Functional dyspepsia （FD） is a prioritized disease category where traditional Chinese medicine （TCM） demonstrates distinct therapeutic advantages. The current western medicine treatment for FD is mainly based on proton pump inhibitors and prokinetic agents， with digestive enzymes， probiotics and antidepressants serving as adjuvant medication， yet such therapies still have certain limitations. TCM treatment for FD includes oral administration of Chinese herbal formulas and Chinese patent medicines， as well as external TCM therapies such as acupuncture and moxibustion， acupoint application， hot medicinal compress therapy， rubbing with ointment， medicinal iontophoresis， auricular acupoint therapy and tui na （Chinese medical massage）. The combined treatment of FD with integrated TCM and western medicine can significantly improve clinical effectiveness and reduce adverse reactions. The common mechanisms underlying the therapeutic effects of both TCM and western medicine revolve around the core pathological processes of FD， mainly focusing on restoring gastrointestinal motility， regulating the levels of brain-gut peptides， modulating intestinal microecology， and ameliorating inflammatory status. The differential mechanisms lie in the precise targeting feature of western medicine versus the holistic-regulating and multi-target characteristics of TCM， and the two approaches exert a synergistic effect to enhance efficacy. This paper proposes to leverage the advantages of TCM in holistic regulation and the strengths of western medicine in targeted treatment， so as to provide personalized and comprehensive treatment regimens for FD patients.

Aim To investigate the effect of cumulative non-high density lipoprotein cholesterol/high density lip-oprotein cholesterol(non-HDLC/HDLC)exposure on atherosclerotic cardiovascular disease(ASCVD).Methods A prospective cohort study was conducted.A total of 50 777 employees of Kailuan Group who participated in three physical examinations in 2006-2007,2008-2009 and 2010-2011 were selected as the study subjects.Groups were divided into Q1,Q2,Q3 and Q4 according to the cumulative non-HDLC/HDLC exposure quartiles.Kaplan-Meier curve was used to calculate the cumulative incidence of ASCVD in different cumulative non-HDLC/HDLC groups,and Log-rank test was used to compare the differences among groups.Cox proportional risk model was used to analyze the effect of cumulative non-HDLC/HDLC exposure on ASCVD.Results The average follow-up was(10.19±2.21)years,and 5 003 new cases of ASCVD occurred.The cumulative incidence of ASCVD in groups Q1 to Q4 was 6.49％,8.71％,10.86％and 14.85％,respectively(Log-rank P＜0.01).Multivariate Cox regression analysis showed that compared with group Q1,the HR(95％CI)of ASCVD in groups Q2,Q3 and Q4 were 1.13(1.03～1.24),1.18(1.07～1.29),1.22(1.12～1.34),respectively;the HR(95％CI)of myocardial infarction were 1.15(0.87～1.53),1.44(1.10～1.88),1.67(1.29～2.17),respectively;the HR(95％CI)of revascularization were 1.21(0.99～1.49),1.31(1.07～1.60)and 1.49(1.22～1.81),respectively;the HR(95％CI)of ischemic stroke were 1.17(1.03～1.32),1.17(1.04～1.33)and 1.21(1.06～1.37),respectively;but the above association was not found when heart failure and atrial fibrillation were used as the outcome events.The restricted cubic spline showed that cumulative non-HDLC/HDLC values were line-arly associated with the risk of ASCVD.Conclusion Cumulative non-HDLC/HDLC exposure was positively associated with the risk of ASCVD.

