Objective To investigate the relationship of miRNA gene polymorphisms with blood pressure(BP)responses to the sodium and potassium diet intervention.Methods In 2004,we recruited 514 participants from 124 families in seven villages of Baoji,Shaanxi Province,China.All subjects were given a three-day normal diet,followed by a seven-day low-salt diet,a seven-day high-salt diet,and finally a seven-day high-salt and potassium supplementation.A total of 19 miRNA single nucleotide polymorphisms(SNPs)were selected for analysis.Results Throughout the sodium-potassium dietary intervention,the BP of the subjects fluctuated across all phases,showing a decrease during the low-salt period and an increase during the high-salt period,followed by a reduction in BP subsequent to potassium supplementation during the high-salt diet.MiR-210-3p SNP rs 12364149 was significantly associated with systolic BP(SBP),diastolic BP(DBP)and mean arterial pressure(MAP)responses to low-salt diet.MiR-4638-3p SNP rs6601178 was significantly associated with SBP while miR-26b-3p SNP rs115254818 was significantly associated with MAP responses to low-salt intervention.In addition,miR-26b-3p SNP rs115254818 was significantly correlated with SBP,DBP and MAP responses to high-salt intervention.MiR-1307-5p SNPs rs1 1191676 and rs2292807 were associated with SBP and MAP responses to high-salt diet.MiR-4638-3p SNP rs6601178,miR-210-3p SNP rs12364149,miR-382-5p SNP rs4906032 and rs4143957 were significantly associated with SBP response to high-salt diet.In addition,miR-26b-3p SNP rs115254818 was significantly associated with SBP,DBP and MAP responses to potassium supplementation.MiR-1307-5p SNPs rs11191676,rs2292807,and miR-19a-3p SNP rs4284505 were significantly associated with SBP responses to high-salt and potassium supplementation.Conclusion miRNA gene polymorphisms are associated with BP response to sodium and potassium,suggesting that miRNA genes may be involved in the pathophysiological process of salt sensitivity and potassium sensitivity.

Objective We aimed to investigate the relationship between microscopic pattern of blood stasis and renal pathological grade and related physical and chemical indexes in children with Henoch-Sch?nlein purpura nephritis(HSPN).Methods We conducted a retrospective analysis of 800 HSPN children from the medical records of the First Affiliated Hospital of Henan University of Chinese Medicine.Laboratory indicators(blood routine test,urine routine test,coagulation test,liver function)and renal pathological indicators of them were collected.According to the severity of renal pathological microscopic lesions,the microscopic pattern of blood stasis was divided into three types,including choroidal discord,dead blood coagulation and intracarenal disease accumulation.The classification of renal microscopic pattern of blood stasis and the correlation between laboratory indexes and renal pathological index were analyzed by Spearman grade correlation and binary Logistic regression analysis.Results(ⅰ)There was no statistical difference of the distribution of the renal microscopic pattern of blood stasis in the different traditional Chinese medicine patterns.(ⅱ)There were significant differences in the contents or the grade of albumin and fibrinogen in the HSPN children with different microscopic pattern of blood stasis(all P＜0.05).(ⅲ)The maximum area under the receiver operating characteristic(ROC)curve between fibrinogen and intracarenal disease accumulation was 0.594(95％CI from 0.540 to 0.633,P＜0.001);sensitivity was 0.447,specificity was 0.725;the best threshold on the ROC curve of 0.172 was 3.755 g/L.(ⅳ)There were positive correlations between the content of fibrinogen,ISKDC grade and Bohle A grade respectively with the scores of intracarenal disease accumulation type(r=0.176,r=0.315,r=0.656;all P＜0.001).(ⅴ)There were positive correlations between the content of fibrinogen,ISKDC grade and Bohle A grade respectively with the renal microscopic pattern of blood stasis(r=0.157,r=0.377,r=0.429;all P＜0.001).Conclusion The microscopic renal pattern of blood stasis can not only reflect the severity of renal blood stasis,but also reflect the severity and long-term prognosis of renal diseases.Albumin and urinary protein grade can reflect the early stage of the microscopic renal pattern of the blood stasis(choroidal discord).The content of fibrinogen increases with the aggravation of renal microscopic pattern of blood stasis,reflecting the end-stage of HSPN,which has the correlation with the formation and severity of related indexes.Fibrinogen can be used as a laboratory indicator to assist in the diagnosis of irreversible lesionsin the renal pathology of HSPN children.

