High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.

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

Objective:To investigate the effect and mechanism of bone marrow mesenchymal stem cell (BMSC) on pyroptosis of rats with kidney injury.Methods:Bone marrow of 4-5 week-old female Sprague-Dawley (SD) rats was isolated in vitro and BMSC was obtained. The third generations of BMSC were used to further experiments. Fifteen 6 week-old SD rats were cluster-randomized divided into control group, kidney injury group and BMSC group (5 rats in each group). Rats in kidney injury group were injected with lipopolysaccharide (LPS) 1 mg/kg via tail vein; the control group was given the same amount of normal saline. BMSC group was injected with 0.5 mL BMSC (including 2×10 6 BMSC) via tail vein after modeling; the kidney injury group received the same amount of normal saline. On day 3 after these injections, serum creatinine (SCr) was detected by picric acid method, and blood urea nitrogen (BUN) was detected by diacetyl monoxime. The levels of cystatin C (Cys C), interleukins (IL-1β and IL-18) in blood were detected by enzyme-linked immunosorbent assay (ELISA). The rats were then sacrificed and their kidneys were removed for subsequent detection. The mRNA expression levels of NOD-like receptor protein 3 (NLRP3) and cysteinyl aspartate-specific protease-1 (caspase-1) of kidney were detected by quantificational real-time quantitative polymerase chain reaction (qRT-PCR). The protein expression levels of NLRP3 and caspase-1 of kidney were detected by Western blotting. Results:In vitro, after bone marrow cell suspension was cultured for 24 hours, a large number of round adherent cells and suspended cells appeared in each culture flask. After 4-5 days of culture, a large number of long spindle cells adhered to the wall, and there were still obvious impurity cells. After trypsin digestion and passage to the third generation, the long spindle adherent cells grew mainly in the culture flask and were basically purified as BMSC. In vivo, compared with the control group, the levels of SCr, BUN, Cys C, IL-1β and IL-18 in kidney injury group were increased [SCr (μmol/L): 85.22±2.29 vs. 21.80±0.59, BUN (mmol/L): 11.50±0.64 vs. 5.86±0.83, Cys C (mg/L): 0.13±0.01 vs. 0.11±0.02, IL-1β (ng/L): 31.49±1.42 vs. 4.74±0.49, IL-18 (ng/L): 29.01±1.95 vs. 1.52±0.03, all P < 0.05]. The mRNA and protein expression levels of NLRP3, caspase-1 were significantly increased [NLRP3 mRNA (2 -ΔΔCt): 3.635±0.296 vs. 1.000±0.002, caspase-1 mRNA (2 -ΔΔCt): 4.020±0.228 vs. 1.001±0.003; NLRP3 protein (NLRP3/β-actin): 1.560±0.868 vs. 0.902±0.036, caspase-1 protein (caspase-1/β-actin): 1.392±0.097 vs. 0.895±0.046, all P < 0.05]. Compared with kidney injury group, the levels of SCr, BUN, IL-1β and IL-18 in BMSC group were significantly decreased [SCr (μmol/L): 51.64±3.84 vs. 85.22±2.29, BUN (mmol/L): 9.90±0.46 vs. 11.50±0.64, IL-1β (ng/L): 24.20±1.45 vs. 31.49±1.42, IL-18 (ng/L): 12.97±1.25 vs. 29.01±1.95, all P < 0.05]. The mRNA and protein expression levels of NLRP3, caspase-1 were significantly decreased [NLRP3 mRNA (2 -ΔΔCt): 1.488±0.136 vs. 3.635±0.296, caspase-1 mRNA (2 -ΔΔCt): 1.643±0.143 vs. 4.020±0.228; NLRP3 protein (NLRP3/β-actin): 1.227±0.053 vs. 1.560±0.868, caspase-1 protein (caspase-1/β-actin): 1.159±0.107 vs. 1.392±0.097, all P < 0.05]. Conclusion:In vivo, BMSC may attenuate pyroptosis in LPS-induced kidney injury rats.

