Therapeutic Efficacy of Shexiang Baoxin Pill Combined with Exercise in Patients with Heart Failure with Preserved Ejection Fraction: A Single-Center, Double-Blind, Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the therapeutic efficacy of Shexiang Baoxin Pill combined with exercise in heart failure patients with preserved ejection fraction (HFpEF).@*METHODS@#Sixty patients with HFpEF were randomly divided into group A (n=20), receiving Shexiang Baoxin Pill combined with home-based exercise training based on conventional drugs for 12 weeks; group B (n=20), receiving conventional drugs combined with home-based exercise training for 12 weeks; and group C (n=20), receiving conventional drug treatment only. Peak oxygen uptake (peakVO2), anaerobic threshold (AT), 6-min walking test (6MWT), Pittsburgh Sleep Quality Index (PSQI), and SF-36 questionnaire (SF-36) results before and after treatment were compared among groups.@*RESULTS@#After the 12-week intervention, patients in group C showed significant declines in peakVO2, AT, 6MWT, PSQI, and SF-36 compared with pre-treatment (P<0.01), while groups A and B both showed significant improvements in peakVO2, AT, 6MWT, PSQI, and SF-36 results compared with pre-treatment (P<0.01). Compared with group C, patients in groups A and B showed significant improvements in peakVO2, AT, 6MWT, PSQI, and SF-36 (P<0.01). In addition, patients in group A showed more significant improvements in physical function, role-physical, vitality, and mental health scores on the SF-36 questionnaire, and PSQI scores than those in group B (P<0.01).@*CONCLUSIONS@#Exercise training improved exercise tolerance, sleep quality and quality of life (QoL) in patients with HFpEF. Notably, Shexiang Baoxin Pill played an active role in sleep quality and QoL of patients with HFpEF. (The trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2100054322)).

Effect of Sodium Salicylate on Calcium Currents and Exocytosis in Cochlear Inner Hair Cells: Implications for Tinnitus Generation / 神经科学通报·英文版

Sodium salicylate is an anti-inflammatory medication with a side-effect of tinnitus. Here, we used mouse cochlear cultures to explore the effects of salicylate treatment on cochlear inner hair cells (IHCs). We found that IHCs showed significant damage after exposure to a high concentration of salicylate. Whole-cell patch clamp recordings showed that 1-5 mmol/L salicylate did not affect the exocytosis of IHCs, indicating that IHCs are not involved in tinnitus generation by enhancing their neuronal input. Instead, salicylate induced a larger peak amplitude, a more negative half-activation voltage, and a steeper slope factor of Ca2+ current. Using noise analysis of Ca2+ tail currents and qRT-PCR, we further found that salicylate increased the number of Ca2+ channels along with CaV1.3 expression. All these changes could act synergistically to enhance the Ca2+ influx into IHCs. Inhibition of intracellular Ca2+ overload significantly attenuated IHC death after 10 mmol/L salicylate treatment. These results implicate a cellular mechanism for tinnitus generation in the peripheral auditory system.

A 3D hydrogel loaded with exosomes derived from bone marrow stem cells promotes cartilage repair in rats by modulating immunological microenvironment / 南方医科大学学报