Objective:To evaluate the effect and causality of serum metabolites on the pathogenesis of ulcerative colitis (UC), so as to provide reference for nutritional programs for patients with UC.Methods:Two-sample Mendelian randomization (MR) analysis was performed to estimate the causal relationship between serum metabolites and UC. Genome-wide association studies (GWAS) of 1 400 metabolites were performed, with the metabolites as exposure and UC as outcome. Inverse-variance weighted (IVW) was used to calculate causal estimates. Four other MR methods with different modeling assumptions including MR-Egger, weighted median, weighted mode, and simple mode were used as additional analyses to improve the stability of the results. The results were validated through heterogeneity and pleiotropy tests. Finally, the possible causal metabolites were analyzed by metabolic pathway analysis.Results:MR analysis revealed that 85 metabolites had a possible causal relationship with UC. Among them, phosphatidylglycerol 1,2-dipalmitoyl-gpc (DPPC) ( P=2.75×10 -6) and isovaleryl carnitine (C5) ( P=1.84×10 -5) were significant risk factors for UC. Metabolic pathway analysis identified 5 metabolic pathways that might be affected by these metabolites (all P<0.05), among which the porphyrin ( P=0.004) and pyrimidine metabolic pathways ( P=0.008) had higher confidence in impacting UC. Conclusions:There are causal relationships between some serum metabolites (in particular 1,2-dipalmitoyl-GPC and isovalerylcarnitine) and the risk of UC. The porphyrin and pyrimidine metabolic pathways may impact the pathogenesis of UC.

Objective:To evaluate the effect and causality of serum metabolites on the pathogenesis of ulcerative colitis (UC), so as to provide reference for nutritional programs for patients with UC.Methods:Two-sample Mendelian randomization (MR) analysis was performed to estimate the causal relationship between serum metabolites and UC. Genome-wide association studies (GWAS) of 1 400 metabolites were performed, with the metabolites as exposure and UC as outcome. Inverse-variance weighted (IVW) was used to calculate causal estimates. Four other MR methods with different modeling assumptions including MR-Egger, weighted median, weighted mode, and simple mode were used as additional analyses to improve the stability of the results. The results were validated through heterogeneity and pleiotropy tests. Finally, the possible causal metabolites were analyzed by metabolic pathway analysis.Results:MR analysis revealed that 85 metabolites had a possible causal relationship with UC. Among them, phosphatidylglycerol 1,2-dipalmitoyl-gpc (DPPC) ( P=2.75×10 -6) and isovaleryl carnitine (C5) ( P=1.84×10 -5) were significant risk factors for UC. Metabolic pathway analysis identified 5 metabolic pathways that might be affected by these metabolites (all P<0.05), among which the porphyrin ( P=0.004) and pyrimidine metabolic pathways ( P=0.008) had higher confidence in impacting UC. Conclusions:There are causal relationships between some serum metabolites (in particular 1,2-dipalmitoyl-GPC and isovalerylcarnitine) and the risk of UC. The porphyrin and pyrimidine metabolic pathways may impact the pathogenesis of UC.

Aim To investigate the effect of cumulative non-high density lipoprotein cholesterol/high density lip-oprotein cholesterol(non-HDLC/HDLC)exposure on atherosclerotic cardiovascular disease(ASCVD).Methods A prospective cohort study was conducted.A total of 50 777 employees of Kailuan Group who participated in three physical examinations in 2006-2007,2008-2009 and 2010-2011 were selected as the study subjects.Groups were divided into Q1,Q2,Q3 and Q4 according to the cumulative non-HDLC/HDLC exposure quartiles.Kaplan-Meier curve was used to calculate the cumulative incidence of ASCVD in different cumulative non-HDLC/HDLC groups,and Log-rank test was used to compare the differences among groups.Cox proportional risk model was used to analyze the effect of cumulative non-HDLC/HDLC exposure on ASCVD.Results The average follow-up was(10.19±2.21)years,and 5 003 new cases of ASCVD occurred.The cumulative incidence of ASCVD in groups Q1 to Q4 was 6.49％,8.71％,10.86％and 14.85％,respectively(Log-rank P＜0.01).Multivariate Cox regression analysis showed that compared with group Q1,the HR(95％CI)of ASCVD in groups Q2,Q3 and Q4 were 1.13(1.03～1.24),1.18(1.07～1.29),1.22(1.12～1.34),respectively;the HR(95％CI)of myocardial infarction were 1.15(0.87～1.53),1.44(1.10～1.88),1.67(1.29～2.17),respectively;the HR(95％CI)of revascularization were 1.21(0.99～1.49),1.31(1.07～1.60)and 1.49(1.22～1.81),respectively;the HR(95％CI)of ischemic stroke were 1.17(1.03～1.32),1.17(1.04～1.33)and 1.21(1.06～1.37),respectively;but the above association was not found when heart failure and atrial fibrillation were used as the outcome events.The restricted cubic spline showed that cumulative non-HDLC/HDLC values were line-arly associated with the risk of ASCVD.Conclusion Cumulative non-HDLC/HDLC exposure was positively associated with the risk of ASCVD.

