Objectives: . This study aimed to investigate the regulatory functions of gamma-aminobutyric acid (GABA)ergic neural circuits from the inferior colliculus (IC) to the medial geniculate body (MGB) in salicylate-induced tinnitus. Methods: . Mice were treated with salicylate to induce tinnitus, and tinnitus-like behaviors were evaluated via gap prepulse inhibition of acoustic startle. Using combined viral tracing methodologies, we identified and mapped the pathways and connections from the IC to the MGB. Furthermore, we employed Gq-coupled human M3 designer receptors exclusively activated by designer drugs (DREADDs) and Gi-coupled human M4 DREADDs to achieve targeted excitation or suppression of GABAergic neurons in the IC and MGB. Following the administration of clozapine N-oxide, which binds to these receptors, we modulated these neural circuits to assess their impact on tinnitus severity in a mouse model. Results: . Our findings demonstrated that mice exposed to salicylate exhibited tinnitus-like behaviors. GABAergic neurons projecting retrogradely from the MGB to the IC were primarily concentrated in the external nucleus of the IC. After clozapine N-oxide administration, chemogenetic activation of IC-MGB GABAergic neurons aggravated salicylate-induced tinnitus. Additionally, activation of GABAergic neurons between the IC and MGB induced the perception of tinnitus even without salicylate. However, chemogenetic inhibition of the IC-MGB GABAergic circuit did not reverse salicylate-induced tinnitus. Conclusion . These findings suggest that activation of the IC-MGB GABAergic neural circuit may contribute to tinnitus generation through a mechanism distinct from that of salicylate-induced tinnitus. This study provides novel insights into the mechanisms underlying tinnitus.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective: To investigate the clinicopathologic features of primary adrenal NK/T cell lymphoma (PANKL). Methods: Six cases of PANKL were collected at Henan Provincial People's Hospital from January 2000 to December 2021. The clinicopathologic features including morphology, immunophenotype, treatment and prognosis were retrospectively analyzed, and relevant literature was reviewed. Results: There were two males and four females. The median age was 63 years (ranged from 57 to 68 years). The tumors involved bilateral adrenal glands in 4 cases and unilateral adrenal gland in 2 cases. The main clinical symptom was low back pain without obvious cause. Serum lactate dehydrogenase (LDH) is elevated in five cases. The imaging feature was rapidly enlarging mass initially confined to unilateral/bilateral adrenal glands. Morphologically, the lymphoid cells were mainly medium-sized with a diffuse growth pattern. Coagulative necrosis and nuclear fragmentation were common. Angioinvasion was seen. Immunophenotypically, the neoplastic cells were positive for CD3, CD56 and TIA-1 while CD5 was negative in 5 cases. All cases were positive for EBER by in situ hybridization with more than 80% proliferative activity by Ki-67. Four cases received chemotherapy, one case underwent surgery, and one case underwent surgery with chemotherapy. Follow-up was done in 5 cases; one case was lost to follow-up. Three patients died with a median survival of 11.6 months (3-42 months). Conclusions: PANKL is rare with highly aggressive clinical presentation and poor prognosis. Accurate diagnosis entails correlation of histomorphology, immunohistochemistry, EBER in situ hybridization and clinical history.
Male ; Female ; Humans ; Middle Aged ; Aged ; Retrospective Studies ; Lymphoma, T-Cell, Peripheral/pathology* ; Killer Cells, Natural/pathology* ; Prognosis ; Immunophenotyping

Objective: To investigate the occupational hazard factors and exposure levels of workers during the construction of power transmission and transformation projects. Methods: Analysis and identification of occupational hazard factors were carried out for typical construction process of 6 power transmission projects and 3 substation projects in September 2018. The on-site occupational health investigation was carried out to detect and analyze the exposure levels of workers to occupational hazard factors. Results: The time weighted average concentration (C(TWA)) of crushing workers exposed to silica dust and welders exposed to welding fume in substation projects were 2.72 and 14.03 mg/m(3), respectively. The 8 h equivalent sound level results of exposure noise of carpenters in power transmission projects and crushing workers, reinforcement workers, carpenters, scaffolders, road builders in substation projects were 87.9, 92.5, 87.1, 92.5, 93.0 and 90.2 dB (A) , respectively. The 4-hour time equal energy frequency weighted vibration acceleration of hand-transmitted vibration of bricklayer in power transmission projects, bricklayer, general worker 3, road builder 1 and road builder 2 of substation projects were 5.36, 5.21, 5.28, 10.71 and 5.22 m/s(2), respectively. The effective irradiance of electric welding arc light of welders' limbs in power transmission projects and substation projects were 401.19, 319.68 μW/cm(2), respectively. All of the above exceeded the requirements of occupational exposure limits. The occupational radiation levels and exposure limits of hazardous chemical factors met the requirements of each post. Conclusion: During the construction of power transmission and transformation projects, the exposure levels of occupational hazard factors in multiple posts exceed the standard. The main responsibility of employers for occupational disease prevention and control should be implemented, and targeted comprehensive measures should be taken to reduce the exposure levels of occupational hazard factors of workers.
Dust ; Humans ; Occupational Diseases ; Occupational Exposure/analysis* ; Occupational Health ; Welding

