to predict the gRNA target sites located at the upstream and downstream of ezrin transcriptional regulatory region. Two recombinant plasmids pX459-sgRNA-L and pX458-sgRNA-R contained these two sequences were constructed for gene editing. Moreover, in order to identify the targeted knockout of ezrin transcriptional regulatory region, the recombinant plasmids were co-transfected into Panc-1 cells, and the genome DNA contained gRNA target sites were amplified, subcloned and sequenced. Finally, Panc-1 cells transfected with recombinant plasmids were preliminary sorted using puromycin treatment. The cell proliferation was detected by water-soluble tetrazolium salt method.ResultsLuciferase data showed that ezrin gene fragment -1297/-1186 enhanced the transcriptional activity of SV40 promoter and ezrin promoter in Panc-1 cells. Subclonal sequencing data revealed that the recombinant plasmids carrying the gRNA target sequence of ezrin transcriptional regulatory region were co-transfected into Panc-1 cells could trigger the genomic DNA fragments, which located between gRNA-L and gRNA-R target sites. Cell proliferation assay showed that the proliferation was significantly inhibited after transfection.ConclusionThe targeted knockout of ezrin transcriptional regulatory region was achieved and the inhibition of Panc-1 cell proliferation may be related to this knockout.

Efficacy of Moxifloxacin against in Zebrafish Model / 生物医学与环境科学（英文）

Objective@#Moxifloxacin (MFX) shows good activity against and can be a possible antibiotic therapy to treat infection; however, other studies have shown a lower or no activity. We aimed to evaluate MFX activity against using zebrafish (ZF) model .@*Methods@#A formulation of labeled with CM-Dil was micro-injected into ZF. Survival curves were determined by recording dead ZF every day. ZF were lysed, and colony-forming units (CFUs) were enumerated. Bacteria dissemination and fluorescence intensity in ZF were analyzed. Inhibition rates of MFX and azithromycin (AZM, positive control) were determined and compared.@*Results@#Significantly increased survival rate was observed with different AZM concentrations. However, increasing MFX concentration did not result in a significant decrease in ZF survival curve. No significant differences in bacterial burdens by CFU loads were observed between AZM and MFX groups at various concentrations. Bacterial fluorescence intensity in ZF was significantly correlated with AZM concentration. However, with increasing MFX concentration, fluorescence intensity decreased slightly when observed under fluorescence microscope. Transferring rates at various concentrations were comparable between the MFX and AZM groups, with no significant difference.@*Conclusion@#MFX showed limited efficacy against using ZF model. Its activity needs to be confirmed.

Advances in Pharmacological Studies of Patchouli Alcohol / 中国实验方剂学杂志

Patchouli Alcohol (PA) is the main bioactive constituent of Pogostemon cablin Pharmacological researches have reported various benefits of PA, including anti-infammatory, anti-gastric ulcer, anticancer, protecting against alung and brain injury, antibacterial, prevention of mastitis, colitis and arteriosclerosis, anti-photoaging, treatment of diarrhea irritable bowel syndrome, antioxidant stress, vasodilation and anti-injury.The preliminary study on the mechanism showed that anti-inflammatory effect was related to the down-regulation of mRNA expression of inflammatory mediators to inhibit the production of proinflammatory cytokines and the reduction of extracellular regulated protein kinases (ERK)-mediated nuclear factor kappa B (NF-κB) activation.The anti-gastric ulcer, protection of lung injury and brain injury and anti-photoaging were related to antioxidant and anti-inflammatory effects.The mechanism of anti-human leukemic cell line MV4-11 migh be associated with the changes of NF-κB, phosphorylated M2 pyruvate kinase (p-PKM2) and cysteine aspartate protease-3 (Caspase-3) protein expressions.The proposed mechanisms of anti-human colorectal cancer cells included the inhibition of histone deacetylase (HDAC)-2 expression and HDAC enzyme activity, and subsequent downregulation of c-myc and activation of NF-κB pathway.Apoptosis of A549 cells was induced by blocking the phosphorylation of epidermal growth factor receptor (EGFR) pathway and activating c-Jun N-terminal kinase (JNK). Anti-prostate cancer was related to the activation of mitochondrial cytochrome C apoptosis pathway, and its antiviral effect may be related to the regulation of RIG-1-like helicases (RLH) signal pathway or the direct binding of virus protein or nucleic acid and the binding site of virus to cells to block the adsorption of virus to cells.The mechanism of its antibacterial, prevention of mastitis, colitis and arteriosclerosis was closely related to anti-inflammation.The pharmacological effects of PA need to be further studied.In order to accelerate the exploration and discovery other molecular mechanism of PA, and expand its application prospects.This review comprehensively summarizes the metabolism, biological activities, and possible mechanism of PA, in order to provide references for the development and application of PA.