Toll-like receptor 3 (TLR3), as an important pattern recognition receptor (PRR), dominates the innate and adaptive immunity regulating many acute and chronic inflammatory diseases. Atherosclerosis is proved as an inflammatory disease, and inflammatory events involved in the entire process of initiation and deterioration. However, the contribution of TLR3 to atherosclerosis remains unclear. Herein, we identified the clinical relevance of TLR3 upregulation and disease processes in human atherosclerosis. Besides, activation of TLR3 also directly led to significant expression of atherogenic chemokines and adhesion molecules. Conversely, silencing TLR3 inhibited the uptake of oxLDL by macrophages and significantly reduced foam cell formation. Given the aberrance in TLR3 functions on atherosclerosis progression, we hypothesized that TLR3 could serve as novel target for clinical atherosclerosis therapy. Therefore, we developed the novel ellipticine derivative SMU-CX24, which specifically inhibited TLR3 (IC₅₀ = 18.87 ± 2.21 nmol/L). In vivo, atherosclerotic burden was alleviated in Western diet fed ApoE^-/- mice in response to SMU-CX24 treatment, accompanying notable reductions in TLR3 expression and inflammation infiltration within atherosclerotic lesion. Thus, for the first time, we revealed that pharmacological downregulation of TLR3 with specific inhibitor regenerated inflammatory environment to counteract atherosclerosis progression, thereby proposing a new strategy and probe for atherosclerosis therapy.

Objective:To evaluate the current situation of comprehensive medical and health services of primary medical institutions in a city under the policy of family doctor contracted service, and explore the influencing factors and put forward improvement strategies, for the reference to improve the medical and health service level of primary medical institutions.Methods:In January 2021, 18 primary medical institutions in 3 counties(cities, districts) of a city in Shandong province were selected by stratified sampling method, and 60-70 contracted residents were selected from each institution for questionnaire survey. The questionnaire covered two dimensions: service provision(19 items) and metion frequency of health problems(12 items). According to the principle of information saturation, qualitative interviews were conducted with 20 family doctors and 15 contracted residents to identify the current service needs and existing problems. Descriptive analysis was used for all data, and single factor analysis of variance and multiple linear regression analysis were used for influencing factors of comprehensive service scores of primary medical institutions.Results:1 098 contracted residents were included in this study, and the comprehensive service score was 3.15±0.42. The vaccination, maternal health care and health education scored higher with 3.80±0.54, 3.70±0.64, 3.78±0.57 respectively; The dermatology, mental health counseling and family sickbed scored lower, with 2.27±1.20, 2.97±1.01 and 1.92±1.18 respectively. Contracted institution, gender, age and marital status were the influencing factors of comprehensive service scores( P<0.05). Residents′ needs for family sickbeds, psychological counseling and fall prevention had not been met. Conclusions:The primary medical institutions of the city had provided better basic public health services, while unmet needs were demand for home sickbeds, psychological counseling and fall prevention. We should take effective measures to increase the service supply based on the needs of residents, and provide more comprehensive medical and health services for residents at primary medical institutions.

