Preparation of 3D printed metoprolol tartrate chewable tablets and optimization of printing process / 药学学报

With the growing demand of personalized medicine for children, it is especially important to develop medicines for children. In this study, using metoprolol tartrate as model drug, we developed 3D printed chewable tablets suitable for children with automated dosage distribution using semi-solid extruded (SSE) 3D printing technology. Based on the quality by design concept, this study prepared a semi-solid material with good printability using gelatin as the substrate, constructed 3D models and printed tablets with the aid of computer-aided design. The printing parameters were optimized and determined as follows: print temperature of 35-37 ℃, print speed of 25 mm·s-1, fill rate of 15%, and number of outer profile layers of 2. Subsequently, the printing process and the quality uniformity of the tablets were verified, and a linear relationship between the dose and the number of model layers was obtained. Finally, 3D printed chewable tablets were superior in terms of appearance, dose accuracy and compliance compared with traditional split-dose commercially available tablets. In this study, 3D printed metoprolol tartrate chewable tablets with good performance were successfully prepared to address the personalized medication needs of pediatric patients.

SUN Shen-tian's clinical experience in treating Tourette's syndrome with acupuncture / 中国针灸

To introduce the clinical experience of professor SUN Shen-tian in treatment of Tourette's syndrome (TS) with acupuncture. TS is a psychosomatic disease and the core pathogenesis refers to blood deficiency producing internal wind. The disease is located in the heart and liver. Acupoints are selected according to the functional orientation of the cerebral cortex. The extrapyramidal system area is preferred for tic disorder, and the emotional area is for behavioral disorder. The treatment focuses on regulating the mind by multiple methods, including manual needling technique used the transcranial repeated acupuncture, and regulating the mind by taking multiple acupoints, Baihui (GV 20), Neiguan (PC 6), Shenmen (HT 7) and Dazhong (KI 4) are stimulated. For abdominal twitching and mental symptoms of TS children, the first and third abdominal areas are selected. The target symptoms (biao) are treated specially by local acupoints, the combination of the starting and ending acupoints of the affected meridian, or the acupoints of the meridians with same name. The modified chaihu longgu muli decoction and siwu decoction are prescribed to sooth liver, nourish blood and soothe wind. In association with the characteristics and target symptoms of TS, the sequential therapy is used with filiform needling, intradermal needling, Chinese herbal medication and psychotherapy.

GAO Wei-bin's clinical experience in treatment of neurogenic bladder with acupuncture / 中国针灸

The paper introduces GAO Wei-bin's clinical experience in acupuncture treatment for neurogenic bladder. In association with the etiology, the location and types of neurogenic bladder and in accordance with nerve anatomy and meridian differentiation, the acupoints are selected accurately in treatment. Four acupoint prescriptions are allocated. For frequent urination and urinary incontinence, the foot-motor-sensory area of scalp acupuncture, Shenshu (BL 23) and Huiyang (BL 35) are used. For all kinds of urine retention, especially the patients who are not suitable for acupuncture at the lumbar region, Zhongji (CV 3), Qugu (CV 2), Henggu (KI 11) and Dahe (KI 12) are selected. For all kinds of urine retention, Zhongliao (BL 33) and Ciliao (BL 32) are applicable. For the patients with both dysuria and urinary incontinence, Zhongliao (BL 33), Ciliao (BL 32) and Huiyang (BL 35) are chosen. In treatment of neurogenic bladder, both biao (root causes) and ben (primary symptoms) are considered, as well as the accompanying symptoms; and electroacupuncture is combined accordingly. During the delivery of acupuncture, the sites where the acupoints located are detected and palpated so as to rationally control the depth of needle insertion and the operation of reinforcing and reducing needling techniques.

