OBJECTIVE To investigate the mechanisms by which Pinggan Yishen Decoction(PGYSD)contributes to alleviating target organ damage in spontaneously hypertensive rats.METHODS The chemical components of PGYSD were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)and were analyzed by target a-nalysis and functional enrichment combined with network pharmacology methods to predict the potential mechanism of PGYSD in trea-ting hypertension and its target organ damage.Spontaneously hypertensive rats were randomly divided into the model group,low-dose PGYSD group(2 g·kg-1),high-dose PGYSD group(5 g·kg-1),and valsartan group(7.2 mg·kg-1),with 6 rats in each group.Wistar-Kyoto rats were used as the control group,and the control group and the model group were gavaged with normal saline for 8 consecutive weeks.HE and Masson staining were used to observe the pathological damage and fibrosis degree of rat heart and tho-racic aorta.Immunohistochemical staining and Western blot were used to detect the expression level of EGFR in the heart,liver and kidney of rats.Immunofluorescence staining was used to detect the co-localization of EGFR and EEA1 in the heart,liver and kidney of rats.RESULTS Twenty-six components of PGYSD were detected by UPLC-Q-TOF/MS.Network pharmacology revealed that EG-FR,PIK3R1 and EP300 may be key therapeutic targets of action of PGYSD for the treatment of hypertension and its target organ dam-age,and that the treatment of hypertension and its target organ damage by PGYSD may be closely related to EGFR tyrosine kinase in-hibitor resistance,lipids and atherosclerosis and HIF-1 signaling pathway.The high-dose group of PGYSD significantly reduced sys-tolic blood pressure and mean blood pressure in rats(P<0.05,P<0.01),attenuated pathological damage and fibrosis in the heart and thoracic aorta(P<0.01,P<0.001),significantly reduced the expression level of EGFR in the liver and kidney of rats(P<0.01),and treated fibrosis in liver and kidney,reduced the co-localization of EGFR and EEA1 in the kidney of rats(P<0.001),attenuated fibro-sis in kidney.CONCLUSION The paper integrates UPLC-Q-TOF/MS,network pharmacology and spontaneously hypertensive rat model and preliminarily explores the effect mechanism of PGYSD in the treatment of hypertension and its target organ damage,provi-ding a scientific basis for further mechanism research and clinical application of PGYSD in the treatment of hypertension.

