Role of apical sodium-dependent bile acid transporter in hepatobiliary diseases / 临床肝胆病杂志

Apical sodium-dependent bile acid transporter （ASBT） is a key transporter responsible for intestinal reabsorption of bile acid and plays an important role in maintaining bile acid and cholesterol homeostasis， and its expression is regulated by various factors including transcription factors， nuclear receptors， and intestinal microflora. The abnormal expression and function of ASBT can lead to disorders in the metabolism of bile acid and cholesterol， causing a variety of hepatobiliary diseases. At present， ASBT has attracted wide attention as a therapeutic target. This article elaborates on the biological characteristics and expression regulation mechanism of ASBT and reviews the role of ASBT in hepatobiliary diseases， in order to provide a new direction for the treatment of related diseases.

Melatonin inhibits arrhythmias induced by increased late sodium currents in ventricular myocytes / 药学学报

Melatonin (Mel) has been shown to have cardioprotective effects, but its action on ion channels is unclear. In this experiment, we investigated the inhibitory effect of Mel on late sodium currents (INa.L) in mouse ventricular myocytes and the anti-arrhythmic effect at the organ level as well as its mechanism. The whole-cell patch clamp technique was applied to record the ionic currents and action potential (AP) in mouse ventricular myocytes while the electrocardiogram (ECG) and monophasic action potential (MAP) were recorded simultaneously in mouse hearts using a multichannel acquisition and analysis system. The results demonstrated that the half maximal inhibitory concentration (IC50) values of Mel on transient sodium current (INa.T) and specific INa.L opener 2 nmol·L-1 sea anemone toxins II (ATX II) increased INa.L were 686.615 and 7.37 μmol·L-1, respectively. Mel did not affect L-type calcium current (ICa.L), transient outward current (Ito), and AP. In addition, 16 μmol·L-1 Mel shortened ATX II-prolonged action potential duration (APD), suppressed ATX II-induced early afterdepolarizations (EADs), and significantly reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) in Langendorff-perfused mouse hearts. In conclusion, Mel exerted its antiarrhythmic effects principally by blocking INa.L, thus providing a significant theoretical basis for new clinical applications of Mel. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of Wuhan University of Science and Technology (2023130).

Bone marrow-derived mesenchymal stem cell-conditioned medium ameliorates diabetic foot ulcers in rats

Abstract Objectives: This study aimed to explore the effects of bone marrow-derived Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) treating diabetic foot ulcers in rats. Methods: Models of T2DM rats were induced by a high-fat diet and intraperitoneal injection of STZ in SD rats. Models of Diabetic Foot Ulcers (DFUs) were made by operation on hind limbs in diabetic rats. Rats were divided into four groups (n = 6 for each group), i.e., Normal Control group (NC), Diabetes Control group (DM-C), MSC-CM group and Mesenchymal Stem Cells group (MSCs). MSC-CM group was treated with an injection of conditioned medium derived from preconditioned rats' bone marrow MSCs around ulcers. MSCs group were treated with an injection of rats' bone marrow MSCs. The other two groups were treated with an injection of PBS. After the treatment, wound closure, re-epithelialization (thickness of the stratum granulosums of the skin, by H&E staining), cell proliferation (Ki67, by IHC), angiogenesis (CD31, by IFC), autophagy (LC3B, by IFC and WB; autoly-sosome, by EM) and pyroptosis (IL-1β, NLRP3, Caspase-1, GSDMD and GSDMD-N, by WB) in ulcers were evaluated. Results: After the treatment wound area rate, IL-1β by ELISA, and IL-1β, Caspase-1, GSDMD and GSDMD-N by WB of MSC-CM group were less than those of DM group. The thickness of the stratum granulosums of the skin, proliferation index of Ki67, mean optic density of CD31 and LC3B by IFC, and LC3B by WB of MSC-CM group were more than those of DM group. The present analysis demonstrated that the injection of MSC-CM into rats with DFUs enhanced the wound-healing process by accelerating wound closure, promoting cell proliferation and angiogenesis, enhancing cell autophagy, and reducing cell pyroptosis in ulcers. Conclusions: Studies conducted indicate that MSC-CM administration could be a novel cell-free therapeutic approach to treat DFUs accelerating the wound healing process and avoiding the risk of living cells therapy.

