ObjectiveTo establish an animal model of atrial fibrillation（AF） that accurately reflects the phlegm-heat and blood stasis（TRYZ） pathogenesis in traditional Chinese medicine. MethodsForty SPF-grade SD rats were randomly assigned using a random number table to the following groups：the control group， the TRYZ+AF group，the AF group and the TRYZ group， with ten rats in each group. The TRYZ+AF and TRYZ groups underwent a high-fat diet combined with intraperitoneal lipopolysaccharide（LPS） injection to simulate the pathological alterations of TRYZ syndrome. Groups TRYZ+AF and AF were induced with acetylcholine-calcium chloride（Ach-CaCl₂） via caudal vein injection to induce AF. The control group received no intervention and was maintained under normal conditions. The modeling period lasted 3 weeks. Electrocardiography was used to assess AF episodes and duration， echocardiography evaluated left atrial dimensions and cardiac function， fully automated biochemical analyzer measured the levels of total cholesterol（TC）， triglycerides（TG）， high-density lipoprotein cholesterol（HDL-C） and low-density lipoprotein cholesterol（LDL-C）， hemoreometer analyzed the whole blood viscosity， plasma viscosity， and whole blood reduced viscosity， a coagulation analyzer assessed prothrombin time（PT）， activated partial thromboplastin time（APTT）， thrombin time（TT）， and fibrinogen（FIB）， enzyme-linked immunosorbent assay（ELISA） was used to determine the levels of C-reactive protein（CRP）， interleukin（IL）-1β， IL-6， IL-17， tumour necrosis factor（TNF）-α， matrix metalloproteinase-9（MMP-9）， galectin-3（Gal-3）， Collagen Ⅰ， and α-smooth muscle actin（α-SMA）. Hematoxylin-eosin（HE） staining and Masson's trichrome staining were used to analyze pathological changes in atrial myocardium， Western blot was employed to detect MMP-9， Collagen Ⅰ and α-SMA protein expression in myocardial tissue， real-time quantitative polymerase chain reaction（Real-time PCR） evaluated fibrous factor gene expression levels. Changes in the TRYZ syndrome were assessed via body weight， tongue color［red（R）， green（G）， and blue（B）］， and rectal temperature. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was employed to detect differential metabolites between the control group and the TRYZ+AF group. ResultsFollowing three weeks of sustained modeling， compared with the control group， rats in the TRYZ+AF and the TRYZ groups exhibited reduced body weight， dry faeces， elevated rectal temperature， dark red tongue， decreased RGB values on the tongue surface， and markedly elevated TC and LDL-C levels（P<0.05， P<0.01）. The TRYZ+AF， TRYZ， and AF groups exhibited significantly decreased TT， APTT and PT， along with markedly elevated whole blood viscosity and FIB（P<0.05， P<0.01）. Rats in the TRYZ+AF and AF groups exhibited AF rhythm， markedly decreased heart rate， prolonged RR intervals， enlarged left atrium， and significantly reduced ejection fraction and shortening fraction（P<0.05， P<0.01）. Serum levels of CRP， IL-1β， IL-6， IL-17， TNF-α， MMP-9， Gal-3， Collagen Ⅰ， and α-SMA were elevated in rats from the TRYZ+AF， TRYZ， and AF groups compared to the control group， with the most pronounced increase observed in the TRYZ+AF group（P<0.05， P<0.01）. Histopathology revealed that the collagen fiber deposition in the atrial of rats in the TRYZ+AF， TRYZ and AF groups was higher than that in the control group（P<0.05， P<0.01）. Western blot and Real-time PCR results further demonstrated that the protein and mRNA expression levels of MMP-9， Collagen Ⅰ and α-SMA in the myocardial tissue of the TRYZ+AF group were higher than those in the other three groups（P<0.05， P<0.01）. Metabolomic analysis revealed 173 differentially expressed metabolites in the TRYZ+AF group and the control group， primarily enriched in pathways such as glycerophospholipid metabolism and glycolysis/gluconeogenesis. ConclusionThis study successfully establishes a rat model of AF integrated with the TRYZ syndrome， demonstrating the pathological process where the interactions of phlegm， heat and stasis jointly trigger tremor， this provides a reliable experimental tool for in-depth research into the biological basis of this disease syndrome.

