Purpose::Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation.Methods::C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference. Results::Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol.Conclusions::Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.

Objectives: To evaluate the positive rate of left posterior lymph nodes of the superior mesenteric artery (14cd-LN) in patients undergoing pancreaticoduodenectomy for pancreatic head carcinoma,to analyze the impact of 14cd-LN dissection on lymph node staging and tumor TNM staging. Methods: The clinical and pathological data of 103 consecutive patients with pancreatic cancer who underwent pancreaticoduodenectomy at Pancreatic Center,the First Affiliated Hospital of Nanjing Medical University from January to December 2022 were analyzed,retrospectively. There were 69 males and 34 females,with an age(M (IQR))of 63.0 (14.0) years (range:48.0 to 86.0 years). The χ² test and Fisher's exact probability method was used for comparison of the count data between the groups,respectively. The rank sum test was used for comparison of the measurement data between groups. Univariate and multivariate Logistic regression analyzes were used for the analysis of risk factors. Results: All 103 patients underwent pancreaticoduodenectomy successfully using the left-sided uncinate process and the artery first approach. Pathological examination showed pancreatic ductal adenocarcinoma in all cases. The location of the tumors was the pancreatic head in 40 cases,pancreatic head-uncinate in 45 cases,and pancreatic head-neck in 18 cases. Of the 103 patients,38 cases had moderately differentiated tumor and 65 cases had poorly differentiated tumor. The diameter of the lesions was 3.2 (0.8) cm (range:1.7 to 6.5 cm),the number of lymph nodes harvested was 25 (10) (range:11 to 53),and the number of positive lymph nodes was 1 (3) (range:0 to 40). The lymph node stage was stage N0 in 35 cases (34.0%),stage N1 in 43 cases (41.7%),and stage N2 in 25 cases (24.3%). TNM staging was stage ⅠA in 5 cases (4.9%),stage ⅠB in 19 cases (18.4%),stage ⅡA in 2 cases (1.9%),stage ⅡB in 38 cases (36.9%),stage Ⅲ in 38 cases (36.9%),and stage Ⅳ in 1 case (1.0%). In 103 patients with pancreatic head cancer,the overall positivity rate for 14cd-LN was 31.1% (32/103),and the positive rates for 14c-LN and 14d-LN were 21.4% (22/103) and 18.4% (19/103),respectively. 14cd-LN dissection increased the number of lymph nodes (P<0.01) and positive lymph nodes (P<0.01). As a result of the 14cd-LN dissection,the lymph node stage was changed in 6 patients,including 5 patients changed from N0 to N1 and 1 patient changed from N1 to N2. Similarly,the TNM stage was changed in 5 patients,including 2 patients changed from stage ⅠB to ⅡB,2 patients changed from stage ⅡA to ⅡB,and 1 patient changed from stage ⅡB to Ⅲ. Tumors located in the pancreatic head-uncinate (OR=3.43,95%CI:1.08 to 10.93,P=0.037) and the positivity of 7,8,9,12 LN (OR=5.45,95%CI:1.45 to 20.44,P=0.012) were independent risk factors for 14c-LN metastasis; while tumors with diameter >3 cm (OR=3.93,95%CI:1.08 to 14.33,P=0.038) and the positivity of 7,8,9,12 LN (OR=11.09,95%CI:2.69 to 45.80,P=0.001) were independent risk factors for 14d-LN metastasis. Conclusion: Due to its high positive rate in pancreatic head cancer,dissection of 14cd-LN during pancreaticoduodenectomy should be recommended,which can increase the number of lymph nodes harvested,provide a more accurate lymph node staging and TNM staging.
Male ; Female ; Humans ; Pancreaticoduodenectomy/methods* ; Retrospective Studies ; Prognosis ; Lymph Node Excision/methods* ; Lymph Nodes/pathology* ; Pancreatic Neoplasms/pathology* ; Neoplasm Staging