Risk factors for residual pain after percutaneous kyphoplasty for osteoporotic vertebral fractures / 中华创伤骨科杂志

Objective:To analyze the risk factors for residual pain after percutaneous kyphoplasty (PKP) for osteoporotic vertebral fractures (OVF).Methods:Retrospectively analyzed were the patients with OVC who had been treated at Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University by single level PKP from January 2020 to December 2021. They were 40 men and 181 women, with an age of (69.6±8.2) years. By the pain score of visual analogue scale (VAS) on the postoperative day 3, they were assigned into 2 groups: a residual pain group (VAS≥4) and a control group (VAS<4). The general demographics, radiographic and surgical related data of the 2 groups were analyzed by single factor analysis, including their gender, age, bone mineral density, body mass index, glucocorticoid usage, follow-up time, duration of symptoms, fracture location, severity of fracture compression, intravertebral cleft, middle column involvement, thoracolumbar fascia injury, anesthesia method, puncture method, volume of bone cement injected, cement-endplates contact, pattern of cement distribution, cement leakage, vertebral height restoration, preoperative cobb angle and correction of cobb angle. The P<0.1 factors screened were further analyzed by the multivariate logistic regression to determine the final variables. Results:In the present study, 19 patients were assigned into the residual pain group and 202 patients the control group. The univariate analysis showed that body mass index ( P=0.059), intravertebral cleft ( P=0.049) and thoracolumbar fascia injury ( P< 0.001) increased the risk for residual pain. The multivariate logistic regression analysis showed that thora-columbar fascia injury was an independent risk factor for residual pain ( OR=6.127, 95% CI: 2.240 to 16.755, P<0.001). Conclusion:Thoracolumbar fascia injury is an independent risk factor for residual pain after PKP for OVF.

A case report of anti-NMDAR encephalitis complicated with acute peripheral nerve damage / 中国综合临床

N-methyl-D-aspartate receptor (NMDAR) encephalitis in combination with acute peripheral nerve damage is rare. A young female patient with anti-NMDAR encephalitis was admitted to Qianfoshan Hospital in Shandong Province on October 23, 2022. The main manifestations were abnormal mental behavior, consciousness disorders, and flaccid paralysis. Electromyography indicated axonal damage to the upper and lower extremities. Patient was in critical condition and admitted to the ICU with tracheal intubation for central hypoventilation. A combination of critical polyneuropathy was considered. The prognosis was good after hormone shock, immunosuppressive therapy, surgical therapy, anti-infection, respiratory support and symptomatic support. The diagnosis of anti-NMDAR encephalitis with acute peripheral nerve damage is difficult. Immune factors need to be considered and paraneoplastic syndrome should be differentially diagnosed.

The prevalence and related influencing factors of adult thyroid nodules in Wuhan City from 2019 to 2021 / 中华地方病学杂志

Objective:To study the prevalence and epidemiological characteristics of adult thyroid nodules in Wuhan City, and to analyze the influencing factors of thyroid nodules, so as to provide basis for prevention and treatment of adult thyroid nodules in Wuhan City.Methods:From 2019 to 2021, two communities or towns were selected from each of the 13 districts in Wuhan City using multi-stage cluster random sampling method. One hundred permanent residents over the age of 16 were selected from each community or town according to the inclusion and exclusion criteria (age and sex ratio balanced), for questionnaire survey, physical examination, urinary iodine test and thyroid ultrasound examination. The influencing factors of thyroid nodules was analyzed using logistic regession and Spearman correlation.Results:A total of 2 578 adults were investigated, including 1 168 men and 1 410 women. The age was (41.79 ± 13.01) years. The prevalence of thyroid nodules was 35.49% (915/2 578). The prevalence of single nodules was 19.16% (494/2 578), which was higher than that of multiple nodules [16.33% (421/2 578), χ 2 = 2 577.00, P < 0.001]. Multivariate logistic regression analysis showed that female ( OR = 2.033, 95% CI: 1.631 - 2.535), older ( OR = 1.404, 95% CI: 1.290 - 1.528), history of thyroid disease ( OR = 1.351, 95% CI: 1.211 - 1.506) and diabetes ( OR = 1.449, 95% CI: 1.083 - 1.938) were independent risk factors for adult thyroid nodules ( P < 0.05). The median urinary iodine of residents in Wuhan City was 185.32 μg/L, at an appropriate level of iodine nutrition, there was no correlation between urinary iodine and thyroid nodules ( r = 0.02, P = 0.391). Conclusions:The prevalence of thyroid nodules of adults in Wuhan City is high. Women, older, a history of thyroid diseases and diabetes are all risk factors for thyroid nodules. No correlation is found between urinary iodine level and thyroid nodules.

Advances in peptidyl Asx-specific ligases for the application of cyclic peptides / 药学学报

Asparaginyl endopeptidases (AEPs) in plants belong to the family of cysteine protease that undergo self-activation in the form of zymogen in acidic vacuole and play important physiological roles in maturation of seed storage proteins, protein degradation, programmed cell death and host defense. Bioprocessing enzymes (peptidyl Asx-specific ligases, PALs) that promote the maturation of cyclotides have recently been isolated and identified from several cyclotide-rich plants. PALs derived from AEPs can site-specifically catalyze the formation of asparagine or aspartate peptide bonds. Due to the advantages of relatively traceless peptide bonds and broad substrate spectrum and high catalytic efficiency, they have been playing important roles in the cyclization and modification of peptides and proteins, and are powerful tools for improving the stability of peptide drugs. This review describes the physiological functions of AEPs in plants and summarizes the discoveries, structural characteristics, catalytic mechanism and protein engineering of PALs, as well as the limitation of their applications and future trends. In addition, the applications of PALs in cyclotides biosynthesis and the development of macrocyclic peptides are highlighted, with the aim of providing a new idea for the biocatalytic synthesis of cyclic peptides.