Correlation between ciliary sulcus diameter and corneal diameter of patients with low to moderate myopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To determine the correlation among horizontal ciliary sulcus(HCS)diameter, vertical ciliary sulcus(VCS)diameter and corneal diameter in different anterior chamber depth(ACD)levels from patients with low to moderate myopia.METHODS: Retrospective study. A total of 78 patients(129 eyes)with low to moderate myopia who had preoperative examination of implantable contact lens(ICL)implantation in Shanghai Bright Eye Hospital from April 2021 to April 2022 were included. HCS, VCS and white to white(WTW)were measured and compared. Patients were divided into shallow ACD group(2.8 mm ≤ ACD ≤3.2 mm), medium ACD group(3.2 mm < ACD ≤3.4 mm)and deep ACD group(ACD > 3.4 mm)based on the ACD obtained by Pentacam. The HCS, VCS and WTW within and among groups were compared, and the correlation of WTW, HCS and VCS among each group was analyzed by Pearson and linear regression equation.RESULTS: There was no statistical difference in WTW and HCS overall and in groups with different ACD(P>0.05), while there was difference between VCS and both HCS and WTW(P<0.01). The WTW had a correlation with both HCS and VCS in each group, while correlation between WTW and VCS was weak in the deep ACD group(r=0.470, R2=0.221, P<0.01). Furthermore, the WTW, HCS and VCS in the shallow ACD group were statistically different from those in the medium and deep ACD groups(P<0.01).CONCLUSION: The WTW was suggested predicting HCS rather than perfectly replacing HCS before patients had the ICL operation among patients with low to moderate myopia. The predictability of VCS would decline as the ACD depth increasing, predicting VCS by WTW was not recommended.

Morphological Characteristics and the Role of Mitochondria in Ferroptosis / 中国生物化学与分子生物学报

Ferroptosis is a unique mode of iron-dependent cell death driven by lipid peroxidation. It is characterized by morphological changes in mitochondria, including densification of mitochondrial membranes and associated reduction in the volume, rupture of outer membranes and reduction or disappearance of the mitochondrial crest, which is different from that of apoptosis, autophagy and pyroptosis. Mitochondria, as the core of cell metabolism, are important organelles for iron metabolism, lipid metabolism and energy metabolism. However, it remains controversial debates as how mitochondria participate in ferroptosis and the underlying mechanisms during its progression. This review summaries the current understanding of the occurrence and defense mechanisms of ferroptosis, and the role of mitochondria in promoting and inhibiting ferroptosis, which includes the tricarboxylic acid cycle and glycolysis, reactive oxygen species, and lipid metabolism in mitochondria and their roles in driving ferroptosis. Moreover, we also summarize the defense mechanisms against ferroptosis through detoxification of mitochondrial lipid peroxidation by mitochondrial dihydroorotate dehydrogenase, as well as mitochondrial ferritin. Other mitochondrial molecules and their regulation of ferroptosis is stated at the end. This paper reviews the latest research progress of mitochondria in the process of ferroptosis, which aims to further understand the function of mitochondria in ferroptosis and its mechanism in the occurrence and development of ferroptosis, and therefore provides a theoretical foundation for the basic research of cell biology and strategies for investigation of clinical diseases.

HIV-1 Subtype Diversity and Factors Affecting Drug Resistance among Patients with Virologic Failure in Antiretroviral Therapy in Hainan Province, China, 2014-2020 / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance (HIVDR) in patients with ART failure from 2014 to 2020 in Hainan, China.@*METHODS@#A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan. We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences. Drug resistance mutations (DRMs) were analyzed using the Stanford University HIV Drug Resistance Database.@*RESULTS@#A total of 307 HIV-infected patients with ART failure were included, and 241 available pol sequences were obtained. Among 241 patients, CRF01_AE accounted for 68.88%, followed by CRF07_BC (17.00%) and eight other subtypes (14.12%). The overall prevalence of HIVDR was 61.41%, and the HIVDR against non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 59.75%, 45.64%, and 2.49%, respectively. Unemployed patients, hypoimmunity or opportunistic infections in individuals, and samples from 2017 to 2020 increased the odd ratios of HIVDR. Also, HIVDR was less likely to affect female patients. The common DRMs to NNRTIs were K103N (21.99%) and Y181C (20.33%), and M184V (28.21%) and K65R (19.09%) were the main DRMs against NRTIs.@*CONCLUSION@#The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.

