Objective:To analyze the values of platelet transforming growth factor-β (TGF-β) and SMAD family member 2 (Smad2) in patients′ peripheral platelets for CRC diagnosis and staging.Methods:Retrospective case-control study. Tumor tissues, paratumor tissues and peripheral blood samples were collected from 248 CRC patients (147 males, 101 females; age 21-93 years) diagnosed in the First Hospital of Jilin University from October 10th, 2020, to March 10th, 2025. Peripheral blood samples were also collected from 40 colorectal adenomatous polyp patients (21 males, 19 females; age 22-74 years) and 75 healthy individuals (43 males, 32 females; age 18-81 years) during the same period. Tissue homogenates and platelets were isolated using tissue disruption and gradient centrifugation, respectively. Total RNA was respectively extracted from tissues and platelets, and the expression levels of TGF-β and Smad2 were quantified by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) expressed as relative quantity 2 -ΔΔCt. Differences of TGF-β and Smad2 expression were compared between CRC tissues and adjacent tissues, as well as among CRC patients, polyp patients, and healthy controls. The relationship of platelet TGF-β and Smad2 expression with pathological features includingtumor stage, pathological type, and metastasis were analyzed. The efficiency of platelet TGF-β, Smad2, and their combination in diagnosing CRC was evaluated using receiver operating characteristic (ROC) curves. Results:The expression levels of TGF-β and Smad2 in CRC tumor tissues[1.09 (0.45, 2.00), 2.93 (0.78, 6.73)] were significantly higher than those in adjacent tissues[0.81 (0.27, 1.50), 1.29 (0.40, 2.63)] ( Z TGF-β=4.54, Z Smad2=6.67, both P<0.001). The expression levels of TGF-β and Smad2 in platelets of CRC patients[2.73(1.53, 4.38), 3.16 (1.58, 4.38)] were significantly higher than those in the colorectal polyp group[1.23(0.70, 2.54), 1.16(0.78, 2.27)] and the healthy control group[0.96(0.51, 1.88), 0.92 (0.55, 1.88)] ( H TGF-β=59.71, H Smad2=78.74, both P<0.001). Platelet TGF-β expression increased progressively with tumor stage (stage 1-4) ( P<0.05), while platelet Smad2 levels were higher in metastatic CRC compared with non-metastatic cases ( P<0.05). ROC curve analysis showed that the area under the curve (AUC) for diagnosing CRC when combining platelet TGF-β and Smad2 was 0.81[95%Confidence interval( CI) 0.77—0.86], which was 0.90 (95% CI 0.86—0.93) if adding serum carcinoembryonic antigen (CEA). Conclusion:Platelet TGF-β and Smad2 expression correlates with the diagnosis and staging of CRC, demonstrating potential as liquid biopsy biomarkers for colorectal malignancies.

Objective:To establish and optimize the cutoff values of D-dimer (D-D) for excluding suspected acute pulmonary embolism (APE).Methods:A retrospective cross-sectional study was conducted by recruiting a total of 428 patients with suspected APE complaining of chest pain, hemoptysis, dyspnea, etc., who underwent computed tomography pulmonary angiography (CTPA) in the Emergency Department of the First Hospital of Jilin University from January 1st, 2022, to October 31st, 2024, taken as observation group. The Median age was 64.0 (55.0, 72.0) years old with male and female 214 respectively. Data collection included clinical manifestations(hemoptysis, swelling and pain in the lower limbs), deep vein thrombosis (DVT) history, Wells scores, laboratory results, CTPA and vascular ultrasound foundings. According to CTPA results, observation group was divided into APE group (233 cases) and non-APE group (195 cases); according to Wells scoring, observation group was divided into APE at low, moderate, or high pre-test probability subgroups. Meanwhile, 196 healthy individuals in the same period were included as the health control group. D-D levels were compared among different groups. Receiver operating characteristic (ROC) curve analysis was used to determine the D-D cutoff values for excluding APE, and the area under the curve (AUC) and negative predictive value (NPV) were evaluated.Results:D-D levels in the CTPA-APE group, CTPA-non APE group, and the healthy control group were [7.77 (4.10, 16.58)] mg/L, [0.53 (0.24, 0.94)] mg/L, and [0.21 (0.15, 0.32)] mg/L, respectively, with statistically significant differences ( P<0.05). In