OBJECTIVE To investigate the effect and mechanism of Tangzhi formula（TZF） on improving glucose and lipid metabolism disorders in type 2 diabetes mellitus （T2DM） rats.METHODS Thirty SPF-grade SD rats were used to establish a T2DM rat model through high-fat diet feeding combined with intraperitoneal injection of streptozotocin. After successful modeling， the rats were divided into the model group， metformin group （positive control， 0.18 g/kg）， and TZF low-， medium-， and high-dose groups （5， 10， and 20 g/kg）， with 6 rats in each group. An additional 6 rats were selected as the blank group. The rats in each group were orally administered the corresponding volume of drug solution or saline， and continuous dosing was performed for 6 weeks， once daily. Fasting blood glucose （FBG）， area under the curve of oral glucose tolerance test （OGTT-AUC）， area under the curve of intraperitoneal insulin tolerance test （IPITT-AUC）， serum total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） levels were measured. Hematoxylin-eosin （HE） staining and oil red O staining were used to observe hepatic pathological morphology and lipid deposition. Differentially expressed proteins in liver tissues were screened by proteomics analysis， and key proteins in signaling pathways were verified by Western blot and immunofluorescence staining.RESULTS Compared with the blank group， the levels of FBG， OGTT-AUC， IPITT-AUC， LDL-C， TG， and TC in the model group were significantly increased （ P ＜0.05）， while HDL-C level was significantly decreased （ P ＜0.05）； the liver tissues showed disordered hepatic cords， punctate necrosis of hepatocytes， and significant lipid deposition， the NAFLD activity score and positive area of lipid droplets were significantly increased（ P ＜0.05）. Compared with the model group， the above indicators in TZF low-， medium-， and high-dose groups and metformin group were significantly reversed （ P ＜0.05）； hepatic pathological injury and lipid deposition were alleviated. Proteomics results showed that a total of 442 differentially expressed proteins were screened between the model group and the blank group， and 358 differentially expressed proteins were screened between the TZF high-dose group and the model group. Among these differentially expressed proteins， multiple proteins closely related to glucose and lipid metabolism showed a reversal trend after TZF intervention. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the peroxisome proliferator-activated receptor （PPAR） signaling pathway was significantly enriched. The validation experiment results showed that TZF could significantly up-regulate the expression of PPARα， PPARγ， and apolipoprotein A1 （ApoA1） in rat liver tissues （ P ＜0.05）， and down-regulate the expression of stearoyl-CoA desaturase 1 （SCD1） and perilipin 2 （PLIN2） （ P ＜0.05）.CONCLUSIONS TZF can improve glucose and lipid metabolism disorders in T2DM rats； its mechanism may be related to the activation of the PPAR signaling pathway and the regulation of downstream lipid metabolism-related proteins SCD1， PLIN2， and ApoA1.

