1.The lysine methyltransferase SMYD2 facilitates neointimal hyperplasia by regulating the HDAC3-SRF axis.
Xiaoxuan ZHONG ; Xiang WEI ; Yan XU ; Xuehai ZHU ; Bo HUO ; Xian GUO ; Gaoke FENG ; Zihao ZHANG ; Xin FENG ; Zemin FANG ; Yuxuan LUO ; Xin YI ; Ding-Sheng JIANG
Acta Pharmaceutica Sinica B 2024;14(2):712-728
Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.
2.Effect of catgut implantation at acupoint on the learning and memory function and hippocampal microangiogenesis in vascular dementia rats
Yun-Zheng LI ; Qiu-Ying SUN ; Zhong-Sheng TANG ; Shi-Jie ZHU
Acta Anatomica Sinica 2024;55(2):150-157
Objective To observe the effect of catgut implantation at acupoint(CIAA)on the learning and memory function,hippocampal microangiogenesis,and the mRNA and protein expression of angiopoietin-1(Ang-1)/vascular endothelialgrowth factor(VEGF)and its receptor TEK tyrosine kinase(TIE2)/VEGF receptor 2(VEGFR2)in rats with vascular dementia(VD).To explore the mechanism of catgut implantation at acupoint in preventing and treating VD.Methods Using a random number table,VD rats were divided into a model group,a nimodipine group,and an catgut implantation at acupoint group,and a sham operation group was set up,with 10 rats in each group.On the 7th day after surgery,the treatment groups were given catgut implantation at acupoint and nimodipine gastric lavage for 21 days.After treatment,Morris water maze behavioral test was performed.HE staining was used to observe hippocampal CA1 tissue.CD34 immunohistochemical staining was used to detect hippocampal microvascular density(MVD).Real-time PCR and Western blotting were used to detect the mRNA and protein expression of Ang-1/VEGF and its receptor TIE2/VEGFR2 in the hippocampus.Results Compared with the model group,the average escape latency of the other groups was significantly shortened,and the target quadrant residence time was significantly prolonged(P<0.01,P<0.05).Compared with the model group,the number of nucleolus and well-formed pyramidal cells in hippocampal CA1 area of the catgut implantation at acupoint group and the nimodipine group increased in varying degrees,and they were arranged more closely,with only a few cells scattered and swollen.In the sham surgery group,a few CD34 positive cells were scattered.The treatment groups had more closely distributed CD34 positive cells with significant staining compared to the model group.The MVD of the model group was significantly higher than that of the sham surgery group(P<0.01).Both nimodipine group and catgut implantation at acupoint group had higher MVD than the model group(P<0.05,P<0.01).Compared with the sham surgery group,the mRNA and protein expression of Ang-1/VEGF and its receptor TIE2/VEGFR2 in the model group increased significantly(P<0.01,P<0.05).Compared with the model group,both nimodipine group and catgut implantation at acupoint group had higher mRNA and protein expression of Ang-1/VEGF and its receptor TIE2/VEGFR2(P<0.01,P<0.05).Conclusion Catgut implantation at acupoint can improve the learning and memory abilities in VD rats,promote hippocampal microvascular angiogenesis,which may be related to the up-regulation of Ang-1/VEGF and its receptor TIE2/VEGFR2 mRNA and protein expression.
3.Diagnostic value of multi-slice spiral computed tomography for acute pulmonary embolism
Zhong ZHENG ; Wen SHENG ; Jun ZHAO ; Qiong LAN
Chinese Journal of Radiological Health 2024;33(3):336-339
Objective To evaluate the value of multi-slice spiral computed tomography (CT) for diagnosing acute pulmonary embolism, and to provide a reference for the precise diagnosis of acute pulmonary embolism. Methods We enrolled a total of 102 patients pathologically diagnosed with acute pulmonary embolism from January 2019 to October 2023. All the patients underwent CT scanning of central and segmental pulmonary arteries with a GE 64-slice spiral CT scanner. The diagnostic efficacy of multi-slice CT scans for acute pulmonary embolism was evaluated with the pathological results as the gold standard. Results Of the 102 patients pathologically diagnosed with acute pulmonary embolism, multi-slice CT detected 92 cases, with an accuracy of 90.20% (92/102), including 17 cases (18.48%) of embolism in left pulmonary arteries, 31 cases (33.70%) of embolism in right pulmonary arteries, and 44 cases (47.82%) of embolism in both pulmonary arteries. Multi-slice CT visualized a total of 9905 pulmonary artery branches, and 304 of them (3.07%) had embolism, with the highest embolism rate in lobar arteries (43.89%). Conclusion Multi-slice spiral CT has high accuracy for diagnosing acute pulmonary embolism by directly and clearly visualizing embolism in the arteries of the lungs, which deserves clinical promotion.