the APE group, D-D levels within low-, moderate-, and high-probability subgroups were [7.48 (3.87, 15.85)] mg/L, [7.92 (4.08, 13.90)] mg/L, and [21.39 (7.92, 89.68)] mg/L, respectively, with statistically significant differences among subgroups ( P<0.05), while no significant difference between low-and moderate-probability subgroups ( P>0.05). For suspected APE with low-probability, exclusive D-D level was 0.62 mg/L with AUC and NPV at 1.000 and 100% taking healthy control group as negative control, and 1.65 mg/L with AUC and NPV at 0.989 and 94.00% taking non-APE group as negative control, while the optimized D-D level was 1.10 mg/L adjusted by NPV ≥98%. For suspected APE with low to moderate-probability, the exclusive D-D level was 0.55 mg/L with AUC and NPV at 0.997 and 99.00% taking healthy control group as negative control, and 1.64 mg/L with AUC and NPV at 0.979 and 92.60%, while the optimized D-D level was 0.55 mg/L adjusted by NPV ≥98%. Conclusion:This study established and optimized the exclusive diagnostic cutoff value of D-D for suspected APE in Emergency Department integrated with the Wells scoring, which may effectively reduce the false-positive rate while improve the clinical application for APE exclusion using D-D.

Objective:To investigate the effect of insulin-like growth factor 1 (IGF-1) on acute lung injury in septic mice and its underlying molecular mechanism.Methods:Twenty SPF male C57BL/6J mice aged 6-8 weeks were randomly (random number) divided into the sham-operated group, sham-operated + IGF-1 group, sepsis group and sepsis + IGF-1 group, with 5 mice in each group. IGF-1 [60 μg/(kg·d)] was injected via the tail vein for 3 consecutive days in the sham-operated + IGF-1 group and sepsis + IGF-1 group, and mice in the sham-operated group and sepsis group were injected with an equal volume of saline. The tissue of the upper lobe of the right lung was taken to calculate the wet-to-dry ratio, and the upper lobe of the left lung was subjected to HE staining to analyze pathological changes and evaluate lung injury. The levels of interleukin (IL)-6 and IL-1β in the bronchoalveolar lavage fluid (BALF) and serum of mice were detected by ELISA. The expression of p-PI3K, PI3K, p-AKT and AKT in lung tissues was determined via Western blotting. The quantitative data with a normal distribution and homogeneity of variance were compared between the two groups by two independent sample t test. Results:Lung volume was reduced in the sepsis group than in the sham-operated group, obvious surface congestion, dark red color, large bruises and hemorrhagic foci were observed under the pericardium, and the wet-to-dry ratio was significantly elevated ( P<0.05). Compared with the sepsis group, the sepsis + IGF-1 group had slightly increased lung volume, less congestion, darker red color, fewer bruises and hemorrhagic foci, and a lower wet-to-dry ratio ( P<0.05). There was no significant change in lung tissue morphology in the sham-operated + IGF-1 group compared with the sham-operated group. HE staining and lung histopathological scores showed that lung tissue was significantly damaged in the sepsis group than the sham-operated group ( P<0.001), and the pathological score of lung tissue was less damaged in the sepsis + IGF-1 group compared with the sepsis group ( P<0.01). The ELISA results demonstrated that the serum levels of IL-6 and IL-1β were markedly decreased in the sepsis + IGF-1 group than in the sepsis group [(26.22±1.60) pg/mL vs. (45.61±7.85) pg/mL, P<0.05; (87.99±11.80) pg/mL vs. (181.26±10.11) pg/mL, P<0.001]. Moreover, the IL-6 and IL-1β contents in the BALF of the sepsis + IGF-1 group were notably lower than those in the BALF of the sepsis group [(7.67±0.42) pg/mL vs. (20.25±0.43) pg/mL, P<0.001; (17.00±6.08) pg/mL vs. (108.61±5.18), pg/mL P <0.001]. Western blot analysis revealed that the expression of p-PI3K, PI3K, p-AKT and AKT in the lung tissues of mice in the sepsis+IGF-1 group were markedly lower than that in the sepsis group [(0.71±0.05) vs. (1.21±0.09), P<0.05; (0.57±0.08) vs. (1.24±0.22), P<0.01; (0.29±0.07) vs. (1.10±0.04), P<0.001; (0.65±0.17) vs. (1.19±0.07), P<0.01]. Conclusion:IGF-1 ameliorates sepsis-induced acute lung injury in mice, and its protective effect may be achieved by inhibiting the PI3K/AKT pathway.