Study on release and antioxidant activity of quercetin after loaded by hot alkali hydrolysis modified UiO-66 material / 药学学报

UiO-66 (University of Oslo 66) is a kind of promising material that can improve the release and bioavailability of poorly water-soluble bioactive compounds of traditional Chinese medicine. However, the loading of quercetin in raw UiO-66 was not ideal. In this study, UiO-66-BH (UiO-66-blend-heating) was obtained by heating UiO-66 and KOH solution following blended them. UiO-66-BH maintained the outline of octahedral structure of UiO-66 but with obvious rough and uneven pores on the surface. UiO-66-BH had good adsorption of quercetin with saturation adsorption was 138.92 mg·g-1, the adsorption process belonged to single molecular layer adsorption and was controlled by chemisorption. UiO-66-BH can control the release of quercetin in simulated gastrointestinal fluid, and the drug concentration was significantly higher than that of free quercetin after long-term release (36% vs 9%). Compared with quercetin, the ABTS (2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) ammonium salt) radical scavenging activity of UiO-66-BH@quercetin drug delivery system decreased, while the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity remained almost unchanged. The drug delivery system showed a strong antioxidant effect similar to quercetin. The findings indicated that UiO-66-BH could control release of quercetin and was expected to be used as a drug carrier material for some insoluble active components of traditional Chinese medicine such as quercetin.

Effectiveness of online and offline health education myopia intervention on primary school students / 中国学校卫生

Objective@#To assess the effectiveness of online and offline myopia prevention and control health education interventions using wearable behavior monitoring tools for non myopic elementary school students,so as to provide evidence based medical support for public health practices.@*Methods@#From May to June in 2021, two schools were selected within the same county in Jiangsu Province. School 1 conducted online and offline parental health education ( n =111), while school 2 exclusively conducted offline health education activities, representing the traditional intervention group ( n =122). Students from both schools underwent monitoring through wearable behavior tracking tools, with feedback reports provided (eye distance, eye duration, ambient light, and outdoor exposure time). Both schools relied on activities to carry out health education interventions, and organized the distribution of promotional materials and display boards. The intervention group also established WeChat groups to conduct online "Healthy Parents Action" (answering and providing feedback on health knowledge related to myopia prevention and control, myopia prevention and control, science popularization, etc. raised by parents). Evaluation criteria included myopia rates, post dilation refractive error, and axial length, with a tracking period of two years (from 2021 to 2023). Additionally, the study collected refractive parameters from non myopic students who did not participate in wearable tool monitoring in the 12 classes across the two schools.@*Results@#The baseline results indicated that there were no significant differences between the two groups in terms of refractive parameters and wearable tool monitoring results (including screen time, viewing distance, outdoor exposure time, and homework light exposure)( t/Z/χ 2=1.94,1.17,0.58,0.40,0.80,0.69,0.32, P >0.05). After a two-year follow up, in the first and second year, the myopia rate of the online Healthy Parents Action group (11.4%, 29.7%) were lower than that of the traditional group (26.2%, 50.9%), and the degree of refractive change in the intervention group [0.63(0.38,1.19)D] was lower than that of the traditional group [0.91(0.40,1.50)D], and all the differences were statistically significant( χ 2/ Z =4.93，10.37，2.29， P <0.05). However, there were no significant differences ( P >0.05) in axial length changes between the two groups over the twoyear intervention period. Nevertheless, in the second year, the axial length change in the traditional group [0.35(0.20,0.65)mm] was lower than that in the natural observation group [0.55(0.30,0.75)mm], and this difference was statistically significant ( Z =1.92, P <0.05).@*Conclusions@#Online and offline myopia prevention and control health education can effectively reduce myopia rates. The intervention mode combining wearable behavior monitoring tools with online health education may have better effects, but further large sample and multi center studies are needed to provide additional evidence and confirmation.

Combining repeated transcranial magnetic stimulation with psychological intervention can synergistically relieve depression among those with Parkinson′s disease / 中华物理医学与康复杂志

Objective:To explore any effect of supplementing psychological intervention with repeated transcranial magnetic stimulation (rTMS) in the rehabilitation of depressed persons with Parkinson′s disease (dPD).Methods:A total of 120 dPD patients were randomly divided into a psychological intervention group, an rTMS treatment group and an observation group, each of 40. In addition to conventional anti-Parkinson′s treatment and anti-depressant treatment, the psychological intervention group received such treatment and the rTMS group received 10Hz rTMS applied over the left dorsolateral prefrontal cortex for 8 weeks. The observation group received both interventions. Before and after the treatment, depression, neurological functioning and life quality were evaluated in all of the subjects using the 24-item Hamilton Depression Scale, the Movement Disorder Society′s unified Parkinson′s disease rating scale and the SF-36 questionnaire.Results:After the intervention, significant improvement was observed in all of the quantitative evaluations as well as in the remission rate (40%) and the reaction rate (90%). On average, the observation group′s results were significantly better than those of the other two groups.Conclusion:Psychological intervention and rTMS a have synergistic effect in treating dPD patients and their combination is worthy of clinical promotion and application, as it can relieve their depression and improve their neurological functioning and life quality.