OBJECTIVE@#To assess the efficacy of GelMA hydrogel loaded with bone marrow stem cell-derived exosomes for repairing injured rat knee articular cartilage.@*METHODS@#The supernatant of cultured bone marrow stem cells was subjected to ultracentrifugation separate and extract the exosomes, which were characterized by transmission electron microscopy, particle size analysis and Western blotting of the surface markers. The changes in rheology and electron microscopic features of GelMA hydrogel were examined after loading the exosomes. We assessed exosome release from the hydrogel was detected by BCA protein detection method, and labeled the exosomes with PKH26 red fluorescent dye to observe their phagocytosis by RAW264.7 cells. The effects of the exosomes alone, unloaded hydrogel, and exosome-loaded hydrogel on the polarization of RAW264.7 cells were detected by q-PCR and immunofluorescence assay. We further tested the effect of the exosome-loaded hydrogel on cartilage repair in a Transwell co-culture cell model of RAW264.7 cells and chondrocytes in a rat model of knee cartilage injury using q-PCR and immunofluorescence assay and HE and Masson staining.@*RESULTS@#GelMA hydrogel loaded with exosomes significantly promoted M2-type polarization of RAW264.7 cells (P < 0.05). In the Transwell co-culture model, the exosome-loaded GelMA hydrogel significantly promoted the repair of injured chondrocytes by regulating RAW264.7 cell transformation from M1 to M2 (P < 0.05). HE and Masson staining showed that the exosome-loaded hydrogel obviously promoted cartilage repair in the rat models damage.@*CONCLUSION@#GelMA hydrogel loaded with bone marrow stem cell-derived exosomes can significantly promote the repair of cartilage damage in rats by improving the immune microenvironment.

A single-center retrospective analysis of 77 traumatic arterial injuries of lower extremities / 中华外科杂志

Objective: To analyze the treatment and clinical prognosis of lower extremity arterial injury caused by trauma. Methods: The clinical data of 77 patients with traumatic lower extremity arterial injury admitted to Department of Vascular Surgery,Yichang Central People's Hospital from January 2013 to June 2021 were collected retrospectively. There were 65 males and 12 females, with an average age of 47.4 years (range: 7 to 75 years). Among the 77 patients, 56 cases (72.7%) had open injury and 21 cases (27.3%) had closed injury. Iliac artery was injured in 9 cases (11.7%), common femoral artery in 7 cases (9.1%), superficial femoral artery in 1 case (1.3%), popliteal artery in 11 cases (14.3%) and inferior knee artery in 49 cases (63.6%). The treatment methods and clinical effects were analyzed. Results: One case with pelvic fracture combined the internal iliac artery injury and 1 case with multiple injuries involving the common femoral artery died of circulatory failure before surgery. Seventy-five cases received vascular-related operations, including arterial ligation in 24 cases, arterial reconstruction in 40 cases, stent graft implantation in 1 case, primary amputation in 2 cases, and arterial embolization in 8 cases. The overall mortality rate was 6.5% (5/77), all of which were closed injuries. Except for 2 cases who died before surgery, 3 cases with pelvic fracture combined the internal iliac artery injury died of multiple organ failure after internal iliac artery embolization. There were 8 cases received amputation (10.4%, 8/77), 5 cases with closed injury and 3 cases with open injury. In addition to 2 cases with primary amputation, 6 cases underwent secondary amputation due to ischemia-reperfusion injury after revascularization (4 cases with popliteal artery injury and 2 cases with subpatellar artery injury). The average followed-up time was 17 months (range: 2 months to 8 years). One patient with femoral artery injury underwent autologous great saphenous vein bypass, and lower limb artery CT angiography was re-examined 6 months after the operation, and 30% distal anastomotic stenosis was found. Ankle brachial index<0.8 was found in two patients 1 year after popliteal artery repair, but none of the patients had intermittent claudication symptoms, and no further intervention was performed. Five patients suffered delayed healing due to severe lower limb injury, fracture and skin injury. Among them, 2 cases had poor wound healing at the stump of amputation, which gradually healed 3 to 5 months after several debridements. The other 3 vascular injury combined with tibial fracture patients had delayed tibial healing after surgery, but no symptoms of vascular ischemia occurred. All the other patients recovered well and no other serious complications occurred. Conclusions: The proportion of death and disability in patients with lower limb artery injury caused by trauma is high. Active and orderly surgical repair according to the site and type of injury can reduce the mortality, save the function of the affected limb, and promote the healing of injury.