Objective:To analyze the clinical characteristics and predictive factors of SSc associated heart disease.Methods:The clinical data of patients with SSc from January 2016 to December 2021 in Ningbo Medical Center Lihuili Hospital were collected. Aight healthy controls come from the medicial examination center. They were divided into a positive group and a negative group based on whether heart involvement was present or not. The clinical manifestations of the two groups were compared by t test, Wilcoxon signed rank test and χ2 test and Logistic regression or ROC curve was used to analyze the prognostic risk of SSc associated heart disease. Then the transcriptome sequencing was used to analyze the differential gene expression. Results:①A total of 75 SSc patients were treated in our hospital, of which 6 patients with overlap syndrome and 1 patient with congenital heart disease were excluded. The clinical data of 68 patients were analyzed including 16 patients in the positive group and 52 patients in the negative group. Among the 16 patients with cardiac involvement, 12 patients (75.0%) had abnormal electrocardiogram, 9 patients (56.2%) with heart valve disease, 8 patients (50.0%) with abnormal cardiac structure and 8 patients (50.0%) with pericardial effusion. The biomarkers were elevated in 10 cases (83.3%). ②Univariate analysis showed that the positive group had a longer course of disease [120(11.2, 132) months vs 48(24, 90)months, Z=-2.08, P=0.037], and the rate of pulmonary arterial hypertension (50.0% vs 11.5%, χ2=11.07, P<0.001) and renal insufficiency(50.0% vs 3.8%, χ2=20.78, P<0.001) in the positive group were significantly higher than those in the negative group. Further Logistic regression analysis revealed that long course of disease [ OR (95% CI) =1.011 (1.001, 1.021), P=0.031], pulmonary arterial hypertension [ OR (95% CI) =5.431, 95% CI (1.065, 27.710), P=0.042] and renal insufficiency [ OR (95% CI) =30.444 (4.139, 223.938), P<0.001] were risk factors for SSc associated heart disease. ③Nail-fold videocapillaroscopy (NVC) was checked in 63 patients. The difference of abnormal NVC changes between the two groups was statistically significant (93.3% vs 58.3%, χ2=5.87, P=0.013). The total number of capillaries in the positive group was significantly less than that in the negative group [3.5(2, 4.8) vs 6 (5, 7), Z=-2.97, P=0.003]. Further ROC curve analysis showed that the total number of capillaries less than 4.5 predicted the occurrence of cardiac involvement (sensitivity was 80.0%, specificity was 83.8%), and the area under the ROC curve (95% CI) was 0.805 (0.061, 1.000, P=0.003).④The transcriptome of a total of 11 SSc patients (including 6 in the positive group and 5 in the negative group) and 8 healthy controls were analyzed to obtain the synchronously down regulated gene TNFRSF13B. The differences between the three groups were statistically significant ( χ2=11.88, P=0.003), especially in the positive group and the healthy controls( χ2=11.19, P=0.004). Conclusion:SSc patients with long course of disease accompanied by PAH and renal insufficiency are prone to have heart involvement. Early capillary endoscopy is also helpful to predict the risk of heart involvement. Moreover, TNFRSF13B genetic testing is helpful but further study is needed.

Objective:To analyze the incidence and risk factors of postoperative new-onset atrial fibrillation(POAF) after lobectomy.Methods:A monocentric ambispective cohort study was conducted. The retrospective cohort included 1 902 patients who underwent lobectomy in our hospital between January 2017 and December 2019. The prospective cohort included 692 patients who underwent lobectomy in our hospital between August 2020 and July 2021. A total of 2 594 patients were enrolled in this study. The median age of enrolled patients was 61 years(interquartile range, 54-67 years), and the cohort consisted of 1 384(51.97%) females and 1 246(48.03%) males. Baseline and perioperative clinical data of enrolled patients were collected. Univariate and multivariate logistic regression analyses were performed to identify the risk factors related to POAF. Results:There was no patient died in hospital after surgery. A total of 111 cases of POAF were followed up during the postoperative hospital period, and the incidence of POAF was 4.28%. Multivariate regression analysis found that the elderly patients(aged 60 and above)( OR=1.58, 95% CI: 1.01-2.47, P=0.044), history of percutaneous coronary intervention( OR=2.50, 95% CI: 1.04-6.03, P=0.041), history of arrhythmia excluding atrial fibrillation/flutter( OR=3.96, 95% CI: 1.95-8.00, P<0.001), left upper lobectomy( OR=1.73, 95% CI: 1.11-2.68, P=0.015), low preoperative albumin level( OR=1.07, 95% CI: 1.00-1.14, P=0.048) and large cell neuroendocrine carcinoma( OR=4.70, 95% CI: 1.38-15.98, P=0.013) were independent risk factors for POAF after lobectomy. Conclusion:The incidence of POAF after lobectomy is 4.28% in this study. Elderly patients(aged 60 and above), history of percutaneous coronary intervention, history of arrhythmia excluding atrial fibrillation/flutter, left upper lobectomy, low preoperative albumin level, and large cell neuroendocrine carcinoma are the independent risk factors related to POAF after lobectomy.