Effect of improved management of placenta accreta spectrum disorders on maternal and infant outcomes / 中华围产医学杂志

Objective:To evaluate the role of improved management procedures in placenta accreta spectrum disorders (PAS) and its impact on maternal and infant outcomes.Methods:This retrospective study involved 164 pregnant women who were diagnosed with PAS complicated with placenta previa and delivered at Nanjing Drum Tower Hospital, Nanjing University Medical School from January 2019 to December 2022. All subjects were allocated to pre-improvement group (January 2019 to December 2020, n=96) and post-improvement group (January 2021 to December 2022, n=68). The management was improved in the following five aspects: (1) The time for scheduled delivery was postponed to 37 weeks from 34-36 weeks;(2) Intraoperative cell salvage was encouraged despite autologous blood donation during pregnancy;(3) Original surgical incision was utilized instead of mid-longitudinal incision in the lower abdomen to reduce operative trauma; (4) A lower segment incision of the uterus was not prohibited based on pre-operative PAS classification and intra-operative situation to enter the uterine cavity, even through the placenta instead of pass-by;(5) The interface between lower uterine segment and bladder was dissected before instead of after the baby was born and uterine blood supply was stopped by tourniquet or Scharr forceps. Statistical methods such as t-test, Chi-square test or Fisher exact probability method were used to compare the difference in maternal and infant outcomes between the two groups. Results:After the improvement, the delivery rate beyond 37 weeks decreased significantly [83.3% (80/96) vs 69.1% (47/68), χ 2=4.60, P=0.038]. There was no significant difference in the distribution of elective, subemergency and emergency surgeries before and after the improvement ( χ 2=0.36, P=0.834). Compared to the pre-improvement group, the proportion of women who underwent cesarean section through previous abdominal incisions increased significantly [74.0% (71/96) vs 91.1% (64/68), χ 2=11.11, P=0.001] in the post-improvement group, while the proportion of application of abdominal longitudinal incision and classical cesarean section decreased significantly [84.3% (81/96) vs 57.3% (39/68), χ 2=14.81, P<0.001; 83.3% (80/96) vs 61.8% (42/68), χ 2=9.72, P=0.003]. No significant difference was found between the two groups in terms of the transfusion rate of allogeneic red blood cell, platelet and other blood components, pre-discharge hemoglobin level, subtotal hysterectomy rate, bladder injury, thrombus event, the admission rate of intensive care unit and unplanned reoperation rate (all P>0.05). The incidence of admission in neonatal intensive care unit (NICU) and necrotizing enterocolitis decreased significantly after improvement [24.7% (24/97) vs 11.8% (8/68), χ 2=4.31, P=0.038; 4.1% (4/97) vs 0.0% (0/68), χ 2=58.06, P<0.001]. The incidence of respiratory distress syndrome, mechanical ventilation, and neonatal septicemia also decreased, but without statistical difference. Conclusions:After adopting a series of improvement measures, such as delaying planned delivery to 37 weeks of gestation, individualized cesarean section plan, and changing the method of obtaining autoblood, the number of premature infants and the NICU admission rate decreased significantly without increasing the risk of maternal complications and emergency operation. Furthermore, the incidence of adverse events such as maternal organ injury, unplanned reoperation, and re-admission remains at a low level. Therefore, this improved management is feasible.

Isolation, culture and validation of CD34+ vascular wall-resident stem cells from mice / 生理学报