Human Serum-derived Extracellular Vesicles Protect A549 from PM / 生物医学与环境科学（英文）

Objective@#Epidemiological studies reveal that exposure to fine particulate matter (aerodynamic diameter ≤ 2.5 μm, PM @*Methods@#EVs were isolated from the serum of healthy subjects, quantified @*Results@#PM @*Conclusions@#EVs treatment promotes cell survival and attenuates PM

Arachidonic acid metabolism in liver glucose and lipid homeostasis / 生理学报

Arachidonic acid (AA) is an ω-6 polyunsaturated fatty acid, which mainly exists in the cell membrane in the form of phospholipid. Three major enzymatic pathways including the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 monooxygenase (CYP450) pathways are involved in AA metabolism leading to the generation of a variety of lipid mediators such as prostaglandins, leukotrienes, hydroxyeicosatetraenoic acids (HETEs) and epoxyeicoastrienoic acids (EETs). These bioactive AA metabolites play an important role in the regulation of many physiological processes including the maintenance of liver glucose and lipid homeostasis. As the central metabolic organ, the liver is essential in metabolism of carbohydrates, lipids and proteins, and its dysfunction is associated with the pathogenesis of many metabolic diseases such as type 2 diabetes mellitus, dyslipidemia and nonalcoholic fatty liver disease (NAFLD). This article aims to provide an overview of the enzymatic pathways of AA and discuss the role of AA-derived lipid mediators in the regulation of hepatic glucose and lipid metabolism and their associations with the pathogenesis of major metabolic disorders.

Farnesoid X receptor (FXR) inhibits coagulation process via inducing hepatic antithrombin III expression in mice / 生理学报

Farnesoid X receptor (FXR) has been identified as an inhibitor of platelet function and an inducer of fibrinogen protein complex. However, the regulatory mechanism of FXR in hemostatic system remains incompletely understood. In this study, we aimed to investigate the functions of FXR in regulating antithrombin III (AT III). C57BL/6 mice and FXR knockout (FXR KO) mice were treated with or without GW4064 (30 mg/kg per day). FXR activation significantly prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT), lowered activity of activated factor X (FXa) and concentrations of thrombin-antithrombin complex (TAT) and activated factor II (FIIa), and increased level of AT III, whereas all of these effects were markedly reversed in FXR KO mice. In vivo, hepatic AT III mRNA and protein expression levels were up-regulated in wild-type mice after FXR activation, but down-regulated in FXR KO mice. In vitro study showed that FXR activation induced, while FXR knockdown inhibited, AT III expression in mouse primary hepatocytes. The luciferase assay and ChIP assay revealed that FXR can bind to the promoter region of AT III gene where FXR activation increased AT III transcription. These results suggest FXR activation inhibits coagulation process via inducing hepatic AT III expression in mice. The present study reveals a new role of FXR in hemostatic homeostasis and indicates that FXR might act as a potential therapeutic target for diseases related to hypercoagulation.

Role of systematic integration teaching reform at the basic medicine teaching stage in Chinese medical education system / 生理学报

Systematic integration teaching is a curriculum system focusing on organs and systems, which is an important direction of medical education reform in China. Based on the practice of integrated curriculum teaching in Dalian Medical University for more than 10 years, combined with the experience in 15 medical colleges and universities in China, this paper analyzed the modes of systematic integrated teaching at the basic medicine teaching stage for medical higher education, and specified the purpose and significance of this teaching reform. The results showed that: (1) The systematic integrated teaching is a well-accepted and widely used teaching mode in domestic medical colleges and universities, which mainly includes three types of methodologies, i.e., integration of basic medicine courses, integration of clinical medicine courses and integration of basic and clinical medicine courses. The systematic integrated teaching is carried out by reforming various teaching methods including problem-based learning (PBL), case-based learning (CBL) and team-based learning (TBL). (2) The systematic integration teaching at the basic medicine teaching stage can significantly optimize the transition between basic and clinical courses, promote the cooperation and exchange between basic and clinical teachers, and improve the medical students' knowledge construction and critical thinking, and teachers' teaching ability as well. (3) The systematic integration teaching concept of "Six focuses" and "Five combinations" effectively guides the design and implementation of the integrated curriculum at the basic medical teaching stage of Dalian Medical University. With the deepening and development of medical education system reform in China, giving full play to the respective advantages of the systematic integrated teaching and traditional single-subject teaching at the basic medicine stage, and strengthening the integration of basic and clinical courses will play an important role in optimizing medical education curriculum system with Chinese characteristics.