Objective:To explore the clinical effects of a series of posture intervention strategies on correcting abnormal fetal position, so as to provide a basis for Clinical position management and promotion of natural delivery.Methods:This study was a randomized controlled trial. The convenience sampling method was used to select 196 full-term primiparas women with abnormal fetal orientation confirmed by ultrasound as single fetal head position in the Women′s Hospital, School of Medicine, Zhejiang University from March to October 2022 as the research objects. They were divided into control group 106 cases and research group 90 cases by random number table method. The control group received normal nursing and chose comfortable position by themselves during labor. The research group received a series of ultrasound-guided postural intervention strategies for postural management in the first and second stages of labor on the basis of normal nursing. The angle of progression and the midline angle, the fetal orientation, fetal orientation during complete uterine orifice and delivery outcome were compared between the two groups.Results:Finally, 190 cases were included, 105 cases in the control group and 85 cases in the research group. There were 76 vaginal deliveries in the research group and 95 in the control group. The rate of anterior occipital position and the angle of fetal head rotation in the research group were 73.68% (56/76) and 64.55 (37.90, 85.55)°, which were higher than 45.26% (43/95) and 33.00 (14.00, 60.00)° in the control group;the midline angle of the research group was 57.10(38.50, 75.80)°, which was lower than 80.00 (52.50, 90.30)° of the control group. There was significant difference between the two groups ( χ2 = 14.14, Z = 4.17, - 3.74, all P<0.01). The first stage of labor was 522.50 (413.00, 695.00) minutes and the total stage of labor was 611.00 (488.00, 812.00) minutes in the research group, which was lower than 620.00 (450.00, 795.00) and 700.00 (539.00, 904.00) minutes in the control group ( Z = - 2.34, - 2.03, both P<0.05). Conclusions:The application of the serial position intervention strategy under the ultrasound guidance during the labor process can improve the abnormal fetal position, shorten the first stage of labor time effectively and safely, while it does not have any significant effect on the improvement of the delivery outcome.

Objective:To explore the efficacy and safety of Ganhai Weikang capsule (GWC) in the treatment of functional dyspepsia (FD).Methods:A randomized, double-blind, placebo-controlled parallel, multi-center, superiority clinical trial was conducted. From March 2018 to April 2020, totally 324 patients with dyspepsia symptoms, who were diagnosed as chronic non-atrophic gastritis by endoscopy and pathology and met the Rome Ⅳ diagnostic criteria for FD from 7 top hospitals were enrolled, including the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital), Heilongjiang Hospital of Traditional Chinese Medicine, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Qilu Hospital of Shandong University, the First Affiliated Hospital of Zhejiang University, Beijing Hospital of Traditional Chinese Medicine of Capital Medical University and the Third Xiangya Hospital of Central South University. The patients were randomly divided into the GWC group and the placebo group according to the ratio of 1∶1. The patients of GWC group were given GWC and the