Vascular wall-resident stem cells (VW-SCs) play a critical role in maintaining normal vascular function and regulating vascular repair. Understanding the basic functional characteristics of the VW-SCs will facilitate the study of their regulation and potential therapeutic applications. The aim of this study was to establish a stable method for the isolation, culture, and validation of the CD34+ VW-SCs from mice, and to provide abundant and reliable cell sources for further study of the mechanisms involved in proliferation, migration and differentiation of the VW-SCs under various physiological and pathological conditions. The vascular wall cells of mouse aortic adventitia and mesenteric artery were obtained by the method of tissue block attachment and purified by magnetic microbead sorting and flow cytometry to obtain the CD34+ VW-SCs. Cell immunofluorescence staining was performed to detect the stem cell markers (CD34, Flk-1, c-kit, Sca-1), smooth muscle markers (SM22, SM MHC), endothelial marker (CD31), and intranuclear division proliferation-related protein (Ki-67). To verify the multipotency of the isolated CD34+ VW-SCs, endothelial differentiation medium EBM-2 and fibroblast differentiation medium FM-2 were used. After culture for 7 days and 3 days respectively, endothelial cell markers and fibroblast markers of the differentiated cells were evaluated by immunofluorescence staining and q-PCR. Furthermore, the intracellular Ca2+ release and extracellular Ca2+ entry signaling were evaluated by TILLvisION system in Fura-2/AM loaded cells. The results showed that: (1) High purity (more than 90%) CD34+ VW-SCs from aortic adventitia and mesenteric artery of mice were harvested by means of tissue block attachment method and magnetic microbead sorting; (2) CD34+ VW-SCs were able to differentiate into endothelial cells and fibroblasts in vitro; (3) Caffeine and ATP significantly activated intracellular Ca2+ release from endoplasmic reticulum of CD34+ VW-SCs. Store-operated Ca2+ entry (SOCE) was activated by using thapsigargin (TG) applied in Ca2+-free/Ca2+ reintroduction protocol. This study successfully established a stable and efficient method for isolation, culture and validation of the CD34+ VW-SCs from mice, which provides an ideal VW-SCs sources for the further study of cardiovascular diseases.

Ketogenic diet improves low temperature tolerance in mice by up-regulating PPARα in the liver and brown adipose tissue / 生理学报

The aim of the present study was to investigate the effects of short-term ketogenic diet on the low temperature tolerance of mice and the involvement of peroxisome proliferator-activated receptor α (PPARα). C57BL/6J mice were divided into two groups: normal diet (WT+ND) group and ketogenic diet (WT+KD) group. After being fed with normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The changes in core temperature, blood glucose, blood pressure of mice under low temperature condition were detected, and the protein expression levels of PPARα and mitochondrial uncoupling protein 1 (UCP1) were detected by Western blot. PPARα knockout mice were divided into normal diet (PPARα-/-+ND) group and ketogenic diet (PPARα-/-+KD) group. After being fed with the normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The above indicators were also detected. The results showed that, at room temperature, the protein expression levels of PPARα and UCP1 in liver and brown adipose tissue of WT+KD group were significantly up-regulated, compared with those of WT+ND group. Under low temperature condition, compared with WT+ND, the core temperature and blood glucose of WT+KD group were increased, while mean arterial pressure was decreased; The ketogenic diet up-regulated PPARα protein expression in brown adipose tissue, as well as UCP1 protein expression in liver and brown adipose tissue of WT+KD group. Under low temperature condition, compared to WT+ND group, PPARα-/-+ND group exhibited decreased core temperature and down-regulated PPARα and UCP1 protein expression levels in liver, skeletal muscle, white and brown adipose tissue. Compared to the PPARα-/-+ND group, the PPARα-/-+KD group exhibited decreased core temperature and did not show any difference in the protein expression of UCP1 in liver, skeletal muscle, white and brown adipose tissue. These results suggest that the ketogenic diet promotes UCP1 expression by up-regulating PPARα, thus improving low temperature tolerance of mice. Therefore, short-term ketogenic diet can be used as a potential intervention to improve the low temperature tolerance.

Work-related musculoskeletal disorders and their influencing factors among workers in a furniture factory / 环境与职业医学

Background Furniture manufacturing is one of the typical labor-intensive industries, and workers in this industry face a high risk of work-related musculoskeletal disorders (WMSDs), which seriously affect the physical and mental health of workers. Objective To explore the prevalence and potential risk factors of WMSDs among workers in a large-scale furniture manufacturing factory. Methods A cross-sectional study of 3431 workers in a furniture factory in Guangdong Province was conducted from September to December 2019. Information including reported WMSDs in various body parts in the past year, demographic characteristics, work organization factors, job characteristics, and work postures was collected by an electronic version of Musculoskeletal Disorders Questionnaire. Pearson χ2 test and binary logistic regression were used to analyze the risk factors leading to WMSDs. Results The overall prevalence rate of WMSDs was 32.12% (1102/3431). The most common WMSDs symptoms occurred in the neck (16.85%), followed by the feet (15.27%), shoulders (14.81%), and hands (14.25%). The prevalence rates of WMSDs in the neck, shoulders, elbows, hands, legs, and feet were significantly different among different types of work (P<0.05). The results of multiple logistic regression analysis showed that individual factors, work organization factors, job characteristics, and awkward work postures were associated with the frequency of reporting WMSDs in specific parts of workers. Comparatively poor physical health (including moderate, poor, and very poor) was positively correlated with neck, shoulder, hand, and foot WMSDs (OR=1.479-4.077); working with an uncomfortable posture (OR=1.983) and doing the same task almost every day (OR=1.783) were positively correlated with neck pain; doing the same task almost every day (OR=2.408) and neck twisting for a long time (OR=1.830) were positively correlated with shoulder pain; bending wrists up and down frequently (OR=1.948) and bending wrists for a long time (OR=2.081) were positively correlated with hand pain; prolonged standing (OR=1.953) and often working overtime (OR=1.627) were positively correlated with feet pain; sufficient rest time was negatively correlated with WMSDs in the neck, shoulders, hands, and foot (OR=0.544-0.717). Conclusion The prevalence rate of WMSDs in furniture manufacturing workers is relatively high, and neck, feet, shoulders, and hands are the most involved body parts. The frequency of reporting WMSDs is related to individual factors, work organization factors, job characteristics, and awkward work postures.