Repeated transcranial acupuncture combined with electroacupuncture for flat descending sudden deafness: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical effect of repeated transcranial acupuncture combined with electroacupuncture on flat descending sudden deafness.@*METHODS@#A total of 80 patients with flat descending sudden deafness were randomly divided into an acupuncture and medication group (39 cases, 1 case dropped off) and a western medication group (39 cases, 1 case dropped off). Patients in the western medication group were treated with glucocorticoid + batroxobin + ginkgo leaf preparation. On the basis of the western medication group, patients in the acupuncture and medication group were treated with acupuncture at Baihui (GV 20), Ningshen, Yunting area, Mastoid 1 point, Mastoid 2 point, Fengchi (GB 20), Gongxue, Tinghui (GB 2), etc., repeated transcranial acupuncture was applied at Baihui (GV 20), Ningshen and Yunting area; Mastoid 1 point and Mastoid 2 point, Fengchi (GB 20) and Gongxue of the affected side were connected to the electroacupuncture instrument, continuous wave, 2 Hz in frequency. The needle was retained for 30 min, once a day, and rest for 1 d after 6 d of continuous treatment. All patients were treated for 3 weeks. The average hearing threshold, tinnitus handicap inventory (THI) score, dizziness handicap inventory (DHI) score and speech discrimination test score were compared between the two groups before and after treatment, and the clinical effect was evaluated.@*RESULTS@#After treatment, the average hearing threshold, THI and DHI scores of the two groups were lower than those before treatment (P<0.05), and above indexes in the acupuncture and medication group were lower than those in the western medication group (P<0.05). The speech discrimination test scores of the two groups were higher than those before treatment (P<0.05), and the score in the acupuncture and medication group was higher than that in the western medication group (P<0.05). The total effective rate was 87.2% (34/39) in the acupuncture and medication group, which was higher than 74.4% (29/39) in the western medication group (P<0.05).@*CONCLUSION@#Repeated transcranial acupuncture combined with electroacupuncture can improve the hearing level of patients with flat descending sudden deafness, relieve tinnitus and vertigo symptoms.

Animal DNA Typing and Its Research Progress in Forensic Medicine / 法医学杂志

With the advance of molecular biology, DNA analysis technology has been widely applied in forensic science. Non-human DNA analysis can be used in some special cases and has unique forensic value to provide investigation clues and trial basis. Animal DNA typing plays a more prominent role in the detection of all kinds of non-human DNA related cases and is the main content of forensic non-human DNA analysis. This paper reviews the development history, present situation, advantages and disadvantages of animal DNA typing according to its technology, characteristic, challenges facing forensic science application scenarios, and also its future development.

Content analysis and quality evaluation of main active components and mineral elements of Cynomorium songaricum in different habitats / 中国中药杂志

To clarify the content characteristics of the main active components and mineral elements of Cynomorium songaricum under different habitat conditions, and further explore the relationship between the quality of C. songaricum and habitats, this study took C. songaricum from 25 different habitats in China as the research object, and measured the contents of 8 main active components and 12 mineral elements separately. Diversity analysis, correlation analysis, principal component analysis and cluster analysis were carried out. The results showed that the genetic diversity of total flavonoids, ursolic acid, ether extract, potassium(K), phosphorus(P) and zinc(Zn) in C. songaricum was high. The coefficient of variation of crude polysaccharide, ether extract, gallic acid, protocatechuic aldehyde, catechin, epicatechin, calcium(Ca), sodium(Na), magnesium(Mg), sulfur(S), iron(Fe), manganese(Mn), selenium(Se) and nickel(Ni) were all over 36%, indicating that the quality of C. songaricum was significantly affected by habitats. There were strong synergistic and weak antagonistic effects among the contents of the 8 active components, and complex antagonistic and synergistic effects among the contents of the 12 mineral elements. Principal component analysis revealed that crude polysaccharide, ursolic acid, catechin, epicatechin and total flavonoids could be used as the characteristic components to evaluate the quality of C. songaricum, and Na, copper(Cu), Mn and Ni were the characteristic elements to evaluate the quality of C. songaricum. In cluster ana-lysis, the second group with the main active components as cluster center had better quality in terms of the content of active substances, and the second group with the mineral elements as cluster center had higher utilization potential in the exploitation of mineral elements. This study could provide a basis for resource evaluation and breeding of excellent varieties of C. songaricum in different habitats, and provide a reference for cultivation and identification of C. songaricum.