Objective:To explore the efficacy and safety of in-class transition from proteasome inhibitor bortezomib to ixazomib in the treatment of newly-treated patients with multiple myeloma (MM).Methods:The clinical data of 63 newly-treated MM patients in Shenzhen Second People's Hospital from January 2018 to December 2020 were retrospectively analyzed. They were divided into transition group (23 cases) and bortezomib group (40 cases). Both groups were treated with bortezomib-containing regimen as the first-line treatment regimen. In case of intolerable adverse reactions, patients in the transition group were treated with ixazomib instead of bortezomib, while the patients in the bortezomib group did not undergo drug transition. The curative effect and progression-free survival (PFS) were compared between the two groups.Results:In the transition group, the overall response rate (ORR) before in-class transition was 95.7% (22/23), the rate of ≥ very good partial remission (VGPR) was 52.2% (12/23); the ORR after transition was 95.7% (22/23), and the rate of ≥ VGPR was 82.6% (19/23). In the bortezomib group, ORR was 90.0% (36/40), and the rate of ≥ VGPR was 72.5% (29/40). There was no significant difference in ORR and the rate of ≥VGPR between the two groups ( χ2 = 0.64, P=0.424; χ2 = 0.82, P = 0.364). The median number of cycles of PI therapy in the transition group was 9, and the median PFS time was not reached. The median number of cycles of PI therapy in the bortezomib group was 7.5, and the median PFS time was 30.0 months (95% CI 19.1-40.9 months), there was no significant difference in PFS between the two groups ( P = 0.275). In the bortezomib group, 12 patients discontinued bortezomib due to adverse reactions, the median PFS time was 20.0 months (95% CI 12.6-27.4 months), and the PFS of patients who discontinued PI in the transition group and the bortezomib group was compared, the difference was statistically significant ( P = 0.043). In the transition group, 21 patients (21/23, 91.3%) developed peripheral neuropathy, and the incidence of ≥grade 3 adverse reactions was 13.0% (3/23); in the bortezomib group, 22 patients (22/40, 55.0%) developed peripheral neuropathy, and the incidence of ≥grade 3 adverse reactions was 12.5% (5/40). Conclusions:For newly-treated MM patients, the transition from bortezomib to ixazomib can improve the depth of remission and reduce the recurrence caused by the discontinuation of PI.