Objective Uranium compounds are critical materials in the nuclear industry, and their mining, processing, and use pose occupational exposure risks. Epidemiological studies have shown that uranium exposure can impair health, with acute uranium poisoning primarily causing structural and functional damage to the kidneys. Currently, the molecular mechanisms underlying uranium-induced kidney injury remain unclear, and traditional biological models used in toxicological research are inadequate for simulating the human microenvironment. This study employed a human kidney organoid model system to elucidate the nephrotoxic mechanisms of uranyl ions, providing a scientific basis for the prevention and control of uranium poisoning. Methods Kidney organoids were constructed using the human embryonic stem cell line H1 and exposed to solutions with different uranyl ion concentrations. Morphological observation, ATP detection, reactive oxygen species detection, apoptosis assay, and untargeted metabolomics analysis were performed. Mechanisms of toxicity were further explored through KEGG pathway enrichment analysis. Results Uranium exposure led to structural damage in the organoids, accompanied by a dose-dependent decrease in ATP levels, accumulation of reactive oxygen species, and increased apoptosis rate. After 24-hour exposure to 300 μmol/L uranium, significantly disturbed differential metabolites and five core metabolic pathways were identified. Conclusion Uranium induces oxidative stress, mitochondrial dysfunction (ATP reduction), and metabolic disorder (disruption of phospholipid/amino acid metabolism), which synergistically cause DNA damage, apoptosis, and/or necrosis. These findings provide new insights into the mechanisms of uranium-induced kidney injury and support the development of prevention and control strategies.

Objective:To evaluate the diagnostic accuracy and application value of high-frequency ultrasonography in proximal radial nerve injuries associated with humeral shaft fractures.Methods:A retrospective case series study was performed for 19 patients with proximal radial nerve injuries associated with humeral shaft fractures treated in Huashan Hospital Affiliated to Fudan University from August 2014 to September 2020. The were 17 males and 2 were females，with the age range of 16-55 years ［（38.1±12.7）years］. Of all，11 patients were injured at the left side and 8 at the right side. All the patients had histories of traumatic humeral shaft fracture and were treated in other hospitals，including internal fixation in 17 patients，external fixation in 1 and internal fixation combined with external fixation in 1. All patients underwent radial nerve exploration surgeries，among which 8 had high-level radial nerve release and 11 had high-level radial nerve suture or graft transplantation. All patients underwent high-frequency ultrasound examination before surgery. The ultrasonographic characteristics of the radial nerve were recorded，including the continuity of the epineurium，honey-comb structure on the transversal section，neuromas on the longitudinal section and external scar or callus or metal fixation compressing the nerve. The injury type and neural continuity of each radial nerve were evaluated. The radial nerves of type Ⅰ，type Ⅱ，type Ⅲa ，type Ⅲa ，type Ⅲb and type Ⅳ appeared as normal，swelling，short-segment compressed，neuroma-like and ruptured，respectively. Taking the intraoperative findings as the gold standard，the diagnostic coincidence rate，sensitivity，specificity，positive predictive value and negative predictive of high-frequency ultrasound were analyzed in diagnosis of proximal radial nerve injuries associated with humeral shaft fractures.Results:According to ultrasonographic characteristics，proximal radial nerve injuries were classified into 4 types in 5 subtypes. It was confirmed by surgeries that there were 1 patient with type Ⅱ，4 with type Ⅲa，1 with type Ⅲb and 13 with type Ⅳ，with no type Ⅰ. The diagnostic coincidence rate of high-frequency ultrasound was 89%. The diagnostic coincidence rate of type Ⅱ，type Ⅲa，type Ⅲa，type Ⅲb and type Ⅳ was 100%，100%，100% and 85%，respectively. The sensitivity of high-frequency ultrasound for evaluating the neural continuity was 75%，the specificity was 100%，the positive predictive value was 100%，the negative predictive value was 85%.Conclusions:The high-frequency ultrasound has a relatively high sensitivity and specificity in diagnosis of proximal radial nerve injuries associated with humeral shaft fractures，which can provide relatively accurate morphological information for clinical diagnosis and treatment.