Objective:To explore the effect of heme-binding protein 1(HEBP1)down-regulation on the function of microglia BV2,and to clarify the key role of HEBP1 in the microglia.Methods:Negative control and HEBP1 knockdown small interfering RNA(siRNA)were constructed to knockdown HEBP1 gene in mouse-derived microglial BV2,and the HEBP1 knockdown BV2 cell models were obtained.The BV2 cells were divided into si-NC group,si-HEBP1-1 group,si-HEBP1-2 group,and si-HEBP1-3 group.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods were used to detect the expression levels of HEBP1 mRNA and protein in the BV2 cells after knockdown;the siRNA with the most significart knockdown effect was selected for stlbsequent expreriments.The proliferation abilities of the cells in si-NC group and si-HEBP1 group were detected by cell counting kit-8(CCK-8)assay,and the cell migration rates were assessed by scratch assay;the cellular mitochondrial membrane potential and reactive oxygen species(ROS)levels were detected by kits;the cellular mitochondrial respiratory function was detected by mitochondrial respirometer.The BV2 cells were divided into si-NC group,si-NC+lipopolysacch aride(LPS)group,si-HEBP1 group,and si-HEBP1+LPS group.RT-qPCR method was used to detect the expression levels of HEBP1,interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)mRNA in the BV2 cells in various groups,and Western blotting method was used to detect the expression levels of HEBP1 protein in the BV2 cells in various groups.Results:When the BV2 cells were transfected with siRNA carrying with red fluorescence tag CY3,the transfect effricacy was above 90％;compared with si-NC group,the expression levels of HEBP1 protein in the BV2 cells in si-HEBP1-1 group,si-HEBP1-2 group,and si-HEBP1-3 group were significantly decreased(P<0.05 or P<0.01),especially in si-HEBP1-1 group.Compared with si-NC group,the expression levels of HEBP1 mRNA in the BV2 cells in si-HEBP1-1 group,si-HEBP1-2 group,and si-HEBP1-3 group were significantly decreased(P<0.01),especially in si-HEBP1-1 group;indicating that si-HEBP1-1 was the siRNA with best HEBP1 knowdown effect,and the HEBP1 knockdown BV2 cell model was successfully constructed.The CCK-8 resuts showed that compared with si-NC group,the proliferation activities of the BV2 cells in si-HEBP1 group were decreased(P<0.05 or P<0.01);from 90 min,the differences in proliferation activities of the BV2 cells in two groups were obvious.The cell scratch experiment results showed that compared with si-NC group,the cell migration rate in si-HEBP1 group was significantly decreased(P<0.05).The fluorescence microscope results showed that compared with si-NC group,the mitochondrial membrane potential of the BV2 cells in si-HEBP1 group was significantly decreased(P<0.05);compared with si-NC group,the ROS level in the BV2 cells in si-HEBP1 group was significantly increased(P<0.05).The mitochondrial respiration function testing results showed that compared with si-NC group,routine respiration(ROUNTINE)and leak respiration(LEAK)in si-HEBP1 group were significautly decreased(P<0.05 or P<0.01),and electron transfer system capacity(ETS)and residual oxygen consumption(ROX)had no significant differences(P>0.05);the ATP amount was decreased(P<0.05).The RT-qPCR results showed that compared with si-NC group,the expression levels of IL-1β,TNF-α,and IL-6 mRNA in the BV2 cells in si-NC+LPS group were significantly decreased(P<0.01);compared with si-HEBP1 group,the expression levels of IL-1β,TNF-α,and IL-6 mRNA in the BV2 cells in si-HEBP1+LPS group were significantly decreased(P<0.01);compared with si-NC+LPS group,the expression levels of IL-1β,TNF-α,and IL-6 mRNA in the BV2 cells in si-HEBP1+LPS group were significantly increased(P<0.01).Conclusion:Knockdown of HEBP1 gene can decrease the proliferation and migration abilities of the microglia BV2 and increase inflammatory response to LPS stimulus,and their mechanisms may be related to mitochondrial function damage and decreased ATP production of the BV2 cells.

Objective To observe the performance of ConvNeXt architecture model(SC2-Net)integrated with feedforward attention(FA)for segmentation of pancreas from abdominal CT images.Methods 3D abdominal CT images of 80 healthy adults(Dataset 1)and 68 patients with pancreatic lesions(Dataset 2)were included.ConvNeXt network model was established and enhanced by introducing a FA mechanism,a scalable convolution block(SCB)and a feature gating(FG)module into the encoder section.The performance of the model for segmenting pancreas were comparatively evaluated with other models(Swin UNETR,nnFormer,UNETR,TransBTS models based on Transformer and 3D UX-NET model based on ConvNeXt),while conduct ablation experiments were performed on the added modules.Results SC2-Net accurately segmented pancreas from abdominal CT images,with Dice similarity coefficient(DSC),95％Hausdorff distance(HD95)and the mean surface distance(MSD)of 0.92±0.01,(1.08±0.05)mm and(2.12±0.01)mm in Dataset 1,respectively.The DSC and HD95 of SC2-Net segmentation of pancreas were both superior to those of other models.In Dataset 2,SC 2-Net achieved DSC,HD95 and MSD of 0.82±0.03,(3.35±0.36)mm and(0.87±0.15)mm,respectively,surpassing all other models.SC2-Net achieved complete pancreas segmentation in both datasets,whereas other models demonstrated under-segmentation or mis-segmentation.FA module significantly improved segmentation performance when integrated into the baseline network.Conclusion SC2-Net could improve segmentation of pancreas from abdominal CT images.