BACKGROUND: Clinical outcomes are poor if patients with acute heart failure (AHF) are discharged with residual congestion in the presence of renal dysfunction. However, there is no single indication to reflect the combined effects of the two related pathophysiological processes. We, therefore, proposed an indicator, congestion and renal index (CRI), and examined the associations between the CRI and one-year outcomes and the incremental prognostic value of CRI compared with the established scoring systems in a multicenter prospective cohort of AHF. METHODS: We enrolled AHF patients and calculated the ratio of thoracic fluid content index divided by estimated glomerular filtration rate before discharge, as CRI. Then we examined the associations between CRI and one-year outcomes. RESULTS: A total of 944 patients were included in the analysis (mean age 63.3 ± 13.8 years, 39.3% women). Compared with patients with CRI ≤ 0.59 mL/min per kΩ, those with CRI > 0.59 mL/min per kΩ had higher risks of cardiovascular death or HF hospitalization (HR = 1.56 [1.13-2.15]) and all-cause death or all-cause hospitalization (HR = 1.33 [1.01-1.74]). CRI had an incremental prognostic value compared with the established scoring system. CONCLUSIONS In patients with AHF, CRI is independently associated with the risk of death or hospitalization within one year, and improves the risk stratification of the established risk models.

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*

Objective: To compare and analyze the clinical efficacy of pancreaticoduodenectomy for distal bile duct cancer and pancreatic head cancer. Methods: Clinical data of 1 005 patients who underwent pancreaticoduodenectomy and postoperative pathological examination confirmed the diagnosis of distal bile duct cancer and pancreatic head cancer at the Pancreas Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to December 2020 were analyzed retrospectively. There were 112 cases in the distal bile duct cancer group, 71 males and 41 females,with age (M(IQR)) of 65(15) years(range: 40 to 87 years); 893 cases in the pancreatic head cancer group, 534 males and 359 females,with age of 64(13)years(range: 16 to 91 years). The differences between clinicopathological characteristics and postoperative overall survival of the two groups were analyzed by χ² test, Fisher's exact probability method, rank sum test or log-rank test, respectively. The difference in postoperative overall survival between the two groups was compared using Kaplan-Meier method after propensity score matching (1∶1). Results: Compared with the pancreatic head cancer group,the distal bile duct cancer group had shorter operative time (240.0(134.0) minutes vs. 261.0(97.0) minutes, Z=2.712, P=0.007),less proportion of combined venous resection (4.5% (5/112) vs. 19.4% (173/893), χ²=15.177,P<0.01),smaller tumor diameter (2.0(1.0) cm vs. 3.0(1.5) cm,Z=10.567,P<0.01),higher well/moderate differentiation ratio (51.4% (56/112) vs. 38.0% (337/893), χ²=7.328, P=0.007),fewer positive lymph nodes (0(1) vs. 1(3), Z=5.824, P<0.01),and higher R0 resection rate (77.7% (87/112) vs. 38.3%(342/893), χ²=64.399, P<0.01),but with a higher incidence of overall postoperative complications (50.0% (56/112) vs. 36.3% (324/892), χ²=7.913,P=0.005),postoperative pancreatic fistula (28.6% (32/112) vs. 13.9% (124/893), χ²=16.318,P<0.01),and postoperative abdominal infection (21.4% (24/112) vs. 8.6% (77/892), χ²=18.001,P<0.01). After propensity score matching, there was no statistical difference in postoperative overall survival time between patients in the distal bile duct cancer group and the pancreatic head cancer group (50.6 months vs. 35.1 months,Z=1.640,P=0.201),and multifactorial analysis showed that tumor site was not an independent risk factor affecting the prognosis of patients in both groups after matching (HR=0.73,95%CI:0.43 to 1.23,P=0.238). Conclusions: Patients with distal bile duct cancer are more likely to benefit from early diagnosis and surgical treatment than patients with pancreatic head cancer,but with a relative higher postoperative complication rates. The different tumor origin site is not an independent risk factor for prognosis of patients with distal bile duct cancer and pancreatic head cancer after propensity score matching.
Bile Ducts ; Female ; Humans ; Male ; Pancreas ; Pancreatic Neoplasms/surgery* ; Pancreaticoduodenectomy ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC). METHODS: This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC). RESULTS: This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified. CONCLUSION Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.
Adolescent ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carcinoma, Hepatocellular/drug therapy* ; Cisplatin/therapeutic use* ; Humans ; Liver Neoplasms/drug therapy* ; Lung Neoplasms/pathology* ; Nasopharyngeal Neoplasms/drug therapy*