Objective:To analyze the correlation between 1H-MRS in hippocampus and peripheral blood cytokines and T lymphocyte subsets in patients with temporal lobe epilepsy, and to explore the relationship between immune dysfunction and the degree of neuronal injury. Methods:Fifty patients with temporal lobe epilepsy were selected from Affiliated Hospital of Xuzhou Medical University from October 2020 to July 2021.Clinical data of all patients were collected and they were divided into two groups according to MRI results of epileptic sequence: abnormal hippocampal MRI group ( n=20) and normal hippocampal MRI group ( n=30). Bilateral 1H-MRS scanning of hippocampal and detection of T lymphocyte subsets and cytokines in peripheral blood during interictal period were performed in both groups. The levels of hippocampal metabolites NAA, NAA/(Cr+ Cho), T lymphocyte subsets and cytokines in peripheral blood of the two groups were compared.At the same time, the levels of NAA and NAA/ (Cr+ Cho) in the hippocampus on the abnormal side and the normal side in the abnormal hippocampal MRI group were compared within the group. Finally, the correlation between the levels of metabolites NAA, NAA/ (Cr+ Cho) in the hippocampus on the abnormal side obtained by 1H-MRS scanning and T lymphocyte subsets and cytokines in the abnormal group of MRI was analyzed. The data were statistically analyzed by SPSS 26.0 software. Independent sample t-test or Mann-Whitney U test was used for comparison between the two groups. Paired sample t-test was used for intra group comparison of different sides. Spearman correlation analysis was used to analyze the correlation between each index. Results:The NAA and NAA/(Cr+ Cho) values of the abnormal MRI group(normal side NAA: (1.22±0.37), NAA/(Cr+ Cho): (0.56±0.15). abnormal side NAA: (1.02±0.34), NAA/(Cr+ Cho): (0.48±0.13)) were significantly lower than those of the normal MRI group (NAA: (1.51±0.36), NAA/(Cr+ Cho): (0.73±0.19))(NAA: t=2.705, 4.800, both P<0 05; NAA/(Cr+ Cho): t=3.394, 4.914, both P<0 05). The values of NAA and NAA/(Cr+ Cho) in the abnormal side in the MRI abnormal group were significantly lower than those in the normal side( t=6.467, P<0 05). The levels of IL-1β(11.19(3.56, 20.98)pg/ml), IL-5 (3.12(1.86, 6.41)pg/ml), TNF-α(2.55(1.19, 8.28)pg/ml), CD4+ T lymphocytes((43.13±6.82)%) and Th/Ts((1.96±0.66)) in the hippocampal MRI abnormal group were significantly higher than those in normal MRI group (IL-1β: 3.27(1.63, 6.17)pg/ml, IL-5: 1.15(0.96, 2.96)pg/ml, TNF-α: 1.34(1.02, 2.36)pg/ml, CD4+ T: (38.01±7.21)%, Th/Ts: (1.48±0.53))( Z=-3.041, -2.516, -2.496, all P<0.05; t=2.511, 2.810, both P<0 05). The level of CD8+ T ((23.48±5.33)%) in peripheral blood of abnormal MRI group was significantly lower than that of normal group CD8+ T((27.18±6.08)%)( t=2.210, P<0.05). In the abnormal MRI group, the levels of NAA and NAA/ (Cr+ Cho) in the abnormal hippocampus were negatively correlated with the levels of IL-1β, IL-5 and TNF- α ( r=-0.612--0.463, all P<0.05), and positively correlated with CD8+ T lymphocytes ( r=0.537, 0.478, P<0.05). Conclusion:There is neuronal damage and dysfunction in the abnormal hippocampal region of patients with temporal lobe epilepsy with abnormal hippocampal formation, and the degree of neuronal damage is highly correlated with CD8+ T lymphocytes, IL-5, IL-1β and TNF-α in peripheral blood. The imbalance of interictal lymphocyte subsets and chronic inflammatory response may play an important role in the pathogenesis of epilepsy and neuronal injury .

Objective To study the effect of non-self-similar hierarchy on fracture mechanical properties and crack propagation of the biocomposite. Methods The numerical models were established by using ABAQUS, and the stiffness and crack initiation and propagation in the biocomposite with the inclination angles between the axis of the prism and mineralized collagen fibrils θ=0°,20°,40°,60°,80° were simulated by extended finite element method. Results The inclination angle θ had limited influences on biocomposite stiffness at θ≤40°, while biocomposite stiffness decreased with θ at θ>40°. The ultimate tensile strain also increased at θ>40°. Asymmetry in the crack was also found during propagation of matrix surrounded-enhanced phases at θ>0°. The crack propagatation on one side of the long axis of the mineral crystal was relatively easier than that on the other side at θ>0°. Conclusions The non-uniform distributions of cracks were found in biological hard tissues arisen from the non-self-similar hierarchy. The non-uniform crystal arrangement in the biocomposite would result in local damage rather than catastrophic fracture. The findings of this study can provide theoretical support for material design.

Objective: To review and discuss the experience of diagnosis and treatment of adrenal ganglioneuroma. Methods: Clinical data of 80 cases of adrenal ganglioneuroma undergoing surgery during January 1982 to May 2017 at Peking Union Medical College Hospital were retrospectively analyzed. There were 36 male and 44 female patients. Age ranged from 8 to 69 years old (mean 37.7 years old). The tumor diameter were 1.5 to 18.0 cm (mean 4.3 cm). There were 61 cases of adrenal ganglioneuroma diagnosed by imaging examination. All patients underwent adrenalectomy. Results: All procedures were performed successfully without serious complication. Including 15 open surgery and 64 retroperitoneal laparoscopic surgery. One laparoscopic case conversion to open surgery. The pathological diagnosis was adrenal ganglioneuroma. Fifteen cases were mixed with other tumor components. No recurrence or metastasis was observed during the follow-up of 2 months to 35 years. Conclusions The diagnostic techniques for adrenal ganglioneuroma are helpful to judge the tumor property before operation. The laparoscopic surgery has become the current method for resecting tumors. It shows advantages of small trauma and speedy recovery. The relationship between tumor and surrounding tissues should be understand clearly before operation. Full preparation must be made before operation if adrenal ganglioneuroma mixed with other tumor components.