Objective To observe the performance of ConvNeXt architecture model(SC2-Net)integrated with feedforward attention(FA)for segmentation of pancreas from abdominal CT images.Methods 3D abdominal CT images of 80 healthy adults(Dataset 1)and 68 patients with pancreatic lesions(Dataset 2)were included.ConvNeXt network model was established and enhanced by introducing a FA mechanism,a scalable convolution block(SCB)and a feature gating(FG)module into the encoder section.The performance of the model for segmenting pancreas were comparatively evaluated with other models(Swin UNETR,nnFormer,UNETR,TransBTS models based on Transformer and 3D UX-NET model based on ConvNeXt),while conduct ablation experiments were performed on the added modules.Results SC2-Net accurately segmented pancreas from abdominal CT images,with Dice similarity coefficient(DSC),95％Hausdorff distance(HD95)and the mean surface distance(MSD)of 0.92±0.01,(1.08±0.05)mm and(2.12±0.01)mm in Dataset 1,respectively.The DSC and HD95 of SC2-Net segmentation of pancreas were both superior to those of other models.In Dataset 2,SC 2-Net achieved DSC,HD95 and MSD of 0.82±0.03,(3.35±0.36)mm and(0.87±0.15)mm,respectively,surpassing all other models.SC2-Net achieved complete pancreas segmentation in both datasets,whereas other models demonstrated under-segmentation or mis-segmentation.FA module significantly improved segmentation performance when integrated into the baseline network.Conclusion SC2-Net could improve segmentation of pancreas from abdominal CT images.

Objective:To investigate the effect of HNRNPL protein on the proliferative ability of primary hepatocellular carcinoma cells and its potential mechanism.Methods:Online public database and real-time quantitative PCR were used to analyze the difference of HNRNPL expression between cancer and adjacent tissues. The effects of HNRNPL on HCC cell MHCC97H and HepG2 proliferation and MAPK pathway were investigated by Western blot, cell counting assay, colony formation assay and nude mouse transplantation tumor experiments.Results:The level of HNRNPL mRNA was validated to be higher in HCC tissue (2.76±0.37) than in normal tissue (1.00±0.14) with statistical difference ( t=3.93, P=0.002). Colony formation assay showed that the colony numbers of two MHCC97H knockdown groups (33.3±7.7) and (43.3±2.2) were lower than their control group (84.3±6.2), and two HepG2 knockdown groups (59.0±15.5) and (41.7±4.8) were lower than their control group (200.3±6.2) with statistical difference (both P<0.01). HNRNPL knockdown decreased the proliferation ability and activation level of MAPK pathway in HCC cells. Overexpression of oncogene c-RAF partially alleviated the anti-proliferation effect of HNRNPL knockdown and rescued the tumorigenic capacity. Conclusion:HNRNPL can promote hepatocellular carcinoma cell proliferation by activating MAPK signaling pathway.