Objective We investigated the effects of Xueguan Ruanhua Pills(XGRHW) on ferroptosis in ApoE-/- atherosclerotic mice through the nuclear factor E2 related factor 2 (Nrf2)/xCT/glutathione peroxidase 4 (GPX4) signaling pathway.Methods Ten male C57BL/6J mice in the normal group were fed normal chow. Additionally, 50 ApoE-/- mice were fed high-fat chow for 12 weeks, and were divided into the following five groups (10 mice per group): the model group, the XGRHW low-dose (2.34g/kg) group, the XGRHW high-dose (4.68 g/kg) group, the XGRHW high-dose combined with the Nrf2 inhibitor ML385 (0.03 g/kg) group, and the ferrostatin-1 (1 mg/kg) group. Drugs were administered for 6 weeks. The blood levels of four types of lipids were detected by an automatic lipid analyzer, lipid deposition in the aorta was observed by Oil Red O staining, histomorphological changes in the aortic sinus were observed by HE staining, the serum levels of Fe2+, MDA, GSH, and SOD were determined by colorimetric assays, and the expression levels of FTH1 and FTL in the aortic sinus were observed by immunofluorescence. The protein levels of Nrf2, xCT, and GPX4 in mouse aortic tissues were detected by Western blotting. The ultrastructural changes of aortic mitochondria were observed by transmission electron microscopy.Results Compared with the normal group, mice in the model group showed obvious lipid plaque deposition in the aorta, severely calcified lesions in the aortic sinus, elevated serum levels of TC, TG, LDL-C, Fe2+, and MDA, decreased levels of HDL-C, SOD, and GSH (P<0.01), and decreased protein expressions of aortic Nrf2, xCT, and GPX4 as well as the iron storage proteins FTH1 and FTL (P<0.01), and serve damage to mitochondrial structure and morphology. Compared with the model group, the relative aortic plaque area was decreased, calcified lesions in the aortic sinus were decreased, serum levels of TC, TG, LDL-C, Fe2+, and MDA were decreased, and HDL-C, SOD, and GSH levels were increased in the XGRHW low-dose and high-dose and ferrostatin-1 groups (P<0.05 or P<0.01), and Nrf2, xCT, GPX4, and the iron storage proteins FTH1 and FTL were upregulated in aortic tissues (P<0.05 or P<0.01), and mitochondrial structure approaching normal. In the XGRHW high-dose+ML385 group, compared with the XGRHW high-dose group, the levels of blood lipids and lipid peroxidation were increased and the protein levels of Nrf2, xCT, and GPX4 in aortic tissue and the iron storage proteins FTH1 and FTL were decreased (P<0.01), and mitochondrial structure was damaged indicating that ML385 could inhibit the therapeutic effect of the XGRHW in atherosclerotic mice.Conclusion The XGRHW can improve blood lipid levels and reduce the degree of arterial plaque lesions in atherosclerotic mice, and its mechanism of action may be related to activation of the Nrf2/xCT/GPX4 pathway to inhibit ferroptosis.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment landscape for chronic myeloid leukemia (CML). However, TKI resistance poses a significant challenge, leading to treatment failure and disease progression. Resistance mechanisms include both BCR::ABL1-dependent and BCR::ABL1-independent pathways. The mechanisms underlying BCR::ABL1 independence remain incompletely understood, with CML cells potentially activating alternative signaling pathways, including the AKT/mTOR and JAK2/STAT5 pathways, to compensate for the loss of BCR::ABL1 kinase activity. This study explored tumoral VISTA (encoded by VSIR) as a contributing factor to TKI resistance in CML patients and identified elevated tumoral VISTA levels as a marker of resistance and poor survival. Through in vitro and in vivo analyses, we demonstrated that VSIR knockdown and the application of NSC-622608, a novel VISTA inhibitor, significantly impeded CML cell proliferation and induced apoptosis by attenuating the AKT/ mTOR and JAK2/STAT5 pathways, which are crucial for CML cell survival independent of BCR::ABL1 kinase activity. Moreover, VSIR overexpression promoted TKI resistance in CML cells. Importantly, the synergistic effect of NSC-622608 with TKIs offers a potent therapeutic avenue against both imatinib-sensitive and imatinib-resistant CML cells, including those harboring the challenging T315I mutation. Our findings highlight the role of tumoral VISTA in mediating TKI resistance in CML, suggesting that inhibition of VISTA, particularly in combination with TKIs, is an innovative approach to enhancing treatment outcomes in CML patients, irrespective of BCR::ABL1 mutation status. This study not only identified a new pathway contributing to TKI resistance but also revealed the possibility of targeting tumoral VISTA as a means of overcoming this significant clinical challenge.

