Research progress of hydroxychloroquine retinopathy / 中华眼底病杂志

Hydroxychloroquine is widely used in a variety of autoimmune diseases. However, long-term use of hydroxychloroquine can cause severe retinopathy, which has a complex pathogenic mechanism and diverse clinical manifestations, mainly manifested as photoreceptor and retinal pigment epithelial damage and irreversible vision loss. Identifying damage before retinitis pigment epithelium lesions preserve central vision, so early detection is crucial to slow disease progression and reduce vision loss. The development of multimodal imaging technology and the issuance of the latest treatment guidelines provide a powerful tool for the early screening and treatment of hydroxychloroquine retinopathy. Proficient in the latest guidelines for the treatment of hydroxychloroquine can better guide clinicians to do a good job in disease screening and management, recommend risks, safe dosages and appropriate screening procedures to patients and strengthen the prevention of hydroxychloroquine retinopathy, which will help save the vision of more patients and reduce the waste of medical resources.

Loss of ATM activity induces GADD45α-dependent apoptosis in cerebellar granular neurons / 中山大学学报(医学科学版)

objectiveTo explore the specific molecular mechanism of neuronal apoptosis induced by ATM inactivation. MethodsCGNs matured 7 days in vitro were cultured 8 h with 25 K， 5 K or 25 K medium containing ATM-specific inhibitors （Ku55933， 10 µmol/L； Ku60019， 15 µmol/L） for Hoechst stain and apoptosis analysis， or cultured for different lengths of time （2， 4， 8 h） to detect the protein expression levels of ATM， caspase-3 and cleaved caspase-3 by Western blotting. ATM and GADD45α specific siRNA was transfected into C6 cells and CGNs， and its interference efficiency was verified by q-PCR and Western blotting. CGNs matured for 5 days in vitro were transfected with ATM specific siRNA and pCMV-EGFP by calcium phosphate for 48 h， Hoechst staining and apoptosis analysis were performed. CGNs matured for 7 days in vitro were treated with 25 K medium containing ATM specific inhibitors for 8 h， transcriptome sequencing， differential expression gene identification and pathway enrichment analysis were performed. CGNs matured for 5 days in vitro were co-transfected with GADD45α specific siRNA and pCMV-EGFP by calcium phosphate for 48 h， then treated with 5 K or 25 K medium containing 15 µmol/L Ku6 for 8 h. Hoechst staining and apoptosis analysis were performed. ResultsCompared with the 25 K， CGNs nuclear pyknosis rate， cleaved Caspase-3 and ATM protein expression level were increased in the 5 K and ATM-specific inhibitor groups. The mRNA and protein expression levels of ATM and GADD45α were effectively reduced after transfection of ATM and GADD45α specific siRNA in C6 cells and CGNs. Compared with control， CGNs transfected with ATM specific siRNA showed a higher nuclear pyknosis rate. Totally 835 genes were identified to be up-regulated and 848 genes to be down-regulated in the Ku55933 treatment group； 454 genes were identified to be up-regulated and 314 genes to be down-regulated in the Ku6 treatment group； 274 genes were co-up regulated in the Ku5 and Ku60019 treatment groups， while 179 genes were co-down-regulated in the Ku5 and Ku6 treatment groups and the expression of ATM downstream target GADD45α was upregulated. The enrichment results showed that TNF signaling pathway， NF-κB signaling pathway and Apoptosis signaling pathway were significantly enriched. Compared with control， mRNA and protein expression levels of GADD45α were increased in inhibitor treatment and 5 K， while knocking down GADD45α resulted in a decrease in nuclear pyknosis rate in the Ku60019 and 5 K treatment group. ConclusionLoss of ATM activity induces GADD45α-dependent cerebellar granular neuronal apoptosis.