Mechanism of lncRNA-miRNA-related Signaling Pathways in Gastric Cancer and Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

Gastric cancer （GC） is one of the most common malignant tumors in the digestive system， with high morbidity and mortality. Early clinical symptoms of GC are not obvious， and most of them have entered the advanced stage after discovery， which greatly reduces the clinical cure rate and affects the quality of life of patients， and the prognosis is very poor. In recent years， with the continuous exploration in the field of bioinformatics， it has been found that micro-RNA （miRNA） and long non-coding RNA （lncRNA） exist as non-coding RNA （ncRNA） without translation ability， and regulate the expression levels of related signal proteins by acting on a certain target， thereby activating or inhibiting a certain signaling pathway， which plays an important role in assisting diagnosis， guiding clinical medication， and judging prognosis in the progress of GC. Chinese medicine is easily accepted by patients because of its good curative effect and less side effects. In the present basic studies， with the interaction mechanism between miRNA， lncRNA and signaling pathways as the breakthrough point， various studies on the regulation of related signaling molecules and signaling pathways by Chinese medicine have been carried out. A large number of experimental data have proved that the development of GC is closely related to the interaction of miRNA， lncRNA， and related signaling pathways， and Chinese medicine， with multi-target， multi-mechanism， and multi-pathway characteristics， affects various signaling molecules and signaling pathways and intervenes in the progress of GC cells. This paper reviewed the basic research on lncRNA， miRNA molecules， and main signaling pathways involved in the occurrence and development of GC， and summarized specific molecular mechanisms of Chinese medicine in the regulation of each signaling pathway， hoping to provide references for modern research of Chinese medicine in the intervention of GC progress at the molecular level.

Epidemiological and etiological characteristics of active surveillance of foodborne illness / 公共卫生与预防医学

Objective To realize the epidemiological and pathogenic characteristics of foodborne illness in Shiyan in 2019 and provide targeted measures for the prevention and control work of the foodborne illness． Methods The active surveillance data of foodborne illness in shiyan in 2019 were collected and analyzed. The Salmonella strains isolated from the patients with foodborne illness were tested with serotyping，PFGE molecular classification and drug sensitivity test respectively according to《National foodborne illness surveillance workbook 2019》. Result A total of 3 191 cases of foodborne illness were analyzed. The pre-school children were the highest-risk group of foodborne diseases. Grain and grain product was the main suspicious contaminated food．The main location of eating place was family. A total of 330 samples were tested. The positive detection rate of foodborne illness was 20.30%（73/330）.The main pathogen were Rotavirus and Salmonella,and the detection rates were 11.21%(37/330) and 4.85%(16/330) respectively. The pre-school children were the group with the highest detection rate, which was 57.27% (63/110). The dominant serotype of the 14 Salmonella strains isolated from patients were Salmonella typhimurium and Salmonella enteritis. 14 different genotypes were obtained through PFGE classification and clustering. 64.29% (9/14) of Salmonella strains were multidrug-resistant strains. The drug resistance rates of ampicillin and tetracycline were the highest, which were 71.43%（11/14）and 64.29%（10/14）respectively. Conclusions The publicity and education of food safety should be strengthened and the surveillance network system of food-borne disease should be further improved according to the epidemiological and pathogenic characteristics of foodborne illness in Shiyan in 2019, and the use of clinical antibiotics should be controlled reasonably as well.

Berberine targets the electron transport chain complex I and reveals the landscape of OXPHOS dependency in acute myeloid leukemia with IDH1 mutation / 中国天然药物

Metabolic reprogramming, a newly recognized trait of tumor biology, is an intensively studied prospect for oncology medicines. For numerous tumors and cancer cell subpopulations, oxidative phosphorylation (OXPHOS) is essential for their biosynthetic and bioenergetic functions. Cancer cells with mutations in isocitrate dehydrogenase 1 (IDH1) exhibit differentiation arrest, epigenetic and transcriptional reprogramming, and sensitivity to mitochondrial OXPHOS inhibitors. In this study, we report that berberine, which is widely used in China to treat intestinal infections, acted solely at the mitochondrial electron transport chain (ETC) complex I, and that its association with IDH1 mutant inhibitor (IDH1mi) AG-120 decreased mitochondrial activity and enhanced antileukemic effect in vitro andin vivo. Our study gives a scientific rationale for the therapy of IDH1 mutant acute myeloid leukemia (AML) patients using combinatory mitochondrial targeted medicines, particularly those who are resistant to or relapsing from IDH1mi.

