1.Analysis of surgical situations and prognosis of pancreaticoduodenectomy in Jiangsu province (a report of 2 886 cases)
Zipeng LU ; Xin GAO ; Hao CHENG ; Ning WANG ; Kai ZHANG ; Jie YIN ; Lingdi YIN ; Youting LIN ; Xinrui ZHU ; Dongzhi WANG ; Hongqin MA ; Tongtai LIU ; Yongzi XU ; Daojun ZHU ; Yabin YU ; Yang YANG ; Fei LIU ; Chao PAN ; Jincao TANG ; Minjie HU ; Zhiyuan HUA ; Fuming XUAN ; Leizhou XIA ; Dong QIAN ; Yong WANG ; Susu WANG ; Wentao GAO ; Yudong QIU ; Dongming ZHU ; Yi MIAO ; Kuirong JIANG
Chinese Journal of Digestive Surgery 2024;23(5):685-693
Objective:To investigate the surgical situations and perioperative outcome of pancreaticoduodenectomy in Jiangsu Province and the influencing factors for postoperative 90-day mortality.Methods:The retrospective case-control study was conducted. The clinicopathological data of 2 886 patients who underwent pancreaticoduodenectomy in 21 large tertiary hospitals of Jiangsu Quality Control Center for Pancreatic Diseases, including The First Affiliated Hospital of Nanjing Medical University, from March 2021 to December 2022 were collected. There were 1 732 males and 1 154 females, aged 65(57,71)years. Under the framework of the Jiangsu Provincial Pancreatic Disease Quality Control Project, the Jiangsu Quality Control Center for Pancreatic Diseases adopted a multi-center registration research method to establish a provincial electronic database for pancrea-ticoduodenectomy. Observation indicators: (1) clinical characteristics; (2) intraoperative and post-operative conditions; (3) influencing factors for 90-day mortality after pancreaticoduodenectomy. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(IQR), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers or constituent ratio, and comparison between groups was conducted using the chi-square test, continuity correction chi-square test and Fisher exact probability. Maximal Youden index method was used to determine the cutoff value of continuous variables. Univariate analysis was performed using the corresponding statistical methods based on data types. Multivariate analysis was performed using the Logistic multiple regression model. Results:(1) Clinical characteristics. Of the 2 886 patients who underwent pancreaticoduodenectomy, there were 1 175 and 1 711 cases in 2021 and 2022, respectively. Of the 21 hospitals, 8 hospitals had an average annual surgical volume of <36 cases for pancreaticoduodenectomy, 10 hospitals had an average annual surgical volume of 36-119 cases, and 3 hospitals had an average annual surgical volume of ≥120 cases. There were 2 584 cases performed pancreaticoduodenectomy in thirteen hospitals with an average annual surgical volume of ≥36 cases, accounting for 89.536%(2 584/2 886)of the total cases. There were 1 357 cases performed pancrea-ticoduodenectomy in three hospitals with an average annual surgical volume of ≥120 cases, accounting for 47.020%(1 357/2 886) of the total cases. (2) Intraoperative and postoperative conditions. Of the 2 886 patients, the surgical approach was open surgery in 2 397 cases, minimally invasive surgery in 488 cases, and it is unknown in 1 case. The pylorus was preserved in 871 cases, not preserved in 1 952 cases, and it is unknown in 63 cases. Combined organ resection was performed in 305 cases (including vascular resection in 209 cases), not combined organ resection in 2 579 cases, and it is unknown in 2 cases. The operation time of 2 885 patients was 290(115)minutes, the volume of intra-operative blood loss of 2 882 patients was 240(250)mL, and the intraoperative blood transfusion rate of 2 880 patients was 27.153%(782/2 880). Of the 2 886 patients, the invasive treatment rate was 11.342%(327/2 883), the unplanned Intensive Care Unit (ICU) treatment rate was 3.087%(89/2 883), the reoperation rate was 1.590%(45/2 830), the duration of postoperative hospital stay was 17(11)days, the hospitalization mortality rate was 0.798%(23/2 882), and the failure rate of rescue data in 2 083 cases with severe complications was 6.529%(19/291). There were 2 477 patients receiving postoperative 90-day follow-up, with the 90-day mortality of 2.705%(67/2477). The total incidence rate of complication in 2 886 patients was 58.997%(1 423/2 412). The incidence rate of severe complication was 13.970%(291/2 083). The comprehensive complication index was 8.7(22.6) in 2 078 patients. (3) Influencing factors for 90-day mortality after pancreaticoduodenectomy. Results of multivariate analysis showed that age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment were independent risk factors for 90-day mortality after pancreaticoduodenectomy ( odds ratio=2.403, 2.609, 16.141, 95% confidence interval as 1.281-4.510, 1.298-5.244, 7.119-36.596, P<0.05). Average annual surgical volume ≥36 cases in the hospital was an independent protective factor for 90-day mortality after pancreaticoduodenectomy ( odds ratio=0.368, 95% confidence interval as 0.168-0.808, P<0.05). Conclusions:Pancreaticoduodenectomy in Jiangsu Province is highly con-centrated in some hospitals, with a high incidence of postoperative complications, and the risk of postoperative 90-day mortality is significant higher than that of hospitallization mortality. Age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment are independent risk factors for 90-day motality after pancreaticoduodenectomy, and average annual surgical volume ≥36 cases in the hospital is an independent protective factor.