Objective:To analyze the values of platelet transforming growth factor-β (TGF-β) and SMAD family member 2 (Smad2) in patients′ peripheral platelets for CRC diagnosis and staging.Methods:Retrospective case-control study. Tumor tissues, paratumor tissues and peripheral blood samples were collected from 248 CRC patients (147 males, 101 females; age 21-93 years) diagnosed in the First Hospital of Jilin University from October 10th, 2020, to March 10th, 2025. Peripheral blood samples were also collected from 40 colorectal adenomatous polyp patients (21 males, 19 females; age 22-74 years) and 75 healthy individuals (43 males, 32 females; age 18-81 years) during the same period. Tissue homogenates and platelets were isolated using tissue disruption and gradient centrifugation, respectively. Total RNA was respectively extracted from tissues and platelets, and the expression levels of TGF-β and Smad2 were quantified by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) expressed as relative quantity 2 -ΔΔCt. Differences of TGF-β and Smad2 expression were compared between CRC tissues and adjacent tissues, as well as among CRC patients, polyp patients, and healthy controls. The relationship of platelet TGF-β and Smad2 expression with pathological features includingtumor stage, pathological type, and metastasis were analyzed. The efficiency of platelet TGF-β, Smad2, and their combination in diagnosing CRC was evaluated using receiver operating characteristic (ROC) curves. Results:The expression levels of TGF-β and Smad2 in CRC tumor tissues[1.09 (0.45, 2.00), 2.93 (0.78, 6.73)] were significantly higher than those in adjacent tissues[0.81 (0.27, 1.50), 1.29 (0.40, 2.63)] ( Z TGF-β=4.54, Z Smad2=6.67, both P<0.001). The expression levels of TGF-β and Smad2 in platelets of CRC patients[2.73(1.53, 4.38), 3.16 (1.58, 4.38)] were significantly higher than those in the colorectal polyp group[1.23(0.70, 2.54), 1.16(0.78, 2.27)] and the healthy control group[0.96(0.51, 1.88), 0.92 (0.55, 1.88)] ( H TGF-β=59.71, H Smad2=78.74, both P<0.001). Platelet TGF-β expression increased progressively with tumor stage (stage 1-4) ( P<0.05), while platelet Smad2 levels were higher in metastatic CRC compared with non-metastatic cases ( P<0.05). ROC curve analysis showed that the area under the curve (AUC) for diagnosing CRC when combining platelet TGF-β and Smad2 was 0.81[95%Confidence interval( CI) 0.77—0.86], which was 0.90 (95% CI 0.86—0.93) if adding serum carcinoembryonic antigen (CEA). Conclusion:Platelet TGF-β and Smad2 expression correlates with the diagnosis and staging of CRC, demonstrating potential as liquid biopsy biomarkers for colorectal malignancies.