OBJECTIVE: To understand the current state and problem of screening and management of chronic kidney disease (CKD) in the community, and to explore the improving strategies. METHODS: We established a community-CKD integrated data science platform based on medical information from 79 community health centers, in Xicheng District, Beijing. Patients who referred to 79 community health centers from 21 June 2015 to 20 November 2021 were retrospectively included in this study using the CKD data platform. The monitoring of the indicator of kidney injury, risk factor control, medicine use and device configuration in community were assessed in the study. RESULTS: In the study, 70.6% of the population were identified with high risk of CKD in the total 374 498 individuals who referred to the community health centers. Hypertension (62.3%), coronary heart disease (43.3%) and diabetes (30.4%) were the most common risk factors in high-risk CKD population. Only 17.2% of the patients with high risk of CKD were screened for kidney injury including at least one serum creatine (Scr) or albuminuria test, among which 10 992 (24.2%) individuals were defined as CKD. 22.7% (11 338/49 908) of the total patients with kidney screening in community were defined as CKD, of whom, 42.6% and 46.1% were identified by estimated glomerular filtration rate (eGFR) < 60 mL/(min·1.73 m²) and abnormalities of urinary proteins, respectively. The overall CKD detection rate in the community was 5.2% (19 299/374 498), and the miss-diagnosis rate of CKD was 38.1%. Of the 79 community health centers, 13 (16.5%) were equipped with ACR testing device, and eGFR was reported directly in 66 (83.5%) centers. Altogether 60.3% and 99.7% of the community CKD patients achieved glucose control and blood pressure control, respectively, and 59.3% of the CKD patients who had proteinuria was treated with renin-angiotensin-aldosterone system (RAAS) inhibitors. CONCLUSION High-risk CKD population account for a substantial proportion of patients who refer to the community. Early screening, prevention and management of CKD in the community are of great importance to improve the prognosis and decrease the burden of CKD. It's essential to establish a screening and monitoring system, strengthen standardized management and clinician training for improving the ability of CKD management in the community.
Albuminuria/epidemiology* ; Blood Glucose ; Creatine ; Glomerular Filtration Rate ; Humans ; Renal Insufficiency, Chronic/therapy* ; Retrospective Studies

Objective:To systematically evaluate the effects of elastic resistance exercise on patients with chronic obstructive pulmonary disease (COPD). Methods:Randomized clinical trials about elastic resistance exercise for chronic obstructive pulmonary disease were searched in the Cochrane Library, PubMed, Web of Science, CNKI, VIP, Wanfang Database and Chinese Biomedical Literature Database from inception to September, 2020. Finally, eleven literatures were included, including 9 in English and 2 in Chinese, with a total of 485 patients. The quality of the articles was evaluated using the Cochrane Library systematic review criteria and Physiotherapy Evidence Database Scale, and the data were analyzed with RevMan 5.2. The system review was registered on PROSPERO (CRD42020208659). Results:There was no significant difference in 6 Minute Walking Distance (6WMD) (MD = 1.19, 95%CI -7.02 to 9.39, P = 0.78), COPD Assessment Test (CAT) (MD = -0.43, 95%CI -2.42 to 1.57, P = 0.68) and the muscle strength (MD = 0.23, 95%CI -1.06 to 1.52, P = 0.73), with no high heterogeneity, between elastic resistance exercise group and the conventional resistance exercise group (such as weight training machine, weight training). There was no significant difference in 6MWD (MD = 18.30, 95%CI -8.92 to 45.52, P = 0.19) and CAT (MD = 0.59, 95%CI -3.78 to 2.60, P = 0.72) between the elastic resistance exercise group and the non-resistance exercise group, however, the heterogeneity between them was high. Conclusion:Elastic resistance exercise may be potentially alternative to conventional resistance training. However, the effects of elastic resistance exercise on exercise endurance, quality of life and lung function are still unclear.