Aerosol transmission of coronavirus in hospital / 上海预防医学

Coronavirus is human-to-human transmissible and often leads to nosocomial outbreak in the early stage, which poses a great threat to healthcare workers.Due to confined space, crowed population and some aerosol-generating medical procedures, hospital is vulnerable to coronavirus transmission and nosocomial infection.We review the mechanism and risk factors of coronavirus aerosol in hospital and summarize the evidence of aerosol transmission of three coronaviruses and the impact of air flow.Furthermore, we evaluate the effectiveness of personal protection in the above-mentioned scenarios for the prevention and control of nosocomial infection.

Drug resistance and pathogenic spectrum of patients coinfected with nontuberculous mycobacteria and human-immunodeficiency virus in Chengdu, China / 中华医学杂志(英文版)

BACKGROUND@#Human-immunodeficiency virus (HIV) infection is increasing worldwide and nontuberculous mycobacteria (NTM) is an established microbiologic cause of pulmonary disease, lymphadenitis, and disseminated disease in cases of advanced immune suppression. Data on patients coinfected with HIV and NTM are limited. Thus, this study aimed to analyze the clinical characteristics, drug resistance, and pathogen spectrum of patients coinfected with both HIV and NTM in the Chengdu area of China.@*METHODS@#Data of 59 patients coinfected with both HIV and NTM collected from the Public Health Clinical Center of Chengdu, between January 2014 and December 2018, were analyzed. NTM drug sensitivity testing was performed using the microporous plate ratio method. Data were analyzed using SPSS 19.0, and the change in drug resistance rate was analyzed using the chi-square (χ) test.@*RESULTS@#Seven species/complex of NTM were identified from patients coinfected with HIV and NTM in this study, with Mycobacterium avium-intracellulare complex (52.5%) and M. kansasii (27.1%) as the predominant species. Male patients were more affected 50/59 (84.7%); the mean age of the 59 cases was 45 years. The clinical characteristics mainly included anemia (86.4%), cough and expectoration (79.7%). The baseline CD4 count was 0.05).@*CONCLUSIONS@#The immune level of patients coinfected with HIV and NTM is low in advanced AIDS stage; more male are affected in patients who are mainly infected with MAC and M. kansasii and with serious drug resistance. The drug resistance rate of ethambutol and clarithromycin is relatively low.

Drug resistance and pathogenic spectrum of patients coinfected with nontuberculous mycobacteria and human-immunodeficiency virus in Chengdu, China / 中华医学杂志(英文版)

Background@#Human-immunodeficiency virus (HIV) infection is increasing worldwide and nontuberculous mycobacteria (NTM) is an established microbiologic cause of pulmonary disease, lymphadenitis, and disseminated disease in cases of advanced immune suppression. Data on patients coinfected with HIV and NTM are limited. Thus, this study aimed to analyze the clinical characteristics, drug resistance, and pathogen spectrum of patients coinfected with both HIV and NTM in the Chengdu area of China.@*Methods@#Data of 59 patients coinfected with both HIV and NTM collected from the Public Health Clinical Center of Chengdu, between January 2014 and December 2018, were analyzed. NTM drug sensitivity testing was performed using the microporous plate ratio method. Data were analyzed using SPSS 19.0, and the change in drug resistance rate was analyzed using the chi-square (χ2) test.@*Results@#Seven species/complex of NTM were identified from patients coinfected with HIV and NTM in this study, with Mycobacterium avium–intracellulare complex (52.5%) and M. kansasii (27.1%) as the predominant species. Male patients were more affected 50/59 (84.7%); the mean age of the 59 cases was 45 years. The clinical characteristics mainly included anemia (86.4%), cough and expectoration (79.7%). The baseline CD4 count was <50 cells/μL (84.7%). Patients were mainly in advanced acquired immunodeficiency syndrome (AIDS) stage. Chest imaging mainly showed patchy shadows (42.4%) and nodules (32.2%), with various degrees of AIDS-defining diseases. The drug resistance of NTM was severe, and the rate of isoniazid resistance (100.0%) was the highest, followed by rifampicin (94.9%), streptomycin (94.9%), ofloxacin (93.2%), and others. Ethambutol (52.5%) and clarithromycin (33.9%) were relatively low. No significant difference was found in the drug resistance rate of NTM strain against nine antituberculosis drugs in 5 years (P > 0.05).@*Conclusions@#The immune level of patients coinfected with HIV and NTM is low in advanced AIDS stage; more male are affected in patients who are mainly infected with MAC and M. kansasii and with serious drug resistance. The drug resistance rate of ethambutol and clarithromycin is relatively low.