With the increasing number of cancer patients, the aging population, the shortage of medical resources and other problems in China, the demand for palliative care is gradually increasing. However, nursing staff are the main implementors of palliative care, and their cognitive level of palliative care is closely related to the quality of palliative care service and the outcome of patients. By summarizing assessment tools of palliative care knowledge, attitudes and skills, this review aims to provide a reference for developing appropriate palliative care assessment tools for nursing staff in China.

【Objective】 Corin, a transmembrane serine protease that can cleave atrial natriuretic peptide precursor (pro-ANP) into atrial natriuretic peptide with smaller bioactive molecules, participates in the pathophysiological process of hypertension and cardiac hypertrophy. The purpose of this study was to explore the relationship of Corin gene variation with blood pressure responses to sodium and potassium dietary interventions. 【Methods】 In 2004, we recruited 514 participants from 124 families in 7 villages of Baoji, Shaanxi Province, China. All the subjects received a 3-day normal diet, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Fifteen single nucleotide polymorphisms (SNPs) of Corin gene were selected for final analysis. 【Results】 SNPs rs12509275 were significantly associated with diastolic blood pressure (DBP) response to low-salt diet, while rs3749584 was associated with pulse pressure (PP) response to low-salt diet.SNP rs3749584 and rs10517195 were significantly associated with PP response to high-salt diet. In addition,rs17654278 were significantly associated with systolic blood pressure (SBP) response to high-salt and potassium supplementation, rs2271037 was significantly correlated with DBP responses to high-salt and potassium supplementation, and rs4695253, rs12509275, rs2351783, rs36090894 were significantly associated with PP response to high-salt and potassium supplementation. 【Conclusion】 Corin gene polymorphisms were associated with blood pressure response to sodium and potassium, suggesting that Corin gene may be involved in pathophysiological process of salt sensitivity and potassium sensitivity.

Objective:To summarize initial experience of applying nanopore third-generation sequencing detection method (nanopore sequencing) for genetic diagnosis of non-classical 21 hydroxylase deficiency (NC 21-OHD), and to explore its performance and application prospects.Methods:Clinical data of the two NC 21-OHD patients, who were hospitalized at the First Affiliated Hospital of Zhengzhou University in May 2019, were collected. Peripheral venous blood was collected and genome DNA extracted. Genetic variants was detected by nanopore sequencing and underwent bioinformatic analysis. Pathogenetic mutations in CYP21A2 gene were validated with PCR-sanger sequencing in the two patients and their parents.Results:The average reads length and sequence depth in the patient one was 12, 792 bp and 27.19×. The average reads length and sequence depth in the patient two was 13, 123 bp and 21.34×. Compound variants of c.293-13C>G/c.844G>T (p.Val282Leu) and c.332_339delGAGACTAC (p.Gly111Valfs)/c.844G>T (p.Val282Leu) were detected in these two patients, which were consistent with clinical phenotype of NC 21-OHD. Further analysis showed that c.293-13C>G mutation was inherited from her father and c.844G>T (p.Val282Leu) mutation was inherited from her mother for the patient one. The c.844G>T (p.Val282Leu) mutation was inherited from her father and c.332_339delGAGACTAC (p.Gly111Valfs) mutation from her mother.Conclusions:The heterozygous mutations in CYP21A2 gene are the cause of NC 21-OHD in these two patients. Nanopore sequencing technique is a reliable new detection method for patients with NC 21-OHD.