Objective:To optimize the paper-roasted technology of Aucklandiae Radix. Methods:With methanol-water (65: 35) as the mobile phase, the contents of costunolide and dehydrocostuslactone were determined by HPLC. Senna was used to make diarrhea model in mice, and the sample decoction was administered for the mice by i. g at the dose of 10 g·kg-1 and the diarrhea index was de-termined. The paper-roasted technology of Aucklandiae Radix was optimized by L9 (34 ) orthogonal design taking the contents of cost-unolide and dehydrocostuslactone, and the diarrhea index in mice as the indices with the paper-roasted time, the paper-roasted temper-ature and the layer number as the influencing factors. Results:The variance analysis results show that the layer number and the paper-roasted temperature has the significant impact on the contents of costunolide and dehydrocostuslactone and the diarrhea index in mice. The best paper-roasted technology of Aucklandiae Radix was as follows:a layer of paper was covered by 4mm Aucklandiae Radix and repeated the same operation 5 times, and put them in drying baker at 120℃ for about 2 hours. After the essential oil of Aucklandi-ae Radix permeated on the paper with burnt flavor and dark brown in color, Aucklandiae Radix could be taken out. Conclusion:The optimum paper-roasted technology of Aucklandiae Radix is reasonable and feasible, which can provide reference for the establishment of the quality standard for paper-roasted Aucklandiae Radix pieces and the expanding of the clinical application.

Objective A classification for hepatic venous outflow obstruction after piggyback liver transplantation (PBLT) and its clinical significance.Methods We conducted a retrospective study on 248 patients who underwent liver transplantation from May 2000 to August 2006.The aims were to elucidate the causes and treatment of postoperative venous outflow obstruction.Results Venous outflow obstruction occurred in 38 patients after transplantation.Among those,2 (5.26％) had superior hepatic inferior vena cava (IVC) stenosis,13 (34,21％) had the hepatic vein anastomosis twisted at an angle,7 (18.42％) had IVC stenosis at the posthepatic segment,and 16 (42.10％) had outflow obstruction at the hepatic veins.In these 38 patients,34 underwent PBLT,2 underwent APBLT,and 2 COLT.Most patients with hepatic venous outflow obstruction improved with surgical treatment and interventional therapy.Conclusions Hepatic vein outflow obstruction was associated with the technique of hepatic vein anastomosis,the type of cavocaval anastomosis and graft size mismatch between the donor and the recipient.Performing piggyback liver transplantation according to the classification of hepatic vein and appropriate treatments could improve the prognosis of venous outflow obstruction in clinical practice.

Objective To investigate the diagnosis and treatment of renal neoplasm with calcification .Methods Retrospectively summarized the clinical data of the 2 patients with calcific renal neoplasm admitted in our hospital from the May to July in 2014, then analyzed and discussed the clinical manifestations , diagnosis and treatment com-bined with the literatures .Results The two cases were both suspected of renal malignant tumor preoperatively .The case 1 was a 32-year-old male , laparoscopic partial resection of the left kidney was performed , and the postoperative pathology was clear cell carcinoma (Fuhrman levelⅠ).The case 2 was a 18-year-old male, partial resection of the right kidney was performed because of the tumor size , and the postoperative pathology was adult nephroblastoma . Conclusions The calcific renal neoplasm is a rare disease , the property determination depends on postoperative pa-thology, and as to the choice of surgical method , the patients'age, the tumor size and the tumor location should be taken into consideration , and intraoperative frozen should be performed when necessary .