Efficacy of alcohol septal ablation in mildly symptomatic or severely symptomatic patients with hypertrophic obstructive cardiomyopathy / 中华心血管病杂志

Objective: To compare the prognosis of mildly or severely symptomatic patients with obstructive hypertrophic cardiomyopathy (OHCM) who underwent alcohol septal ablation (ASA). Methods: This retrospective study cohort consisted of patients with OHCM who received ASA treatment in Beijing Anzhen Hospital, Capital Medical University from March 2001 to August 2021. These patients were divided into mildly and severely symptomatic groups according to the severity of clinical symptoms. Long-term follow-up was conducted, and the following data were collected: duration of follow-up, postoperatire treatment, New York Heart Association (NYHA) classification, arrhythmia events and pacemaker implantation, echocardiographic parameters, and cause of death. Overall survival and survival free from OHCM-related death were observed, and the improvement of clinical symptoms and resting left ventricular outflow tract gradient (LVOTG) and the incidence of new-onset atrial fibrillation were evaluated. The Kaplan-Meier method and log-rank test were used to determine and compare the cumulative survival rates of the different groups. Cox regression analysis models were used to determine predictors of clinical events. Results: A total of 189 OHCM patients were included in this study, including 68 in the mildly symptomatic group and 121 in the severely symptomatic group. The median follow-up of the study was 6.0 (2.7, 10.6) years. There was no statistical difference in overall survival between the mildly symptomatic group (5-year and 10-year overall survival were 97.0% and 94.4%, respectively) and the severely symptomatic group (5-year and 10-year overall survival were 94.2% and 83.9%, respectively, P=0.405); there was also no statistical difference in survival free from OHCM-related death between the mildly symptomatic group (5-year and 10-year survival free from HCM-related death were 97.0% and 94.4%, respectively) and the severely symptomatic group (5-year and 10-year survival free from HCM-related death were 95.2% and 92.6%, respectively, P=0.846). In the mildly symptomatic group, NYHA classification was improved after ASA (P<0.001), among which 37 patients (54.4%) were in NYHA class Ⅰ, and the resting left ventricular outflow tract gradient (LVOTG) decreased from 67.6 (42.7, 90.1) mmHg (1 mmHg=0.133 kPa) to 24.4 (11.7, 35.6) mmHg (P<0.001). In severely symptomatic group, NYHA classification was also improved post ASA (P<0.001), among which 96 patients (79.3%) improved by at least one NYHA classification, and the resting LVOTG decreased from 69.6 (38.4, 96.1) mmHg to 19.0 (10.6, 39.8) mmHg (P<0.001). The incidence of new-onset atrial fibrillation was similar between the mildly and severely symptomatic groups (10.2% vs. 13.3%, P=0.565). Cox multivariate regression analysis showed that age was an independent predictor of all-cause mortality in OHCM patients post ASA (HR=1.068, 95%CI 1.002-1.139, P=0.042). Conclusions: Among patients with OHCM treated with ASA, overall survival and survival free from HCM-related death were similar between mildly symptomatic group and severely symptomatic group. ASA therapy can effectively relieve resting LVOTG and improve clinical symptoms in mildly or severely symptomatic patients with OHCM. Age was an independent predictor of all-cause mortality in OHCM patients post ASA.