2.Clinical efficacy of hypofractionated radiotherapy combined with immune checkpoint inhibitors in treating advanced metastatic solid tumors
Jia LIU ; Jian WANG ; Xiaowei GU ; Yiling CAI ; Jia HE ; Lingdi SUN ; Bo YU ; Zhongqin SHU ; Sha SHA
Journal of Clinical Medicine in Practice 2024;28(6):19-23
Objective To investigate the efficacy of hypofractionated radiotherapy (HFRT) combined with programmed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors in sequential with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) for the treatment of advanced metastatic solid tumors. Methods A prospective single-center single-arm study was designed for patients failed standard treatments for advanced refractory solid tumors in the Department of Radiotherapy of Jiangyin Hospital affiliated to Nantong University, and eligible patients were given quadruple therapy: HFRT (5 to 8 Gy × 2 to 3 f) once every 21 days for at least 2 cycles; 200 μg GM-CSF from the 1st to 7th day of radiotherapy, and 2 million IU IL-2 from the 8thto 14th day. Within 1 week after the completion of HFRT, PD-1/PD-L1 inhibitors were used for treatment. The above treatment strategy was repeated. GM-CSF and IL-2 were treated for 6 cycles, followed by maintenance with PD-1/PD-L1 inhibitors until disease progression (PD) or intolerable toxicity occurred. Objective response rate (ORR) and treatment-related adverse events were analyzed. Results From January 9, 2021 to June 15, 2023, totally 40 patients were enrolled, with follow-up of 2.8 to 31.0 months and a median follow-up of 9.9 months, and 39 patients (97.5%) completed at least one time tumorsite evaluation within the non-radiotherapy target area. 97.5% of patients had cancers, 2.5% had soft tissue sarcomas, and 20.0% had received immune checkpoint inhibitors (ICIs) at baseline check. The ORR was 30.8%, and the disease control rate (DCR) was 71.8%; the ORR for non-small cell lung cancer (NSCLC) was 28.6%, and the DCR was 57.1%; the ORR for colorectal cancer was 14.3%, and the DCR was 71.4%; the ORR for gastric cancer was 16.7%, and the DCR was 66.7%; 28 patients (70.0%) had treatment-related adverse events (TRAE), 4 patients (10%) had TRAE≥level 3, and the most common types of TRAE were fatigue, fever and hypothyroidism. Conclusion The treatment of HFRT combined with immune checkpoint inhibitors in sequential with GM-CSF and IL-2 is well tolerated and toxicity accepted in patients with advanced metastatic solid tumors, which may provide a new method for salvage treatment of patients with advanced metastatic solid tumors.
3.Research progress in the molecular mechanisms and prevention strategies of ovarian injury related to cervical cancer radiotherapy
Huafang YIN ; Sha SHA ; Yiling CAI ; Bo YU ; Jia LIU ; Jia HE ; Lingdi SUN ; Jian WANG
Journal of Clinical Medicine in Practice 2024;28(10):141-144
Radiotherapy, as an important means of tumor treatment, plays a significant role in the treatment of cervical cancer. However, the ovaries are highly sensitive to radiation, which is prone to appear radiation-related injuries, leading to ovarian dysfunction and loss of fertility in young female patients, seriously affecting their physical and mental health. The degree of ovarian injury is influenced by various factors such as the dose, volume, and duration of radiation exposure to the ovaries, as well as the patient's age. Ovarian displacement and advancements in radiotherapy techniques can significantly relieve radiation-related ovarian injury. Currently, drug protection techniques are still immature, and new fertility preservation methods are receiving increasing attention but require further improvement. This article reviewed the research progress in the molecular mechanisms, prevention strategies, and new fertility preservation techniques for ovarian injury related to cervical cancer radiotherapy, aiming to provide a reference for ovarian function protection during radiotherapy for young cervical cancer patients.