Objective To investigate the onset of liver inflammation and related predictive factors in patients with HBeAg-positive chronic hepatitis B virus (HBV) infection who have normal alanine aminotransferase (ALT) and a high viral load. Methods A retrospective analysis was performed for the clinical data of 183 patients with HBeAg-positive chronic HBV infection who had normal ALT and a high viral load and were treated from October 2008 to May 2015, and according to the results of liver biopsy, they were divided into hepatitis group and non- hepatitis group. The t -test or Mann-Whitney U testwas used for comparison of normally distributed continuous data between groups, the chi-square test was used for comparison of categorical data. The predictive factors were analyzed by univariate binary logistic regression, the multivariate binary logistic regression was carried out by stepback method, and the cut-off values were analyzed by receiver operating characteristic curve (ROC) and Jordan index. Results There were 37 patients (20.2%) in the hepatitis group and 146 patients (79.8%) in the non-hepatitis group. Compared with the non-hepatitis group, the hepatitis group had a significantly lower proportion of male patients (45.9% vs 68.5%, χ 2 =6.508, P =0.011), a significantly higher level of aspartate aminotransferase [24 (21.25~35.55) U/L vs 21.2 (18.08~ 24.65) U/L, Z =-3.344, P =0.001], and a significantly lower log(HBsAg) value [4.4(4.28~4.49) vs 4.46(4.4~4.74), Z =-2.184, P =0.029]. Log(HBsAg) value was a predictive factor for hepatitis (odds ratio=0.077, P =0.017), and the cutoff value of HBsAg was 33884.4I U/mL. Conclusion Among the patients with HBeAg-positive chronic HBV infection who have normal ALT and a high viral load, 20.2% have liver inflammation, and HBsAg may be a predictive factor for liver inflammation.

Objective:To study the use of primary continuous single-layer pancreaticojejunostomy after linear stapler closure of pancreatic neck in pancreaticoduodenectomy (PD).Methods:The clinical data of 21 patients who were treated with primary continuous single-layer pancreaticojejunostomy after linear stapler closure of pancreatic neck in PD at Beijing Chaoyang Hospital Affiliated, West Campus, Capital Medical University, Rizhao Hepatobiliary-pancreatic-splenic Surgery Research Institute, Binzhou Second People’s Hospital, Chaoyang Central Hospital from February 2022 to May 2022 were retrospectively analyzed. There were 12 males and 9 females, with ages ranging from 31.0 to 82.0 years (median age 63.0 years). The success rates of linear stapling at pancreatic neck, time of pancreaticojejunostomy, postoperative complications, pancreatic fistula risk score, and length of hospital stay were studied.Results:Among the 21 patients, there were 3 patients who underwent open PD and 18 patients who underwent laparoscopic PD. Primary continuous single-layer pancreaticojejunostomy after linear stapler closure of pancreatic neck was successfully carried out in all these patients. The success rate was 100.0%. The success rate of finding pancreatic ducts at the pancreatic stumps and inserting an drainage tube was 100.0%(21/21). In the 3 patients who underwent open PD, the operation time were 230.0, 245.0 and 250.0 minutes respectively. The time for completing pancreaticojejunostomy were 12.0, 13.0 and 12.0 minutes respectively. The estimated blood loss were 300.0, 450.0 and 600.0 ml respectively. The length of hospital stay were 14.0, 15.0 and 21.0 days. In the 18 patients who underwent laparoscopic PD, the operation time was (295.9±14.5) min, the time for constructing pancreaticojejunostomy was (22.3±1.5) min, the blood loss was (180.0±40.0) ml, the length of hospital stay ranging from 8.0 to 16.0 days (median 10.5 days). Among all the 21 patients, the pancreatic fistula risk score was (4.7±1.5). Postoperative acute pancreatitis occurred in 3 patients (14.3%), delayed gastric emptying occurred in 4 patients (19.0%), and all of them recovered after conservative treatment. There was no postoperative bleeding, nosocomial infection, grade B and C postoperative pancreatic fistula or perioperative death.Conclusion:The continuous single-layer pancreaticojejunostomy after linear stapler closure of the pancreatic neck was safe, reliable, simple and technically easy. It has the potential to prevent clinical postoperative pancreatic fistula and pancreaticojejunostomy bleeding. It is worth to popularize this surgical procedure.