Objective:To establish and optimize the cutoff values of D-dimer (D-D) for excluding suspected acute pulmonary embolism (APE).Methods:A retrospective cross-sectional study was conducted by recruiting a total of 428 patients with suspected APE complaining of chest pain, hemoptysis, dyspnea, etc., who underwent computed tomography pulmonary angiography (CTPA) in the Emergency Department of the First Hospital of Jilin University from January 1st, 2022, to October 31st, 2024, taken as observation group. The Median age was 64.0 (55.0, 72.0) years old with male and female 214 respectively. Data collection included clinical manifestations(hemoptysis, swelling and pain in the lower limbs), deep vein thrombosis (DVT) history, Wells scores, laboratory results, CTPA and vascular ultrasound foundings. According to CTPA results, observation group was divided into APE group (233 cases) and non-APE group (195 cases); according to Wells scoring, observation group was divided into APE at low, moderate, or high pre-test probability subgroups. Meanwhile, 196 healthy individuals in the same period were included as the health control group. D-D levels were compared among different groups. Receiver operating characteristic (ROC) curve analysis was used to determine the D-D cutoff values for excluding APE, and the area under the curve (AUC) and negative predictive value (NPV) were evaluated.Results:D-D levels in the CTPA-APE group, CTPA-non APE group, and the healthy control group were [7.77 (4.10, 16.58)] mg/L, [0.53 (0.24, 0.94)] mg/L, and [0.21 (0.15, 0.32)] mg/L, respectively, with statistically significant differences ( P<0.05). In the APE group, D-D levels within low-, moderate-, and high-probability subgroups were [7.48 (3.87, 15.85)] mg/L, [7.92 (4.08, 13.90)] mg/L, and [21.39 (7.92, 89.68)] mg/L, respectively, with statistically significant differences among subgroups ( P<0.05), while no significant difference between low-and moderate-probability subgroups ( P>0.05). For suspected APE with low-probability, exclusive D-D level was 0.62 mg/L with AUC and NPV at 1.000 and 100% taking healthy control group as negative control, and 1.65 mg/L with AUC and NPV at 0.989 and 94.00% taking non-APE group as negative control, while the optimized D-D level was 1.10 mg/L adjusted by NPV ≥98%. For suspected APE with low to moderate-probability, the exclusive D-D level was 0.55 mg/L with AUC and NPV at 0.997 and 99.00% taking healthy control group as negative control, and 1.64 mg/L with AUC and NPV at 0.979 and 92.60%, while the optimized D-D level was 0.55 mg/L adjusted by NPV ≥98%. Conclusion:This study established and optimized the exclusive diagnostic cutoff value of D-D for suspected APE in Emergency Department integrated with the Wells scoring, which may effectively reduce the false-positive rate while improve the clinical application for APE exclusion using D-D.

Objective:To establish and validate the prediction model for bone marrow metastasis (BMM) in malignant tumors by screening out laboratory multiparameters.Methods:This case-control study collected 444 cases of malignant tumor patients who were hospitalized in the First Hospital of Jilin University from March 2018 to March 2024, including 243 cases for model establishment set and 201 cases for model validation set. The model establishment set was divided into BMM positive group (81 cases) and BMM negative group (162 cases), and the model validation set was divided into positive group (67 cases) and a negative group (134 cases). We collected patients′ clinical information such as gender, age, clinical diagnosis, and results of 47 laboratory tests including routine blood analysis, coagulation, liver function, tumor markers, potassium, sodium, chloride, and calcium ion tests, bone marrow morphology, and bone marrow biopsy. BMM was taken as the outcome event, differencial variables were analyzed using inter group comparisons, the correlation among parameters was analyzed using Pearson correlation analysis, the risk factors for BMM were analyzed using multivariate conditional logistic regression analysis, to establish logistic model, followed by efficiency evaluation on BMM predictive model using receiver operating characteristic (ROC) curves.Results:In the model establishment set, Pearson correlation analysis of 28 parameters that differed between the BMM positive and negative groups revealed that the correlation coefficients of 17 parameters, including mean platelet volume (MPV), hematocrit (HCT), hemoglobin (HGB), and prothrombin time (PT), were no more than 0.6 ( P<0.05). Further multivariate conditional logistic regression analysis demonstrated that MPV, HGB, HCT, PT, red cell distribution width (RDW), platelet count (PLT), alkaline phosphatase (ALP), chloride (Cl -), and mean erythrocyte hemoglobin concentration (MCHC) were the risk factors of BMM occurence in malignancy [MPV ( OR=9.929, 95% CI 2.688-71.335), HCT ( OR=8.232, 95% CI 6.223-9.841), HGB ( OR=4.300, 95% CI 1.947-16.577), PT ( OR=3.738, 95% CI 1.359-11.666), RDW ( OR=1.995, 95% CI 1.275-3.807), ALP ( OR=1.025, 95% CI 1.012-1.045), PLT ( OR=1.014, 95% CI 1.002-1.031), MCHC ( OR=0.724, 95% CI 0.523-0.880) and Cl -( OR=0.703, 95% CI 0.472-0.967)]. In the model establishment set, combiation of risk factors provided an AUC of 0.943 (95% CI 0.898-0.987, P<0.001), a sensitivity of 86.3%, and a specificity of 89.2% for BMM prediction. In the model validation set, the AUC was 0.924 (95% CI 0.854-0.960, P<0.001), with a sensitivity and specificity of 86.7% and 83.8%, respectively. Conclusion:This study built and validated a multiple-parameter model for BMM, which may facilitate the timely detection of BMM and provide reference for decision making of bone marrow aspiration.