Objective Hilar cholangiocarcinoma (HC) is invariably fatal without surgical resection. The primary aim of the current study was to determine the safety of variable surgical resections for patient with HC and their survival after surgical resection. In addition, prognostic factor for the overall survival was also evaluated. Methods The study included 59 consecutive patients who were newly diagnosed with HC and underwent surgical resections with curative intend between February 2009 and February 2017. Patients were followed up at 3-6 months intervals after hospital discharge. Postoperative complications and overall survival were determined. Associations of clinicopathologic and surgeon-related factors with overall survival were evaluated through univariate analysis and Cox regression analysis. Results Of patients with Bismuth and Corlette (B & C) type Ⅲ (=19) and Ⅳ (=25) HC lesions, 33 (55.9%) were treated with hilar resection combined with major liver resection (MLR), while the other 11 patients with type Ⅲ and Ⅳ, and those with type Ⅰ (=8) and Ⅱ (=7) HC lesions were treated with hilar resection. The overall surgical mortality was 5.1% and surgical morbidity was 35.6%. There was no statistical difference in the mortality between MLR group and hilar resection group (6.1% 3.8%; =0.703, =0.145). The median follow-up period was 18 months (range, 1-94 months). The 1-, 3-, 5-year survival rate was 59.3%, 36.5%, and 17.7%, respectively. The overall survival after resections was 18 months. In HC patients with B & C type Ⅲ and Ⅳ lesions, the median survival was 23 months for hilar resection with MLR and 8 months for hilar resection alone; the 1-, 3-, 5-year cumulative survival rate was 63.9%, 23.3%, and 15.5%, respectively for hilar resection with MLR, and 11.1%, 0, and 0, respectively for hilar resection alone, with significant differene observed (, 9.902; 95% , 2.636-19.571, =0.001). Four factors were independently associated with overall survival: preoperative serum Ca19-9 (, 7.039; 95% , 2.803-17.678, <0.001), histopathologic grade (, 4.964; 95% , 1.046-23.552, =0.044), surgical margins (=0.031), and AJCC staging (=0.015). Conclusions R0 resection is efficacious in surgical treatment of HC. MLR in combination with caudate lobe resection may increase the chance of R0 resection and improve survival of HC patients with B & C type Ⅲ and Ⅳ lesions. Preoperatively prepared for biliary drainage may ensure the safety of MLR in most HC patients. Novel adjuvant therapies are needed to improve the survival of HC patients with poor prognostic factors.

Objective To select and develop a SNP-STR multiplex amplification system with genetic markers compatible with current STR databases. To understand its genetic polymorphisms in Sichuan Han population and its application value in DNA mixture analysis. Methods Based on the STR genetic markers in commercial kits, SNPs adjacent to these STR markers were selected to be SNP-STR genetic markers. A SNP-STR multiplex amplification system with genetic markers based on allele-specific amplification was constructed using allele-specific amplification primers. The genetic polymorphism of the system in the Sichuan Han population was investigated and the efficiency of systems with different numbers of loci to detect the two individual DNA mixture samples was evaluated. Results An allele-specific multiplex amplification system constituted of 13 SNP-STR genetic markers was selected and constructed. In Sichuan Han population, the heterozygosity of each locus ranged from 0.76 to 0.88, and the combined discrimination power reached 0.999 999 999 999 999 968. In the analysis of the two individual DNA mixture samples： for single-locus amplification, the genotype of the minor components can still be detected when the mixture ratio reaches 1 000∶1; for multiple loci multiplex amplification, the maximum mixture ratio can reach 500∶1. As the number of loci in the system increased, the detection efficiency of the minor components in the DNA mixture decreased. Conclusion SNP-STR genetic markers have a higher polymorphism than STR. The multiplex amplification system made of SNP-STR genetic markers has a better analysis efficiency for mixed samples than traditional STR multiplex amplification system.
China ; DNA Fingerprinting ; DNA Primers ; Gene Frequency ; Genetic Markers ; Humans ; Microsatellite Repeats ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide