[Advances in warfarin's anticoagulation therapy in Chinese population after mechanical valve replacement].

Warfarin is an irreplaceable oral anticoagulant for patients with mechanical heart valves, the stable pharmacogenetic-based warfarin dose prediction algorithms have improved the effectiveness and safety of warfarin anticoagulation therapy. Genetic factors are the main factors affecting the stable dose of warfarin. Single nucleotide polymorphisms such as VKORC1 and CYP2C9 affect the anticoagulation effect of warfarin through pharmacodynamic or pharmacokinetic pathways. Age, body surface area, combined use of drugs, and other nongenetic factors also affect the stable dose of warfarin. Previously published algorithms for warfarin dose prediction included mainly the white race, and most algorithms were constructed using traditional multiple linear regression. However, domestic studies have used machine learning methods to construct warfarin dose prediction algorithms based on the Chinese Han post-mechanical valve replacement population and have achieved better prediction efficiency. This article reviews the advances of warfarin anticoagulation influencing factors and the clinical application of stable dose prediction algorithms.

Safety and immunogenicity of a subtype C ALVAC-HIV (vCP2438) vaccine prime plus bivalent subtype C gp120 vaccine boost adjuvanted with MF59 or alum in healthy adults without HIV (HVTN 107): A phase 1/2a randomized trial.

BACKGROUND: Adjuvants are widely used to enhance and/or direct vaccine-induced immune responses yet rarely evaluated head-to-head. Our trial directly compared immune responses elicited by MF59 versus alum adjuvants in the RV144-like HIV vaccine regimen modified for the Southern African region. The RV144 trial of a recombinant canarypox vaccine vector expressing HIV env subtype B (ALVAC-HIV) prime followed by ALVAC-HIV plus a bivalent gp120 protein vaccine boost adjuvanted with alum is the only trial to have shown modest HIV vaccine efficacy. Data generated after RV144 suggested that use of MF59 adjuvant might allow lower protein doses to be used while maintaining robust immune responses. We evaluated safety and immunogenicity of an HIV recombinant canarypox vaccine vector expressing HIV env subtype C (ALVAC-HIV) prime followed by ALVAC-HIV plus a bivalent gp120 protein vaccine boost (gp120) adjuvanted with alum (ALVAC-HIV+gp120/alum) or MF59 (ALVAC-HIV+gp120/MF59) or unadjuvanted (ALVAC-HIV+gp120/no-adjuvant) and a regimen where ALVAC-HIV+gp120 adjuvanted with MF59 was used for the prime and boost (ALVAC-HIV+gp120/MF59 coadministration). METHODS AND FINDINGS: Between June 19, 2017 and June 14, 2018, 132 healthy adults without HIV in South Africa, Zimbabwe, and Mozambique were randomized to receive intramuscularly: (1) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/MF59 (months 3, 6, and 12), n = 36; (2) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/alum (months 3, 6, and 12), n = 36; (3) 4 doses of ALVAC-HIV+gp120/MF59 coadministered (months 0, 1, 6, and 12), n = 36; or (4) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/no adjuvant (months 3, 6, and 12), n = 24. Primary outcomes were safety and occurrence and mean fluorescence intensity (MFI) of vaccine-induced gp120-specific IgG and IgA binding antibodies at month 6.5. All vaccinations were safe and well-tolerated; increased alanine aminotransferase was the most frequent related adverse event, occurring in 2 (1.5%) participants (1 severe, 1 mild). At month 6.5, vaccine-specific gp120 IgG binding antibodies were detected in 100% of vaccinees for all 4 vaccine groups. No significant differences were seen in the occurrence and net MFI of vaccine-specific IgA responses between the ALVAC-HIV+gp120/MF59-prime-boost and ALVAC-HIV+gp120/alum-prime-boost groups or between the ALVAC-HIV+gp120/MF59-prime-boost and ALVAC-HIV+gp120/MF59 coadministration groups. Limitations were the relatively small sample size per group and lack of evaluation of higher gp120 doses. CONCLUSIONS: Although MF59 was expected to enhance immune responses, alum induced similar responses to MF59, suggesting that the choice between these adjuvants may not be critical for the ALVAC+gp120 regimen. TRIAL REGISTRATION: HVTN 107 was registered with the South African National Clinical Trials Registry (DOH-27-0715-4894) and ClinicalTrials.gov (NCT03284710).

[Analysis of the therapeutic effect of aspiration thrombectomy for early carotid stent thrombosis].