4.Clinical trial of postauricular injection of compound betamethasone injection in the treatment of patients with sudden deafness
Shu-Fang ZHOU ; Zhi-Sheng ZHONG ; Dian LI ; Xu WANG
The Chinese Journal of Clinical Pharmacology 2024;40(7):977-980
Objective To observe the efficacy of postauricular injection of compound betamethasone injection in the treatment of sudden deafness and its influence on transcranial doppler(TCD)parameters and fibrinolysis-coagulation indicators.Methods Patients with sudden deafness were divided into control group and treatment group according to cohort methed.The control group was given intravenous injection of dexamethasone sodium phosphate for 10 days on the basis of conventional treatment,and the treatment group was given postauricular injection of compound betamethasone injection 0.8 g for once every other day for 5 times in addition to conventional treatment.The clinical efficacy,hearing level,haemodynamics and laboratory indicators[homocysteine(Hcy),platelet(PLT)count]were compared between the two groups of patients,and the adverse drug reactions or complications were counted.Results There were 50 cases in treatment group and 50 cases in control group.After treatment,the total effective rates in treatment group and control group were 94.00%(47 cases/50 cases)and 80.00%(40 cases/50 cases),with significant difference(P<0.05).After treatment,the acoustic thresholds under 0.5 kHz,1 kHz,2 kHz and 4 kHz in treatment group were(42.48±5.65),(45.35±6.44),(48.67±5.58)and(50.25±6.06)dB,which in control group were(50.64±6.92),(57.66±7.41),(60.24±8.31)and(63.15±8.25)dB,all with significant difference(all P<0.05).After treatment,the whole blood high-shear viscosities in treatment group and control group were(4.18±0.58)and(4.99±0.76)mpa·s;the whole blood low-shear viscosities were(9.18±1.15)and(10.31±1.28)mpa·s;the plasma viscosities were(1.44±0.32)and(1.76±0.25)mpa·s;the Hcy levels in treatment group and control group were(15.57±4.25)and(21.75±4.93)μmol·L-1;PLT levels were(198.72±21.41)×109·L-1and(212.67±18.46)×109·L-1 respectively,all with significant difference(all P<0.05).There were no obvious adverse drug reactions in treatment group and control group.Conclusion Postauricular injection of compound betamethasone injection can improve the hearing level and enhance the clinical efficacy in patients with sudden deafness,and it is helpful to improve haemodynamics and reduce serum Hcy level,with good safety.
