Objective To explore the efficacy and safety of dapagliflozin in patients with paroxysmal atrial fibrillation (PAF) combined with heart failure with preserved ejection fraction (HFpEF). Methods A total of 120 patients with PAF combined with HFpEF treated at Jinshan Hospital of Fudan University from July 2022 to July 2023 were selected and randomly divided into the dapagliflozin group (n＝60, standard treatment combined with dapagliflozin) and the control group (n＝60, standard treatment combined with placebo). After 12 months of follow-up, the Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS), PAF duration, recurrence rate and frequency of PAF, left atrial diameter, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, left ventricular ejection fraction, P-wave dispersion, blood pressure, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP), estimated glomerular filtration rate (eGFR), and glycated hemoglobin A_1C (HbA_1C) were compared between the two groups. Cardiovascular outcomes and adverse events were observed. Results A total of 10 patients lost to follow-up, and 110 patients were included in the analysis (55 in each group). After 12 months of treatment, the KCCQ-TSS in the dapagliflozin group was significantly higher than that in the control group ([61.68±2.65] points vs [44.98±4.76] points, P＜0.001). The PAF duration in the dapagliflozin group was significantly shorter than that in the control group ([144±18] min vs [270±24] min, P＝0.045). After treatment, frequency of PAF, NT-proBNP levels, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, left atrial diameter, P-wave dispersion, and HbA_1C levels showed statistical differences between the two groups (P＜0.05). The heart failure readmission rate and PAF recurrence rate in the dapagliflozin group were significantly lower than those in the control group (P＜0.05). There was no significant difference in the incidence of adverse events between the two groups during treatment. Conclusions Dapagliflozin improves patients’ quality of life, reduces PAF duration and recurrence rate, decreases heart failure readmission rate, lowers NT-proBNP levels, reverses cardiac remodeling, and demonstrates favorable safety in patients with PAF combined with HFpEF.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To establish a prediction model for symptomatic radiation pneumonitis (SRP) after radiotherapy for thoracic cancer based on a longitudinal cohort and dose interval variations.Methods:Clinical data of 587 patients who received thoracic radiotherapy in Department of Radiotherapy of Yunnan Cancer Hospital from July 2022 to June 2023 were retrospectively analyzed. The National Cancer Institute common terminology criteria for adverse events (CTCAE) version 5.0 was used to grade radiation pneumonitis, and clinical factors, traditional independent dosimetric characteristics and dose interval variation characteristics were collected. Features used to predict the occurrence of SRP were screened using genetic algorithms and analyzed the correlation between the selected features and SRP occurrence. Predictive models for SRP occurrence were established using the selected features and evaluated, and the optimal predictive model was visualized using a column chart.Results:The incidence of SRP was 35.94%. Five clinical factors, seven independent dosimetric features and six dose interval variation features were screened out by genetic algorithms to effectively predict the occurrence of SRP. The area under ROC curve (AUC) of clinical factors combined with traditional independent dosimetric factors and dose interval variation factors was 76%. The AUC of clinical factors combined with traditional independent dosimetric factors and that of clinical factors combined with dose interval variation factors was 69% and 67%, respectively. The addition of the characteristics of dose interval variation factors significantly improved the effectiveness of the prediction model.Conclusions:The supplement of the characteristics of dose interval variation factors can significantly improve the performance of the SRP prediction model for thoracic tumors after radiotherapy. The SRP prediction model based on dose interval variations can effectively predict the occurrence of SRP.

Humans ; Atrial Fibrillation/surgery* ; Left Atrial Appendage Closure ; Heart Atria/surgery* ; Catheter Ablation/methods* ; Atrial Appendage/surgery* ; Treatment Outcome

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

Postzygotic mutations are acquired in normal tissues throughout an individual's lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clock-like mutational processes,and the polymorphisms of epigenetic regulation genes influence the pro-portion of signature B in mutation profiles.Notably,signature C,characterized by C＞T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6％of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C＞T transitions at GpCpN sites;and indi-viduals'genetic background may also influence their postzygotic mutation profiles.

The current study aims to rapidly and comprehensively profile the chemical composition of Cistanche salsa using direct infusion coupled with MS/MS~(ALL)(DI-MS/MS~(ALL)). The C. salsa extract was directly imported into electrospray ionization(ESI) source of quadrupole time-of-flight(Q-TOF) mass spectrometer with an infusion pump at a flow rate of 10 μL·min~(-1). Acquisition program was applied under negative ionization polarity to collect one MS~1 spectrum(m/z 50-1 200), followed by 1 150 MS~2 spectra with precursor isolation window(m/z 1) amongst mass range m/z 50-1 200. After each MS~2 spectrum was matched to its precursor ion, putative identification was conducted through matching mass spectral data with literature and database. A total of 31 components were identified from C. salsa, including 9 phenylethanoid glycosides, 2 iridoids, 4 saccharides, 9 organic acids, and 7 other compounds, similar to those from C. tubulosa and C. deserticola. In conclusion, DI-MS/MS~(ALL), a facile and reliable analytical tool, can be employed for qualitative analysis of chemical constituents in C. salsa. The research offers a promising strategy to achieve rapid chemome profiling of herbal medicine and provides an alternative source of Cistanches Herba.
Chromatography, High Pressure Liquid ; Cistanche ; Drugs, Chinese Herbal ; Glycosides ; Plants, Medicinal ; Tandem Mass Spectrometry