Cuproptosis-Related 4-Gene Risk Model for Predicting Immunotherapy Drug Response and Prognosis of Kidney Renal Clear Cell Carcinoma / 中国医学科学杂志(英文版)

Background Kidney renal clear cell carcinoma (KIRC) is one of the most common renal malignancies with a high mortality rate. Cuproptosis, a novel form of cell death, is strongly linked to mitochondrial metabolism and is mediated by protein lipoylation, leading to a proteotoxic stress response and cell death. To date, few studies have ellucidated the holistic role of cuproptosis-related genes (CRGs) in the pathogenesis of KIRC.Methods We comprehensively and completely analyzed the RNA sequencing data and corresponding clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We screened for differentially expressed CRGs and constructed a prognostic risk model using univariate and multivariate Cox proportional regression analyses. Kaplan-Meier analysis was performed and receiver operating characteristic (ROC) curves were plotted to predict the prognosis of KIRC patients. Functional enrichment analysis was utilized to explore the internal mechanisms. Immune-related functions were analyzed using single-sample gene set enrichment analysis (ssGSEA), tumour immune dysfunction and exclusion (TIDE) scores, and drug sensitivity analysis.Results We established a concise prognostic risk model consisting of four CRGs (DBT, DLAT, LIAS and PDHB) to predict the overall survival (OS) in KIRC patients. The results of the survival analysis indicated a significantly lower OS in the high-risk group as compared to the patients in the low-risk group. The area under the time-dependent ROC curve (AUC) at 1, 3, and 5 year was 0.691, 0.618, and 0.614 in KIRC. Functional enrichment analysis demonstrated that CRGs were significantly enriched in tricarboxylic acid (TCA) cycle-related processes and metabolism-related pathways. Sorafenib, doxorubicin, embelin, and vinorelbine were more sensitive in the high-risk group.Conclusions We constructed a concise CRGs risk model to evaluate the prognosis of KIRC patients and this may be a new direction for the diagnosis and treatment of KIRC.

Progress in Biomechanics and Mechanobiology of Dendritic Cells / 医用生物力学

Dendritic cells (DCs) are now known as the most powerful antigen-presenting cells in vivo, with efficient antigen uptaking, and processing capabilities. They can present antigens to naïve T cells in secondary lymphoid tissues, thereby induce immune response or tolerance, and play a key role in initiating and amplifying innate and adaptive immunity. DCs experience complex chemical and mechanical microenvironment changes and show different mechanophenotypes and immunophenotypes in the process of exerting their physiological functions. Deeply understanding the chemical and mechanical factors that regulate the mechanophenotypes and immunophenotypes of DCs is a prerequisite for using DCs to treat immune related diseases. In this review, the progress in the biomechanics and mechanobiology research of DCs was mainly introduced, and their potential applications and future development directions in the treatment of immune related diseases were explored.

A nomogram for preoperative prediction of lymph node metastasis in patients with intrahepatic cholangiocarcinoma based on inflammation-related markers / 中华外科杂志