Antibody-drug conjugates(ADCs)are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies.In this study,we report the generation of a monoclonal antibody against monomethyl auristatin E(MMAE)and the development,validation,and application of sensitive and high-throughput enzyme-linked immunosor-bent assays(ELISA)to measure the concentrations of MMAE-conjugated ADCs and total antibodies(tAb,antibodies in ADC plus unconjugated antibodies)in cynomolgus monkey sera.These assays were suc-cessfully applied to in vitro plasma stability and pharmacokinetic(PK)studies of SMADC001,an MMAE-conjugated ADC against trophoblast cell surface antigen 2(TROP-2).The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit,Lys(m-dPEG24)-Cit,and Val-Cit linkers.The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation be-tween serum concentrations and the OD450 values,with R2 at 1.000,and the dynamic range was 0.3-35.0 ng/mL and 0.2-22.0 ng/mL,respectively;the intra-and inter-assay accuracy bias％ranged from-12.2％to-5.2％,precision ranged from-12.4％to-1.4％,and the relative standard deviation(RSD)was less than 6.6％and 8.7％,respectively.The total error was less than 20.4％.The development and validation steps of these two assays met the acceptance criteria for all addressed validation parameters,which suggested that these can be applied to quantify MMAE-conjugated ADCs,as well as in PK studies.Furthermore,these assays can be easily adopted for development of other similar immunoassays.

Objective:To explore the effect of self-made protective clothing in tracheal intubation for the patients with respiratory infectious diseases.Methods:Self-made protective clothing were made by adult model plastic raincoat with sleeve lets and goggles. A prospective randomized controlled study was conducted. Patients with severe respiratory infectious diseases who needed tracheal intubation admitted to the department of intensive medicine of the Third Affiliated Hospital of Gansu University of Chinese Medicine from January 1st 2018 to March 31st 2020 were enrolled. According to the random number table method, they were divided into two groups. The control group was wearing standard protective clothing, while the test group was wearing self-made protective clothing for endotracheal intubation. The wearing time, infection rate of operators and costs of protective clothing were compared between the two groups. The patients were sprayed with trypanosome blue diluent before tracheal intubation, and the whole body of the operator was photographed with fluorescence before wearing self-made protective clothing and after doing tracheal intubation to take off the self-made protective clothing, in order to evaluate the permeability resistance of self-made protective clothing.Results:A total of 86 patients were enrolled. There were 46 cases in the test group, included 28 cases of influenza A (H1N1) virus infection, 11 cases of influenza B virus infection and 7 cases of adenovirus infection. There were 40 cases in the control group, included 15 cases of H1N1 virus infection, 10 cases of influenza B virus infection, 10 cases of adenovirus infection and 5 cases of unknown pathogen. There was no significant difference in respiratory etiology between the two groups ( χ2 = 3.789, P = 0.435). The wearing protective clothing time of the control group was 11.6 times than that of the test group (minutes: 22.23±1.45 vs. 1.86±0.24, χ2 = 19.023, P < 0.001). The cost of standard protective clothing was 12.5 times than that of self-made protective clothing (Yuan/set: 500 vs. 40). Fluorescent photography showed that the whole body of the operator was not stained after tracheal intubation, indicating that the protective clothing had good anti permeability and achieved the protective effect. There was no operator infection in the test group and the control group. Conclusion:Self-made protective clothing has short wearing time, low cost and equivalent isolation effect compared with standard protective clothing, which is worthy of clinical promotion.