Role of pregnane X receptor (PXR) in endobiotic metabolism / 生理学报

As a member of the nuclear receptor superfamily, the pregnane X receptor (PXR) is a ligand-activated transcription factor. PXR is highly expressed in liver and intestinal tissues, and also found in other tissues and organs, such as stomach and kidney. After heterodimerization with retinoid X receptor (RXR), PXR recruits numerous co-activating factors, and binds to specific DNA response elements to perform transcriptional regulation of the downstream target genes. As an acknowledged receptor for xenobiotics, PXR was initially considered as a nuclear receptor regulating drug metabolizing enzymes and transporters. However, nowadays, PXR has also been recognized as an important endobiotic receptor. Recent studies have shown that PXR activation can regulate glucose metabolism, lipid metabolism, steroid endocrine homeostasis, detoxification of cholic acid and bilirubin, bone mineral balance, and immune inflammation in vivo. This review focuses on the role of PXR in metabolism of endogenous substances.

Role of prostaglandin E2 receptor 4 in cardiovascular diseases / 生理学报

Prostaglandin E2 (PGE2) is a cyclooxygenase metabolite of arachidonic acid. It acts as a bioactive lipid and plays an important role in regulating many biological processes. PGE2 binds to 4 different G protein-coupled receptors including prostaglandin E2 receptor subtypes EP1, EP2, EP3 and EP4. The EP4 receptor is widely expressed in most of human organs and tissues. Increasing evidence demonstrates that EP4 is essential for cardiovascular homeostasis and participates in the pathogenesis of many cardiovascular diseases. Here we summarize the role of EP4 in the regulation of cardiovascular function and discuss potential mechanisms by which EP4 is involved in the development of cardiovascular disorders with a focus on its effect on inflammation.

Role of prostaglandin E receptor EP4 in the regulation of adipogenesis and adipose metabolism / 生理学报

Adipose tissue is the energy storage organ of the body, and excess energy is stored in adipocytes in the form of lipid droplets. The homeostasis of adipose tissue is the basis for the body to maintain normal metabolic activity. Prostaglandin E (PGE) is an important lipid mediator in the body. It is synthesized in almost all tissues and participates in the regulation of many physiological processes such as blood pressure, glucose and lipid metabolism, and inflammation. PGE is abundant in white adipose tissue, where it is involved in the regulation of fat metabolism. PGE plays its biological role through binding to four G protein coupled receptors (prostaglandin E receptors), including EP-1, -2, -3, and -4. The EP4 subtype has been proved to play an important role in adipogenesis and adipose metabolism: it could inhibit adipogenesis while it was activated, whereas its knockout could promote lipolysis. This review summarized the relationship between EP4 and adipose metabolism, hoping to identify new targets of drug development for metabolic disorders.

Hyperhomocysteinemia and kidney diseases / 生理学报

Homocysteine (Hcy) is an intermediate metabolite of methionine metabolism. Hyperhomocysteinemia (HHcy) is defined as a condition characterized by plasma Hcy level above 16 μmol/L which can result from abnormal Hcy metabolism. HHcy has been confirmed to be related to cardio-cerebrovascular disease, peripheral vascular disorders, neurodegenerative diseases, diabetes, pregnancy-induced hypertension syndrome, liver cirrhosis and kidney diseases. In this review, we summarize the correlation between HHcy and kidney diseases. Elucidating the role of HHcy in kidney diseases may provide a new strategy to prevent and treat kidney diseases.