5.Effects of propranolol on femoral fracture healing in mice via miR-92a-3p
Jin ZHANG ; Zhi-Wei CHEN ; Sheng-Zhong XUE ; Wen-Jie ZHOU ; Jiu-Xia WANG ; Jian-Jun SHEN
The Chinese Journal of Clinical Pharmacology 2024;40(20):3028-3032
Objective To explore the effect of propranolol on femoral fracture healing in mice through regulation of microRNA-92a-3p(miR-92a-3p)and its mechanism.Methods C57BL/6J male mice were randomly divided into sham group(equal amount of 0.9%NaCl),model group(equal amount of 0.9%NaCl),experimental group(50 mg·kg-1 propranolol administration),inhibitor group(mice were injected with 100 mg·kg-1 miR-92a-3p inhibitor via tail vein on the basis of the experimental group).Femur was severed and molded in all mice except sham operation group.X-ray was used to observe bone healing.Quantitative real time polymerase chain reaction was used to detect the expression of miR-92a-3p in femur tissues.The expression level of bone formation and bone metabolism markers was detected by enzyme linked immunosorbent assay.Western blot was used to detect the expression of pathway-related proteins.Results The X-ray scores of femur in sham group,model group and experimental group were 11.20±2.60,4.70±1.50 and 9.60±2.40,respectively;the relative expression levels of miR-92a-3p in sham operation group,model group,experimental group and inhibitor group were 1.00±0.09,0.73±0.06,0.90±0.07 and 0.78±0.06;alkaline phosphatase levels were(35.21±2.63),(43.16±3.29),(67.58±5.37)and(49.62±4.05)U·L-1,respectively;crosslaps levels were(4.57±0.52),(8.41±0.91),(4.26±0.67)and(5.73±0.84)ng·mL-1,respectively;the relative expression levels of brain derived neurotrophic factor were 1.00±0.14,0.58±0.05,0.83±0.09 and 0.71±0.06,respectively;the relative expression levels of phospho-tyrosine kinase receptor B were 1.00±0.12,0.62±0.05,0.89±0.08 and 0.76±0.07,respectively;the relative expression levels of phospho-extracellular regulated protein kinases were 1.00±0.11,0.54±0.04,0.78±0.07 and 0.65±0.05,respectively.The above indexes in the model group were compared with those in the sham group,those in the experimental group were compared with those in the model group,and those in the inhibitor group were compared with those in the experimental group,and the differences were statistically significant(P<0.05,P<0.001).Conclusion Propranolol can promote femoral fracture healing in mice,which may be achieved by up-regulating miR-92a-3p activation of brain derived neurotrophic factor/tyrosine kinase receptor B/extracellular regulated protein kinases signaling pathway.
6.Effect of loading angle and fabrication materials on stress distribution with periodontal splint in compromised periodontal tissues: a finite element study
Ming FANG ; Yuchen LIU ; Sheng ZHONG ; Dongmei LI ; Tong YANG ; Shizhu BAI
Chinese Journal of Stomatology 2024;59(11):1120-1125
Objective:To evaluate the effect of polyetheretherketone (PEEK) periodontal splints and splints made from other materials under static loading on stress distributions in periodontal tissues, cement layer, and splints themselves.Methods:A finite element model based on cone-beam CT imaging data of a 25-year-old male patient (treated at the Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University in October 2021 for a cracked maxillary molar) with a healthy and intact mandibular dentition and periodontal health was constructed. The finite element model included anterior mandible dentition, mandibular bone model without bone resorption (WBR group), a periodontally compromised mandible model (control group), and three types of periodontal splints: a PEEK periodontal splint (0.7 mm thick, Young′s modulus: 4.1 MPa), a fiber-reinforced resin (FRC) splint (1.0 mm thick, Young′s modulus: 37.0 MPa), and a titanium splint (1.2 mm thick, Young′s modulus: 110.0 MPa). The bone resorption models fixed with different periodontal splints constituted the experimental groups (PEEK group, FRC group and titanium group). Loading of 100 N was applied on the midpoint of the incisal edge of tooth 41. The direction was set at 0°, which was parallel to the long axis of the tooth and downward. The buccal to lingual and downward angles were 30°and 60°, respectively, perpendicular to the long axis of the tooth and 90° to the lingual side. The finite element analysis software was utilized to analyze the stress distribution characteristics of the periodontal tissues, adhesive layer, and the splint itself in the anterior mandibular teeth among the different group.Results:Under the different loading simulation, in the control group, the maximal von Mises stresses of periodontal ligament and bone were 15.7-50.2 MPa and 38.8-130.3 MPa, respectively, and in the WBR group, the maximal von Mises stresses of periodontal ligament and bone were 3.6-6.4 MPa and 16.5-42.7 MPa, respectively. Under the same loading conditions, the magnitude of maximal von Mises stresses in periodontal tissues in the PEEK group was 4.6-6.2 MPa, and the magnitude of stresses in the periodontal ligament of 41 teeth in the WBR group was similar to that in the PEEK group, but higher than that in the FRC and titanium groups. The maximal von Mises stresses of each group is primarily distributed in the periodontal ligament and alveolar bone at the cervical area of the tooth. The higher the elastic modulus of the splint, the higher its own maximal von Mises stresses, and the smaller the maximal principal stresses transmitted to the adhesive layer. In the PEEK group and titanium group, the stress distribution area in the adhesive layer and the splint was near the splint connection adjacent to tooth 41.Conclusions:Periodontal splints fabricated from three types of materials, are effective in distributing stress within the periodontal tissues of the abutment teeth. Compared to FRC and titanium group, the higher PEEK splint stress value was obtained, and the smaller the stress value was transmitted to its adhesive layer.