Objective: To investigate the clinical characteristics and the efficacy of thrombus aspiration in patients with early intrastent thrombosis (EST) following carotid artery stenting (CAS). Methods: This study is a retrospective case series, collecting clinical data of five patients who developed EST after CAS in the Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University from January 2021 to September 2023.All patients were male, with an age of (64.0±11.9) years (range:48 to 77 years), accounting for 2.0% (5/244) of CAS procedures during the same period.Among them, three patients did not receive standard dual antiplatelet therapy before the procedure, and one had an inadequate ADP inhibition rate (45.6%).Four patients received XACT carotid stents, while one received a Wallstent carotid stent.All five patients showed significant residual stenosis ranging from 43% to 55% after CAS.Emergency thrombus aspiration was performed in all cases, and data regarding perioperative conditions, vascular patency, and clinical outcomes were collected. Results: The interval between CAS and the occurrence of EST ranged from 3 hours to 14 days.The main clinical symptoms included sudden onset of consciousness disorders and contralateral limb weakness.None of the patients received preoperative intravenous thrombolysis, and thrombus aspiration was performed during the procedure to restore vascular patency.Four cases underwent balloon angioplasty during the procedure, and two cases utilized overlapping stents.Two patients experienced intraoperative embolization of thrombus to the C2 segment.In one case, the embolized thrombus was retrieved using an intracranial thrombectomy stent, while in another case, it was aspirated using a guiding catheter.Postoperatively, all patients had a thrombolysis in cerebral infarction grade of 3, and symptoms improved in four cases.One patient showed no improvement in symptoms, and MRI revealed extensive new infarction in the right frontal and insular regions, adjacent to the right lateral ventricle.Regular follow-up examinations after discharge did not reveal restenosis or embolism within the stent.The follow-up period ranged from 7.6 to 21.2 months, with modified Rankin scale scores of 0 to 1 point in four cases and 2 points in one case, indicating good recovery in all patients. Conclusions: Acute intrastent thrombosis is a rare complication after carotid artery stenting.The combined use of percutaneous thrombus aspiration and endovascular techniques, such as balloon angioplasty and stent overlapping, can rapidly restore vessel patency with favorable outcomes.However, further large-scale clinical studies are needed to confirm the effectiveness of these treatments for acute intrastent thrombosis.

[Comparison of robotic-assisted single-incision-plus-one-port laparoscopic pyeloplasty and single-incision laparoscopic pyeloplasty in the treatment of pediatric ureteropelvic junction obstruction].

Objective: To compare the efficacy of robotic-assisted single-incision-plus- one-port laparoscopic pyeloplasty (R-SILP+1) with single-incision laparoscopic pyeloplasty (SILP) in pediatric ureteropelvic junction obstruction (UPJO). Methods: The clinical data of 47 children with UPJO who underwent surgery from October 2020 to September 2022 in the Department of Pediatric Surgery of Fujian Provincial Hospital were retrospectively analyzed. According to the surgical method chosen by parents, the children were divided into R-SILP+1 group and SILP group. Baseline data, operative time, intraoperative anastomosis time, volume of blood loss, postoperative hospitalization time, complications, total costs, preoperative and postoperative renal parenchymal thickness (PT), anterior posterior diameter of renal pelvis (APD), and differential renal function (DRF) before and after operation were compared between the two groups, and the clinical efficacy of the two kinds of operation was evaluated. Results: Among the 47 children, 27 were in R-SILP+1 group, including 16 males and 11 females, aged (6.6±3.5) years; 20 were in SILP group, including 12 males and 8 females, aged (6.5±3.5) years. The operations were successful in both groups without conversion to open operation. There were no significant differences between the two groups in baseline data, volume of blood loss, complications, APD and PT at postoperative 6 months, APD, PT and DRF at postoperative 12 months (all P>0.05). Compared with the SILP group, the operative time [(153.0±14.4) vs (189.9±32.6) minutes, P<0.001], intraoperative anastomosis time [(68.8±16.8) vs (97.5±12.0) minutes, P<0.001], postoperative hospitalization time [(6.0±1.3) vs (9.0±1.3) d, P<0.001] were shorter, but the total cost was higher[(57 390±7 664) vs (30 183±4 219) yuan RMB, P<0.001]. Conclusions: Compared with the SILP group, R-SILP+1 can achieve considerable efficacy in treating pediatric UPJO, and has certain advantages in shortening operative time, intraoperative anastomosis time, and postoperative hospitalization time. However, the cost is high.

Associations between abdominal obesity indices with hypertension in type 2 diabetes mellitus: Chinese visceral adiposity index.