Preliminary analysis of primary and secondary factors of γ-aminobutyric acid enrichment in fermentation process of Sojae Semen Praeparatum / 中草药

Objective: To study the primary and secondary factors of γ-aminobutyric acid (GABA) enrichment in the processing of Sojae Semen Praeparatum (SSP), and lay the foundation for revealing the formation mechanism of high content of GABA in SSP. Methods: The dynamic changes of pH value, temperature, moisture, protease and glutamic acid decarboxylase (GAD) in the processing of SSP were determined by conventional methods. The GABA content of each sample was determined by pre-column on-line derivatization established by our laboratory. The correlation between each indicator and GABA was analyzed by SPSS software. Results: Correlation analysis and multiple regression analysis showed that the correlation coefficient between water, acid protease and GABA was 0.211 and -0.340, respectively, and the P values were 0.324 and 0.228, respectively. The correlation was small and there was no statistical difference. The absolute value of the regression coefficient showed that the primary and secondary status of other indicators in the formation of GABA was pH value (-0.375) > temperature (-0.284) > GAD (0.140) > alkaline protease (0.047) > neu-protease (-0.030), in which pH value, temperature and neutral protease had a negative correlation with GABA, and GAD activity and alkaline protease had a positive correlation with GABA. Conclusion: The temperature, pH value, GAD, neutral and alkaline protease are important factors affecting the formation of GABA in the fermentation process of SSP.

The Zuo Jin Wan Formula increases chemosensitivity of human primary gastric cancer cells by AKT mediated mitochondrial translocation of cofilin-1 / 中国天然药物

Resistance to cisplatin (DDP)-based chemotherapy is a major cause of treatment failure in human gastric cancer (GC). It is necessary to identify the drugs to re-sensitize GC cells to DDP. In our previous research, Zuo Jin Wan Formula (ZJW) has been proved could increase the mitochondrial apoptosis via cofilin-1 in a immortalized cell line, SGC-7901/DDP. Due to the immortalized cells may still difficult highly recapitulate the important molecular events in vivo, primary GC cells model derived from clinical patient was constructed in the present study to further evaluate the effect of ZJW and the underlying molecular mechanism. Immunofluorescent staining was used to indentify primary cultured human GC cells. Western blotting was carried out to detect the protein expression. Cell Counting Kit-8 (CCK-8) was used to evaluate cell proliferation. Flow cytometry analysis was performed to assess cell apoptosis. ZJW inhibited proliferation and induced apoptosis in primary DDP-resistant GC cells. Notably, the apoptosis in GC cells was mediated by inducing cofilin-1 mitochondrial translocation, down-regulating Bcl-2 and up-regulating Bax expression. Surprisingly, the level of p-AKT protein was higher in DDP-resistant GC cells than that of the DDP-sensitive GC cells, and the activation of AKT could attenuate ZJW-induced sensitivity to DDP. These data revealed that ZJW can increase the chemosensitivity in DDP-resistant primary GC cells by inducing mitochondrial apoptosis and AKT inactivation. The combining chemotherapy with ZJW may be an effective therapeutic strategy for GC chemoresistance patients.

Cell models and drug discovery for mitochondrial diseases / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Mitochondrion is a semi-autonomous organelle, important for cell energy metabolism, apoptosis, the production of reactive oxygen species (ROS), and Ca homeostasis. Mitochondrial DNA (mtDNA) mutation is one of the primary factors in mitochondrial disorders. Though much progress has been made, there remain many difficulties in constructing cell models for mitochondrial diseases. This seriously restricts studies related to targeted drug discovery and the mechanism and therapy for such diseases. Here we summarize the characteristics of patient-specific immortalized lymphoblastoid cells, fibroblastoid cells, cytoplasmic hybrid (cybrid) cell lines, and induced pluripotent stem cells (iPSCs)-derived differentiation cells in the study of mitochondrial disorders, as well as offering discussion of roles and advances of these cell models, particularly in the screening of drugs.