Objective To compare clinical and pathological features between autoimmune hepatitis (AIH) patients with positive and negative autoantibodies, and to summarize the experience in diagnosis. Methods A retrospective analysis was performed for the patients who attended Beijing Ditan Hospital from January 2010 to August 2021 and were diagnosed with AIH by liver histopathology, and according to the presence or absence of autoantibodies, they were divided into positive autoantibody group and negative autoantibody group. The two groups were compared in terms of biochemical parameters, immunological features, histopathological features, disease stage, and clinical symptoms and signs. The t -test or the Mann-Whitney U test was used for comparison of continuous data between groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data. Results A total of 110 patients were enrolled, among whom 78 (71%) had positive autoantibodies and 32 (29%) had negative autoantibodies. Anti-nuclear antibody (ANA), anti-mitochondrial antibody (AMA), and anti-smooth muscle antibody (ASMA) were the main autoantibodies detected, and of all 110 patients, 74 (67.27%) had positive ANA, 1 (0.91%) had positive AMA, 5 (4.55%) had positive ASMA, and 14 (12.73%) had positive anti-Ro-52 antibody. As for clinical and immunological features, compared with the positive autoantibody group, the negative autoantibody group had significantly lower incidence rates of jaundice of the skin and sclera (21.90% vs 50.00%, χ 2 =7.377, P =0.007) and poor appetite (18.80% vs 41.00%, χ 2 =4.979, P =0.026) and significantly lower median levels of direct bilirubin [7.30(4.05~12.10) μmol/L vs 16.80(6.48~69.75) μmol/L, Z =-2.304, P =0.021], IgG [16.40(13.15~18.05) g/L vs 20.30(16.00~27.15) g/L, Z =-2.715, P =0.007], and GLo [30.60(26.00~34.90) g/L vs 37.30(30.50~42.50) g/L, Z =-3.356, P =0.001]. In terms of liver histopathology, compared with the negative autoantibody group, the positive autoantibody group had a significantly higher proportion of patients with lymphocyte infiltration (91.03% vs 68.75%, χ 2 =6.997, P =0.008) and plasma cell infiltration (82.05% vs 50.00%, χ 2 =11.572, P =0.001); compared with the ANA-negative patients, the ANA-positive patients had significantly higher inflammation grade (G1-G4) (9.46%/16.22%/44.59%/29.73% vs 5.56%/27.78%/63.89%/2.78%, Z =-2.179, P =0.029) and fibrosis degree (S1-S4) (37.84%/25.68%/32.43%/4.05% vs 13.89%/41.67%/30.56%/13.89%, Z =-0.082, P =0.037). Conclusion Compared with AIH patients with positive autoantibodies, AIH patients with negative autoantibodies are mostly in the early stage of the disease and tend to have a low level of IgG, with a relatively high rate of missed diagnosis in clinical practice. Early and active liver biopsy is of particular importance.