Objectives: To construct a nomogram for prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis based on inflammation-related markers,and to conduct its clinical verification. Methods: Clinical and pathological data of 858 ICC patients who underwent radical resection were retrospectively collected at 10 domestic tertiary hospitals in China from January 2010 to December 2018. Among the 508 patients who underwent lymph node dissection,207 cases had complete variable clinical data for constructing the nomogram,including 84 males,123 females,109 patients≥60 years old,98 patients<60 years old and 69 patients were pathologically diagnosed with positive lymph nodes after surgery. Receiver operating characteristic curve was drawn to calculate the accuracy of preoperative imaging examinations to determine lymph node status,and the difference in overall survival time was compared by Log-rank test. Partial regression squares and statistically significant preoperative variables were screened by backward stepwise regression analysis. R software was applied to construct a nomogram,clinical decision curve and clinical influence curve,and Bootstrap method was used for internal verification. Moreover,retrospectively collecting clinical information of 107 ICC patients with intraoperative lymph node dissection admitted to 9 tertiary hospitals in China from January 2019 to June 2021 was for external verification to verify the accuracy of the nomogram. 80 patients with complete clinical data but without lymph node dissection were divided into lymph node metastasis high-risk group and low-risk group according to the score of the nomogram among the 858 patients. Log-rank test was used to compare the overall survival of patients with or without lymph node metastasis diagnosed by pathology. Results: The area under the curve of preoperative imaging examinations for lymph node status assessment of 440 patients was 0.615,with a false negative rate of 62.8% (113/180) and a false positive rate of 14.2% (37/260). The median survival time of 207 patients used to construct a nomogram with positive or negative postoperative pathological lymph node metastases was 18.5 months and 27.1 months,respectively (P<0.05). Five variables related to lymph node metastasis were screened out by backward stepwise regression analysis,which were combined calculi,neutrophil/lymphocyte ratio,albumin,liver capsule invasion and systemic immune inflammation index,according to which a nomogram was constructed with concordance index(C-index) of 0.737 (95%CI: 0.667 to 0.806). The C-index of external verification was 0.674 (95%CI:0.569 to 0.779). The calibration prediction curve was in good agreement with the reference curve. The results of the clinical decision curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.32,the maximum net benefit could be obtained by 0.11,and the cost/benefit ratio was 1∶2. The results of clinical influence curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.6,the probability of correctly predicting lymph node metastasis could reach more than 90%. There was no significant difference in overall survival time between patients with high/low risk of lymph node metastasis assessed by the nomogram and those with pathologically confirmed lymph node metastasis or without lymph node metastasis (Log-rank test:P=0.082 and 0.510,respectively). Conclusion: The prediction accuracy of preoperative nomogram for ICC lymph node metastasis based on inflammation-related markers is satisfactory,which can be used as a supplementary method for preoperative diagnosis of lymph node metastasis and is helpful for clinicians to make personalized decision of lymph node dissection for patients with ICC.

Survival analysis of patients with intrahepatic cholangiocarcinoma treated with adjuvant chemotherapy after radical resection based on CoxPH model and deep learning algorithm / 中华外科杂志

Objective: To establish a predictive model for survival benefit of patients with intrahepatic cholangiocarcinoma (ICC) who received adjuvant chemotherapy after radical resection. Methods: The clinical and pathological data of 249 patients with ICC who underwent radical resection and adjuvant chemotherapy at 8 hospitals in China from January 2010 to December 2018 were retrospectively collected. There were 121 males and 128 females,with 88 cases>60 years old and 161 cases≤60 years old. Feature selection was performed by univariate and multivariate Cox regression analysis. Overall survival time and survival status were used as outcome indicators,then target clinical features were selected. Patients were stratified into high-risk group and low-risk group,survival differences between the two groups were analyzed. Using the selected clinical features, the traditional CoxPH model and deep learning DeepSurv survival prediction model were constructed, and the performance of the models were evaluated according to concordance index(C-index). Results: Portal vein invasion, carcinoembryonic antigen>5 μg/L,abnormal lymphocyte count, low grade tumor pathological differentiation and positive lymph nodes>0 were independent adverse prognostic factors for overall survival in 249 patients with adjuvant chemotherapy after radical resection (all P<0.05). The survival benefit of adjuvant chemotherapy in the high-risk group was significantly lower than that in the low-risk group (P<0.05). Using the above five features, the traditional CoxPH model and the deep learning DeepSurv survival prediction model were constructed. The C-index values of the training set were 0.687 and 0.770, and the C-index values of the test set were 0.606 and 0.763,respectively. Conclusion: Compared with the traditional Cox model, the DeepSurv model can more accurately predict the survival probability of patients with ICC undergoing adjuvant chemotherapy at a certain time point, and more accurately judge the survival benefit of adjuvant chemotherapy.