Effect of MG53 on Cardiac Function Affected by Acute Doxorubicin-Induced Cardiotoxicity in Mice and Its Mechanism / 中山大学学报(医学科学版)

ObjectiveThis study was designed to explore the effect of MG53 on cardiac function affected by acute doxorubicin （DOX）-induced cardiotoxicity （DIC） in mice and its possible mechanism. MethodsIn vivo， C57BL/6 mice were injected intraperitoneally with twenty mg/kg DOX for one week to induce the acute DIC. In vitro， neonatal rat cardiomyocytes （NRCs） were treated with 1 μmol/L DOX to induce DIC. A small animal ultrasound imaging system was used to evaluate cardiac function， and the left ventricular changes in ejection fraction （EF） and fraction shortening （FS） were measured. qPCR technology was used to evaluate cardiac remodeling related factors ANP， BNP and α-MHC， autophagy-related factors Beclin1 and LC3， and apoptosis-related factor CASPASE3. Autophagy-related protein levels of Beclin1， LC3 and apoptosis-related protein levels of caspase3 were assessed by Western Blot. Transmission electron microscopy （TEM） was used to detect autophagosomes in heart tissues. TUNEL assay kit was used to detect apoptosis in neonatal murine cardiomyocytes. ResultsThe small animal ultrasound imaging revealed cardiac function was significantly reduced by doxorubicin in the DOX group and DOX+AAV9-NC group compared with the sham group （EF： Sham： 86.06 ± 2.08 vs. DOX：58.97 ± 1.62， P < 0.000 1； Sham： 86.06 ± 2.08 vs. DOX+AAV9-NC： 59.00 ± 1.86， P < 0.000 1. FS： Sham： 45.47 ± 1.95 vs. DOX：30.68 ± 1.21， P < 0.000 1； Sham： 45.47 ± 1.95 vs. DOX+AAV9-NC： 30.79 ± 1.13， P < 0.000 1）. However， the overexpression of MG53 with adeno-associated virus9 （AAV9） ameliorated cardiac dysfunction （EF： DOX+AAV9-MG53： 66.93 ± 1.78 vs. DOX+AAV9-NC： 59.00 ± 1.86， P < 0.000 1. FS： DOX+AAV9-MG53： 36.35 ± 1.33 vs. DOX+AAV9-NC： 30.79 ± 1.13， P < 0.000 1）. TEM showed autophagosomes were increased in the DOX+AAV9-MG53 group compared with the DOX group and DOX+AAV9-NC. qPCR results suggested that MG53 down-regulated the mRNA expression of cardiac remodeling related genes. Additionally， Western blot results confirmed that the protein level of caspases3 was decreased and Beclin1 and LC3 expression was increased in the DOX+AAV9-MG53 group compared with those in the DOX group and DOX+AAV9-NC group （caspase： DOX+AAV9-MG53： 1.49 ± 0.13 vs. DOX+AAV9-NC： 2.49 ± 0.46， P = 0.000 2； Beclin-1： DOX+AAV9-MG53：0.82 ± 0.02 vs. DOX+AAV9-NC： 0.62 ± 0.05， P < 0.000 1； LC3： DOX+AAV9-MG53： 0.83 ± 0.04 vs. DOX+AAV9-NC： 0.40 ± 0.05， P < 0.000 1）. In contrast， knockdown of MG53 significantly up-regulated the protein level of Caspase3 and significantly down-regulated the protein level of Beclin1 and LC3 （caspase： DOX+si-MG53： 4.52 ± 0.28 vs. DOX+si-NC： 3.37 ± 0.08， P < 0.000 1； Beclin-1： DOX+si-MG53： 0.34 ± 0.06 vs. DOX+si-NC： 0.54 ± 0.07， P = 0.026 2； LC3： DOX+si-MG53： 0.41 ± 0.12 vs. DOX+si-NC： 0.70 ± 0.07， P = 0.001 5）. TUNEL analysis showed overexpression of MG53 significantly inhibited the apoptosis of cardiomyocytes （DOX+Ad-MG53： 9.41 ± 0.53 vs. DOX+Ad-NC： 29.34 ± 7.29， P < 0.000 1）， and knockdown of MG53 significantly facilitate the apoptosis of cardiomyocytes （DOX+si-MG53： 71.34 ± 5.90 vs. DOX+si-NC： 32.19 ± 9.91， P < 0.000 1）. ConclusionMG53 inhibits cardiac apoptosis and enhances autophagy， which delays cardiac remodeling and ameliorates cardiac dysfunction.