PURPOSE: This research was performed to evaluate the relationship between hypertension (HTN) and abdominal obesity index in patients with type 2 diabetes mellitus (T2DM). METHODS: Totally 1657 participants with T2DM (mean age 54 ± 12 years; 38.02% female) were enrolled. They were divided into the groups of HTN (n = 775) and non-HTN (n = 882). Anthropometric and biochemical indicators were measured and collected. A bioelectrical impedance analyzer was used to measure visceral and subcutaneous fat areas. RESULTS: Compared with the HTN group, the non-HTN group had a lower level of Chinese visceral adiposity index (CVAI) (p < 0.001). Meanwhile, among tertiles of CVAI, as CVAI increased, the proportion of patients with HTN increased, which was 33.51%, 44.30%, and 62.50%, respectively. CVAI was shown to have a significant positive correlation with HTN. (r = 0.258, p < 0.001). CVAI was independently related to an elevated risk of HTN by binary logistic regression analyses, and the OR was (95% CI) 1.013 (1.010-1.016, p < 0.001) after adjustment. The area under the receiver operating characteristic curve (AUC) of CVAI predicted HTN in T2DM patients was greater than those of other abdominal obesity indices (p < 0.001). CONCLUSION: We found that CVAI was highly positively correlated with HTN in T2DM. Compared with other indices of abdominal obesity, such as WC, BMI, WHR, VAI, and LAP, the CVAI showed superior discriminative ability in T2DM complicated with HTN. Therefore, more attention should be paid to CVAI in T2DM.

Point of Care Abdominal Ultrasound.

Abdominal pain is a common emergency department complaint, and point-of-care ultrasound (POCUS) of the abdomen is increasingly being utilized to evaluate clinical manifestations. It aids in accurate diagnoses and assists in procedures, particularly in emergency and critical care settings. Imaging is often required to confirm the etiology of abdominal pain. POCUS provides the benefit of avoiding radiation exposure and enables quicker diagnosis compared to computed tomography scans. There is growing evidence of the diagnostic accuracy for numerous abdominal POCUS applications, including appendicitis, intussusception, diverticulitis, gastric ultrasound and contrast-enhanced ultrasound.

Sarcopenia and its clinical correlation in elderly chronic obstructive pulmonary disease: a prospective cohort study.

OBJECTIVE: The aim of this study was to examine the effects of sarcopenia on clinical characteristics and short-term outcomes in elderly chronic obstructive pulmonary disease (COPD) patients. PATIENTS AND METHODS: One hundred twenty elderly COPD patients (age>60) recruited from Beijing Shijingshan Hospital were divided into sarcopenia and non-sarcopenia groups according to the severity of sarcopenia at the first admission. Baseline data, geriatric syndrome, laboratory indicators and body composition analysis were analyzed. One year followed-up by outpatient visits was focused on clinical characteristics and telephone follow-ups for collecting all-cause deaths and acute exacerbations of chronic obstructive pulmonary disease as end-point events. The risk factors for sarcopenia were analyzed by univariate analysis and multivariate logical regression. The proportional hazards model (COX) regression was performed to determine the effect of sarcopenia on COPD patients' prognoses. RESULTS: One hundred twenty patients (76 men and 44 women) with an average age of 76.7±8.78 years were included, of which 63 patients (52.5%) were diagnosed with sarcopenia. Compared to the non-sarcopenia group, the sarcopenia group exhibited worse lung function and more severe geriatric syndromes with significantly higher incidence ratios of somnipathy and frailty. The sarcopenia group also showed worse muscle indicators and declined body composition. Multivariate analysis showed that the occurrence of sarcopenia in elderly COPD patients was correlated with forced expiratory volume in the first second (FEV1) (OR=0.97, 95% CI: 0.94-1.0, p=0.035), body mass index (BMI) (OR=0.80, 95% CI: 0.71-0.89, p=0.035) and hemoglobin (OR=0.98, 95% CI: 0.96-1.0, p=0.023). Furthermore, the COX regression indicated the association of sarcopenia with acute exacerbations of COPD within the follow-up period (HR=2.4, 95% CI: 1.01-5.72, p=0.048). CONCLUSIONS: Sarcopenia increases the risk of acute exacerbations of chronic obstructive pulmonary disease in the elderly. Sarcopenia incidence in elderly COPD is associated with FEV1, BMI, and hemoglobin and closely monitoring indicators is useful for early diagnosis of sarcopenia.

[Establishment of a nomogram prediction model using common preoperative indicators for early weight loss after laparoscopic sleeve gastrectomy].

