Objectives: To construct a nomogram for prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis based on inflammation-related markers,and to conduct its clinical verification. Methods: Clinical and pathological data of 858 ICC patients who underwent radical resection were retrospectively collected at 10 domestic tertiary hospitals in China from January 2010 to December 2018. Among the 508 patients who underwent lymph node dissection,207 cases had complete variable clinical data for constructing the nomogram,including 84 males,123 females,109 patients≥60 years old,98 patients<60 years old and 69 patients were pathologically diagnosed with positive lymph nodes after surgery. Receiver operating characteristic curve was drawn to calculate the accuracy of preoperative imaging examinations to determine lymph node status,and the difference in overall survival time was compared by Log-rank test. Partial regression squares and statistically significant preoperative variables were screened by backward stepwise regression analysis. R software was applied to construct a nomogram,clinical decision curve and clinical influence curve,and Bootstrap method was used for internal verification. Moreover,retrospectively collecting clinical information of 107 ICC patients with intraoperative lymph node dissection admitted to 9 tertiary hospitals in China from January 2019 to June 2021 was for external verification to verify the accuracy of the nomogram. 80 patients with complete clinical data but without lymph node dissection were divided into lymph node metastasis high-risk group and low-risk group according to the score of the nomogram among the 858 patients. Log-rank test was used to compare the overall survival of patients with or without lymph node metastasis diagnosed by pathology. Results: The area under the curve of preoperative imaging examinations for lymph node status assessment of 440 patients was 0.615,with a false negative rate of 62.8% (113/180) and a false positive rate of 14.2% (37/260). The median survival time of 207 patients used to construct a nomogram with positive or negative postoperative pathological lymph node metastases was 18.5 months and 27.1 months,respectively (P<0.05). Five variables related to lymph node metastasis were screened out by backward stepwise regression analysis,which were combined calculi,neutrophil/lymphocyte ratio,albumin,liver capsule invasion and systemic immune inflammation index,according to which a nomogram was constructed with concordance index(C-index) of 0.737 (95%CI: 0.667 to 0.806). The C-index of external verification was 0.674 (95%CI:0.569 to 0.779). The calibration prediction curve was in good agreement with the reference curve. The results of the clinical decision curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.32,the maximum net benefit could be obtained by 0.11,and the cost/benefit ratio was 1∶2. The results of clinical influence curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.6,the probability of correctly predicting lymph node metastasis could reach more than 90%. There was no significant difference in overall survival time between patients with high/low risk of lymph node metastasis assessed by the nomogram and those with pathologically confirmed lymph node metastasis or without lymph node metastasis (Log-rank test:P=0.082 and 0.510,respectively). Conclusion: The prediction accuracy of preoperative nomogram for ICC lymph node metastasis based on inflammation-related markers is satisfactory,which can be used as a supplementary method for preoperative diagnosis of lymph node metastasis and is helpful for clinicians to make personalized decision of lymph node dissection for patients with ICC.