Objective:To explore the effect of miR-7 on the formation of abdominal aortic aneurysm by up-regulating the expression of ERK and MMP-9 proteins.Methods:Download the miRNAs expression profile chip data from the GEO database, the differentially expressed miRNAs were screened out by GEO2R and the correlation between target genes and ERK genes was analyzed; twenty 4-week male C57BL/6J mice with SPF grade were selected and randomly divided into a model group (only 0.6% BAPN solution was given, n=10) and miR-7 group (fed with 0.6% BAPN solution+ injected with 1×10 9 PFU/ml lentivirus containing miR-7 over expression gene via tail vein, n=10), after 7 weeks of continuous feeding, the mice were anesthetized intraperitoneally with chloral hydrate. After the abdominal cavity and thorax were dissected, the abdominal aorta was separated from the left ventricle perfusion with normal saline under physiological pressure and pathological sections were prepared. Masson staining and α-SMA staining were used to evaluate the lesion degree of abdominal aortic vessels in each group; the protein expression levels of p-ERK1/2 and MMP-9 in the diseased abdominal aorta of each group were detected by WB. Results:By screening differential genes, we found that miR-7 was highly expressed in patients with abdominal aortic aneurysm, and further analysis revealed that miR-7 was positively correlated with ERK1/2; Masson staining showed that the tumor of abdominal aortic aneurysm in miR -7 group was significantly larger than that in the model group, and the difference was statistically significant ( P<0.05), the results of α-SMA histochemical staining showed that the number of α-SMA positive VSMC in miR-7 group was significantly lower than that in the model group, and there was almost no-SMA staining in some VSMC; WB results showed that the highest expressions of P-ERK1/2 and MMP-9 proteins in the abdominal aorta of miR-7 group were significantly higher than that of the model group, with statistically significant differences ( P<0.05). Conclusion:MiR-7 accelerated the formation of abdominal aortic aneurysms by up-regulating the expression of ERK and MMP-9 proteins.

Objective:To evaluate the diagnosis, surgical treatment, and neurological function recovery after surgery of patients with intraspinal tumors. Methods:The clinical data of 69 patients who suffered from intraspinal tumors and underwent surgery from Janu-ary 2008 to December 2012 were retrospectively analyzed. Neuroimaging and ASIA scoring were performed to examine the pathologi-cal characteristics of tumors and the neurological function of these patients before and after treatment. The major factors affecting prognosis were also probed, and the average follow-up period was 12.2 months. Results:Of the total cases, 62.3%showed intradural extramedullary intraspinal tumors located in the thoracic vertebra. Neurilemoma (Schwannoma) and meningioma were the most com-mon pathological types (53.5%). Posterior approaches with hemi-and complete-laminectomy were conducted to expose the intraspi-nal tumors, and the separation and removal of the tumors located at the cervical and thoracic levels were aided with surgical microsco-py. The main clinical symptoms, including back pain, radicular neuralgia, sensory disturbance, and motor dysfunction, were significant-ly improved after surgery, and this observation was supported by the follow-up ASIA scores before and after treatment. Of the in-volved cases, 91%were successfully treated, and their tumors were totally resected. Conclusion:Total or subtotal intraspinal tumor re-section enhanced with surgical microscopy could achieve satisfactory clinical results through posterior hemi-or complete-laminectomy.

Objective To investigate the mechanism of sleeve gastrectomy combined with modified jejunoileal bypass (SG/MJIB) in improving the blood glucose of Goto-kakizaki (GK) rats.Methods According to the random meter method,the 28 GK rats were divided into 4 groups:sleeve gastrectomy with modified jejunoileal bypass (SG/MJIB),sleeve gastrectomy (SG),modified jejunoileal bypass (MJIB) and sham operation (SHAM).The changes of weight,food intake,fasting blood glucose,oral glucose tolerance test (OGTT),insulin tolerance test (ITT),plasma insulin and gastrointestinal hormonal (ghrelin and GLP-1) were monitored before and 16 weeks after surgery respectively.Results After surgery,the fasting blood glucose level in SG/MJIB group was obviously lower than that in SG,MJIB and SHAM groups (P＜0.05).From the 2nd week after surgery,OGTT of the SG/MJIB group was obviously improved compared to SG,MJIB,and SHAM groups (P＜0.02).In our post-op erative study,the insulin levels in SG/MJIB group were lower than those in SG,and SHAM groups (P＜0.05).Compared to MJIB and SHAM groups,ghrelin levels of SG/MJIB group were significantly decreased (P＜0.001),while GLP-1 levels of SG/MJIB group were higher than those of SG and SHAM groups (P＜0.01).Conclusions SG/ MJIB can improve insulin sensitivity and insulin secretion,and this effect is independent of the body weight and food intake.This study further validates that the gastrointestinal hormones play an important role in the pathogenesis and treatment mechanisms of type 2 diabetes mellitus.