ATP-P2X7R signalling pathway and its effects in parasitic diseases / 中国血吸虫病防治杂志

ATP (Adenosine triphosphate) is an important endogenous damage-associated molecular pattern (DAMP). P2X7R is an ATP-gated cation channel. ATP-P2X7R plays a vital role in the pathophysiology of many diseases because P2X7R is distributed on various immune cells. ATP-P2X7R signal transduction pathway has been implicated to participate in the body's im-mune defense against pathogens. This paper reviews the recent progress regarding ATP-P2X7R and its effects on parasitic diseas-es.

Establishment of an Embryonic Tip Regeneration System of Soybean

ABSTRACT In order to establish an optimal soybean embryonic tip regeneration system that can serve as soybean genetic transformation receptor, and be used for the study of genetic function verification, the influences of single factor on the adventitious bud of embryonic tip induction, elongation and rooting stage, are researched and compared.The single factors includes seeds soaking time, different kinds of hormones, different concentration of hormone and different concentration of sucrose. By one-way ANOVA and LSD ad hoc test , the results show that, for the embryonic tip adventitious bud induction stage, 12h is the optimal seeds soaking time, 2.0mg·L-1 is the optimal concentration of 6-Benzyl Aminopurine(6-BA), for the embryonic tip adventitious bud elongation stage, 0.2mg·L-1 indole-3-butyric acid (IBA) is optimal and 2.0mg·L-1Gibberellic acid (GA3) is optimal, and for the adventitious bud of embryonic tip rooting stage, 2.0mg·L-1 IBA is optimal,the average rooting rate is 93.34%. An Optimal embryonic tip regeneration system is established, and optimum mediums in different stages are found.

Clinicopathological characteristics and prognosis of uterine malignant mixed Mullerian tumor / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the clinicopathological characteristics, treatment and prognosis of uterine malignant mixed mullerian tumor.</p><p><b>METHODS</b>The clinical, pathologic and follow-up data of 16 patients with uterine malignant mixed Mullerian tumor treated in our hospital between March, 2003 and June, 2015 were analyzed.</p><p><b>RESULTS</b>The 16 patients had a median age of 58 years at diagnosis, and 13 of them were postmenopausal. The number of patients with FIGO stage Ia, Ib, II, IIIa, IIIc2, and IV was 7, 3, 1, 3, 1, and 1, respectively. In 15 patients who received uterine segment diagnostic curettage, pathological examination all reported malignant results. Among the 15 patients having serum CA125 level test upon admission, 2 had elevated CA125 levels. The overall and disease-free survival rates of the 16 patients were 75% and 68.8%, respectively, and the 3-year survival rate of 13 patients who were followed up for at least 3 years was 72.7%. Two out of 12 patients receiving retroperitoneal lymph?node?dissection?had had postoperative recurrence, as compared with 3 out 4 who did not had the operation; tumor recurrence was found in 3 out of 13 patients receiving postoperative chemotherapy, as compared with 2 out of 3 patients who did not have chemotherapy; tumor recurrence occurred in 1 out of 10 patients receiving radiotherapy, as compared with 4 out of 6 patients without radiotherapy. The recurrence rates in 11 patients with FIGO stage I-II was 18.2%, and that among the 5 patients with FIGO stage III-IV was 60.0%.</p><p><b>CONCLUSIONS</b>Uterine segment diagnostic curettage has a high diagnostic value for uterine malignant mixed Mullerian tumor. FIGO stage is the important prognostic factor for these patients, and early?diagnosis, accurate surgical staging, platinum-based chemotherapy and postoperative pelvic radiotherapy are all associated with a better prognosis.</p>

Pestalotiolide A, a New Antiviral Phthalide Derivative from a Soft Coral-derived Fungus Pestalotiopsis sp

Chemical investigation of the fermentation broth of a Soft Coral-Derived fungus Pestalotiopsis sp., led to the isolation of a new phthalide derivative, pestalotiolide A (1), three known analogues (2, 3 and 4), along with 5'-O-acetyl uridine (5) first isolated as a natural product. The structure of the new compound (1) was established by comprehensive spectroscopic analysis and chemical methods. Compounds 1 - 4 possessed varying degrees of antiviral activities, which was reported for the first time. Compared to the positive control ribavirin (IC50 = 418.0 microM), pestalotiolide A (1) exhibited significant anti-EV71 activity in vitro, with an IC50 value of 27.7 microM. Furthermore, the preliminary structure-activity relationship of antiviral activities was also discussed.