Objective: To establish a survival prediction model based on the independent prognostic factors of long-term prognosis after laparoscopic liver resection(LLR) for intrahepatic cholangiocarcinoma(ICC). Methods: The clinical and pathological data of 351 consecutive patients with ICC who received radical LLR in 13 Chinese medical centers from August 2010 to May 2021 were collected retrospectively. There were 190 males and 161 females,aged(M(IQR)) 61(14)years(range:23 to 93 years). The total cohort was randomly divided into a training dataset(264 cases) and a validation dataset(87 cases). The patients were followed up by outpatient service or telephone,and the deadline for follow-up was October 2021. Based on the training dataset,the multivariate Cox proportional hazards regression model was used to screen the independent influencing factors of long-term prognosis to construct a Nomogram model. The Nomogram model's discrimination,calibration,and clinical benefit were evaluated through internal and external validation,and an assessment of the overall value of two groups was made through the use of a receiver operating characteristic(ROC) curve. Results: There was no significant difference in clinical and pathological characteristics and long-term survival results between the training and validation datasets(all P>0.05). The multivariate Cox analysis showed that CA19-9,CA125,conversion to laparotomy during laparoscopic surgery,and lymph node metastasis were independent prognostic factors for ICC patients after LLR(all P<0.05). The survival Nomogram was established based on the independent prognostic factors obtained from the above screening. The ROC curve showed that the area under the curve of 1, 3 and 5-year overall survival rates of patients in the training dataset were 0.794(95%CI:0.721 to 0.867),0.728(95%CI:0.618 to 0.839) and 0.799(95%CI:0.670 to 0.928),and those in the validation dataset were 0.787(95%CI:0.660 to 0.915),0.831(95%CI:0.678 to 0.983) and 0.810(95%CI:0.639 to 0.982). Internal and external validation proved that the model exhibited a certain discrimination,calibration,and clinical applicability. Conclusion: The survival Nomogram model based on the independent influencing factors of long-term prognosis after LLR for ICC(including CA19-9,CA125,conversion to laparotomy during laparoscopic surgery,and lymph node metastasis) exhibites a certain differentiation,calibration,and clinical practicability.
Bile Duct Neoplasms/surgery* ; Bile Ducts, Intrahepatic/pathology* ; CA-19-9 Antigen ; Cholangiocarcinoma/diagnosis* ; Female ; Humans ; Laparoscopy ; Lymphatic Metastasis ; Male ; Nomograms ; Prognosis ; Retrospective Studies

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*

The aim of the present study was to determine the metabolic changes and possible toxic mechanisms of ketamine-associated bladder toxicity. Twenty-four male Sprague-Dawley (SD) rats were randomly allocated into a control group, a low-dose group and a high-dose group. The behavior of these rats was observed every day. In addition, the weight, 2 h urinary frequency and organ coefficient of the bladder were measured. Serum IL-6 and TNF-α levels were measured using an enzyme-linked immunosorbent assay (ELISA). Urinary metabolites were analyzed using gas chromatography-mass spectrometry (GC-MS). This research was approved by the Ethics Committee of the Animal Experiment Center of Southwest Medical University (No. 201901-98). After 12 weeks of administration, the frequency of 2 h urination and the bladder mass index were significantly different in the low-dose and high-dose groups compared with the control group. Serum IL-6 and TNF-α levels were higher than those of the control group (P<0.05). Bladder HE staining showed that long-term administration of ketamine could induce cystitis. The concentrations of the three common differential metabolites, including 3-aminoisobutyric acid, citric acid and uric acid in the low-dose and the high-dose groups were increased compared with those in the control group. This study indicates that 3-aminoisobutyric acid, citric acid and uric acid and their related metabolic pathways may be closely related to ketamine-associated bladder toxicity.

Periplocae Cortex is a traditional Chinese medicine in China, which is mainly produced in northeast China, north China, northwest China, southwest China. In recent years, the increasing in-depth research resulted in the discovery of anti-tumor and cardiac pharmacological activities of Periplocae Cortex, which has broad application prospects. On the basis of summarizing chemical components and pharmacological effects, combined with the theoretical system of Q-marker, the quality control components of Periplocae Cortex were predicted from the aspects of the correlation between chemical composition and traditional medicinal properties, traditional efficacy, and new clinical use, plasma composition, measurable composition, storage time by analyzing literature. Among the components, periplocoside, periplocin, periplogenin, 4-methoxy salicylaldehyde showed significant activity, which provides a scientific basis for quality evaluation of Periplocae Cortex.
Biomarkers ; China ; Drugs, Chinese Herbal ; analysis ; Medicine, Chinese Traditional ; Quality Control