Objective:To investigate the surgical indications of gallbladder polyps.Methods:The retrospective case-control study was conducted. The clinicopathological data of 2 272 patients with gallbladder polyps who underwent cholecystectomy in 11 medical centers from January 2015 to December 2019 were collected, including 585 in the First Affiliated Hospital of Xi′an Jiaotong University, 352 in No. 215 Hospital of Shaanxi Nuclear Industry, 332 in the First People′s Hospital of Xianyang, 233 in Shaanxi Provincial People′s Hospital, 152 in the Second Affiliated Hospital of Xi′an Jiaotong University, 138 in Xianyang Hospital of Yan′an University, 137 in People′s Hospital of Baoji, 125 in Hanzhong Central Hospital, 95 in Baoji Central Hospital, 72 in Ankang Central Hospital, 51 in Yulin No.2 Hospital. There were 887 males and 1 385 females, aged (48±12)years, with a range from 12 to 86 years. Observation indicators: (1) surgical treatment, pathological examination and hospitalization; (2) follow-up and complications; (3) comparison of clinicopathological data between patients with non-neoplastic polyps and neoplastic polyps; (4) comparison of clinicopathological data among patients who had gallbladder polyp diameter of 7 to 9 mm, 10 to 12 mm, or ≥13 mm without cholecystolithiasis; (5) analysis of influence factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis; (6) construction and evaluation of nomogram prediction model for neoplastic polyps of patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis. Follow-up using outpatient examination or telephone interview was conducted to detect complications and survival of patients up to April 2020. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range), and comparison between groups was analyzed using the rank-sum test. Ordinal data was analyzed using the rank-sum test of multi-samples. Analysis of influence factors for the incidence of neoplastic polyps was conducted after excluding missing data of CEA and CA19-9. Univariate analysis was conducted using the chi-square test or rank-sum test of multi-samples, and multivariate analysis was conducted using Logistic regression model. Based on Logistic regression model multivariate analysis, the nomogram prediction model was constructed using the R 3.6.0 version software. Results:(1) Surgical treatment, pathological examination and hospitalization: of the 2 272 patients, 2 199 cases underwent laparoscopic cholecystectomy, 43 cases underwent open cholecystectomy, 28 cases underwent radical resection for gallbladder carcinoma, and 2 cases underwent laparoscopic gallbladder preservation and polypectomy. There were 1 050 of the 2 272 patients undergoing intraoperative frozen section examination. Results of pathological examination showed that 1 953 of the 2 272 patients had non-neoplastic polyps including 1 681 cases with cholesterol polyps and 272 cases with inflammatory polyps; 319 cases had neoplastic polyps including 274 with benign polyps (93 cases with adenoma, 66 cases with adenomyoma, 81 cases with adenoma-like hyperplasia, 34 cases with adenoma combined with intraepithelial neoplasia); and 45 cases had malignant polyps including 43 cases with adenocarcinoma, 1 case with adenosquamous carcinoma and 1 case with sarcomatoid carcinoma. The duration of postoperative hospital stay of 2 272 patients was 3 days(range, 1 to 27 days). (2) Follow-up and complications: of the 2 272 patients, 1 932 were followed up for 3.5 to 63.5 months, with a median follow-up time of 31.0 months. During the follow-up, 180 patients had short-term complications and 170 patients had long-term complications. (3) Comparison of clinicopathological data between patients with non-neoplastic polyps and neoplastic polyps: cases with age ≤50 years or >50 years, cases with time from first discovery of polyp to operation <1 year, 1-3 years, >3 years and ≤5 years or >5 years, CEA, CA19-9, CA125, cases with single or multiple polyps in preoperative ultrasonography examination, cases with diameter of polyps in preoperative ultrasonography examination as 1-6 mm, 7-9 mm, 10-12 mm or ≥13 mm, cases with pedicled or broad based polyp wall in preoperative ultrasonography examination, cases with polyp morphology in preoperative ultrasono-graphy examination as nodular, papillary, globular