Objectives: To construct a nomogram prediction model using common preoperative indicators for early weight loss (EWL) 1 year after laparoscopic sleeve gastrectomy (LSG). Methods: Relevant data of obese patients who had undergone LSG from January 2015 to May 2022 in Fujian Medical University Union Hospital and Quanzhou First Hospital Affiliated Fujian Medical University were analyzed. Patients with a history of major abdominal surgery, severe gastroesophageal reflux disease, pregnancy within 1 year after surgery, or who were lost to follow-up were excluded, resulting in a total of 200 patients in the study (190 from Fujian Medical University Union Hospital and 10 from Quanzhou First Hospital Affiliated Fujian Medical University). The participants were 51 men and 149 women of a mean age 29.9±8.2 years and a body mass index (BMI) 38.7±6.5 kg/m2. All patients in this group underwent standardized LSG procedure. Achieving ideal weight (BMI≤25 kg/m2) 1 year after LSG was defined as goal of EWL. Logistic regression analyses were performed to identify factors that independently influenced EWL. These factors were incorporated into the nomogram model. Receiver operating characteristic (ROC) curves (the larger the area under the curve [AUC], the better the predictive ability and accuracy of the model), likelihood ratio test (higher likelihood ratio indicates greater model homogeneity), decision curve analysis (higher net benefit indicates a better model), Akaike information criterion (AIC; smaller AIC indicates a better model), and Bayesian information criterion (BIC; smaller BIC indicates a better model) were used to validate the predictive ability of the column line diagram model. Results: In this study of 200 obese patients who underwent LSG surgery, 136 achieved EWL goal, whereas the remaining 64 did not. The rate of EWL goal achievement of the entire group was 68.0%. Compared with patients who did not achieve EWL goal, those who did had lower BMI, alanine transaminase, aspartate transaminase, triglycerides, and higher cholesterol. Additionally, the proportion of female was higher and the proportions of patients with fatty liver and hypertension lower in those who achieved EWL goal (all P<0.05). Univariate and multivariate logistic regression analysis revealed that preoperative BMI (OR=0.852, 95%CI: 0.796-0.912, P<0.001), alanine transaminase (OR=0.992, 95%CI: 0.985-0.999, P=0.024), presence of fatty liver (OR=0.185, 95%CI: 0.038-0.887, P=0.035) and hypertension (OR=0.374, 95%CI: 0.144-0.969, P=0.043) were independently associated with failure to achieve EWL goal. Cholesterol (OR=1.428, 95%CI: 1.052-1.939, P=0.022) was independently associated with achieving EWL goal. We used the above variables to establish an EWL nomogram model. ROC analysis, the likelihood ratio test, decision curve analysis, and AIC all revealed that the predictive value of the model was better than that of BMI alone (nomogram model vs. BMI: area under the curve 0.840 vs. 0.798, P=0.047; likelihood ratio: 58.785 vs. 36.565, AIC: 193.066 vs. 207.063, BIC: 212.856 vs. 213.660). Conclusion: Our predictive model is more accurate in predicting EWL after LSG compared with using BMI.

[Clinical effects of free pre-expanded internal thoracic artery perforator pedicled deltopectoral flap transfer in facial scar reconstruction].

Objective: To explore the clinical effects of free pre-expanded deltopectoral flap transfer in facial scar reconstruction by selecting appropriate internal thoracic artery perforator as the pedicle through preoperative color Doppler ultrasonic vascular assessment. Methods: A retrospective observational study was conducted. From September 2017 to March 2021, 11 patients with facial scar who met the inclusion criteria were admitted to the First Affiliated Hospital of Xi'an Jiaotong University, including 6 males and 5 females, aged 16-58 (31±12) years. The scar with area ranging from 7 cm×5 cm to 14 cm×9 cm was reconstructed by free pre-expanded internal thoracic artery perforator pedicled deltopectoral flap transfer. The operation was performed in 2 or 3 stages. Before operation, color Doppler ultrasonography was performed to evaluate the internal thoracic artery perforator. In the first stage, skin and soft tissue expander (hereinafter referred to as expander) implantation was performed, and a cylindrical expander with rated capacity of 400 to 600 mL was placed in the chest wall. The expansion time was 3 to 4 months, and the water injection volume reached 1.2-1.5 times of the rated capacity of expander. In the second stage, scar excision+free pre-expanded deltopectoral flap transfer was performed, with harvested flap area ranging from 9 cm×7 cm to 16 cm×10 cm. The vascular pedicle of flap (intercostal perforator of internal thoracic artery) was anastomosed end-to-end to the facial artery and vein or superficial temporal artery and vein. The wound in donor site was closed directly. Third stage operation thinning was performed at 3-6 months after the second stage operation in 5 patients because of bloated flap pedicle. At 6 months after the last operation, the flap survival and complications were recorded, the sensation of flap was evaluated by Semmes-Weinstein monofilament test, the color of flap was evaluated by color contrast of the flap to surrounding normal skin, and the curative effect satisfaction degree of patients was evaluated by 5-grade Likert scale. Results: At 6 months after the last operation, all the flaps of 11 patients survived well. One patient experienced venous congestion after flap transplantation, but the flap survived after re-anastomosis. One patient experienced hematoma after the first stage operation of expander implantation, but the rest treatment was not influenced after hematoma removal. No complications such as infection or expander exposure occurred in any patient. At 6 months after the last operation, the sensation of flap of patient was as follows: 9 cases recovered to protective sensation decrease or better, 1 case had protective sensation defect, and 1 case only had deep touch and pressure sensation; the color of flap of patient was as follows: 3 cases were very close to the color of surrounding normal skin, 6 cases were close to the color of surrounding normal skin, and 2 cases were different to the color of surrounding normal skin; the curative effect satisfaction degree of patients was as follows: 2 patients were very satisfied, 6 patients were satisfied, 2 patients were somewhat satisfied, and 1 patient was a little not satisfied. Conclusions: The large area facial scar can be treated safely and effectively by free pre-expanded deltopectoral flap with appropriate single internal thoracic artery perforator as vascular pedicle selected through vascular assessment by color Doppler ultrasonography before operation. After operation, the color of flap of patients is close to the surrounding normal skin and the sensation of flap can be partially recovered, with high curative effect satisfaction degree of patients.