4.Protein expression, purification and mouse antiserum preparation of monkeypox virus A23R.
Yihao WANG ; Mingzhi LI ; Mengle JIA ; Lingdi YANG ; Jiaqi XIONG ; Ting WANG ; Yu WANG ; Shurong LIU ; Wenli GUO ; Lingbao KONG ; Meifeng LI
Chinese Journal of Cellular and Molecular Immunology 2023;39(7):642-648
Objective To express the monkeypox virus (MPXV) A23R protein in Escherichia coli and purify by Ni-NTA affinity column, and to prepare mouse antiserum against MPXV A23R. Methods The recombinant plasmid pET-28a-MPXV-A23R was constructed and transformed into Escherichia coli BL21 to induce the expression of A23R protein. After optimizing the conditions of expression, A23R protein was highly expressed. Recombinant A23R protein was purified by Ni-NTA affinity column and identified by Western blot analysis. The purified protein was used to immunize mice for preparing the A23R polyclonal antibody, and the antibody titer was detected by ELISA. Results The expression of A23R recombinant protein reached the peak under the induced conditions of 0.6 mmol/L isopropyl-β-D-thiogalactoside (IPTG), 37 DegreesCelsius and 20 hours. The purity of the protein was about 96.07% and was identified by Western blot analysis. The mice were immunized with recombinant protein, and the titer of antibody reached 1:102 400 at the 6th week after immunization. Conclusion MPXV A23R is expressed highly and purified with a high purity and its antiserum from mouse is obtained with a high titre.
Animals
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Mice
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Monkeypox virus
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Antibodies
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Enzyme-Linked Immunosorbent Assay
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Blotting, Western
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Recombinant Proteins
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Escherichia coli/genetics*
5.Emphasis on targeted and immunotherapy for liver injury in hepatocellular carcinoma
Yuemin NAN ; Lingdi LIU ; Suxian ZHAO
Chinese Journal of Hepatology 2023;31(11):1121-1124
Treatment with molecular targeted drugs and immune checkpoint inhibitors (ICIs) has become the first-line treatment options for unresectable HCC (hepatocellular carcinoma) and is also one of the anti-recurrence therapies of choice for patients at high risk of recurrence following radical treatment. First-line molecular targeted drugs combined with ICIs or dual-immune therapy significantly increase the median overall survival and objective response rate compared to single-targeted drugs. Targeted therapy and immunotherapy are suitable for HCC patients with Child-Pugh classes A~B. Liver damage caused by targeted drugs includes abnormal transaminases and bilirubin and, in severe cases, hypoproteinemia, ascites, and other occurrences. ICIs-associated immune-mediated hepatitis (IMH) mostly occurs within one to three sessions of treatment (4~12 weeks) and can be treated with glucocorticoids. However, immunosuppressants such as mycophenolate mofetil may be used as necessary.Targeted drugs and ICIs with different mechanisms of action can be selected based on the systemic condition and tumor treatment needs following the restoration of normal liver function.
6.A clinical study of targeted immunotherapy combined with hepatic arterial chemoembolization in the treatment of liver injury associated with primary liver cancer
Lingdi LIU ; Shiming DONG ; Yuanyuan LI ; Yuemin NAN
Chinese Journal of Hepatology 2023;31(11):1156-1162
Objective:To investigate the conditions of occurrence and factors influencing liver injury caused by molecular targeted drugs and immune checkpoint inhibitors combined with hepatic arterial chemoembolization (TACE) in the treatment of primary liver cancer.Methods:105 cases of primary liver cancer admitted to the Third Hospital of Hebei Medical University from January 2020 to June 2023 were selected. Patients liver biochemical indicators conditional changes before and after treatment with targeted drugs+TACE and targeted drugs+immune checkpoint inhibitors (ICIs)+TACE were analyzed. Liver injuries above grade 2 and its independent risk factors to predict and evaluate model accuracy were established. Independent samples t-test, analysis of variance, and rank sum test were used for comparison of measurement data between groups. Count data were compared with a χ2 test between groups. Results:A total of 50 (47.62%) of the 105 cases developed liver injury during the treatment course, with 26 (52%) cases of first-grade liver injury, 16 (32%) cases of second-grade liver injury, 8 (16%) cases of third-grade liver injury, and none of fourth-grade liver injury. There was no statistically significant difference in the incidence of liver injury between the two groups of patients ( χ2=1.299, P = 0.637). Multivariate logistic regression analysis showed that total bilirubin, prealbumin, and prothrombin activity were independent risk factors for the occurrence of liver injury. The total bilirubin-prealbumin-prothrombin activity (TAP) model was established. TAP diagnosis of grade 2 or higher liver injury had an area under the receiver characteristic curve of 0.935, sensitivity of 84.35%, and specificity of 92.31% at a cut-off value of 1.24, and significantly better diagnostic performance than albumin-bilirubin (ALBI) grade. Conclusion:The occurrence of severe liver injury is minimal and well tolerated in the targeted drug + TACE treatment group and targeted drug + ICIs + TACE treatment group. The TAP model can be used as a new method to assess the risk of liver injury above grade 2 in patients treated with targeted immunotherapy combined with TACE.