Adenocarcinoma/pathology* ; Humans ; Stomach Neoplasms/pathology* ; Tumor Suppressor Protein p53/metabolism*

BACKGROUND: Catheter ablation is effective in restoring sinus rhythm and left atrial appendage closure (LAAC) is increasingly used for stroke prevention in patients with atrial fibrillation (AF). We aimed to observe the feasibility and safety of performing AF ablation and LAAC in a single (one-stop) procedure. METHODS: Consecutive AF patients who underwent the combined procedure of AF ablation and LAAC with WATCHMAN device between March 2017 and September 2018 were prospectively enrolled. Baseline and intra-procedural parameters were evaluated. Three-month and subsequent 1-year follow-up were performed in all and earlier-enrolled subjects, respectively. RESULTS: A total of 178 AF patients (94 males, 68.9 ± 8.1 years) underwent the one-stop procedure with CHA2DS2-VASc score 3.3 ± 1.5 and HAS-BLED score 1.6 ± 1.0, respectively. Pulmonary vein isolation was achieved in all patients while additional linear ablation was applied if the operator deemed necessary, yielding immediate ablation success rate of 98.9% (176/178). In the subsequent LAAC, satisfactory seal (residual leak <5 mm) was achieved in all patients. One stroke and four cardiac perforations occurred peri-operatively. At 3-month follow-up, sinus rhythm and satisfactory seal were maintained in 153/178 (86.0%) and 178/178 (100%) patients, respectively. One stroke and one delayed cardiac tamponade occurred, while no device-related thrombus or device migration was observed. During the 1-year follow-up for the earlier enrolled subjects, 52/72 (72.2%) of the patients maintained sinus rhythm. There was no stroke or systemic embolism observed. CONCLUSION Combining catheter ablation and LAAC in a single procedure can be successfully and safely performed in non-valvular AF patients of Chinese population.

BACKGROUND: We previously found that the intestinal epithelial chemokine (C-C motif) ligand 7 (CCL7) plays an important role in the development of toxin-induced acute liver damage. The detailed effects of intestinal epithelial CCL7 on chronic diseases; however, are still unclear. Here, we aimed to investigate the impact of intestinal epithelial CCL7 overexpression on high-fat diet (HFD)-induced obesity and steatohepatitis in mice. METHODS: Intestinal epithelial CCL7 overexpression (CCL7) mice and their wild-type (WT) littermates were fed with normal chow or HFD for 16 weeks to induce obesity and non-alcoholic fatty liver disease. Body weight gain, as well as adipose tissue index were assessed. Liver injury was monitored by histological analysis and real time polymerase chain reaction. Gut microbial composition was analyzed by 16S rRNA gene sequencing. RESULTS: We found that the CCL7 mice on a HFD had markedly decreased weight gain (8.9 vs. 17.0 g, P < 0.05) and a lower adipose tissue index that include mesenteric fat (1.0% vs. 1.76%, P < 0.05), gonadal fat (2.1% vs. 6.1%, P < 0.05), subcutaneous fat (1.0% vs. 2.8%, P < 0.05) compared to WT animals. HFD-induced glucose intolerance and insulin resistance were also significantly improved in CCL7 mice compared to WT. Furthermore, HFD-fed CCL7 mice displayed less hepatic lipid accumulation and lower expression of inflammatory factors than WT mice. 16S rRNA gene sequencing demonstrated that CCL7 overexpression in intestinal epithelial cells improved HFD-induced gut microbial dysbiosis. CONCLUSIONS Our study revealed that CCL7 overexpression in the intestinal epithelium protects mice against the progression of diet-induced obesity, hepatic steatosis, and enteric dysbiosis.