[Introduction and application of European Academy of Paediatric Dentistry judgment criteria and scoring system for molar-incisor hypomineralization].

Molar-incisor hypomineralization (MIH) is defined as an enamel mineralization defect caused by systemic factors, which is characterized by demarcated opacities. These opacities are liable to result in brittle hypomineralized enamel breakdown, which expediting the eventual development of cavities, even tooth loss. Early diagnosis and prompt intervention are essential. The MIH scoring system based on the diagnostic criteria of the European Academy of Paediatric Dentistry (EAPD) is internationally recognized. This system is particularly helpful to diagnose and evaluate the MIH, as well as conductive to the performance of epidemiological investigations. This paper gives a presentation on the EAPD judgment criteria and scoring system as well as their applications, based on the current situation of MIH studies and our findings of MIH epidemiological investigation.

[Recompensation of complications in patients with hepatitis B virus-related decompensated cirrhosis treated with entecavir antiviral therapy].

Objective: To analyze the occurrence of recompensation conditions in patients with chronic hepatitis B virus-related decompensated cirrhosis after entecavir antiviral therapy. Methods: Patients with hepatitis B virus-related decompensated cirrhosis with ascites as the initial manifestation were prospectively enrolled. Patients who received entecavir treatment for 120 weeks and were followed up every 24 weeks (including clinical endpoint events, hematological and imaging indicators, and others) were calculated for recompensation rates according to the Baveno VII criteria. Measurement data were compared using the Student t-test or Mann-Whitney U test between groups. Categorical data were compared by the χ (2) test or Fisher's exact probability method between groups. Results: 283 of the 320 enrolled cases completed the 120-week follow-up, and 92.2% (261/283) achieved a virological response (HBV DNA 20 IU/ml). Child-Pugh and MELD scores were significantly improved after treatment (8.33 ± 1.90 vs. 5.77 ± 1.37, t = 12.70, P < 0.001; 13.37 ± 4.44 vs. 10.45 ± 4.58, t = 5.963, P < 0.001). During the 120-week follow-up period, 14 cases died, two received liver transplants, 19 developed hepatocellular cancer, 11 developed gastroesophageal variceal bleeding, and four developed hepatic encephalopathy. 60.4% (171/283) (no decompensation events occurred for 12 months) and 56.2% (159/283) (no decompensation events occurred for 12 months and improved liver function) of the patients had achieved clinical recompensation within 120 weeks. Patients with baseline MELD scores > 15 after active antiviral therapy achieved higher recompensation than patients with baseline MELD scores ≤15 [50/74 (67.6%) vs. 109/209 (52.2%), χ (2) = 5.275, P = 0.029]. Conclusion: Antiviral therapy can significantly improve the prognosis of patients with hepatitis B virus-related decompensated cirrhosis. The majority of patients (56.2%) had achieved recompensation. Patients with severe disease did not have a lower probability of recompensation at baseline than other patients.

[Clinical features and long-term prognosis of primary biliary cholangitis in patients with past hepatitis B virus infection].