7.Reliability and validity of community commitment scale in community-dwelling elderly
Mei ZHANG ; Lina GUO ; Lingdi MENG ; Kun LIU
Chinese Journal of Behavioral Medicine and Brain Science 2021;30(8):751-755
Objective:To explore the reliability and validity of the community commitment scale (CCS) in community-dwelling elderly people.Methods:From May to August in 2020, a total of 526 community-dwelling elderly were investigated by community commitment scale, community's self-efficacy scale for preventing social isolation (CSES). SPSS 25.0 and AMOS 22.0 softwares were used to analyze the reliability and validity.Results:The overall Cronbach's α coefficient of the community commitment scale was 0.818, and the Cronbach's α coefficients of social and belonging dimensions were 0.750 and 0.777, respectively. The Guttman split-half reliability coefficients were 0.799-0.835, and the test-retest reliability was 0.802. Each item-to-total score correlations were 0.614-0.753 (all P<0.05). The item level content validity index (I-CVI) was 0.830-1.000, the scale level content validity index (S-CVI/UA) was 0.875, and the average content validity index (S-CVI/Ave) was 0.972. Two common factors were extracted by exploratory factor analysis, and the cumulative variance contribution rate was 57.019%. The confirmatory factor analysis all indicators reached the adaptation standard (χ 2/ df=2.638, RMSEA=0.079, GFI=0.957, AGFI=0.918, TLI=0.936, CFI=0.956, IFI=0.957), and standardized regression coefficients were 0.63-0.80. Conclusion:The Chinese version of the community commitment scale has good reliability and validity and can be used to evaluate the social isolation of the elderly in the community.
8.Study on plasma Golgi protein 73 and related models in the diagnosis of nonalcoholic fatty liver disease
Yiqi WANG ; Xiwei YUAN ; Dongdong LI ; Yuhui TANG ; Ningning XUE ; Luyao CUI ; Lingdi LIU ; Yuemin NAN
Chinese Journal of Hepatology 2021;29(12):1170-1176
Objective:To investigate the relationship between plasma Golgi protein 73 (GP73) levels and the occurrence and development of non-alcoholic fatty liver disease (NAFLD), and to establish a diagnostic model based on this combination with lipid metabolism indicators to clarify its diagnostic efficacy and clinical application value for NAFLD.Methods:225 cases with NAFLD [diagnosed by ultrasound, transient elastography (FibroScan502) and liver biopsy (some patients)] and 108 healthy controls were selected from the Department of Hepatology and Physical Examination Center of Integrated Traditional Chinese and Western Medicine, The Third Hospital of Hebei Medical University. Clinical data, routine peripheral blood and serum biochemical test results were collected. The plasma GP73 level was detected by enzyme-linked immunosorbent assay. SPSS 21.0 statistical software was used for statistical analysis. Binary logistic regression model was used to calculate the NAFLD diagnostic model. Receiver operating characteristic curve was used to evaluate the NAFLD constructed model diagnostic efficacy.Results:NAFLD incidence was significantly reduced in younger age group, mostly in young and middle-aged male. However, the NAFLD incidence was increased with increasing age in female. The analysis of age ratio composition showed that the average age for NAFLD onset was 20 ~ 50 years old, and the incidence rate was as high as 47% in among 30 ~ 39 years old, but the incidence rate was significantly decreased in over 60 years old (4.00%). GP73 was an independent risk factor for the occurrence and development of NAFLD. The diagnostic models of GBT, GB and GT were established by GP73 (G) combined with body mass index (BMI, B) and serum triglyceride (TG, T), and the results showed that the areas under the curves of GBT, GB and GT models were 0.969, 0.937 and 0.909, respectively. The sensitivity and the specificity were 84.90%, 77.80% and 84.00%, and 95.40%, 95.40% and 82.40%, respectively, P < 0.05. The GBT model had efficacy of best diagnostic performance. Conclusion:NAFLD is more common in young and middle-aged male, but with advanced age, the incidence of female patients gradually increases. Plasma GP73 levels are related to the occurrence and development of NAFLD. The GBT model can be used as a new model for non-invasive diagnosis and one of the indicators for clinical evaluation of diagnostic efficacy of NAFLD.