patients of placebo group were given GWC capsule simulant. The patients of both groups orally took capsules before meals, 2.4 g each time and 3 times per day, and the course of treatment was 4 weeks. The main efficacy index was the total clinical effective rate after 4 weeks, and the secondary efficacy index was the changes of clinical symptom scores of upper abdominal pain, upper abdominal burning, postprandial fullness and early satiety. The safety index included laboratory tests and adverse events. Chi-square test and Wilcoxon rank sum test were used for statistical analysis.Results:A total of 320 FD patients were enrolled in the full analysis set (FAS), which included 161 cases in GWC group and 159 cases in placebo group. A total of 298 cases were in the per-protocol set (PPS), 149 cases each in GWC group and placebo group. The results of FAS and PPS both showed that the total clinical effective rates of the GWC group were higher than those of the placebo group (84.5%, 136/161 vs. 44.0%, 70/159 and 83.9%, 125/149 vs. 46.3%, 69/149), and the differences were statistically significant ( χ2=57.07 and 46.32, both P<0.001). In addition, the differences of the total score of main symptoms and each symptom (upper abdominal pain, upper abdominal burning, postprandial fullness and early satiety) before and after treatment of GWC group were all higher than those of the placebo group (FAS: 10 (7, 14) vs. 5 (3, 11); 3 (2, 4) vs. 2 (0, 3); 2 (0, 4) vs. 1 (0, 3); 3 (1, 4) vs. 2 (1, 3); 2 (0, 4) vs. 1 (0, 3). PPS: 10 (7, 13) vs. 5 (3, 11); 3 (2, 4) vs. 2 (0, 3); 2 (0, 4) vs. 1 (0, 2); 3 (1, 4) vs. 2 (1, 3); 2 (0, 4) vs.1 (0, 3)), and the differences were statistically significant (FAS: Z=5.80, 5.91, 3.19, 3.72 and 3.30; PPS: Z=5.14, 5.11, 2.86, 3.21 and 2.84; all P<0.01). The results of FAS and PPS indicated that the improvement rates of main symptoms and each symptom (upper abdominal pain, upper abdominal burning, postprandial fullness and early satiety) of GWC group were all higher than those of the placebo group (FAS: 77.8% (54.6%, 91.3%) vs. 42.9% (28.6%, 61.5%); 100.0% (60.0%, 100.0%) vs. 50.0% (25.0%, 60.0%); 100.0% (50.0%, 100.0%) vs. 50.0% (25.0%, 100.0%); 71.4% (33.3%, 100.0%) vs. 41.4% (25.0%, 66.7%); 100.0% (50.0%, 100.0%) vs. 50.0% (20.0%, 100.0%). PPS: 77.8% (54.2%, 89.5%) vs. 44.0% (28.6%, 65.0%); 100.0% (60.0%, 100.0%) vs. 50.0% (25.0%, 100.0%); 100.0% (50.0%, 100.0%) vs. 50.0% (25.0%, 100.0%); 71.4% (33.3%, 100.0%) vs. 46.4% (25.0%, 66.7%); 100.0% (50.0%, 100.0%) vs. 50.0% (20.0%, 100.0%)), and the differences were statistically significant (FAS: Z=8.60, 7.72, 4.98, 4.24 and 5.61; PPS: Z=7.90, 7.03, 4.49, 3.88 and 4.83; all P<0.001). After 2 weeks of treatment, the differences of the total score of main symptoms and score of each symptom (upper abdominal pain, upper abdominal burning and early satiety) before and after treatment of GWC group were all higher than those of the placebo group (5.0 (3.0, 8.0) vs. 4.0 (2.0, 6.0); 2.0 (1.0, 2.0) vs. 2.0 (0.0, 2.0); 1.5 (0.0, 2.0) vs. 1.0 (0.0, 2.0); 1.5 (0.0, 2.0) vs. 1.0 (0.0, 2.0)), and the differences were statistically significant ( Z=2.95, 3.44, 2.43 and 2.79, all P<0.05). There was no significant difference in the incidence of adverse events between the GWC group and the placebo group (0.6%, 1/163 vs. 0, 0/159). Conclusion:The clinical total effective rate of GWC in the treatment of FD is superior to that of placebo and it has good safety.