Objective: To investigate the clinical features and long-term prognosis of primary biliary cholangitis (PBC) in patients with past hepatitis B virus (HBV) infection. Methods: 353 cases with PBC who visited the Liver Disease Center of Beijing Friendship Hospital Affiliated to Capital Medical University between January 2000 and January 2018 were retrospectively analyzed and were divided into the past HBV infection group (156 cases) and the no HBV infection group (197 cases). The two groups' baseline clinical features were compared. Ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, and long-term liver transplantation-free survival rate were compared through outpatient and telephone follow-up. Results: PBC with past HBV infection had a significantly reduced female proportion compared to the no HBV infection group (91.9% vs. 79.5%, P = 0.001). However, there were no statistically significant differences in age, biochemical indices, immunological indicators, platelet count, cirrhosis proportion, and others. Ursodeoxycholic acid biochemical response rate was reduced in patients with past HBV infection at the end of one year of treatment, but the difference was not statistically significant (65.8% vs. 78.2%, P = 0.068). In addition, there were no statistically significant differences between the GLOBE score (0.57 vs. 0.59, P = 0.26) and UK-PBC 5-year (2.87% vs. 2.87%, P = 0.38), 10-year (9.29% vs. 8.2%, P = 0.39) and 15-year liver transplantation rates (16.6% vs. 14.73%, P = 0.39). Lastly, the overall 5-year liver transplantation-free survival rate had no statistically significant difference between the two groups of patients (86.4% vs. 87.5%, P = 0.796). Conclusion: Primary biliary cholangitis had no discernible effect in terms of age at onset, biochemical indices, immunological indicators, cirrhosis proportion, ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, or overall liver transplantation-free survival rate in patients with past hepatitis B virus infections.

[Ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China: a CR-HepB-based real-world study].

Objective: To understand ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China. Methods: Patients with chronic HBV infection:demographic, virologic, hematologic, blood biochemistry, and antiviral treatment data were extracted from the China Registry of Hepatitis B (CR-HepB) database between 2012 and 2022 for descriptive statistics and change trend analysis. Multiple group comparisons were conducted using the Kruskal Wallis H test, while counting data was compared between groups using χ (2) test. Results: A total of 180 012 patients with chronic HBV infection were included, with a median age of 40 years old, and a male proportion accounting for 60.2%. The HBeAg positive rate was 43.3%. Over time, the median age of new patients each year increased from 39 to 47 years, while the HBeAg positive rate decreased from 51.3% to 32.8%. The initial diagnosis of patients was mainly CHB (71.4%), followed by hepatitis B cirrhosis (11.8%), inactive HBsAg carrier status (10.6%), and chronic HBV carrier status (6.2%). Among the newly registered patients every year from 2012 to 2022, the proportion of hepatitis B cirrhosis remained stable, but after 2019, the proportion of CHB increased and the proportion of other diagnoses decreased. The proportion of patients with cirrhosis increased with age in different age groups, with 3.5%, 19.3%, and 30.4% in the < 40, 40-69, and≥70 age groups, respectively. The proportion of women in patients with cirrhosis also increased with age, from 16.1% in those < 30 years old to 44.3% in those≥80 years old. From 2012 to 2022, the proportion of patients receiving first-line nucleos(t)ide analog antiviral treatment increased year by year, from 51.0% in 2012-2013 to 99.8% in 2022. Conclusion: The CR-HepB registration data reflect the changes in clinical characteristics and antiviral treatment patterns in patients with chronic HBV infection in China over the past ten years and can thus provide a reference to promote hepatitis B diagnosis and treatment practice, as well as scientific research.

[Tanshinone â ¡A activates PI3K/AKT signaling pathway to inhibit the apoptosis of mice cochlear pericytes induced by high glucose].