Exploring the significance of chemotherapy in the perioperative application of biliary tract carcinomas / 中华外科杂志

Biliary tract cancer is extremely malignant with a poor prognosis. At the moment, the only curative method available is radical resection. Targeted and immunotherapy are currently advancing quickly, but chemotherapy still holds a key role in the perioperative management of biliary cancer. Perioperative chemotherapy aims to decrease tumor volume before surgery so that patients can have their tumors surgically removed or have a higher radical resection rate. It also aims to remove any tumor cells that remain after surgery and prevent the growth of new tumors. Chemotherapy-based combination treatment techniques have been increasingly investigated in recent years to improve perioperative care and patient survival. From the standpoint of chemotherapy regimens and clinical trial success in the perioperative phase of radical surgery, the value of chemotherapy in the perioperative period of biliary tract cancer were explored in this paper.

Accelerated stability test of sustained-release thienorphine loaded microspheres for injection / 药学学报

In order to meet the clinical needs of long-acting sustained-release thienorphine, injectable thienorphine loaded microspheres were developed, and the accelerated stability study was carried out to explore the suitable storage and transportation conditions of the microspheres. Using poly(lactic-co-glycolic acid) (PLGA) as carrier material, 3 batches of microspheres were prepared in pilot scale with emulsion solvent evaporation method. By investigating the in vitro release of thienorphine loaded microspheres at 37, 45, 52, and 60 ℃, and applying the Arrhenius equation, the linear relationship between the release rate constant (lgk) and the temperature (1/T) was established to obtain the equation: lgk = -8.073/T + 24.35 (R2 = 0.985 3), which showed that the release of microspheres at high temperature can be used to predict the release in vitro at 37 ℃, and 52.0 ± 0.5 ℃ was selected as the accelerated release condition in vitro. The quality research methods were established to investigate the changes of critical quality attributes such as microsphere morphology, drug loading, particle size and distribution, polymer molecular weight, and the related substances under accelerated conditions. The difference factor f1 and similarity factor f2 were used to assess the similarity of release behavior under accelerated conditions. The results showed that under the accelerated experimental conditions of 25 ± 2 ℃ and relative humidity (RH) 60% ± 5%, the critical quality attributes of injectable thienorphine loaded microspheres had no significant change in 6 months, suggesting that the long-term storage condition could be 5 ± 3 ℃.

Significance of combination of targeted therapy and immunotherapy in conversion therapy of biliary tract cancer / 中华外科杂志

Biliary tract cancer has insidious onset and high degree of malignancy, and radical resection is often impossible when it is diagnosed.Conversion therapy can achieve tumor downgrading, so that patients who were initially unresectable have a chance to achieve R0 resection.However, due to the high heterogeneity and complex immune microenvironment of biliary tract cancer, conversion therapy is still in the stage of active exploration.As a new type of conversion therapy, combination of targeted therapy and immunotherapy is of great significance to effectively improve the efficiency of conversion therapy.Further exploration of combination mechanism and improvement of immune microenvironment are expected to become the future direction of combination of targeted therapy and immunotherapy.

Therapeutic effects of alcohol septal ablation in mildly symptomatic patients with hypertrophic obstructive cardiomyopathy / 中华心血管病杂志