Expression and localization of vascular endothelial growth factor-B in diencephalon and brainstem related tissues of the Yak’s brain / 解剖学报

Objective To explore the expression and distribution characteristics of vascular endothelial growth factor-B(VEGF-B) in diencephalon and brainstem of Yak’s brain tissues, and to investigate the associations between its expression and hypoxia adaptation. Methods Five healthy yaks were selected, and the brain tissues were divided and collected according to the gross anatomical structure of the brain, including pituitary, thalamus, hypothalamus, oblongata and pons. The characteristics of expression and location of VEGF-B in different regions of Yak’s brain tissues were detected by Real-time PCR, Western blotting and immunohistochemical techniques. Results The results showed that the highest expression level of VEGF-B mRNA of yak brain tissue was in the pituitary, and the content was significantly higher than that found in other parts of the brain(P<0. 05). Following the expressions were in the hypothalamus, thalamus and medulla oblongata, while the lowest expression level was in pons. The expression level of VEGF-B protein in Yak’s brain tissue was similar to the mRNA expression level except that the thalamus was higher than that of hypothalamus. The result of immunohistochemistry showed that VEGF-B protein-positive substances were mainly distributed in the cytoplasm of various types of cells. Among them, the positive staining of VEGF-B was mainly concentrated in eosinophils of pituitary. The positive staining of VEGF-B was mainly concentrated in pleomorphic cells of thalamus and hypothalamus. The distribution of VEGF-B protein-positive substances were mainly focused in nerve cell body of medulla oblongata and pons. Conclusion VEGF-B protein is expressed in both diencephalon and brainstem of yak, which may be closely related to its functions of anti-apoptosis, "survival factor" and angiogenesis. However, the specific mechanism of its neuroprotective effect on Yak brain under hypoxic environment needs to be further studied. The difference of expression in different regions may be related to the tissue specificity and function in different regions of the brain.

Mechanism of Bawei Chenxiang powder in treatment of ischemie heart disease through mitophagy based on network pharmacology / 中国药理学通报

Aim To explore the potential mechanism of Bawei Chenxiang powder against ischemie heart disease (IHD) through mitophagy based on network pharmacology, molecular docking and verification in vitro. Methods The targets of serum constituents of Bawei Chenxiang powder were mined by Swiss target predic-tion, and then the targets related to IHD and mitophagy were selected from Genecards, NCBI and OMIM data-bases to obtain the intersection targets of the three as the potential targets of Bawei Chenxiang powder for the treatment of IHD through mitophagy. Then the "ingre-dients-disease-potential target " network and " protein-protein interaction" (PPI) network were constructed to perform network analysis in order to screen the key ac-tive ingredients and core targets, using Autodock vina software for molecular docking operation. The targets CO function enrichment analysis and KEGG pathway enrichment analysis were analyzed by DAVID databas-es. The effeets of Bawei Chenxiang powder containing serum on celi viability, levels expressions mitophagy and key signaling pathway related protein in H9C2 cells were investigated by hypoxia-induced injury of H9c2 myocardial cells model in vitro. Results The 9 key active compounds and 8 core targets of Bawei Chenxiang powder were screened; molecular docking showed a good binding ability of key active ingredients and core targets. KEGG pathway enrichment analysis showed that the effect of Bawei Chenxiang powder on IHD through mitophagy was related to EGFR, PI3K-Akt, MAPK, FoxO signaling pathway, etc. Celi ex-periments showed that Bawei Chenxiang powder containing serum treatment could significantly improve the survival rate by hypoxia-induced injury in H9c2, the expression of LC3II and p62 were significantly down-regulated, and the expressions of p-PI3K/PI3K and p-AKT/AKT were significantly up-regulated. Conclu-sions Bawei Chenxiang powder plays an anti-IHD role by regulating mitophagy, which may be involved in AKT1, STAT3, MAPK3 and EGFR and other targets, through quercetin, Kaempferol, Naringenin and De-hydrodiisoeugenol as well as other components. Its mechanism may be related to improving PI3K-AKT pathway.

Second allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning and donor changes in relapsed hematological malignancies after the first allogeneic transplant / 中华血液学杂志