7.PENG Peichu's Experience in Staged Differentiation and Treatment of Prostate Cancer
Xinyu XU ; Yu PENG ; Wenjing ZHU ; Jing ZHAI ; Dongya SHENG ; Mingyang WANG ; Yiqun SHAO ; Boyang LI ; Qi ZHONG
Journal of Traditional Chinese Medicine 2024;65(7):678-683
This paper summarized Professor PENG Peichu's experience in the differentiation and treatment of prostate cancer in three phases and four stages. It is considered that prostatic cancer is categorized into root deficiency and branch excess, with depletion of healthy qi as the root, and the accumulation of cancer toxin as the minifestation. Clinical diagnosis and treatment of prostatic cancer can be divided into three phases and four stages according to the exuberance and decline of pathogenic and healthy qi and the changes of deficiency and excess of yin and yang. In the initial accumulation phase of cancer toxin (yang excess stage), the key pathogenesis is the accumulation of dampness, heat and static blood, and internal generation of cancer toxin, and the treatment should be resolving toxins, fighting cancer and dispelling yang excess. In the phase of healthy qi deficiency and toxin accumulation (yin deficiency stage), with the lung and kidney yin deficiency, dampness, heat and static toxin accumulation as the key pathogenesis, the treatment should be centered on mutual generation between metal and water to nourish kidney yin, supplemented with the method of clearing heat and draining dampness, activating blood and resolving toxins, for which self-made Nanbei Formula(南北方)is usually used. In the phase of yang deficiency and cold stagnation (yang deficiency stage and yin excess stage), with the spleen and kidney yang deficiency, cold dampness stagnation, static heat and toxin accumulation as the key pathogenesis, the treatment should be warming and tonifying spleen and kidney to dissipate cold accumulation; for deficiency of both yin and yang, and excess pathogen obstruction, modified Yanghe Decoction(阳和汤) is recommended, while for yang deficiency, cold congealing and blood stasis, self-made Wenshen Sanjie Formula(温肾散结方) can be used, and for cold dampness binding with cancer toxin, and cold complex with heat, self-made Quanan Formula (泉安方) is advised.
8.Clinical application of inferior pancreaticoduodenal artery management in laparoscopic pancreaticoduodenectomy
Zhantao SHEN ; Zhimin YU ; Xiaosheng ZHONG ; Youxing HUANG ; Chengjiang QIU ; Yanchen CHEN ; Guihao CHEN ; Sheng ZHANG ; Chunbao ZHU ; Zhangyuanzhu LIU ; Yifeng LIU ; Zhijian TAN
Chinese Journal of Surgery 2024;62(10):947-952
Objective:To investigate the clinical effect of proper management of inferior pancreaticoduodenal artery (IPDA) in laparoscopic pancreaticoduodenectomy (LPD).Methods:This is a retrospective case series study. The clinical and pathological data of 70 patients who received LPD due to pancreatic head tumors, periampullary tumors, or distal common bile duct tumors in the Pancreatic Center of the Second Clinical College of Guangzhou University of Chinese Medicine from January to December 2022 were retrospectively collected. There were 47 males(67.1%) and 23 females(32.9%),aged (59.9±12.8)years(range:13 to 87 years).The procedure of IPDA exposure was as follows:a middle approach was utilized to expose the right half of superior mesenteric artery(SMA) and its right branches between the SMA and superior mesenteric vein(SMV) in superior colonic region. In the subcolonic region,SMA trunk exposure via dissection along the jejunal artery from feet to head and identification the association between IPDA and jejunal artery were prior to IPDA root ligation and dissection. The safety and efficacy of intraoperative IPDA handling were assessed based on surgical videos. Follow-up was carried out in outpatient clinic or by telephone, and outpatient follow-up was conducted once every 1 to 3 months after surgery.Results:The percentage of total LPD was 98.6%(69/70),with all patients achieving R0 resection. Nine cases(12.9%) were involved in combined vascular resection and reconstruction,with 1 case (1.4%) requiring additional upper abdominal incision for vascular and gastrointestinal reconstruction,while the remaining eight cases (11.4%) were completed laparoscopically. The operative time was (432.7±115.4)minutes(range:282 to 727 minutes), and the blood loss was (140.0±125.7)ml(range:20 to 800 ml). Only two