Aconiti Radix is a commonly used traditional Chinese medicine( TCM) herb in clinic,with the effects in expelling wind and removing damness,warming menstruation and relieving pain. With a long medicinal history and high medicinal value,it was used for anemofrigid-damp arthralgia,arthralgia,cold hernia and anesthesia analgesia. Modern pharmacological studies have shown that Aconiti Radix has a good therapeutic effect on rheumatoid arthritis,neuropathic pain and hypertension. As a well-known toxic TCM herb,its main pharmacodynamic and toxic components are alkaloids,which can lead to neurotoxicity and cardiotoxicity while exerting anti-inflammatory,analgesic,anti-tumor and other pharmacodynamic effects. Therefore,it is often processed to reduce its toxicity or combined with Paeoniae Radix Alba and Stephaniae Tetrandrae Radix to achieve the purpose of reducing toxicity and increasing efficacy in clinic.In recent years,with the deepening of the study on the incompatibility of TCM represented by " eighteen incompatible herbs",there have been new findings about TCM incompatibility. It has been found complementary effect,rather than no obvious toxic and side effects after the combination with incompatible herbs of Aconiti Radix. To provide the basis for further study and clinical application of Aconiti Radix,this paper reviewed chemical components,pharmacological action,toxicity and compatibility of Aconiti Radix by consulting relevant literatures published in recent years at home and abroad. Meanwhile,this paper also described the relationship between chemical constituents,as well as anti-inflammatory,analgesic,anti-tumor and other pharmacological effects and toxicity.
Aconitum ; chemistry ; Alkaloids ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Medicine, Chinese Traditional ; Plant Roots ; chemistry

Objective: To compare the sensitivity of 8-color panels and next generation flow cytometry (NGF) for detecting minimal residual disease of multiple myeloma patients. Methods: 8-color-membrane antigens (8C-Mem) panel was built including CD45, CD38, CD138, CD19, CD56, CD81, CD27 and CD117 to identify the plasma cells, while 8-color-cytoplasmic antigens (8C-Cyto) panel was built including CD45, CD38, CD138, CD19, CD56, CD81, cKappa (cK) and cLambda (cλ) , and 8-color-two-tubes (8C-2tubes) panel were built including 8C-Mem and 8C-Cyto panels, the data of three groups was analyzed by Diva software. NGF uses Infinicyt software to fuse 8C-2tubes data to further analyze the expression of plasma antigens. Bone marrow aspiration obtained from 20 controls and 76 multiple myeloma patients who achieved complete remission were measured and analyzed. Results: Positive MRD samples were discriminated in 88.2% of the specimen evaluated through either abnormal plasma cells (aPCs) or clonal plasma cells (cPCs) by NGF antigens panel, Among of them, consistency was 94.7%. The median percentage of cPCs was 0.3530%, The lowest sensitivity of NGF was 0.0003%. In 8-color panels, the positive MRD rates of 8C-Mem, 8C-Cyto and 8C-2tubes panels were 84.2%, 85.5% and 86.8%, respectively, which lower than that of NGF (P<0.001) . The positive MRD rate of 8C-Mem and 8C-Cyto panels were lower than that of 8C-2tubes panel (P<0.001) , and the positive MRD rate of 8C-Mem panel was lower than that of 8C-Cyto panel (P<0.001) . Sensitivity and specificity of NGF was higher than that of 8-color panels. 8C-2tubes panel has the best sensitivity, accuracy, negative predicted value, positive predicted value and specificity than other 8-color panels. However, huge data and low efficiency for analysis is the disadvantage. 8C-Cyto panel was the second choice, and 8C-Mem panel was the last. Conclusions: Membrane and cytoplasmic light chain is a better method for multiple myeloma-MRD detection and NGF panel is an ideal approach. 8C-Cyto panel is recommended in 8-MFC groups.
Bone Marrow ; Flow Cytometry ; Humans ; Immunophenotyping ; Multiple Myeloma/diagnosis* ; Neoplasm, Residual ; Plasma Cells

Objective:Our study was aimed to analyze the therapeutic effect of early sequential enteral nutrition on postoperative rehabilitation in patients with gastric cancer.Methods:Patients with gastric cancer receiving surgery at our hospital from 2016 to 2017 included and the clinical information was prospective collected and analyzed.Patients were randomly divided into two groups using random number table.Patients in group A were sequentially given amino acid type,short peptide type and then whole protein type,while those in group B received whole protein formulation only.The recovery of gastrointestinal function,postoperative systemic inflammatory response,six-minutes walking test,and enteral nutrition-related complications were compared between the two groups.Results:A total of 71 patients were included in this study (Group A 36 cases,Group B 35 cases).There was no significant difference in terms of the restart anal exhaust between the two groups (P ＞ 0.05).Patients in group A had a significantly shorter postoperative hospitalization (t =4.070;P ＜ 0.01) and the earlier restoration of oral intake than that of Group B (t =3.400;P =0.001).One week after surgery,the levels of CRP (t =2.547;P =0.013) and IL-6 (t =3.172;P =0.002) were significant lower in group A when compared with group B.In addition,patients in group A had a significant higher six minutes walk steps than those in Group B [(416.1 + 36.7) m vs (358.9 ± 32.7) m;t =6.927,P ＜ 0.01].However,no significant difference in enteral nutrition-related complications was found between the two groups (P ＞ 0.05).Conclusion:In patients with gastric cancer,early sequential enteral nutrition can effectively accelerate the postoperative rehabilitation.