Objective: The purpose of this study was to assess the safety and efficacy of a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced-intensity conditioning (RIC) in patients with hematological malignancies who had relapsed after the first allo-HSCT. Methods: Between April 2018 and June 2021, 44 patients with hematological malignancies (B-ALL 23, T-ALL/T-LBL 4, AML15, and MDS 2) were enrolled and retrospectively examined. Unrelated donors (n=12) or haploidentical donors (n=32) were used. Donors were replaced in all patients for the second allo-HSCT. Hematological and immunological germline predisposition genes and hematopoietic and immune function tests were used to select the best-related donor. Total body irradiation (TBI) /fludarabine (FLU) -based (n=38), busulfan (BU) /FLU-based (n=4), total marrow irradiation (TMI) /FLU-based (n=1), and BU/cladribine-based (n=1) were the RIC regimens used. For graft versus host disease (GVHD) prevention, cyclosporine, mycophenolate mofetil, short-term methotrexate, and ATG were used. Eighteen (40.9%) of 44 patients with gene variations for which targeted medications are available underwent post-transplant maintenance therapy. Results: The median age was 25 years old (range: 7-55). The median interval between the first and second HSCT was 19.5 months (range: 6-77). Before the second allo-HSCT, 33 (75%) of the patients were in complete remission (CR), whereas 11 (25%) were not. All patients had long-term engraftment. The grade Ⅱ-Ⅳ GVHD and severe acute GVHD rates were 20.5% and 9.1%, respectively. Chronic GVHD was found in 20.5% of limited patterns and 22.7% of severe patterns. CMV and EBV reactivation rates were 29.5% and 6.8%, respectively. Hemorrhage cystitis occurred in 15.9% of cases, grade Ⅰ or Ⅱ. The 1-yr disease-free survival (DFS), overall survival (OS), and cumulative recurrence incidence (RI) rates of all patients were 72.5% (95% CI, 54.5%-84.3%), 80.6% (95% CI, 63.4%-90.3%), and 25.1% (95% CI, 13.7%-43.2%), respectively, with a median follow-up of 14 (2-39) months. There were eight deaths (seven relapses and one infection). The rate of non-relapse mortality (NRM) was only 2.3%. The CR patients' 1-yr RI rate was significantly lower than the NR patients (16.8% vs 48.1%, P=0.026). The DFS rate in CR patients was greater than in NR patients, although there was no statistical difference (79.9% vs 51.9%, P=0.072). Univariate analysis revealed that CR before the second allo-HSCT was an important prognostic factor. Conclusion: With our RIC regimens, donor change, and post-transplant maintenance therapy, the second allo-HSCT in relapsed hematological malignancies after the first allo-HSCT is a safe and effective treatment with high OS and DFS and low NRM and relapse rate. The most important factor influencing the prognosis of the second allo-HSCT is the patient's illness condition before the transplant.

Pathological Changes and Cause of Death Associated with the Global Novel Coronavirus Disease (COVID-19) / 法医学杂志

The coronavirus disease 2019 (COVID-19) has been a global epidemic for more than three years, causing more than 6.9 million deaths. COVID-19 has the clinical characteristics of strong infectivity and long incubation period, and can cause multi-system damage, mainly lung damage, clinical symptoms of acute respiratory distress syndrome (ARDS) and systemic multiple organ damage. The SARS-CoV-2 virus is still constantly mutating. At present, there is no global consensus on the pathological changes of COVID-19 associated deaths and even no consensus on the criteria for determining the cause of death. The investigation of the basic pathological changes and progression of the disease is helpful to guide the clinical treatment and the development of therapeutic drugs. This paper reviews the autopsy reports and related literature published worldwide from February 2020 to June 2023, with a clear number of autopsy cases and corresponding pathological changes of vital organs as the inclusion criteria. A total of 1 111 autopsy cases from 65 papers in 18 countries are included. Pathological manifestations and causes of death are classified and statistically analyzed, common pathological changes of COVID-19 are summarized, and analytical conclusions are drawn, suggesting that COVID-19 infection can cause life-threatening pathological changes in vital organs. On the basis of different health levels of infected groups, the direct cause of death is mainly severe lung damage and secondary systemic multiple organ failure.

Metabonomics Analysis of Brain Stem Tissue in Rats with Primary Brain Stem Injury Caused Death / 法医学杂志

OBJECTIVES@#To explore the potential biomarkers for the diagnosis of primary brain stem injury (PBSI) by using metabonomics method to observe the changes of metabolites in rats with PBSI caused death.@*METHODS@#PBSI, non-brain stem brain injury and decapitation rat models were established, and metabolic maps of brain stem were obtained by LC-MS metabonomics method and annotated to the HMDB database. Partial least square-discriminant analysis (PLS-DA) and random forest methods were used to screen potential biomarkers associated with PBSI diagnosis.@*RESULTS@#Eighty-six potential metabolic markers associated with PBSI were screened by PLS-DA. They were modeled and predicted by random forest algorithm with an accuracy rate of 83.3%. The 818 metabolic markers annotated to HMDB database were used for random forest modeling and prediction, and the accuracy rate was 88.9%. According to the importance in the identification of cause of death, the most important metabolic markers that were significantly up-regulated in PBSI group were HMDB0038126 (genipinic acid, GA), HMDB0013272 (N-lauroylglycine), HMDB0005199 [(R)-salsolinol] and HMDB0013645 (N,N-dimethylsphingosine).@*CONCLUSIONS@#GA, N-lauroylglycine, (R)-salsolinol and N,N-dimethylsphingosine are expected to be important metabolite indicators in the diagnosis of PBSI caused death, thus providing clues for forensic medicine practice.