Objective To study the effect of Kangdaxin on cardiac function in rats with cardio-renal syndrome, and to explore its protective mechanism based on ASK1-JNK/p 38 pathway. Methods Sixty SD rats were divided into sham group, heart failure group (HF group) , cardio-renal syndrome group (CRS group) , heart failure interventiongroup and cardio-renal syndrome intervention group. The sham group, heart failure group, cardio-renal syndrome group were given normal saline, the heart failure intervention group, and the cardio-renal syndrome intervention group were given 2. 7 m L·kg-1·d-1 Kangdaxin oral solution. Left ventricular shortening fraction and left ventricular ejection fraction were measured by cardiac ultrasound after modeling or treatment; heart weight/body weight (Hw/W) and left ventricular weight/body weight (LVw/W) were calculated after sacrifice of the rats. The gene and protein expression levels of ASK1, JNK and p38 in heart tissue of each group were detected by real-time quantitative polymerase chain reaction (q PCR) and immunob-lotting. The myocardial cells of each group were detected by flow cytometry.Results The left ventricular fraction, left ventricular ejection fraction, Hw/W and LVw/W in sham group were (31. 17 ± 2. 15) ％, (61. 08 ± 3. 45) ％, (3. 43 ± 0. 31) mg·g-1 and (2. 50 ± 0. 27) mg·g-1; the above indicators in heart failure group were (24. 42 ± 1. 98) ％, (42. 08 ± 4. 57) ％, (4. 10 ± 0. 21) mg · g-1, (2. 89 ± 0. 26) mg·g-1, the above indicators in cardio-renal syndrome group were (18. 50 ± 2. 84) ％, (38. 25 ± 3. 96) ％, (4. 84 ± 0. 32) mg·g-1, (3. 89 ± 0. 18) mg·g-1, compared with the sham operation group, all differences were statistically significant (all P < 0. 05) . The left ventricular shortening scores of heart failure intervention group and cardio-renal syndrome inte-rvention group were (27. 33 ± 3. 14) ％, (22. 67 ± 2. 66) ％, and the left ventricular ejection fraction were (50. 00 ± 3. 70) ％, (43. 83 ± 3. 78) ％, LVw/W were (2. 60 ± 0. 25) , (3. 63 ± 0. 22) mg·g-1.The differences between the heart failure group and the cardio-renal syndrome group were all statistically significant (all P < 0. 05) . The expressions of ASK1, JNK and p38 mRNA and protein in heart tissue of heart failure group and cardio-renal syndrome group were significantly lower than those in sham operation group (all P < 0. 05) .The apoptotic rate of cardiomyocytes in heart failure group and cardio-renal syndrome group were (24. 14 ± 5. 51) ％, (35. 60 ± 8. 75) ％, which was significantly higher than that in sham operation group (7. 87 ± 3. 13) ％ (all P < 0. 05) . The apoptotic rate of cardiomyocytes in heart failure intervention group and cardio-renal syndrome intervention group were (14. 12 ± 5. 98) ％, (26. 50 ± 7. 22) ％, compared with heart failure group and cardio-renal syndrome group, the differences were all statistically significant (all P < 0. 05) .Conclusion Kangdaxin oral solution has cardioprotective effect on cardio-renal syndrome rats which can inhibit the expressions of ASK1, JNK and p38 mRNA and protein in heart tissue, inhibit ASK1-JNK/p38 signaling pathway and decrease myocardial cell apoptosis.

OBJECTIVETo investigate the changes of tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) in mice with cholestatic cirrhosis and their role in regulating the balance of liver stem cell differentiation.

METHODSBalb/c mice were subjected to bile duct ligation (BDL), and serum biochemical parameters were measured and hepatic histopathology was observed using HE staining to evaluate the modeling of cholestatic cirrhosis. Immunohistochemistry and Western blotting were used to detect the changes of TNF-α and TGF-β in the mice after modeling. Mouse embryonic hepatic stem cells (HP14-19) were treated with different concentrations of TNF-α and TGF-β, and the cell differentiation was assessed using Western blotting, real-time PCR, and PAS staining.

RESULTSThe mice receiving BDL showed significantly increased blood biochemical parameters (P<0.05), and HE staining revealed obviously increased collagen fibers in the liver with significantly increased expressions of TNF-α and TGF-β (P<0.05). In HP14-19 cells, induction with TNF-α and TGF-β for 3 days did not cause significant changes in cell differentiation, but induction for 5 days resulted in significantly increases intensity of PAS staining in the cells. The cells induced with 20, 40, and 80 ng/mL TNF-α for 5 days exhibited a significantly stronger expression of cytokeratin 18 than cytokeratin 19 (P<0.05), while induction with 20, 40, and 80 ng/mL TGF-β produced opposite changes in cytokeratin 18 and cytokeratin 19 expressions. Further induction of the cells with TNF-α and TGF-β for 10 days, did not alter the expression patterns of cytokeratin 18 and cytokeratin 19 observed on day 5, but their protein expression levels and PAS staining intensity of the cells were enhanced and their mRNA expressions became lowered.

CONCLUSIONCommon bile duct ligation can induce conditions simulating cholestatic cirrhosis in mice. TNF-α and TGF-β are elevated in cholestatic cirrhosis and play opposite roles in regulating the differentiation balance of liver stem cells: the former promotes the differentiation of liver stem cells into hepatocytes, while the latter promotes the cell differentiation into colangiocytes.