patients(2.9%) received fresh frozen plasma transfusion,with an average volume of 650 ml. Reliable ligation and safe handling of the IPDA were achieved in 91.4%(64/70) of cases, with 8.6%(6/70) suffering from IPDA injury-related bleeding. No one was converted to opened surgery. Pathologically,the mean tumor size was (3.3±1.6)cm (range:1 to 7 cm),and the mean number of harvested lymph nodes was 17.0±7.3(range:0 to 46). Lymph node metastasis was observed in 13 cases (18.6%). Five cases (13.2%) developed grade B pancreatic fistula,while no grade C pancreatic fistula occurred. Other complications included bile leakage in one case(1.4%),delayed gastric emptying in two cases(2.9%), lymphatic leakage in 2 cases(2.9%),intra-abdominal infection in 9 cases(12.9%),and fat liquefaction of surgical incision in 1 case(1.4%). Two cases(2.9%) experienced postoperative intra-abdominal bleeding,one due to mesangial bleeding of lesser curvature of the stomach and the other due to oozing from the hepatic arterial sheath. These bleeding events were not concerned with IPDA. The average length of postoperative hospital stay was (15.2±4.6)days(range:9 to 28 days).Conclusion:Proper intraoperative management of IPDA in LPD might reduce IPDA-related bleeding during and after surgery and improve the safety of LPD.
9.Utilization of 3D printing technology in hepatopancreatobiliary surgery
SHI WUJIANG ; WANG JIANGANG ; GAO JIANJUN ; ZOU XINLEI ; DONG QINGFU ; HUANG ZIYUE ; SHENG JIALIN ; GUAN CANGHAI ; XU YI ; CUI YUNFU ; ZHONG XIANGYU
Journal of Zhejiang University. Science. B 2024;25(2):123-134
The technology of three-dimensional(3D)printing emerged in the late 1970s and has since undergone considerable development to find numerous applications in mechanical engineering,industrial design,and biomedicine.In biomedical science,several studies have initially found that 3D printing technology can play an important role in the treatment of diseases in hepatopancreatobiliary surgery.For example,3D printing technology has been applied to create detailed anatomical models of disease organs for preoperative personalized surgical strategies,surgical simulation,intraoperative navigation,medical training,and patient education.Moreover,cancer models have been created using 3D printing technology for the research and selection of chemotherapy drugs.With the aim to clarify the development and application of 3D printing technology in hepatopancreatobiliary surgery,we introduce seven common types of 3D printing technology and review the status of research and application of 3D printing technology in the field of hepatopancreatobiliary surgery.
10.Rupture-A symbolic timing point of the natural abdominal rupture during cadaver decay
Xingchun ZHAO ; Fan YANG ; Sheng HU ; Hao NIE ; Jiajia FAN ; Zhen PENG ; Gengqian ZHANG ; Peng GUI ; Zengtao ZHONG
Chinese Journal of Forensic Medicine 2024;39(1):68-74
Objective Corruption is the most common cadaver phenomenon in forensic practice and an important basis for inferring time of death(PMI),but the definition of corruption degree and the construction of model inference models have always been difficult in the practice of forensic science.Methods In this study,the late postmortem phenomena were observed.Meanwhile,the microbial flora structure of gut and gravesoil and the nature of gravesoil were detected,for analyzing the changes before and after the key moment of abdominal rupture which naturally happened during the cadaver decay.Results The results found that from the macroscopic and microscopic levels,there were significant differences in cadaver decay,including microbial flora structure and gravesoil properties before and after the key moment of the natural abdominal rupture during cadaver decay.The phenomena are highly observable and can be accurately judged by forensic examinations,as well as related means in the field of biology and physiochemistry.In this study,this critical event was called Rupture Point.Conclusion The Rupture Point can be used as an important node for the assessment of cadaver decay degree in the practice of forensic medicine.It can be utilized for a cut-off point as well when constructing PMI inference models based on microbial flora structure changes.The accuracy of PMI inference models can be improved when the models were constructed in segments.

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