Objective: To observe the therapeutic effects of alcohol septal ablation (ASA) in mildly symptomatic patients (NYHA class Ⅱ) with hypertrophic obstructive cardiomyopathy(HOCM). Methods: This retrospective study included 150 mildly symptomatic patients with HOCM hospitalized in Beijing Anzhen Hospital affiliated to Capital Medical University from March 2001 to December 2017, consisting of medical therapy group (n=102) and ASA group (n=48). Baseline clinical data were collected, patients were followed up to a mean of 6.0 (3.5, 8.1) years. Overall and HCM-related mortality events (including chronic heart failure, atrial fibrillation related stroke, sudden cardiac death) were observed in the two groups. Moreover, the improvement of NYHA function classification and left ventricular outflow tract gradient (LVOTG) were also evaluated. Survival analysis was performed by Kaplan-Meier method. Results: Age of this cohort was (52.9±14.5)years, 92 cases(61.3%) were male. In the follow-up, LVOTG was reduced from (85.8±35.4)mmHg (1 mmHg=0.133 kPa) to (27.7±19.8)mmHg (P<0.001) in the ASA group, and from (66.3±35.0)mmHg to (56.5±27.7)mmHg in medical therapy group(P<0.01). At the last clinical follow-up, there were 32 patients (66.7%) whose LVOTG were<30 mmHg, septal thickness decreased from (20.3±3.8)mm to (16.1±3.4)mm (P<0.001), NYHA classification was also remarkably improved (P<0.001). New-onset atrial fibrillation tended to be lower in the ASA group compared to medical therapy group (9.3%(4/43) vs. 20.8%(20/96),P=0.096). Eleven patients (10.8%) in the medical therapy group and 2 patients (4.2%) in the ASA group died during the follow-up. One patient received pacemaker during the peri-procedural period, 1 patient was implanted with two-chamber pacemaker due to Ⅲ° atrioventricular block at 10 years after operation in the ASA group. Survival free of all-cause mortality of ASA group at 5 and 10 years was 97.9% and 97.9%, respectively, which was comparable to the medical therapy group (P=0.231). Survival free of HCM-related mortality was similar between the two groups (P=0.397). Conclusions: Compared with medical therapy in mildly symptomatic patients with HOCM, long-term survival rate is similar after ASA. Meanwhile, ASA can remarkably reduce LVOTG and improve the clinical status of the patients. Therefore, ASA may be used as an alternative therapy for mildly symptomatic HOCM patients.

Head acupuncture combined with exercise therapy for nonspecific low back pain：a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical effect between head acupuncture combined with exercise therapy and conventional acupuncture for nonspecific low back pain.@*METHODS@#A total of 64 patients with nonspecific low back pain were randomized into an observation group (32 cases, 2 cases dropped off) and a control group (32 cases, 2 cases dropped off). In the control group, conventional acupuncture was applied at Jiaji (EX-B 2) of L1 to L3, ashi point, Shenshu (BL 23), Dachangshu (BL 25), Yaoyangguan (GV 3) and Weizhong (BL 40). The observation group was treated with head acupuncture combined with exercise therapy, head acupuncture was applied at foot-motor-sensory area on the healthy side and Cuanzhu (BL 2), Tongziliao (GB 1) on the affected side, and McKenzie therapy was performed during retention. The needles were retained for 40 min, once a day, continuous treatment for 6 days with the interval of 1 day, 14 days were required in the two groups. Before and after treatment, the pain visual analogue scale (VAS) score, Oswestry disability index (ODI) score and infrared thermography temperature of pain area in the low back were compared in the two groups.@*RESULTS@#Compared before treatment, the VAS and ODI scores after treatment were decreased in the two groups (P<0.01), and those in the observation group were lower than the control group (P<0.01). Compared before treatment, the infrared thermography temperature of pain area in the low back after treatment was increased in the two groups (P<0.01), and that in the observation group was higher than the control group (P<0.01).@*CONCLUSION@#Head acupuncture combined with exercise therapy could relieve pain, improve dysfunction and increase the local temperature of pain area in patients with nonspecific low back pain, and its curative effect is better than conventional acupuncture.

Essence of SUN Shen-tian's clinical features on acupuncture and moxibustion / 中国针灸

To summarize SUN Shen-tian's treatment ideas and clinical features. SUN applies meridian syndrome differentiation to the diagnosis and treatment of diseases; advocates that prevention and treatment of diseases should be regulated mind firstly; applies transcranial repetitive acupuncture combined modern cerebral cortex function positioning; emphasizes the application of multiple acupuncture methods and manipulation, and includes the meridian penetrating needling method, the flat needling and penetrating needling method, and the stagnant needle lifting method, pays attention to the importance of achieving qi and manipulation for the effect.