Safety of butylphthalide and edaravone in patients with ischemic stroke: a multicenter real-world study / 老年心脏病学杂志（英文版）

BACKGROUND@#Butylphthalide (NBP) and edaravone (EDV) injection are common acute ischemic stroke medications in China, but there is a lack of large real-world safety studies on them. This study aimed to determine the incidence of adverse events, detect relevant safety signals, and assess the risk factors associated with these medications in real-world populations.@*METHODS@#In this study, data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021. Baseline confounders were eliminated using propensity score matching. The drugs' safety was estimated by comparing the results of 24 laboratory tests standards on liver function, kidney function, lipid level, and coagulation function. The drugs' relative risk was estimated by logistic regression. A third group with patients who did not receive NBP or EDV was constructed as a reference. Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV, respectively.@*RESULTS@#81,292 patients were included in this study. After propensity score matching, the NBP, EDV, and third groups with 727 patients in each group. Among the 15 test items, the incidence of adverse events was lower in the NBP group than in the EDV group, and the differences were statistically significant. The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results, whereas EDV had statistically significant effects on aspartate transaminase, low-density lipoprotein cholesterol and total cholesterol. Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count. EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and platelet count.@*CONCLUSIONS@#In a large real-world population, NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.

Advances in research on myopic traction maculopathy / 中华眼底病杂志

High myopia is a disease with a high incidence rate and an increasing trend, which could lead to irreversible visual impairment worldwide. Myopia traction maculopathy (MTM), belonging to one of the pathological changes of high myopia, could cause vision damage and even blindness in patients. Recently, a new classification of MTM based on optical coherence tomography can effectively evaluate the condition of patients and is helpful for the diagnosis and treatment of MTM. Moreover, the improvement of internal limiting membrane peeling method and the innovation of macular buckle material provide new ideas for the treatment of MTM based on traditional surgery. New treatment such as vitreal traction release laser surgery, enzymatic vitreolysis and posterior scleral crosslinking have gained increasing attention. By combining these new treatments with artificial intelligence, 3D printing technology and advanced vitrectomy equipment, it is hoped that a safer and more effective treatment for MTM will be found in the future.

Advances in research on myopic traction maculopathy / 中华眼底病杂志

High myopia is a disease with a high incidence rate and an increasing trend, which could lead to irreversible visual impairment worldwide. Myopia traction maculopathy (MTM), belonging to one of the pathological changes of high myopia, could cause vision damage and even blindness in patients. Recently, a new classification of MTM based on optical coherence tomography can effectively evaluate the condition of patients and is helpful for the diagnosis and treatment of MTM. Moreover, the improvement of internal limiting membrane peeling method and the innovation of macular buckle material provide new ideas for the treatment of MTM based on traditional surgery. New treatment such as vitreal traction release laser surgery, enzymatic vitreolysis and posterior scleral crosslinking have gained increasing attention. By combining these new treatments with artificial intelligence, 3D printing technology and advanced vitrectomy equipment, it is hoped that a safer and more effective treatment for MTM will be found in the future.

Testosterone levels in patients with varicocele and azoospermia / 北京大学学报(医学版)