Objective To explore the aging mechanisms of human adult adipose-derived stem cells (hADSCs) in vitro.Methods The hADSCs came from the production of normal patients with liposuction.The hADSCs were cultured in the 37℃ incubator and passed until the cells were senescent.The senescence-associated β-gal staining (SA-β-gal) and histone protein γH2AX staining were carried out in both young and old hADSCs.The quantitative real-time PCR (qRT-PCR) was conducted to check the difference of the transcription function of the young and old hADSCs.Results The cultured hADSCs would be the senescent cells when the PD number was more than 35.The aging cells became big and had large flat nuclei and much more lososomes in the cytoplasm.The SA-β-gal staining and γH2AX staining were mostly positive in the aging hADSCs (PD>35) compared with the self-renewing hADSCs (PD<20).The qRT-PCR results showed that the transcription levels of Nanog and Oct4 gene were very low in aging hADSCs compared with the self-renewing ones.Conclusions The hADSCs will be senescent (SEN) when cultured and passed in vitro for long time and the aging process is similar to that of stem cells in vivo.The aging model of hADSCs can be established by this method and will be very useful in the anti-aging drug, regeneration medicine, tissue engineering and stem cell therapy.

Background and purpose:It has confirmed that docetaxel, in combination with cisplatin or oxaliplatin have good effect in the treatment of advanced gastric cancer. This study in order to observe the clinical efficacy and adverse reaction of weekly docetaxel combined with cisplatin (DP) versus weekly docetaxel combined with oxaliplatin (DO) as the firrst-line treatment of advanced gastric cancer.Methods:A total number of 76 cases of advanced gastric cancer were randomly assigned 2 arms, 38 per arm. DP regimen group (docetaxel 35 mg/m2,ivgtt,dl,d8 combined with cisplatin 60 mg/m2, ivgtt,dl,repeated every 3 weeks) and DO regimen group(docetaxel 35 mg/m2,ivgtt,dl,d8 combined with oxaliplatin 120 mg/m2 ivgtt,dl,repeated every 3 weeks). Results:No significant difference was found between DP regimen group and DO regimen group on the objective RR(37%vs 41%),PFS (4.9vs 4.4 months) and OS (9.7vs 12.3 months). The main grade 3 or 4 toxicity in the DP and DO groups was neutropenia, DO was less associated with nausea and vomiting, but more associated with peripheral neuropathy than DP group. No signiifcant difference was found between DP regimen group and DO regimen group on the anemia, thrombocytopenia, diarrhea, alopecia (P>0.05).Conclusion:Weekly docetaxel combined with cisplatin (DP) shows similar efifcacy and toxicity compared with weekly docetaxel combined with oxaliplatin (DO) as the ifrst-line treatment of advanced gastric cancer and worthy of further study.

Objective To investigate the relationship between vascular injury of diabetic rats with hind limb ischemia and endothelial nitric oxide synthase(eNOS) uncoupling.Methods 15 SD rats were randomly divided into 3 groups:control group (n =5),diabetes group (n =5) and diabetes ischemia group (n =5).Two weeks after the diabetic rat model and hind limb ischemia of diabetic rat model were set up,Enzyme linked immunosorbent assay(ELISA) was used to detect nitric oxide(NO) expression in the rat femoral artery; Dihydroethidium(DHE) fluorescent probe was used to detect superoxide(O2-) production in the frozen section of femoral artery; and Western blot was used to examine GTP cyclohydrolase 1 (GTPCH-1)expression in femoral artery.Results ①Compared with the control group,NO expression of femoral artery in diabetes group was significantly reduced,diabetes ischemia group decreased more significantly,and the difference between the 3 groups had statistical significance(P =0.000,P =0.000,P =0.001).②Frozen section showed:compared with the control group,O2-expression of diabetes group significantly increased,but not as much as diabetes hind limb ischemia group.③Western blot results showed that compared with the control group,the expression of GTPCH-1 in diabetes group reduced,diabetes hind limb ischemia group decreased more significantly,and the difference between the 3 groups had statistical significance (P =0.001,P =0.000,P =0.012).Conclusion eNOS uncoupling is present in diabetic rats with hind limb ischemia and vascular injury.

Objective To investigate the application of the parietal branches of superficial temporal artery island flap in the complex scalp defects.Methods A parietal branches of superficial temporal artery island flap on the ectatic scalp flap was designed to repair the complex scalp defects in 25cases and the repairing effect was observed.Results The island flaps were survived completely in 24patients,in which 1 patient had partial necrosis because of the flap tension was too large,but healed after local dressing and debridement.After followed up 6～ 12 months,the color and texture of the flap were the same to the surrounding normal scalp,and the shape was satisfactory.The flap donor site of hair growth was good,with well healing and no obvious complications.Conclusions The parietal branches of superficial temporal artery island flap can repair the complex scalp defects with the flexible flap design and movement.The flap survives well and the repair area is large.The flap and the surrounding scalp connects good.Therefore,it is a good method strongly recommended for small area complex scalp defects repair in clinics.