Objective:To study the influence of intensive magnet fields on radiation dose measurement, and to demonstrate the feasibility of measuring magnet field correction factor by a combination of medical linac with variable magnet fields in view of needing for accurate measurement of the doses from reference beam arising in MR image-guided radiotherapy.Methods:A photon radiation field and a variable field with 6 MV nominal high voltage were produced by using conventional medical electron linear accelerator equipped with a pair of electromagnets with magnetic field strength up to 1.5 T. Both PTW30013 and PTW31010 ionization chambers were used to test the responses of ionization chambers under different magnetic field strengths at four orientations in which the angles between ionization chamber axis and magnetic field direction were 0°, 180°, 90° and 270°, respectively. The magnetic factors, kB, M was calculated and compared with the reported values in literature. Results:The response of ionization chamber was proportional to the magnetic field strength before it reached to a peak around 1 T, and then fell down as the magnetic field continued to rise. When the magnetic field was 0.35 T, the magnetic factors of PTW31010 were 0.988 2±0.000 3 and 0.997 4±0.000 4 corresponding to 90° and 0° directions, the discrepancy between 0° scenario and literature was 0.05% ± 0.04%. When the magnetic field reached 1.5 T, the magnetic factor of PTW30013 was 0.958 9±0.000 5 at the situation of 90°, which was 0.60% ± 0.05% different from the literature value.Conclusions:Conventional 6 MV medical accelerator equipped with electromagnet can be used to measure the magnetic field factor of reference dosimetry for MRIgRT.

Objective:To study the clinical efficacy of laparoscopic radical cholecystectomy in the treatment of stage Ⅲ gallbladder cancer.Methods:The clinical characteristics and postoperative follow-up data of 184 patients (male 66, and female 118) who underwent radical cholecystectomy for stage Ⅲ gallbladder cancer at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, from May 2015 to May 2022, were retrospectively analyzed. The age was (67.0±8.6) years old (range 38 to 85 years old). There were 71 patients in the laparoscopic group and 113 in the open group. The general medical data, surgery-related indicators and complications were analyzed. Follow-up was completed by outpatient visits and by telephone.Results:The laparoscopic group showed better postoperative alanine aminotransferase [67.5 (40.0, 138.5) vs. 104.0 (45.0, 252.2) U/L] and aspartate aminotransferase [41.5 (26.0, 71.2) vs. 53.0 (30.2, 153.5) U/L] recovery, higher albumin levels [32.05 (30.18, 35.20) vs. 30.50 (27.70, 33.50) g/L], earlier abdominal drainage tube removal [8.00(6.00, 10.25) vs. 10.00(6.00, 13.00)d], shorter hospital stay [10.00(8.00, 15.25) vs. 14.00(9.00, 19.00) d] and lower incidences of complications [(14.1%(10/71) vs. 31.9%(36/113)] when compared with the open group (all P<0.05). The 1 year (49.1% vs 61.0%), 2 years (24.0% vs. 28.5%), 3 years (16.0% vs. 14.5%) overall survival ( P=0.640), and the 3 years progression-free survival (18.3% vs. 15.0%, P=0.463) showed no significant difference between the 2 groups. Conclusion:Laparoscopic surgery for AJCC TNM stage Ⅲ gallbladder cancer showed comparable results with open surgery. When compared with open surgery, laparoscopic radical resection of gallbladder cancer had the advantages of earlier removal of abdominal drainage tube, lower incidence of postoperative complications, and shorter hospital stay.

Objective:To study the effect of preoperative transcatheter arterial chemoembolization (TACE) on postoperative complications after hepatectomy in patients with hepatocellular carcinoma (HCC) by propensity score matching analysis.Methods:Of 1 666 patients with HCC undergoing hepatectomy in Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology and Tianyou Hospital of Wuhan University of Science and Technology from March 2015 to March 2021 were retrospectively screened. Of 262 patients were enrolled, including 236 males and 26 females, aged (50.3±11.8) years. Of 131 patients were enrolled in both the single surgery group and the combined group (preoperative TACE + surgical resection). Factors affecting the complications after hepatectomy in patients with HCC were analyzed using univariate and multivariate logistic regression method.Results:After matching the propensity score, the incidence of postoperative complications in the single surgery group was 22.1% (29/131), lower than that in the combined group [41.2% (54/131), χ 2=11.02, P<0.001]. The incidence of bile leakage in the single surgery group [2.3% (3/131)] was also lower than that in the combined group [(9.2% (12/131), χ 2=5.73, P=0.017]. Multivariate logistic regression analysis showed that the combined group ( OR=2.43, 95% CI: 1.28-4.61, P=0.007) had an increased incidence of postoperative complications, so did patients with a preoperative alpha-fetoprotein > 400 μg/L, anatomic hepatectomy, long operation time, and hilar occlusion. Conclusion:Preoperative TACE could be a risk factor for postoperative complications in patients with HCC, especially for the postoperative biliary leakage.