Objective: To compare the outcomes of modified Appleby procedure and sub-adventitial divestment technique for locally advanced or borderline resectable pancreatic body cancer. Methods: A total of consecutive 58 patients(33 males and 25 females) who were diagnosed as locally advanced or borderline resectable pancreatic body cancer and underwent distal pancreatectomy at Pancreas Center, First Affiliated Hospital of Nanjing Medical University between September 2013 and May 2019 were retrospectively reviewed. The age(M(IQR)) was 62(9)years(range: 43 to 79 years). Thirty-one patients underwent distal pancreatectomy with celiac axis resection (DP-CAR) and 27 patients underwent distal pancreatectomy with sub-adventitial divestment technique(SDT). Perioperative parameters and follow-up data of these patients were analyzed. Quantitative data were compared with Wilcoxon test while categorical variables were compared with χ² test or Fisher's exact test. Survival results were estimated by the Kaplan-Meier survival method with a Log-rank test. Results: There were no differences in age,gender,body mass index,abdominal symptoms,comorbidity or preoperative serum CA19-9 between two groups(all P>0.05). Obvious preoperative weight loss was more common in the group of SDT(48.1%(13/27) vs. 19.4%(6/31),χ²=5.431,P=0.020). Longer operative time(310(123) minutes vs. 254(137)minutes, Z=2.277,P=0.023),higher rate of combined organ resection(41.9%(13/31) vs. 14.8%(4/27),χ²=5.123,P=0.041) and longer postoperative hospital stay(15(10) days vs. 11(5)days,Z=2.292,P=0.022) were observed in the group of DP-CAR. Moreover,rate of overall morbidities was also higher (71.0%(22/31) vs. 29.6%(8/27),χ²=9.876,P=0.003),implicated by clinically relevant postoperative pancreatic fistula(61.3%(19/31) vs. 29.6%(8/27),χ²=5.814,P=0.020) in the DP-CAR group. Tumor size of the DP-CAR group was bigger(4.9(1.5)cm vs. 4.0(1.2)cm,Z=2.343,P=0.019) but no difference was seen between the DP-CAR group and SDT group in R0+R1(<1 mm) resection rate (84.0%(21/25) vs. 90.0%(18/20),P=0.678) and LNR(12.0(23.0)% vs. 9.0(18.0)%,Z=1.238,P=0.216),as well as median disease free survival(11.7 months vs. 11.4 months,Z=0.019,P=0.892) and median overall survival(16.3 months vs. 13.7 months,Z=0.172,P=0.679). Conclusions: Both DP-CAR and distal pancreatectomy with SDT are relatively safe and feasible for locally advanced or borderline resectable pancreatic body cancer. Compared with arterial resection,SDT may contribute to lower rates of postoperative complications and shorter duration of hospitalization,but no significant benefit is seen in long-term survival.
Celiac Artery/surgery* ; Female ; Humans ; Male ; Pancreatectomy/methods* ; Pancreatic Neoplasms/pathology* ; Postoperative Complications ; Retrospective Studies

Objective: To investigate the functional changes of key gut microbiota (GM) that produce lipopolysaccharide (LPS) in atrial fibrillation (AF) patients and to explore their potential role in the pathogenesis of AF. Methods: This was a prospective cross-sectional study. Patients with AF admitted to Beijing Chaoyang Hospital of Capital Medical University were enrolled from March 2016 to December 2018. Subjects with matched genetic backgrounds undergoing physical examination during the same period were selected as controls. Clinical baseline data and fecal samples were collected. Bacterial DNA was extracted and metagenomic sequencing was performed by using Illumina Novaseq. Based on metagenomic data, the relative abundances of KEGG Orthology (KO), enzymatic genes and species that harbored enzymatic genes were acquired. The key features were selected via the least absolute shrinkage and selection operator (LASSO) analysis. The role of GM-derived LPS biosynthetic feature in the development of AF was assessed by receiver operating characteristic (ROC) curve, partial least squares structural equation modeling (PLS-SEM) and logistic regression analysis. Results: Fifty nonvalvular AF patients (mean age: 66.0 (57.0, 71.3), 32 males(64%)) were enrolled as AF group. Fifty individuals (mean age 55.0 (50.5, 57.5), 41 males(82%)) were recruited as controls. Compared with the controls, AF patients showed a marked difference in the GM genes underlying LPS-biosynthesis, including 20 potential LPS-synthesis KO, 7 LPS-biosynthesis enzymatic genes and 89 species that were assigned as taxa harbored nine LPS-enzymatic genes. LASSO regression analysis showed that 5 KO, 3 enzymatic genes and 9 species could be selected to construct the KO, enzyme and species scoring system. Genes enriched in AF group included 2 KO (K02851 and K00972), 3 enzymatic genes (LpxH, LpxC and LpxK) and 7 species (Intestinibacter bartlettii、Ruminococcus sp. JC304、Coprococcus catus、uncultured Eubacterium sp.、Eubacterium sp. CAG:251、Anaerostipes hadrus、Dorea longicatena). ROC curve analysis revealed the predictive capacity of differential GM-derived LPS signatures to distinguish AF patients in terms of above KO, enzymatic and species scores: area under curve (AUC)=0.957, 95%CI: 0.918-0.995, AUC=0.940, 95%CI 0.889-0.991, AUC=0.972, 95%CI 0.948-0.997. PLS-SEM showed that changes in lipopolysaccharide-producing bacteria could be involved in the pathogenesis of AF. The key KO mediated 35.17% of the total effect of key bacteria on AF. After incorporating the clinical factors of AF, the KO score was positively associated with the significantly increased risk of AF (OR<0.001, 95%CI:<0.001-0.021, P<0.001). Conclusion: Microbes involved in LPS synthesis are enriched in the gut of AF patients, accompanied with up-regulated LPS synthesis function by encoding the LPS-enzymatic biosynthesis gene.
Aged ; Atrial Fibrillation/complications* ; Cross-Sectional Studies ; Gastrointestinal Microbiome ; Humans ; Lipopolysaccharides ; Male ; Middle Aged ; Prospective Studies