OBJECTIVE@#Androgen deficiency is common in aging males and may have unfavourable health consequences. Large-scale studies suggested low testosterone level might increse mortality and morbidity in ageing males. However, young men with low testosterone level might be neglected. Recent studies reported young men with infertility may have reduced testosterone level. To investigate the incidence of androgen deficiency in males with infertility and possible factors affecting the low testosterone level.@*METHODS@#Between January 2011 and December 2012, 407 men with infertility caused by varicocele (VC), obstructive azoospermia (OA) and nonobstructive azoospermia (NOA) in our center were included. The number of men in each group of OA, NOA and VC was 141, 97 and 169, respectively. All the eligible patients underwent a serum testosterone assessment by a single morning blood draw (between 8:00 to noon) to test for concentration of the total testosterone. All serum samples were determined by radioimmunoassay in our andrology laboratory. Androgen deficiency was defined as having a total testosterone level less than 300 ng/dL.@*RESULTS@#The mean age was (30.4±5.8) years. The mean testosterone level was (4.18±1.64) ng/dL (range 0.30 to 11.32 ng/dL). The overall incidence of androgen deficiency was 26.5% (108/407). The incidences of androgen deficiency in NOA, OA and VC groups were 40.2% (39/97), 19.1% (27/141) and 24.9% (42/169), respectively, which were significantly higher in the NOA than in the VC and OA groups (P < 0.001). The incidences had no difference between the VC and OA groups (P=0.229). Univariate analysis revealed the cause of infertility, FSH and the mean testis volume as possible affecting factors for androgen deficiency. However, on multivariate analysis the only cause of infertility was an independent predictor. The incidence of androgen deficiency was the highest in the NOA group [OR 0.492 (95% confidence interval 0.288-0.840)].@*CONCLUSION@#NOA and varicocele might be risk factors of androgen deficiency. Young men with NOA may have a higher possibility of low testosterone level. Testosterone level should be followed up after NOA and varicocele treatment. Androgen deficiency should be assessed in males with infertility in clinical practice.

A comparative study of multiple parallel mediation analysis methods / 中华流行病学杂志

Objective: To introduce and compare four analysis methods of multiple parallel mediation model, including pure regression method, method based on inverse probability weighting, extended natural effect model method and weight-based imputation strategies. Methods: For the multiple parallel mediation model, the simulation experiments of three scenarios were carried out to compare the performance of different methods in estimating direct and indirect effects in different situations. Dataset from UK Biobank was then analyzed by using the four methods. Results: The estimation biases of the regression method and the inverse probability weighting method were relatively small, followed by the extended natural effect model method, and the estimation results of the weight-based imputation strategies were quite different from the other three methods. Conclusions: Different multiple parallel mediation analysis methods have different application situations and their own advantages and disadvantages. The regression method is more suitable for continuous mediator, and the inverse probability weighting method is more suitable for binary mediator. The extended natural effect model method has better performances when the residuals of two parallel mediators are positively correlated and the correlation degree is small. The weight-based imputation strategies might not be appropriate for parallel mediation analysis. Therefore, appropriate methods should be selected according to the specific situation in practice.

Clinical effect of different maintenance doses of caffeine citrate in the treatment of preterm infants requiring assisted ventilation: a pilot multicenter study / 中国当代儿科杂志

OBJECTIVES@#To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment.@*METHODS@#A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group.@*RESULTS@#Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05).@*CONCLUSIONS@#This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.

Advances in clinical application of obstruction catheter in prevention and treatment of intestinal obstruction / 中华胃肠外科杂志

Intestinal obstruction is one of the most common diseases in abdominal surgery, and its prevention and treatment is a clinical difficulty. Although surgical operation can solve the symptoms of obstruction, there are many postoperative complications, and it is easy to develop re-obstruction due to postoperative abdominal adhesion. The internal fixation of small intestine with obstruction catheter provides a new idea for the prevention of postoperative adhesive bowel obstruction. The use of transanal ileus catheter provides the possibility of direct intestinal anastomosis after resection of malignant obstruction in the left hemicolon and can reduce the incidence of postoperative complications. However, sufficient attention should be paid to the related complications, and prevention and treatment should be planned. It is important to note that the use of obstruction catheter is only one of the conservative treatments for bowel obstruction, and it is not a complete replacement of surgery. Surgical treatment should still be considered, if the catheter fails to significantly move, if the obstructive symptoms do not significantly improve 5 days after catheterization.

A multi-center retrospective study of perioperative chemotherapy for gastric cancer based on real-world data / 中华胃肠外科杂志

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.

Expert consensus on Tongsaimai Tablets/Capsules in treatment of peripheral vascular diseases in clinical practice / 中国中药杂志

Tongsaimai Tablets/Capsules are composed of Lonicerae Japonicae Flos, Angelicae Sinensis Radix, Achyranthis Bidentatae Radix, Codonopsis Radix, Dendrobii Caulis, Astragali Radix, Scrophulariae Radix, and Glycyrrhizae Radix et Rhizoma, and are effective in promoting blood circulation, removing blood stasis, supplementing Qi, and nourishing Yin. It is widely used in the treatment of peripheral vascular diseases. With 40 years of clinical application, it has accumulated substantial research data and application experience. Its good clinical efficacy and pharmacoeconomic benefits in improving the clinical symptoms of peripheral vascular diseases have been confirmed by relevant research. Meanwhile, this drug has also been recommended by many expert consensus, guidelines, and teaching materials, serving as one of the most commonly used Chinese patent medicines in clinical practice. To further improve the understanding of the drug among clinicians and properly guide its clinical medication, the China Association of Chinese Medicine took the lead and organized experts to jointly formulate this expert consensus. Based on the questionnaire survey of clinicians and the systematic review of research literature on Tongsaimai Tablets/Capsules with clinical problems in the PICO framework, the consensus, combined with expert experience, concludes recommendations or consensus suggestions by GRADE system with the optimal evidence available through the nominal group technique. This consensus defines the indications, usage, dosage, course of treatment, medication time, combined medication, and precautions of Tongsaimai Tablets/Capsules in the treatment of peripheral vascular diseases, and explains the safety of its clinical application. It is recommended for clinicians and pharmacists in the peripheral vascular department(vascular surgery), traditional Chinese medicine surgery(general surgery), and endocrinology department of hospitals at all levels in China.

Effect of different parts of Pinelliae Rhizoma Decoction against airway inflammation and analysis of effective components / 中国中药杂志

This study investigated the material basis and mechanism of Pinelliae Rhizoma Decoction in the treatment of airway inflammation. The cigarette smoke combined with lipopolysaccharide(LPS) was used to induce an airway inflammation model in mice. The expression levels of IL-6 and IL-8 in the bronchoalveolar lavage fluid(BALF) and the phosphorylation levels of p38 and IκB in the lungs of mice were taken as indexes to screen the effective extracts by system solvent extraction from Pinelliae Rhizoma Decoction(dichloromethane extract, ethyl acetate extract, n-butanol extract, etc.). Meanwhile, the human bronchial epithelial(16-HBE) cell model of cigarette smoke extract(CSE)-induced injury was established, and the mRNA expression levels of IL-6 and IL-8 and the phosphorylation levels of p38 and IκB proteins were also taken as indexes to evaluate the anti-inflammatory effect of different extracts of Pinelliae Rhizoma Decoction. The results showed that Pinelliae Rhizoma Decoction significantly antagonized airway inflammation in mice by down-regulating the expression levels of IL-6 and IL-8 in mice with airway inflammation and 16-HBE cells with CSE-induced injury and inhibiting the phosphorylation levels of p38 and IκB. The dichloromethane and ethyl acetate extracts of Pinelliae Rhizoma Decoction showed significant anti-inflammatory effects, while such effects of other extracts were not prominent. Furthermore, the database of Pinelliae Rhizoma composition was constructed, and the components in effective extracts were analyzed by HPLC-TOF-MS and Nano-LC-MS/MS. As revealed by the results, the compositions of the two effective extracts were similar with 36 common components. They were combined and then divided into Pinelliae Rhizoma alkaloids(PTAs) and Pinelliae Rhizoma non-alkaloids(PTNAs) by 732 cation-exchange resin. Further in vitro investigation confirmed the significant anti-inflammatory effect of PTNAs, while such effect of PTAs was not manifest. The MS analysis showed 172 peptides and 7 organic acids in PTNAs. The peptide content in PTNAs was 63.5% measured by quantitative analysis of BCA assay, and the organic acid content was 9.92% by potentiometric titration method. The findings of this study suggested that Pinelliae Rhizoma Decoction could antagonize airway inflammation in mice by inhibiting phosphorylation of p38 and IκB and blocking the activation of MAPK and NF-κB signaling pathways, and the effective components were related to the peptides and organic acids in PTNAs. The above results lay a foundation for the research on the mechanism and material basis of Pinelliae Rhizoma in antagonizing airway inflammation.

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.