or mulberry-like, cases undergoing or not undergoing intraoperative frozen section examination, cases with diameter of polyps in postoperative pathological examination as 1-6 mm, 7-9 mm, 10-12 mm or ≥13 mm, cases with gallbladder wall thickness in postoperative pathological examination as ≤4 mm or >4 mm of the 1 953 patients with non-neoplastic polyps were 1 118, 835, 1 027, 422, 230, 274, 2.0 mg/L(range, 0.2-8.6 mg/L), 14.5 U/mL(range, 2.6-116.4 U/mL), 10.5 U/mL(range, 1.2-58.7 U/mL), 658, 1 295, 674, 741, 413, 125, 1 389, 564, 407, 1 119, 292, 135, 832, 1 121, 698, 774, 385, 96, 1 719, 234, respectively. The above indicators of the 319 patients with neoplastic polyps were 160, 159, 204, 55, 26, 34, 2.9 mg/L(range, 0.2-28.8 mg/L), 19.7 U/mL(range, 3.5-437.1 U/mL), 15.0 U/mL(range, 1.0-945.0 U/mL), 203, 116, 49, 59, 100, 111, 154, 165, 92, 153, 49, 25, 218, 101, 53, 85, 90, 91, 263, 56, respectively. There were significant differences in the above indicators between the non-neoplastic polyps and neoplastic polyps patients ( χ2=5.599, Z=-3.668, -2.407, -3.023, -3.403, χ2=104.474, Z=-13.367, χ2=65.676, 12.622, 73.075, Z=-11.874, χ2=7.649, P<0.05). (4) Comparison of clinicopathological data among patients who had gallbladder polyp diameter of 7 to 9 mm, 10 to 12 mm, or ≥13 mm without cholecystolithiasis: after excluding 311 of the 2 272 patients with cholecystolithiasis, there were 706 cases with gallbladder polyp diameter of 7 to 9 mm, 459 cases with gallbladder polyp diameter of 10 to 12 mm, and 205 cases with gallbladder polyp diameter ≥13 mm, respectively. Cases with time from first discovery of polyp to operation <1 year, 1-3 years, >3 years and ≤5 years or >5 years, CEA, CA19-9, cases with single or multiple polyps in preoperative ultrasonography examination, cases with pedicled or broad based polyp wall in preoperative ultrasonography examination, cases with polyp morphology in preoperative ultrasonography examination as nodular, papillary, globular or mulberry-like, cases with echo intensity of preoperative ultrasonography examination as slightly strong, medium or weak, cases undergoing or not undergoing intraoperative frozen section examination, and cases with pathological types of polyps as non-neoplastic polyps, benign polyps or malignant polyps of the 706 patients with gallbladder polyp diameter of 7 to 9 mm were 291, 170, 107, 138, 2.2 mg/L(range, 0.5-8.6 mg/L), 21.0 U/mL(range, 2.8-116.4 U/mL), 207, 499, 620, 86, 118, 463, 75, 50, 252, 410, 44, 379, 327, 657, 49, 0, respectively. The above indicators of the 459 patients with gallbladder polyp diameter of 10 to 12 mm were 267, 85, 43, 64, 1.6 mg/L(range, 0.4-9.3 mg/L), 10.4 U/mL(range, 3.3-354.0 U/mL), 205, 254, 237, 222, 158, 223, 51, 27, 222, 213, 24, 263, 196, 373, 79, 7, respectively. The above indicators of the 205 patients with gallbladder polyp diameter ≥13 mm were 128, 38, 20, 19, 2.1 mg/L(range, 0.6-28.8 mg/L), 10.2 U/mL(range, 3.6-307.0 U/mL), 120, 85, 75, 130, 68, 97, 22, 18, 98, 95, 12, 148, 57, 113, 71, 21, respectively. There were significant differences in the above indicators among patients who had gallbladder polyp diameter of 7 to 9 mm, 10 to 12 mm, or ≥ 13 mm ( χ2=46.482, 8.093, 39.504, 66.971, 277.043, 60.945, 19.672, 22.340, 197.854, P<0.05). (5) Analysis of influence factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis: of the 459 patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis, there were 373 cases with non-neoplastic polyps, and 86 cases with neoplastic polyps, respectively. Results of univariate analysis showed that CEA, CA19-9, the number of polyps in preoperative ultrasonography examination, diameter of polyps in preoperative ultrasonography examination, polyp wall in preoperative ultrasonography examination were influence factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis ( χ2=10.342, 5.616, 20.009, Z=-4.352, χ2=6.203, P<0.05). Results of multivariate analysis showed that CEA>5.0 mg/L, CA19-9>39.0 U/mL, single polyp in preoperative ultrasonography examination, polyp diameter of 11 mm in preoperative ultrasonography examination, polyps of broad base in preoperative ultrasonography examination were independent risk factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis ( odds ratio=8.423, 0.082, 0.337, 