Objective: To investigate whether tanshinone ⅡA can protect the apoptosis of mice cochlear pericytes induced by high glucose and its specific protective mechanism, so as to provide experimental evidence for the prevention and treatment of diabetic hearing loss. Methods: C57BL/6J male mice were used to prepare type 2 diabetes model, which were divided into normal (NG) group, diabetic (DM) group, diabetic+tanshinone ⅡA (HG+tanshinone ⅡA) group and tanshinone ⅡA group. Each group had 10 animals. Primary cochlear pericytes were divided into NG group, HG group (high glucose 35 mmol/L), HG+tanshinone ⅡA (1, 3, 5 µmol/L) group, HG+Tanshinone ⅡA+LY294002 (PI3K/AKT pathway inhibitor) group, LY294002 group, tanshinone ⅡA group and DMSO group. Auditory brainstem response (ABR) was used to measure hearing threshold. Evans blue was used to detect the permeability of blood labyrinth barrier in each group. TBA methods were used to detect oxidative stress levels in various organs of mice. Morphological changes of stria vascularis were observed by hematoxylin-eosin staining (HE). Evans blue was used to detect the vascular labyrinth barrier permeability in cochlea. The expression of apoptosis protein in stria vascularis pericytes was observed by immunofluorescence. Pericytes apoptosis rate was observed by flow cytometry. DCFH-DA was combined with flow cytometry to detect intracellular ROS content, and Western blot was used to detect the expression of apoptotic proteins (Cleaved-caspase3, Bax), anti-apoptotic proteins (BCL-2) and pathway proteins (PI3K, p-PI3K, AKT, p-AKT). SPSS software was used for statistical analysis. Independent sample t test was performed, and P<0.05 was considered statistically significant. Results: Animal experiments: Tanshinone ⅡA decreased the hearing threshold of DM group [(35.0±3.5) dB SPL vs. (55.3±8.1) dB SPL] (t=4.899, P<0.01), decreased the oxidative stress level in cochlea (t=4.384, P<0.05), improved the structure disorder, atrophy of cochlea vascular lines, vacuole increased phenomenon. Tanshinone ⅡA alleviated the increased permeability of the blood labyrinth barrier [Evans blue leakage (6.84±0.27) AU vs. (8.59±0.85) AU] in the cochlea of DM mice (t=2.770, P<0.05), reversed the apoptotic protein: Caspase3 (t=4.956, P<0.01) and Bax (t=4.388, P<0.05) in cochlear vascularis. Cell experiments: Tanshinone ⅡA decreased intracellular ROS content in a concentration-dependent way (t=3.569, P<0.05; t=4.772, P<0.01; t=7.494, P<0.01); Tanshinone ⅡA decreased apoptosis rate and apoptotic protein, and increased the expression of anti-apoptotic protein, p-PI3K/PI3K and p-AKT/AKT in concentration-dependent manner (all P values<0.05); LY294002 reversed the protective effect of tanshinone ⅡA on pericytes apoptosis (all P values<0.05). Conclusion: Tanshinone ⅡA can inhibit the apoptosis of cochlear pericytes induced by high glucose by reducing oxidative stress level and activating PI3K/AKT signaling pathway under high glucose environment, thus playing a protective role in diabetic hearing loss.

NSD2 maintains lineage plasticity and castration-resistance in neuroendocrine prostate cancer.

The clinical use of potent androgen receptor (AR) inhibitors has promoted the emergence of novel subtypes of metastatic castration-resistant prostate cancer (mCRPC), including neuroendocrine prostate cancer (CRPC-NE), which is highly aggressive and lethal 1 . These mCRPC subtypes display increased lineage plasticity and often lack AR expression 2-5 . Here we show that neuroendocrine differentiation and castration-resistance in CRPC-NE are maintained by the activity of Nuclear Receptor Binding SET Domain Protein 2 (NSD2) 6 , which catalyzes histone H3 lysine 36 dimethylation (H3K36me2). We find that organoid lines established from genetically-engineered mice 7 recapitulate key features of human CRPC-NE, and can display transdifferentiation to neuroendocrine states in culture. CRPC-NE organoids express elevated levels of NSD2 and H3K36me2 marks, but relatively low levels of H3K27me3, consistent with antagonism of EZH2 activity by H3K36me2. Human CRPC-NE but not primary NEPC tumors expresses high levels of NSD2, consistent with a key role for NSD2 in lineage plasticity, and high NSD2 expression in mCRPC correlates with poor survival outcomes. Notably, CRISPR/Cas9 targeting of NSD2 or expression of a dominant-negative oncohistone H3.3K36M mutant results in loss of neuroendocrine phenotypes and restores responsiveness to the AR inhibitor enzalutamide in mouse and human CRPC-NE organoids and grafts. Our findings indicate that NSD2 inhibition can reverse lineage plasticity and castration-resistance, and provide a potential new therapeutic target for CRPC-NE.

[Efficacy of machine learning models versus Cox regression model for predicting prognosis of esophagogastric junction adenocarcinoma].

OBJECTIVE: To compare the performance of machine learning models and traditional Cox regression model in predicting postoperative outcomes of patients with esophagogastric junction adenocarcinoma (AEG). METHODS: This study was conducted among 203 AEG patients with complete clinical and follow-up data, who were treated in our hospital between September, 2015 and October, 2020. The clinicopathological data of the patients were processed for analysis using R language package and divided into training and validation datasets at the ratio of 3:1. The Cox proportional hazards regression model and 4 machine learning models were constructed for analyzing the datasets. ROC curves, calibration curves and clinical decision curves (DCA) were plotted. Internal validation of the machine learning models was performed to assess their predictive efficacy. The predictive performance of each model was evaluated by calculating the area under the curve (AUC), and the model fitting was assessed using the calibration curve. RESULTS: For predicting 3-year survival based on the validation dataset, the AUC was 0.870 for Cox proportional hazard regression model, 0.901 for eXtreme Gradient Boosting (XGBoost), 0.791 for random forest, 0.832 for support vector machine, and 0.725 for multilayer perceptron; For predicting 5-year survival, the AUCs of these models were 0.915, 0.916, 0.758, 0.905, and 0.737, respectively. For internal validation, the AUCs of the 4 machine learning models decreased in the order of XGBoost (0.818), random forest (0.758), support vector machine (0.0.804), and multilayer perceptron (0.745). CONCLUSION: The machine learning models show better predictive efficacy for survival outcomes of patients with AEG than Cox proportional hazard regression model, especially when proportional odds assumption or linear regression models are not applicable. XGBoost models have better performance than the other machine learning models, and the multi-layer perception model may have poor fitting results for a limited data volume.