Objective:To evaluate the clinical characteristics and prognosis of gallbladder cancer (GBC) patients in China.Methods:This retrospective multicenter cohort study enrolled 3 528 consecutive GBC patients diagnosed between January 2010 to December 2017 in 15 hospitals from 10 provinces. There were 1 345 (38.12%) males and 2 183 (61.88%) females.The age of diagnosis was (63.7±10.8) years old (range: 26 to 99 years old) .There were 213 patients (6.04%) in stage 0 to Ⅰ, whereas 1 059 (30.02%) in stage Ⅱ to Ⅲ, 1 874 (53.12%) in stage Ⅳ, and 382 (10.83%) unavailable. Surgery was performed on 2 255 patients (63.92%) . Three hundred and thirty-six patients received chemotherapy or radiotherapy (9.52%; of which 172 were palliative); 1 101 (31.21%) received only supportive treatment.The patient source, treatment and surgery, pathology, concomitant gallstone, and prognosis were analyzed.Results:Among the 3 528 GBC patients, 959 (27.18%) were from East China, 603 (17.09%) from East-North China, 1 533 (43.45%) from Central China, and 433(12.27%) from West China. Among the 1 578 resectable tumor, 665 (42.14%) underwent radical surgery, 913 (57.86%) underwent surgery that failed to follow the guidelines.Eight hundred and ninety-one (56.46%) patients were diagnosed before surgery, 254 (16.10%) during surgery, and 381 (24.14%) after surgery (time point of diagnosis couldn′t be determined in 52 patients) .Among the 1 578 patients with resectable tumor, 759 (48.10%) had concomitant gallstone.Among the 665 patients underwent radical surgery, 69 (10.4%) showed positive resection margin, 510 (76.7%) showed negative resection margin, and 86 (12.9%) unreported margin status.The 5-year overall survival rate (5yOS) for the 3 528-patient cohort was 23.0%.The 5yOS for patients with resectable tumor was 39.6%, for patients with stage ⅣB tumor without surgery was 5.4%, and for patients with stage ⅣB tumor underwent palliative surgery was 4.7%.Conclusions:More than half GBC patients in China are diagnosed in stage Ⅳ.Curative intent surgery is valuable in improving prognosis of resectable GBC.The treatment of GBC needs further standardization.Effective comprehensive treatment for GBC is in urgent need.

Objective:To evaluate the clinical characteristics and prognosis of gallbladder cancer (GBC) patients in China.Methods:This retrospective multicenter cohort study enrolled 3 528 consecutive GBC patients diagnosed between January 2010 to December 2017 in 15 hospitals from 10 provinces. There were 1 345 (38.12%) males and 2 183 (61.88%) females.The age of diagnosis was (63.7±10.8) years old (range: 26 to 99 years old) .There were 213 patients (6.04%) in stage 0 to Ⅰ, whereas 1 059 (30.02%) in stage Ⅱ to Ⅲ, 1 874 (53.12%) in stage Ⅳ, and 382 (10.83%) unavailable. Surgery was performed on 2 255 patients (63.92%) . Three hundred and thirty-six patients received chemotherapy or radiotherapy (9.52%; of which 172 were palliative); 1 101 (31.21%) received only supportive treatment.The patient source, treatment and surgery, pathology, concomitant gallstone, and prognosis were analyzed.Results:Among the 3 528 GBC patients, 959 (27.18%) were from East China, 603 (17.09%) from East-North China, 1 533 (43.45%) from Central China, and 433(12.27%) from West China. Among the 1 578 resectable tumor, 665 (42.14%) underwent radical surgery, 913 (57.86%) underwent surgery that failed to follow the guidelines.Eight hundred and ninety-one (56.46%) patients were diagnosed before surgery, 254 (16.10%) during surgery, and 381 (24.14%) after surgery (time point of diagnosis couldn′t be determined in 52 patients) .Among the 1 578 patients with resectable tumor, 759 (48.10%) had concomitant gallstone.Among the 665 patients underwent radical surgery, 69 (10.4%) showed positive resection margin, 510 (76.7%) showed negative resection margin, and 86 (12.9%) unreported margin status.The 5-year overall survival rate (5yOS) for the 3 528-patient cohort was 23.0%.The 5yOS for patients with resectable tumor was 39.6%, for patients with stage ⅣB tumor without surgery was 5.4%, and for patients with stage ⅣB tumor underwent palliative surgery was 4.7%.Conclusions:More than half GBC patients in China are diagnosed in stage Ⅳ.Curative intent surgery is valuable in improving prognosis of resectable GBC.The treatment of GBC needs further standardization.Effective comprehensive treatment for GBC is in urgent need.

Etelcalcetide (ParsabivTM) is a second generation calcimimetic agent newly developed by Amgen,mainly used for the treatment of secondary hyperparathyroidism.Etetcalcetide not only decreases calcium concentration by directly binding with the calcium sensing receptor,but also reduces the parathyroid hormone level.The European Union has approved for chronic kidney disease patients with secondary hyperparathyroidism in dialysis with Etelcalcetide injection.This paper summarized the pharmacological effects,pharmacokinetics,clinical trials,and adverse reaction of Etelcalcetide.