Objective To observe the clinical efficacy and safety of butylphthalide injection combined with atorvastatin tablets in the treatment of patients with cerebral infarction.Methods A total of 100 patients with cerebral infarction were randomly divided into control group (n =48 cases) and treatment group (n =52 cases).Control group was treated with aspirin enteric-coated tablets 200 mg + atorvastatin 10 mg,orally,Ginkgo leaf extract and dipyridamole injection 20 mL intravenous drip,qd.Treatment group was treated with butylphthalide injection 100 mL on the basis of control group,intravenous drip,2 times a day.All patients were treated for 20 d.The levels of low density lipoprotein (LDL),fasting blood glucose,2 h postprandial blood glucose,fibrinogen,platelet count,National Institute of Health stroke scale (NIHSS),Barthel index and adverse drug reactions were compared between the two groups.Results After treatment,the total effective rates of treatment group and control group were 92.31％ (45 cases/52 cases),75.00％ (36 cases/48 cases),with significant difference (P ＜ 0.05).After treatment,the 2 h postprandial blood glucose in treatment group and control group were (7.30 ± 0.61),(7.05 ± 0.48) mmol · L-1,fibrinogen were (3.55 ± 0.14),(3.45 ± 0.11) g · L-1,low density lipoprotein were (2.67 ± 0.42),(3.13 ± 0.41) mmol · L-1,fasting blood glucose were (4.69±0.31),(5.12±0.50) mmol·L-1,platelet count were (211.14±7.71) ×109/L,(221.23 ±7.81) × 109/L,all with significant difference (all P ＜ 0.05).After treatment,the NIHSS scores of treatment group and control group were 8.28 ± 2.36,13.50 ± 4.24,Barthel index were 73.67 ± 11.32,57.91 ± 9.87,all with significant difference (all P ＜0.05).The incidence of adverse drug reactions in treatment group and control group were 9.62％ (5 cases/52 cases) and 6.25％ (3 cases/48 cases),with no significant difference (P ＜ 0.05).Conclusion Butylphthalide combined with atorvastatin calcium tablets in the treatment of patients with cerebral infarction had significant clinical effect,with high safety.

Objective: To detect the clinical relevance of mannose-binding lectin 2 (MBL2) gene polymorphism and sepsis in Chinese lived in Hainan island. Methods: Blood samples from 57 patients with sepsis and 69 patients without sepsis were collected in the ICU of several large hospitals in Hainan province. Genomic DNA was extracted from whole blood and then PCR purification product was sequenced and typed by 3730 sequencing analyzer. The concentration of MBL2 in serum was detected by ELISA. Results: We found that genotype and allele distributions in two groups were in accordance with the Hardy-Weinberg Equilibrium. The frequency of GA genotype was significantly higher than that in non-sepsis group (P=0.013). A allele frequency in sepsis group was also much higher than that in non-sepsis group (P=0.028). Logister regression analysis showed that the patients who carried A allele were more prone to get sepsis than G allele carrier (P=0.014, 0R=2.550, 95%CI=1.207-5.386). The MBL2 level in serum of sepsis patients with genotype GG and GA was significantly lower than that in non-sepsis group (P<0.05). In sepsis group, the MBL2 serum level of patients with genotype GA was obviously lower than that in patients with genotype GG (P<0.05). Conclusions: The variation of rs1800450 G→A increased the incidence of sepsis and decreased the level of MBL2 in serum.