Efficacy of Jianpi Xiaoai Prescription in Inhibition of Metastasis of Colon Cancer HCT116 Cells： An Exploration Based on LncRNA HOTAIR/JAK2/STAT3 Signaling Pathway / 中国实验方剂学杂志

Objective:To observe the effect of Jianpi Xiaoai prescription on long non-coding RNA Hox transcript antisense intergenic RNA （lncRNA HOTAIR）/Janus kinase 2 （JAK2） /signal transducer and activator of transcription 3 （STAT3） signaling pathway and to explore the potential mechanism of Jianpi Xiaoai prescription in suppressing the metastasis of colon cancer. Method:The expression of lncRNA HOTAIR in different cells was analyzed. Following the treatment of HCT116 cells with 10%，15%，and 20% Jianpi Xiaoai prescription -containing serum， the invasive ability of Jianpi Xiaoai prescription on HCT116 cells was assessed by transwell assay. The mRNA expression levels of lncRNA HOTAIR，JAK2，and STAT3 were measured by Real-time polymerase chain reaction （Real-time PCR）， and the protein expression levels of JAK2， phosphorylated STAT3 （p-STAT3） and STAT3 by Western blot. Result:The highest expression of lncRNA HOTAIR was detected in HCT116 cells. Compared with the blank group， each Jianpi Xiaoai prescription group exhibited a decreased number of invasive cells （<italic>P</italic><0.05， <italic>P</italic><0.01）. The relative JAK2 mRNA expression in the middle-dose Jianpi Xiaoai prescription group was down-regulated （<italic>P</italic><0.05）， and the relative lncRNA HOTAIR mRNA expression in the middle- and high-dose Jianpi Xiaoai prescription groups and the relative JAK2 mRNA expression in the high-dose Jianpi Xiaoai prescription group were remarkably down-regulated （<italic>P</italic><0.01）. Compared with the blank group，the relative p-STAT3 protein expression was down-regulated in the middle-dose Jianpi Xiaoai prescription group （<italic>P</italic><0.05）， and the relative JAK2 protein expression in the middle- and high-dose Jianpi Xiaoai prescription groups and the relative p-STAT3 protein expression in the high-dose Jianpi Xiaoai prescription group were remarkably down-regulated （<italic>P</italic><0.01）. Conclusion:Jianpi Xiaoai prescription effectively inhibits the metastasis of colon cancer cells， which may be related to the inhibition of lncRNA HOTAIR/JAK2/STAT3 signaling pathway.

Analysis and Identification of Chemical Constituents in Hypoglycemic Effective Fractions of Longan Folium Based on UPLC-Q-Orbitrap HRMS / 中国实验方剂学杂志

Objective:Chemical constituents in hypoglycemic effective fractions of Longan Folium were isolated and identified by ultra performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry （UPLC-Q-Orbitrap HRMS） to clarify the hypoglycemic substance basis of Longan Folium. Method:Chemical constituents in hypoglycemic effective fractions of Longan Folium were isolated on a Thermo Hypersil GOLD C₁₈ column （2.1 mm×100 mm， 1.9 μm）， the mobile phase was 0.1% formic acid acetonitrile solution and 0.1% formic acid solution （containing and 10 mmol ammonium acetate） for gradient elution. HRMS was operated in the positive and negative ion modes with the scanning range of <italic>m</italic>/<italic>z</italic> 100-1 500. Result:The secondary fragment ion information of target compounds was selected and compared with the compounds reported in the databases and related literature to further confirm these compounds. Nine compounds were identified in the ethanol fraction of Longan Folium， including cynaroside， kaempferol， quercitrin， luteolin， shikimic acid， citric acid， <italic>L</italic>-tyrosine， adenosine and nicotinamide. A total of 11 compounds were determined in the ethyl acetate fraction （cynaroside， quercitrin， kaempferol， luteolin， shikimic acid， gallic acid， protocatechuic acid， adenosine， nicotinamide， <italic>L</italic>-phenylalanine and scopoletin）， and 10 compounds were identified in the <italic>n</italic>-butanol fraction （cynaroside， kaempferol-3-<italic>O</italic>-rutinoside， kaempferol， astragalin， luteolin， citric acid， gallic acid， adenosine， nicotinamide and 5-hydroxymethylfurfural）. And five common compounds were identified in these three hypoglycemic effective fractions. Conclusion:The established UPLC-Q-Orbitrap HRMS can quickly identify chemical constituents in three hypoglycemic effective fractions of Longan Folium， their main chemical constituents are flavonoids and their glycosides， organic acids and nitrogen-containing compounds， which provides technical support and scientific evidence for the study on pharmacodynamic material basis and quality control of Longan Folium.