Objective: To investigate the effect and safety of intensive hyperthermia combined with low-dose cisplatin plus radiotherapy in the treatment of patients with locally advanced NSCLC. Methods: From January 2012 to December 2015, 104 patients with locally advanced NSCLC were chosen in the Second People's Hospital of Weifang and randomly divided into two groups according to the digital table, with 52 patients in each group.The control group was given low-dose cisplatin plus radiotherapy, and the observation group was given intensive hyperthermia on the basis of control group.The ORR, DCR, median OS, median PFS, KPS score, the levels of coagulation function index and tumor markers before and after treatment and incidence of side effects in the two groups were compared. Results: The DCR of the observation group was significantly higher than that of the control group(86.54% vs.69.23%, χ²=8.24, P<0.05). The median OS and median PFS of the observation group were significantly longer than those of the control group(11.9 months vs.8.3 months; 7.5 months vs.4.7 months, t=2.56, 3.01, P<0.05). The KPS scores after treatment of the observation group were significantly higher than those of the control group and before treatment[(75.49±8.94)points vs.(68.65±7.06)points; (75.49±8.94)points vs.(62.23±6.34)points, t=2.78, 5.11, all P<0.05]. The levels of coagulation function index and tumor markers after treatment of the observation group were significantly lower than those of the control group and before treatment(t=3.14, 2.67, 3.59, 7.31; 4.89, 4.02, 4.70, 9.21; 2.44, 2.60, 3.20; 3.15, 3.78, 4.06; all P<0.05). There was no statistically significant difference in the incidence of side effects between the two groups(P>0.05). Conclusion Intensive hyperthermia combined with low-dose cisplatin plus radiotherapy in the treatment of patients with locally advanced NSCLC can efficiently control disease progress, increase survival benefits, higher quality of life, improve coagulation function, reduce the levels of tumor markers and possess satisfactory safety.

Objective To investigate the effect of acidic tumor microenvironment on invasion and migration and its mechanism in glioma cells. Methods (1) The pH value of the medium was adjusted by acid-base titration. Human glioma cells U87 and U251 were cultured in the acid group and the normal group with pH values of 6.4 and 7.4, respectively; and 3 d after cultivation, the expressions of hypoxia-inducible factor-2α (HIF-2α) and CD44 were detected by Western blotting; Transwell assay was used to examine the invasion and migration of U87 and U251 cells; immunofluorescence was employed to examine the CD44 expression. (2) The U87 and U251 cells were divided into small interfering RNA (siRNA) -nonsense sequence group and siRNA-CD44-1 group, and the siRNA nonsense sequences and siRNA-CD44-1 interfering fragments were transfected by lipofectin-3000, respectively; three d after transfection, the migration and invasion abilities of cells from the two groups were detected by Transwell assay. (3) U87 and U251 cells were divided into acid group (cultured with a pH value of 6.4), blank control group, siRNA nonsense sequence group, siRNA-CD44-1 group, and siRNA-CD44-2 group; and cells from the later four groups were cultured with a pH value of 7.4; after culture for 4 d, the siRNA-nonsense sequence group, siRNA-CD44-1 group and siRNA-CD44-2 group were transfected with siRNA-nonsense sequences, siRNA-cd44-1 interfering fragments and siRNA-CD44-2 interfering fragments, respectively; three d after transfection, the expressions of CD44, N-Ca, Vimentin, and matrix metalloproteinase (MMP)-2 proteins in these 5 groups were detected by Western blotting. Results (1) As compared with the normal group, the expression levels of HIF-2α and CD44 in U87 and U251 cells of the acid group were significantly increased; both Transwell and invasion experiments showed that the number of transmembrane cells in the acid group was significantly larger than that in the normal group (P<0.05); immunofluorescence staining showed that the CD44 expression in acid group was significantly higher than that in normal group (P<0.05). (2) Both Transwell and invasion experiments showed that the number of transmembrane cells in the siRNA-CD44-1 group was significantly smaller than that in the siRNA nonsense sequence group (P<0.05). (3) Western blotting showed that the expression levels of CD44, N-Ca, Vimentin and MMP-2 in U87 and U251 cells of the blank control group, siRNA nonsense sequence group, siRNA-CD44-1 group, and siRNA-CD44-2 group were obviously decreased as compared with those in the acid group; the expression levels of CD44, N-Ca, Vimentin and MMP-2 in U87 and U251 cells of the siRNA-CD44-1 group and siRNA-CD44-2 group were obviously lower than those in the siRNA nonsense sequence group. Conclusion Acidic tumor microenvironment enhances the capabilities of invasion and migration of glioma cells through increasing CD44 expression.