9.Clinical study of yiqi huoxue recipe in the treatment of liver fibrosis of chronic viral hepatitis
Luyao CUI ; Xiaoxiao ZHANG ; Po CUI ; Wencong LI ; Yuguo ZHANG ; Rongqi WANG ; Suxian ZHAO ; Weiguang REN ; Lingbo KONG ; Fang HAN ; Xiwei YUAN ; Lingdi LIU ; Ying ZHANG ; Qingshan ZHANG ; Li KONG ; Yuemin NAN
Chinese Journal of Hepatology 2020;28(5):403-409
Objective:To clarify the clinical efficacy of Yiqi Huoxue recipe in the treatment of liver fibrosis of chronic viral hepatitis.Methods:An open, positive-drug, parallel-controlled study method was applied. A total of 207 cases of liver fibrosis with chronic hepatitis B and C diagnosed with liver biopsy and transient elastography were selected. According to the principle of syndrome differentiation in traditional Chinese medicine, self-made Yiqi Huoxue recipe ( n = 127) and Fuzheng Huayu capsule ( n = 80) were used for the treatment course of 24-48 weeks. Change score of TCM symptom, liver biochemistry, liver stiffness measurement (LSM), and noninvasive liver fibrosis index [aspartate transaminase to platelet ratio index (APRI), and fibrosis-4 score (FIB-4)] were compared between the two groups to evaluate the therapeutic effect of Yiqi Huoxue recipe on liver fibrosis. Results:Yiqi Huoxue recipe group and Fuzheng Huayu capsule group baseline LSM, APRI and FIB-4 was compared, and there was no statistically significant difference between them ( P > 0.05). Yiqi Huoxue recipe and Fuzheng Huayu capsule received patients had improved symptom scores to a certain extent. Hepatic facies, discomfort over liver area, and soreness and weakness of waist and knees ( P < 0.05) was significantly improved in Yiqi Huoxue recipe than Fuzheng Huayu capsule. Liver biochemical indicators (ALT, AST, GGT, ALP) had gradually relapsed with the extension of treatment duration and the normalization rate between the two groups after 24 to 48 weeks had reached 100% vs. 100%, 100% vs. 93.8%, 96.8% vs. 92.3% and 87.5% vs. 81.8%. After 12 weeks of treatment, APRI values ??of both groups had significantly reduced, and after 48 weeks of treatment, LSM values of both groups had significantly improved. Moreover, Yiqi Huoxue recipe FIB-4 score was significantly improved after 48 weeks of treatment, and the difference was statistically significant compared to Fuzheng Huayu capsule group ( P < 0.05). After treatment, LSM, APRI, and FIB-4 total effectiveness in the two groups were 80.0% vs. 63.6%, P = 0.046; 68.4% vs. 52.0%, P = 0.052; 68.4% vs. 62.0%, P = 0.437, respectively. LSM total effectiveness was significantly higher in Yiqi Huoxue recipe treated group than Fuzheng Huayu capsule group. Conclusion:Traditional Chinese medicine Yiqi Huoxue decoction can be used as an optimal treatment for liver fibrosis of chronic viral hepatitis.
10.Diagnosis and treatment strategies for end-stage liver disease combined with infection
Chinese Journal of Hepatology 2020;28(7):545-547
Patients with end-stage liver disease are more likely to be infected due to the changes in the liver’s internal environment, low immune defense capabilities and reduced gut barrier function. Common infections include pneumonia, spontaneous bacterial peritonitis, biliary and urinary tract infections, skin and soft tissue infections, and spontaneous bacteremia, which in severe cases can lead to sepsis and septic shock. Importantly, infections can aggravate and progress to the liver and damage correlated organs, and thus can be life-threatening in severe cases. Therefore, early detection and diagnosis, as well as the use of effective antibacterial agents, and supportive treatment are keys to saving patients' lives.


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