Objective:To systematically evaluate the relationship between gestational vitamin D deficiency and spontaneous abortion.Methods:Databases including PubMed, Web of Science, Ebsco, Cochrane, Embase, CNKI, Wanfang database, China Biomedical Literature Service System, etc. were searched for cohort studies and case-control studies on the correlation between gestational vitamin D deficiency/insufficiency and abortion outcomes, respectively from the establishment of individual database to December 2021. Two investigators independently performed literature screening, data extraction and risk of bias assessment for included studies. Meta-analysis was conducted with RevMan 5.4.1 and Stata 15.1.Results:Eventually, 12 cohort studies and 5 case-control studies were included. A total of 19,308 pregnant women were enrolled, among whom 1 405 abortions were observed. 8 studies were published in Chinese and 9 in English. 10 studies were from China and 1 study each was from Iran, Egypt, Sweden, United States, Denmark, Turkey and Australia. The standards for vitamin D deficiency and the diagnostic criteria for miscarriage were basically the same across studies. After adjusting for confounding factors such as age and race, the meta-analysis showed that gestational vitamin D deficiency/insufficiency would increase the risk of miscarriage. A subgroup analysis of women with miscarriage in early pregnancy showed results consistent with that in overall population. No significant publication bias were identified via meta-analysis.Conclusion:Gestational vitamin D deficiency and insufficiency are related to the occurrence of spontaneous abortion and can increase the risk of early spontaneous abortion.

Objective To investigate the drug resistance of pseudomonas aeruginosa changes in the Sixth Hospital of Ningbo, Zhejiang province, in order to provide a basis for clinical rational use of antimicrobial drugs. Methods The clinical distribution and drug resistance to commonly used antimicrobial agents in 1970 strains of pseudomonas aeruginosa from the Sixth Hospital of Ningbo in 2014 －2016 were retrospectively analyzed. The data were statistically analyzed using WHONET 5. 6 software, excel software, SPSS17. 0 software. Results Clinical specimens isolated 15 963 strains of pathogenic bacteria,including 1 970 strains pseudomonas aeruginosa,accounted for 12. 34% . The detection rate of multi－drug resistance pseudomonas aeruginosa( MDRPA) reduced year by year, the detection rate in 2014 was 60. 95% ,which in 2015 was 58. 00% ,which in 2016 was 45. 58% . Pseudomonas aeruginosa was mainly isolated from sputum(67. 16% ),followed by wound secretion(23. 05% ). The detection rate of pseudomonas aeruginosa in ICU and geriatric department was higher,accounted for 20. 25% and 25. 28% respectively. The resistance of pseudomonas aeruginosa to many kinds of antimicrobial agents was increased from 2014 to 2016,the resistance rates to cefoperazone/ sulbactam were＞30% in 3 years,the resistance rate to imipenem was higher than meropenem. The drug resistance of pseudomonas aeruginosa isolated from sputum in ICU was higher than that in geriatric department(all P＜0. 05). Conclusion Pseudomonas aeruginosa nosocomial infection in the Sixth Hospital of Ningbo is severe,the infection rate and drug resistance monitoring should be strengthened,in order to reduce the infection rate and drug resistance.