BACKGROUND: Epoxyeicosatrienoic acids (EETs), which are metabolites of arachidonic acid catalyzed by cytochrome P450 epoxygenase, are degraded into inactive dihydroxyeicosatrienoic acids by soluble epoxide hydrolase (sEH). Many studies have revealed that sEH gene deletion exerts protective effects against diabetes. Vascular calcification is a common complication of diabetes, but the potential effects of sEH on diabetic vascular calcification are still unknown. METHODS: The level of aortic calcification in wild-type and Ephx2-/- C57BL/6 diabetic mice induced with streptozotocin was evaluated by measuring the aortic calcium content through alizarin red staining, immunohistochemistry staining, and immunofluorescence staining. Mouse vascular smooth muscle cell lines (MOVAS cells) treated with β-glycerol phosphate (0.01 mol/L) plus advanced glycation end products (50 mg/L) were used to investigate the effects of sEH inhibitors or sEH knockdown and EETs on the calcification of vascular smooth muscle cells, which was detected by Western blotting, alizarin red staining, and Von Kossa staining. RESULTS: sEH gene deletion significantly inhibited diabetic vascular calcification by increasing levels of EETs in the aortas of mice. EETs (especially 11,12-EET and 14,15-EET) efficiently prevented the osteogenic transdifferentiation of MOVAS cells by decreasing nidogen-2 (NID2) expression. Interestingly, suppressing sEH activity by small interfering ribonucleic acid or specific inhibitors did not block osteogenic transdifferentiation of MOVAS cells induced by β-glycerol phosphate and advanced glycation end products. NID2 overexpression significantly abolished the inhibitory effect of sEH gene deletion on diabetic vascular calcification. Moreover, NID2 overexpression mediated by adeno-associated virus 9 vectors markedly increased insulin-like growth factor 2 (IGF2) and phospho-ERK1/2 expression in MOVAS cells. Overall, sEH gene knockout inhibited diabetic vascular calcification by decreasing aortic NID2 expression and, then, inactivating the downstream IGF2-ERK1/2 signaling pathway. CONCLUSIONS sEH gene deletion markedly inhibited diabetic vascular calcification through repressed osteogenic transdifferentiation of vascular smooth muscle cells mediated by increased aortic EET levels, which was associated with decreased NID2 expression and inactivation of the downstream IGF2-ERK1/2 signaling pathway.
Animals ; Mice ; Vascular Calcification/metabolism* ; Mice, Inbred C57BL ; Epoxide Hydrolases/metabolism* ; Diabetes Mellitus, Experimental/genetics* ; Male ; Gene Deletion ; MAP Kinase Signaling System/genetics* ; Cell Line ; Immunohistochemistry ; Muscle, Smooth, Vascular/metabolism* ; Signal Transduction/genetics* ; Mice, Knockout

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Chronic pain causes physical suffering and can have major psychological impacts in patients.Chronic pain can induce depressive disorder,and clinical studies have consistently shown that chronic pain and depression frequently co-occur,suggesting the possibility of shared pathogenic mechanisms underlying these conditions.Acupuncture,as an alternative therapy,has been widely used for analgesia and to treat depression,with demonstrated clinical efficacy.The therapeutic mechanism of acupuncture is related to neural and endocrine regulation.This review considers the mechanism of chronic pain accompanied by depression,in relation to the brain regions and neural circuits affected by acupuncture treatment.This review provides a new approach for the treatment of depression caused by chronic pain.