Optimization of the preparation process of ethanol extracts from Centipeda minima and study on its anti-inflammatory activity of different extraction sites / 中国药房

OBJECTIVE To optimize the preparation technology of ethanol extracts from Centipeda minima， and investigate the anti-inflammatory activities of different extraction sites. METHODS Single factor test and response surface methodology were adopted to investigate the effects of ethanol volume fraction， extraction time， solid-liquid ratio and extraction times on the heating reflux extraction technology of total triterpenoids ethanol extract using the extraction rate of total triterpenoids of C. minima as indexes， optimize the extraction technology and carry out validation. Using dexamethasone as positive control drug， the effects of different extraction sites of C. minima （petroleum ether part， ethyl acetate part， n-butanol part， water part） on nitric oxide （NO） production in mononuclear macrophage RAW 264.7 cells of mice induced by lipopolysaccharide （LPS） were compared； the half inhibitory concentration （IC50） was calculated. RESULTS The optimal extraction technology of total triterpenoids ethanol extracts of C. minima was as follows： ethanol volume fraction of 70%， solid-liquid ratio of 1∶40 （g/mL）， extraction time of 2.0 h and extraction times of 3 times. The 3 times of validation tests showed that average extraction rate of total triterpenoids of C. minima was 1.134%， relative error of which with the predicted value was 0.02%. The petroleum ether part and ethyl acetate part of C. minima could inhibit the generation of NO in RAW 264.7 cells induced by lipopolysaccharide to different degrees. IC50 values of NO production were 2.44 μg/mL and 2.22 μg/mL， respectively， and both of them were lower than those of positive control drug dexamethasone （7.65 μg/mL）. CONCLUSIONS The optimized preparation process of ethanol extracts from C. minima is stability and feasibility. The petroleum ether part and ethyl acetate part have obvious anti-inflammatory effects.

Detection of aqueous humor cytokines in diabetic retinopathy and its clinical significance / 中华实验眼科杂志

Objective:To detect the concentration of various cytokines in aqueous humor of patients with diabetes retinopathy (DR) with Luminex liquid chip, and analyze the relationship between the cytokines and the occurrence and development of DR.Methods:A cross-sectional study was conducted.Sixty-three DR patients (97 eyes) treated with anti-vascular endothelial growth factor (VEGF) drugs in the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine from March 1, 2019 to December 31, 2019 were enrolled as DR group, including 38 nonproliferative DR (NPDR) eyes in NPDR group and 59 proliferative DR (PDR) eyes in PDR group, 39 eyes in photocoagulation group and 58 eyes in non-photocoagulation group.Twenty-seven patients (31 eyes) hospitalized for cataract surgery at the same time were collected as the control group.Aqueous humor was extracted during the operation, and Luminex liquid chip was used to detect the concentrations of vascular endothelial growth factor-A (VEGF-A), placental growth factor (PLGF), platelet-derived growth factor (PDGF)-AA, PDGF-BB, angiopoietin-like protein 4 (ANGPTL4), interleukin-6 (IL-6), IL-8, IL-1β, monocyte chemotactic protein-1 (MCP-1), intercellular cell adhesion molecule-1 (ICAM-1) and tumor necrosis factor-α (TNF-α) in aqueous humor.The concentrations of various cytokines of different groups were compared, and the correlation among various aqueous humor cytokines was analyzed by Spearman rank correlation analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of First Affiliated Hospital of Guangzhou University of Chinese Medicine (No.Y[2019]230). Written informed consent was obtained from each patient.Results:The concentrations of VEGF-A, PLGF, PDGF-AA, ANGPTL4, IL-6, IL-8, MCP-1 and ICAM-1 in DR group were significantly higher and the concentration of IL-1β was significantly lower than those of control group ( Z=-4.747, -5.164, -3.373, -8.062, -4.535, -5.954, -5.098, -3.228, -5.954, all at P<0.01). The concentrations of VEGF-A, PLGF, PDGF-AA, ANGPTL4, IL-6, IL-8 and MCP-1 of the photocoagulation and non-photocoagulation groups were higher and the concentration of IL-1β was significantly lower than those in the control group (all at P<0.017). The concentration of ICAM-1 in the photocoagulation group was significantly higher than that in the control group ( P<0.017). The concentrations of PLGF, PDGF-AA and ANGPTL4 of PDR group were higher than those of NPDR group, and the differences were statistically significant ( Z=-2.291, -3.396, -2.276, all at P<0.05). VEGF-A was positively correlated with the other cytokines except ICAM-1 ( rs=0.237-0.540, all at P<0.05). ANGPTL4 was positively correlated with the other cytokines except IL-1β ( rs=0.361-0.733, all at P<0.01). Conclusions:The occurrence and development of DR are closely related to VEGF family, PDGF family, ANGPTL family and inflammatory factors.The concentrations of PLGF, PDGF-AA and ANGPTL4 are higher in PDR eyes.There are close and complex relationships among a variety of cytokines in the eyes of DR patients.