3.694, 2.318, 95% confidence interval: 1.547-45.843, 0.015-0.443, 0.198-0.575, 1.987-6.866, 1.372-3.916, P<0.05). (6) Construction and evaluation of nomogram prediction model for neoplastic polyps of patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis: CEA, CA19-9, the number of polyps in preoperative ultrasonography examination, diameter of polyps in preoperative ultrasonography examination, polyp wall in preoperative ultrasonography examination were imported into R 3.6.0 version software to establish the nomogram prediction model for neoplastic polyps. The results showed the score for CEA>5.0 mg/L, CA19-9>39.0 U/mL, cases with single polyp in preoperative ultrasonography examination, cases with polyp diameter of 10 mm in preoperative ultrasonography examination, cases with polyp diameter of 11 mm in preoperative ultrasonography examination, cases with polyp diameter of 12 mm in preoperative ultrasonography examination, polyps of broad base in preoperative ultrasonography examination were 25, 27, 100, 0, 26, 72, 98 in the nomogram prediction model, respectively. The C-index of nomogram prediction model was 0.768. Result of nomogram prediction model showed that the incidence of tumor polyps was 0, 6% and 10% in patients with multiple and pedicled gallbladder polyps with diameter of 10, 11, 12 mm and with CEA ≤5.0 mg/L and CA19-9 ≤39.0 U/mL, the incidence of tumor polyps was 43%, 53% and 70% in patients with single and broad base gallbladder polyps with diameter of 10, 11, 12 mm. The calibration curve showed that the probability of the nomogram prediction model predicting neoplastic polyps was nearly consistent with the actual probability. Conclusions:CEA>5.0 mg/L, CA19-9>39.0 U/mL, single polyp in preoperative ultrasonography examination, polyp diameter of 11 mm in preoperative ultrasonography examination, polyps of broad base in preoperative ultrasonography examination are independent risk factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis. Cholecystectomy should be performed in time for patients with single and broad based gallbladder polyps with diameter of 10, 11, 12 mm.

OBJECTIVE：To reference for the rational use of sodium va lproate in clinic. METHODS ：By retrospective analysis，blood concentration monitoring results of sodium valproate and medical record data in 856 patients were collected from the Affiliated Tianyou Hospital of Wuhan University of Science and Technology during Jan. 2016-Dec. 2018. The dosage form of sodium valproate ，monitoring times of therapeutic drugs ，monitoring results of steady-state blood concentration of sodium valproate up to the standard ，dosage adjustment and the combination with carbamazepin ，fluconazol and carbapenem drugs were analyzed. Fisher exact test was used to analyze the factors influencing the steady-state blood concentration of sodium valproate up to the standard. RESULTS ：A total of 1 270 cases of sodium valproate were monitored in 856 patients，involving 407 males and 449 females，with age of （38.2±13.8）years and body mass of （52.3±10.0）kg. Among 1 270 cases of monitoring ，steady-state blood concentration of sodium valproate in 554 cases were in the range of 50-100 µg/mL，and 43.6％ of which reached the standard. The rate of reaching the standard in patients with multiple monitoring was higher than patients with single monitoring ；the dosage of patients with last monitoring reaching the standard was higher than that of patients with the first monitoring reaching the standard. The rate of reaching the standard in Sodium valproate sustained-release tablet group was higher than general Sodium valproate tablet group；the carbamazepin/fluconazol free group was higher than the carbamazepin combination group and fluconazol combination group；the carbapenem free group was higher than the carbapenem combination group （all P＜0.05）. CONCLUSIONS ：Clinical pharmacists should pay attention to the monitoring of sodium valproate treatment drugs ， strengthen the publicity and 3551851542@qq.com education of patients and their families ，and try to use Sodium valproate sustained-release tablets. When patients additionally receive carbapenem drugs like carbamazepin or fluconazol ， the standard level of sodium valproate will be reduced ，then the dosage of sodium valproate should be adjusted.