Chronic pain causes physical suffering and can have major psychological impacts in patients.Chronic pain can induce depressive disorder,and clinical studies have consistently shown that chronic pain and depression frequently co-occur,suggesting the possibility of shared pathogenic mechanisms underlying these conditions.Acupuncture,as an alternative therapy,has been widely used for analgesia and to treat depression,with demonstrated clinical efficacy.The therapeutic mechanism of acupuncture is related to neural and endocrine regulation.This review considers the mechanism of chronic pain accompanied by depression,in relation to the brain regions and neural circuits affected by acupuncture treatment.This review provides a new approach for the treatment of depression caused by chronic pain.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Objective:To investigate the risk factors and their early warning effectiveness for the occurrence of early neurological deterioration (END) in patients with moderate traumatic brain injury (modTBI).Methods:A retrospective cohort study was conducted to analyze the clinical data of 265 patients with modTBI admitted to the Second Affiliated Hospital of Fuyang Normal University from January 2018 to April 2023. There were 165 males and 100 females, with age range of 20-91 years [(59.5±14.4)years]. The patients were divided into END group ( n=46) (17.4%) and non-END group ( n=219) (82.6%) according to whether the Glasgow Coma Score (GCS) decreased by 2 points or more within 72 hours after injury. Data of the two groups were recorded, including gender, age, basic diseases (hypertension and diabetes), cause of injury (traffic injuries, falls, etc), vomiting before admission, admission GCS, first CT scan time, epilepsy, brain contusion, subarachnoid hemorrhage, types of intracranial hematoma (epidural, subdural, and intracerebral hematoma), types of fracture (skull base fracture and skull fracture), laboratory indicators [platelet count (PLT), blood potassium level, serum total calcium concentration, thrombin time (TT), prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), level of fibrinogen (FIB), and level of D-dimer. Correlations between above-mentioned indicators and occurrence of END among modTBI patients were assessed and the independent risk factors were revealed by univariate and multivariate binary Logistic regression analysis. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to evaluate the early-warning effectiveness of each risk factor for END. Results:Univariate analysis showed that admission GCS, first CT scan time, epidural hematoma, subdural hematoma, intracerebral hematoma, serum potassium level, FIB and D-dimer were statistically correlated with occurrence of END among modTBI patients ( P<0.05 or 0.01). Multivariate binary Logistic regression analysis showed that admission GCS≤10 points ( OR=0.53, 95% CI 0.34, 0.84, P<0.01), first CT scan time≤2.0 hours ( OR=0.58, 95% CI 0.37, 0.92, P<0.05), epidural hematoma ( OR=0.26, 95% CI 0.10, 0.69, P<0.05), intracerebral hematoma ( OR=0.14, 95% CI 0.04, 0.44, P<0.01), level of FIB≤2.3 g/L ( OR=0.34, 95% CI 0.18, 0.64, P<0.01), level of D-dimer>10.4 mg/L ( OR=1.04, 95% CI 1.02, 1.07, P<0.01) were independent risk factors for END among modTBI patients. ROC curve analysis showed that the first CT scan time had relatively higher early warning value (AUC=0.79, 95% CI 0.74, 0.84), level of D-dimer (AUC=0.75, 95% CI 0.70, 0.80) and level of FIB (AUC=0.70, 95% CI 0.65, 0.76) had moderate early warning value, which was higher than that of admission GCS (AUC=0.62, 95% CI 0.56, 0.68), intracerebral hematoma (AUC=0.62, 95% CI 0.56, 0.68) and epidural hematoma (AUC=0.60, 95% CI 0.54, 0.66). The combination of the risk factors revealed superior early warning efficiency for END (AUC=0.90, 95% CI 0.85, 0.93). Conclusions:Admission GCS≤10 points, first CT scan time≤2.0 hours, epidural hematoma, intracerebral hematoma, level of FIB≤2.3 g/L and level of D-dimer>10.4 mg/L are independent risk factors for END among modTBI patients. The early warning value of the first CT scan is the highest, followed by D-dimer and FIB, and the early warning effectiveness of admission GCS, intracerebral hematoma and epidural hematoma is ordinary.The combination of the above risk factors has better early warning efficiency for occurrence of END among modTBI patients.

Objective:To explore the effect of family empowerment scheme combined with cardiac rehabilitation guidance on patients with myocardial infarction after percutaneous coronary intervention (PCI) .Methods:Using the convenient sampling method, a total of 100 patients with myocardial infarction who underwent PCI in Affiliated Hospital of Jining Medical University from July 2018 to January 2020 were selected as the research objects. According to the random number table method, they were divided into the control group and the observation group, with 50 cases in each group. The control group was given cardiac rehabilitation guidance, while the observation group was given the family empowerment scheme combined with cardiac rehabilitation guidance. The scores of Chinese version of Family Caregiver Task Inventory (FCTI) and The World Health Organization Quality of Life (WHOQOL) -BREF (WHOQOL-BREF) were compared between the two groups before the intervention and after 3 months of the intervention.Results:After 3 months of intervention, scores of each dimension of the FCTI scale of family members of patients in two groups were lower than those before the intervention and the scores of family members of the observation group were lower than those of the control group, and the differences were statistically significant ( P<0.05) . The scores of each dimension of the WHOQOL-BREF in the observation group were higher than those before intervention and the score in the observation group were higher than that in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The family empowerment scheme combined with cardiac rehabilitation guidance is beneficial to improve the caring ability of family members of patients with myocardial infarction after PCI and improve quality of life of patients.