Dietary alpha-ketoglutarate enhances intestinal immunity by Th17/Treg immune response in piglets after lipopolysaccharide challenge.

Alpha-ketoglutarate (AKG) is important for improving intestinal and systemic immune function. This study aimed to explore whether AKG enhances gut immunity in lipopolysaccharide (LPS)-challenged piglets by modulating the immune-related helper T cells 17 (Th17)/regulatory T cells (Treg) balance pathway. A 2 × 2 factor design was used on 24 pigs, with the major factors being diet (basal diet or 1% AKG diet) and immunological challenge (saline or LPS). Piglets were fed with a basal or AKG diet for 21 d and then received intraperitoneal injection of LPS or saline. The results demonstrated that AKG supplementation enhanced growth performance compared with the control group (P < 0.05). AKG improved the ileal morphological structure (P < 0.01). Finally, AKG supplementation increased interleukin (IL)-10, transforming growth factor beta-1, forkhead box P3, and signal transducer and activator of transcription 5 genes expression whereas decreasing IL-6, IL-8, IL-1ß, tumor necrosis factor-α, IL-17, IL-21, signal transducer and activator of transcription 3 and rar-related orphan receptor c genes expression (P < 0.05). These findings suggested that dietary AKG can improve the growth performance of piglets. Meanwhile, dietary AKG can alleviate LPS-induced intestinal inflammation through Th17/Treg immune response signaling pathway.

Immature digestive and immune systems cause a variety of problems. The balance of helper Tcells 17 (Th17) and regulatory T cells (Treg) is critical in maintaining normal immune function in animals. Piglets' growth performance and immune function are all influenced by alpha-ketoglutarate (AKG). However, how AKG exerts its effect on intestinal immunity in piglets through modulating the immune signaling of Th17/Treg biology has not been explored. In this study, an inflammation model was established by lipopolysaccharide (LPS) injection. This study was to test the hypothesis that AKG can enhance growth performance and attenuate LPS-challenged intestinal inflammation by modulating Th17/Treg response. We concluded that dietary AKG can improve the growth performance of piglets. Dietary AKG alleviated intestinal inflammation induced by LPS through the Th17/Treg response, thereby improving intestinal immunity. These findings can provide a theoretical foundation for utilizing AKG in weaned piglet diets for the regulation of intestinal immune activity through nutrition.

[Infiltration and significance of M1 macrophage in breast cancer: an analysis of METABRIC database and clinical validation].

Objective: To investigate the differences of immune microenvironment between stage T1N3 and stage T3N0 breast cancer patients and explore the relationship between M1 macrophage infiltration and lymph node metastasis in breast cancer. Methods: Clinical information and RNA-sequencing (RNA-Seq) expression data of stage T1N3 (n=9) and stage T3N0 (n=11) breast cancer patients were extracted from Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases. Using CIBERSORT, the proportions of 22 types of immune cells were calculated, and then the differences of immune cell infiltration between stage T1N3 and T3N0 patients were compared. From 2011 to 2022, pathologic specimens were collected from breast cancer patients who underwent curative resection at the Cancer Hospital, Chinese Academy of Medical Sciences, including 77 at stage T1N3 and 58 at stage T3N0.The METABRIC database analysis results were verified by examining the density of M1 macrophages in tissues using dual-staining immunohistochemistry. Results: METABRIC data analysis showed M1 macrophage was the highest proportion, 15.85% in stage T1N3 breast cancer; M2 macrophage was the highest proportion, 13.07% in stage T3N0 breast cancer.M1 macrophage proportions were statistically different between patients with stage T1N3 and stage T3N0 (P=0.010). The dual-staining immunohistochemistry analysis of breast cancer tissues showed M1 macrophage density (median) of 62.0 and 38.0 cells/mm(2) for stage T1N3 and T3N0, respectively. The difference was statistically significant (P=0.002). Conclusion: The density of M1 macrophages is notably higher in stage T1N3 patients and is associated with lymph node metastasis.