Objective To study the influence of micro (miR)-325 in progression of glioma and its molecular mechanism by regulating transferrin receptor (TFRC) gene expression in glioma cells. Methods (1) Thirty-five glioma tissues and paired adjacent normal tissues were collected during surgical excision performed in our hospital from January 2015 to January 2018. The miR-325 and TFRC mRNA expression levels in the glioma tissues and paired adjacent normal tissues were detected by inverse transcription-quantitative PCR (RT-qPCR); the expression of miR-325 in glioma tissues of patients with different clinical characteristics and the survival curves of patients with low or high miR-325 expressions were compared. (2) RT-qPCR was used to examine the miR-325 expression in HA, U251, and U87 cell lines in vitro; the regulatory relations between miR-325 and its potential target gene TFRC in U251, and U87 cell lines were measured by luciferase report assay; miR-325 mimic and its negative control were transfected into U251 and U87 cell lines for 48 h, and then, the mRNA and protein expressions of TFRC were detected by RT-qPCR and Western blotting, respectively; control small interfering RNA (siRNA)+nonsense inhibitor, TFRC siRNA+nonsense inhibitor, and siTFRC+miR-325 inhibitor were transfected into U251 and U87 cell lines for 48 h, respectively, Western blotting was employed to detect the TFRC protein expression, cell proliferation was detected by CCK-8 assay, and cell invasion was detected by Transwell assay; pcDNA3.1 empty vector+nonsense sequence, TFRC pcDNA3. 1+nonsense sequence, TFRC pcDNA3.1+miR-325 mimic were transfected into U251 and U87 cell lines for 48 h, respectively, TFRC protein expression was detected by Western blotting, cell proliferation was detected by CCK-8 assay, and cell invasion was detected by Transwell assay. Results (1) As compared with those in the adjacent tissues, the miR-325 expression was significantly decreased and the TFRC mRNA expression was statistically increased in glioma tissues (P<0.05); the TFRC mRNA expression and miR-325 expression were negatively correlated in glioma tissues (P<0.05); as compared with patients with Karnofsky functional status scores≥80, patients with scores<80 had significantly decreased miR-325 expression; as compared with glioma tissues of WHO grading I-II, glioma tissues of grading III-IV had significantly decreased miR-325 expression (P<0.05); the survival rate of patients with low miR-325 expression was statistically lower than that of patients with high miR-325 expression (P< 0.05). (2) As compared with that in HA cells, the miR-325 expression was statistically down-regulated in U87 and U251 cells (P<0.05); in TFRC wild-type (TFRC WT) transfected cells, the miR-325 mimic group had significantly lower luciferase activity than the nonsense sequence group, while the miR-325 inhibitor group had significantly higher luciferase activity than the nonsense inhibitor group (P<0.05); as compared with those in the nonsense sequence group, the TFRC mRNA and protein expressions were statistically decreased in U87 and U251 cells of miR-325 mimic group; as compared with those in the control siRNA+nonsense inhibitor group, the TFRC protein expression and absorbance value were significantly decreased, and number of invasive cells was significantly smaller in the siTFRC+nonsense inhibitor group; and as compared with those in the siTFRC+nonsense inhibitor group, the TFRC protein expression and absorbance value were significantly increased, and number of invasive cells was significantly larger in the siTFRC+miR-325 inhibitor group (P<0.05); as compared with the pcDNA3.1 empty vector+nonsense sequence group, the TFRC protein expression and absorbance value were significantly increased, and number of invasive cells was significantly larger in the TFRC pcDNA3.1 +nonsense sequence group, and as compared with the TFRC pcDNA3.1+nonsense sequence group, the TFRC protein expression and absorbance value were significantly decreased, and number of invasive cells was significantly smaller in the TFRC pcDNA3.1+miR-325 mimic group (P<0.05). Conclusion The miR-325 expression is decreased in glioma cells and has a tumor suppressor effect; patients with low miR-325 expression have poor prognosis; miR-325 inhibits cancer cell progression by inhibiting the expression of the target gene TFRC.