We conducted a randomized, open-label, parallel-controlled, multicenter trial on the use of Shuanghuanglian (SHL), a traditional Chinese patent medicine, in treating cases of COVID-19. A total of 176 patients received SHL by three doses (56 in low dose, 61 in middle dose, and 59 in high dose) in addition to standard care. The control group was composed of 59 patients who received standard therapy alone. Treatment with SHL was not associated with a difference from standard care in the time to disease recovery. Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group (93.4% vs. 73.9%, P = 0.006). Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia, which was evaluated by density reduction of inflammatory focus from baseline, at day 7 (mean difference (95% CI), -46.39 (-86.83 to -5.94) HU; P = 0.025) and day 14 (mean difference (95% CI), -74.21 (-133.35 to -15.08) HU; P = 0.014). No serious adverse events occurred in the SHL groups. This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.
COVID-19 ; Humans ; Medicine, Chinese Traditional ; Research ; SARS-CoV-2 ; Treatment Outcome

Objective To explore the diagnostic value of ESWAN in uterine fibroids by analyzing the ESWAN signal of uterine fibroid. Methods Conventional MRI and ESWAN were carried out in thirty-seven patients with uterine fibroids.The differences of ESWAN indexes between uterine fibroids and myometrium were analyzed by paired t-test.The value of ESWAN on diagnosing uterine fibroids was analyzed by receiver operating characteristic curve(ROC curve).Results The magnitude value,phase value,R2* value and T2*value of uterine fibroids were 1 661.69 ± 45.24,(0.006 7 ± 0.007 7)Hz,(26.69 ± 1.04)Hz and(34.68 ± 1.73)ms,respectively.The magnitude value,phase value,R2* value and T2* value of myometrium were 1 790.95 ± 49.04,(0.013 1 ± 0.011 8)Hz,(22.35 ± 0.84)Hz and(42.53 ± 2.16)ms.The magnitude value,phase value and T2* value of uterine fibroids were lower than those of myometrium (P=0.008,P=0.659 and P=0.002).While the R2* value of of uterine fibroids was higher than that of myometrium(P=0.001). The area under curve(AUC)of magnitude value,phase value,R2* value and T2* value were 0.604,0.553,0.666 and 0.662.Conclusion ESWAN can show the differences between uterine fibroids and myometrium ，while the ability to independently diagnose uterine fibroids was modest.

Objective:To investigate the clinicopathological characteristics and immunohistochemical features of tumor-infiltrating lymphocyte(TIL) in ovarian serous adenocarcinoma,and their clinical value.Methods:The immunohistochemistry was used to observe 68 ovarian serous adenocarcinomacases'immunohistochemical features,and their correlations with clinicopathological characteristics were analyzed.Results:There were 43 cases with a large amount of TIL infiltrating in the 68 cases of serous adenocarcinoma,account for 63.24％.There were significant differences on the with or without a large amount of TIL infiltrating among the different tumor grade,different clinical stage,and different CA125 level (P ＜ 0.05).The numbers of CD3 +,CD4 + and CD8 + TIL in the cancer nest were significantly less than those in the stroma,with significantly statistical difference (P ＜ 0.05),Meanwhile the ratio of CD4 +/CD8 + in the cancer nest was significantly less than that in the stroma(P＜0.05).The ratio of CD4 +/CD8 + in the cancer nest and stroma at stage Ⅲ and with poor differentiation was significantly lower than in those at stage Ⅰ-Ⅱ and with good differentiation(P＜0.05).Meanwhile the ratio of CD8 +/FoxP3 + Treg in the cancer nest was less than that in the stroma(P＜0.05).The ratio of CD8 +/FoxP3 + Treg in the cancer nest at stage Ⅲ and with poor differentiation tumor was significantly lower than in those at stage Ⅰ-Ⅱ and with good differentiation(P＜0.05).The expression of GzmB in the cancer nest at stage Ⅲ and with poor differentiation tumor was significantly lower than that in the cancer nest at stage Ⅰ-Ⅱ and with good differentiation tumor(P＜0.05).Conclusions:With or without a large amount of TIL is related to tumor grade,clinical stage,and CA125 level inovarian serous adenocarcinoma.The numbers of TIL in ovarian serous adenocarcinoma increase considerably,but mainly in the stroma,and which may be related to several factors such as tumor cell differentiation and clinical stage.