OBJECTIVE: To explore the mechanism of Pi (Spleen)-deficiency-induced functional diarrhea (FD) model rats treated by Shenling Baizhu Powder (, SBP). METHODS: Thirty male Sprague-Dawley rats were randomly divided into 5 groups including control, model, low-, medium-, and high-dose SBP groups (SBPLDG, SBPMDG, SBPHDG), 6 rats in each group, respectively. Pi-deficiency-induced FD rats model was developed through Radix et Rhizoma Rhei gavage for 7 days. After modeling, the rats were treated with 3 doses of SBP [0.93, 1.86, and 3.72 g/(kg·d)], and the rats in the control and model groups were given pure water for 7 days. The diarrhea index was calculated. On the 7th and 14th days, the traveled distance of rat was measured by the open field test. Serum D-xylose content was determined by the phloroglucinol method and interleukin (IL)-10 and IL-17 levels were measured using an enzyme-linked immunosorbent assay kit. The content of Treg cells was determined by flow cytometry. RESULTS: Compared with the control group, the diarrhea index and IL-17 level in the model group were significantly higher and the total exercise distance and D-xylose content significantly decreased (P>0.05). The expression of IL-10 in the SBPHDG group was significantly up-regulated, and serum D-xylose level and Treg cells increased significantly compared with the model group (P>0.05). CONCLUSION High-dose SBP exhibited ameliorating effects against Pi-deficiency induced FD, which might be attributed to its modulations on intestinal absorption function as well as adaptive immunity in mesenteric lymph nodes of rat.

Objective:To analyze the cognition and willingness of family physicians on contracted service, and to explore the implementation obstacles and feasible strategies of implementing contracted service of family physicians from the perspective of suppliers.Methods:From July to October 2020, 850 family physicians in community health service centers or township health centers in three cities of Shandong Province were investigated by questionnaire survey and key person interview. Descriptive analysis and binary logistic regression model were used to analyze the willingness of family physicians to provide contracted service. Through questionnaire survey and key person interview, the implementation obstacles and service optimization strategies of family physicians were discussed.Results:791 valid questionnaires were obtained, of which 688(87.0%) approved the implementation of family physician contract service, and 679(85.8%) expressed willingness to provide family physician contract service. Marital status, recognition of service policy, satisfaction of service operation effect, optimistic degree of service development prospect and residents′ first choice of illness were the factors influencing family physician′s service willingness.Conclusions:We should effectively improve the family doctor′s service intention and promote the efficient and orderly implementation of family doctor′s contract service policy through enriching policy supporting measures, innovating the application of " Internet plus" , increasing personnel training, optimizing performance appraisal work and creating favorable public opinion environment.