Effect of tongue tie corrective surgery on the development of language in children with short lingual frenulum / 中国基层医药

Objective To investigate the effect of tongue tie corrective surgery on the development of language in children with short lingual frenulum.Methods 94 children with short lingual frenulum were selected,and under the permission of the patients'family they were randomly divided into two groups.The treatment group received ankylotomy and language training.The control group was only given language training.The clinical efficacy,improvement time of pronunciation and adverse reactions were compared between the two groups.Results The total effective rate of the treatment group was 91.49％,which was significantly higher than 72.34％ of the control group (x2 =5.816,P ＜0.05).The improvement time of pronunciation in the treatment group was significantly shorter than the control group(t =21.250,P ＜ 0.01).There were no serious adverse reactions observed in two groups.Conclusion Tongue tie correction surgery can significantly affect the language development in children with short lingual frenulum,the improvement time of pronunciation is short,which is worthy of clinical application.

Construction of the skeletal muscle-specific TbetaR II knockout mice / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To generate the skeletal muscle-specific transforming growth factor beta receptor II (TbetaR II) gene knockout mice for the research on the function of the TbetaR II gene in skeletal muscles.</p><p><b>METHODS</b>TbetaR II (flox/flox) mice were generated using embryonic stem cell technology. The MCK-Cre mice were engineered containing Cre recombinase under the control of creatine kinase (MCK) muscle-specific promoter. TbetaR II (flox/flox) mice were crossed with MCK-Cre mice generating TbetaR II (flox/flox)/MCK-Cre double Tg mice. And then, TbetaR II (flox/wt) /MCK-Cre(+) double Tg mice were crossed with TbetaR II (flox/flox) mice to generate TbetaR II (flox/flox)/MCK- Cre(+) mice genetically ablating TbetaR II in cre-expressing skeletal muscle cells.</p><p><b>RESULTS</b>As predicted, mice lacking TbetaR II by gene targeting in skeletal muscles were generated first in the world using Cre/loxP system. TbetaR II null mutant mice were viable, fertile and showed apparently normal development.</p>

Reasons for the upsetting cholesterol level during the community investigation from residents, physicians, and social aspects: the China Cholesterol Education Program (CCEP) / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The community medical center is the first barrier for lipid control. We aimed to survey the residents' cholesterol condition in the community, and pursue the reasons for the upsetting results from various aspects.</p><p><b>METHODS</b>Residents and physicians were recruited from four community centers. Residents completed questionnaires and a physical examination as well as biochemical analysis. Physicians were also asked to complete a questionnaire, some of which were about basic knowledge of lipids.</p><p><b>RESULTS</b>About 37.0% male and 48.1% female had elevated cholesterol levels. Residents' blood pressure (BP), fasting glucose (FG), body mass index (BMI), and waist circumference (WC) were positively associated with their low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). Framingham risk scoring (FRS) was strongly related to cholesterol (P < 0.001 for LDL-C and TC). Residents' higher education grade was positively related to a normal cholesterol condition (P < 0.001), while personal income was negatively related to it. Rural residents had higher percent of population with normal cholesterol level (normal cholesterol rate) than their city counterpart (P < 0.001). Although physicians with college education had a much higher lipid knowledge level themselves, the physicians' factors had almost no relationship with the residents' cholesterol levels.</p><p><b>CONCLUSIONS</b>Management of hypercholesterolemia should be an important component of health strategy in Beijing. Education is imperative for residents as well as for physicians.</p>