ObjectiveTo study the effect of Taikong Yangxin Pills on the metabolism of simulated weightless rats based on metabolomics and discuss the metabolism mechanism. MethodsIn the simulated space capsule environment on the ground， the rat model of simulated weightlessness was established by the tail suspension method. Rats were randomly grouped as follows： out-of-capsule control， in-capsule control， model， and high （3.0 g·kg^-1） and low （1.5 g·kg^-1） doses of Taikong Yangxin Pills， and they were administrated with corresponding drugs by gavage for 28 days. The serum levels of endogenous metabolites in rats were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF/MS）. The obtained data were processed by principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） to screen for differential metabolites and potential biomarkers. MetaboAnalyst 5.0 was used for pathway enrichment analysis to explain the metabolic regulation mechanism of the drug. ResultsCompared with the out-of-capsule control group， the in-capsule control group showed elevated levels of thirteen metabolites， including 14-hydroxyhexadecanoic acid， linoleic acid， and α-linolenic acid （P<0.05）， which suggested that the space capsule environment mainly affected the metabolism of α-linolenic acid and linoleic acid in the rats. Compared with the in-capsule control group， the model group showed lowered levels of fourteen metabolites， including 4-imidazolone-5-propionic acid， isocitric acid/citric acid， and L-tyrosine （P<0.05）， which were recovered after the treatment with Taikong Yangxin pills （P<0.05）. The pathway enrichment analysis revealed that weightlessness induced by tail suspension and drug intervention mainly involved the phenylalanine， tyrosine， and tryptophan biosynthesis， tyrosine metabolism， histidine metabolism， and citric acid cycle. ConclusionThe simulated space capsule environment and simulated weightlessness induced by tail suspension can both affect the metabolism level of rats. Taikong Yangxin pills can ameliorate the metabolic abnormality in the rat model of weightlessness by regulating various amino acids and energy metabolism-related pathways.

ObjectiveTo systematically evaluate the efficacy and safety of Qi-reinforcing and blood-activating/stasis-expelling Chinese patent medicines in the treatment of coronary microvascular disease （CMD）. MethodsPubMed， Cochrane Library， CNKI， Wanfang Data， and VIP were searched for the randomized controlled trials （RCTs） on the treatment of CMD with Chinese patent medicines for reinforcing Qi and activating blood/expelling stasis with the time interval from inception to December 31， 2023. The primary outcome indicators included the index of microcirculatory resistance （IMR）， coronary flow reserve （CFR）， and corrected TIMI flow frame count （cTFC）. The secondary outcome indicators included symptomatic efficacy， left ventricular ejection fraction （LVEF）， hypersensitive C-reactive protein （hs-CRP）， nitric oxide （NO）， and adverse events. Cochrane risk-of-bias assessment tool 2.0 （RoB 2.0） and Stata 17.0 were used for literature quality evaluation and meta-analysis of the included RCTs. The Grading of Recommendations， Assessment， Development and Evaluation （GRADE） was used to evaluate the quality of evidence. ResultsA total of 36 RCTs were included in this study， involving 3 029 patients. Compared with conventional Western medicine alone， the combined use of Chinese patent medicines for reinforcing Qi and activating blood/expelling stasis and Western medicine reduced the IMR ［mean difference （MD）=-5.93， 95% confidence interval （95%CI） ［-8.73，-3.14］， n=382， P<0.01］， cTFC （MD=-9.35， 95%CI ［-13.94，-4.76］， n=618， P<0.01）， and hs-CRP ［standard mean difference （SMD）=-1.50， 95%CI ［-1.90，-1.11］， n=1 483， P<0.01］， improved the CFR （SMD=1.14， 95%CI ［0.08，2.19］， n=304， P=0.03）， symptomatic efficacy ［relative risk （RR）=1.36， 95%CI ［1.21，1.53］， n=756， P<0.01］， LVEF （MD=4.39， 95%CI ［2.31，6.47］， n=533， P<0.01）， and NO （SMD=3.16， 95%CI ［2.07，4.25］， n=946， P<0.01） of CMD patients. In terms of safety， the combined therapy reduced the occurrence of adverse events in CMD patients （RR=0.49， 95%CI ［0.29，0.82］， n=591， P=0.01）. GRADE showed moderate quality evidence for adverse events， low quality evidence for cTFC， symptomatic efficacy， LVEF， and NO， and very low quality evidence for IMR， CFR， and hs-CRP. ConclusionBased on microcirculatory function indicators， the combined use of Qi-reinforcing and blood-activating/stasis-expelling Chinese patent medicines and Western medicine may further improve the coronary microvascular function in CMD patients with good safety. The above conclusions remain to be verified with high-quality clinical trials.

OBJECTIVES: To investigate the effect of BRD4 inhibition on migration of esophageal squamous cell carcinoma (ESCC) cells with low acetyl-CoA carboxylase 1 (ACC1) expression. METHODS: ESCC cell lines with lentivirus-mediated ACC1 knockdown or transfected with a negative control sequence (shNC) were treated with DMSO, JQ1 (a BRD4 inhibitor), co-transfection with shNC-siBRD4 or siNC with additional DMSO or C646 (an ahistone acetyltransferase inhibitor) treatment, or JQ1combined with 3-MA (an autophagy inhibitor). BRD4 mRNA expression in the cells was detected using RT-qPCR. The changes in cell proliferation, migration, autophagy, and epithelial-mesenchymal transition (EMT) were examined with CCK8 assay, Transwell migration assay, and Western blotting. RESULTS: ACC1 knockdown did not significantly affect BRD4 expression in the cells but obviously increased their sensitivity to JQ1. JQ1 treatment at 1 and 2 μmol/L significantly inhibited ESCC cell proliferation, while JQ1 at 0.2 and 2 μmol/L promoted cell migration. The cells with ACC1 knockdown and JQ1 treatment showed increased expresisons of vimentin and Slug and decreased expression of E-cadherin. BRD4 knockdown promoted migration of ESCC cells, and co-transfection with shACC1 and siBRD4 resulted in increased vimentin and Slug expressions and decreased E-cadherin expression in the cells. C646 treatment of the co-transfected cells reduced acetylation levels, decreased vimentin and Slug expressions, and increased E-cadherin expression. Treatment with JQ1 alone obviously increased LC3A/B-II levels in the cells either with or without ACC1 knockdown. In the cells with ACC1 knockdown and JQ1 treatment, additional 3-MA treatment significantly decreased the expressions of vimentin, Slug and LC3A/B-II and increased the expression of E-cadherin. CONCLUSIONS BRD4 inhibition promotes autophagy of ESCC cells via a histone acetylation-dependent mechanism, thereby enhancing EMT and ultimately increasing cell migration driven by ACC1 deficiency.
Humans ; Cell Movement ; Transcription Factors/metabolism* ; Esophageal Neoplasms/metabolism* ; Cell Line, Tumor ; Cell Cycle Proteins ; Azepines/pharmacology* ; Epithelial-Mesenchymal Transition ; Carcinoma, Squamous Cell/metabolism* ; Esophageal Squamous Cell Carcinoma ; Triazoles/pharmacology* ; Nuclear Proteins/genetics* ; Cell Proliferation ; Acetyl-CoA Carboxylase/genetics* ; Transfection ; Autophagy ; Bromodomain Containing Proteins

Objective This study aims to assess the role of DNA methylation changes in tongue cancer through a comprehensive analysis of global DNA methylation alterations during experimental lingual carcinogenesis.Methods C57BL/6J mice were subjected to 16-week oral administration of 4-nitroquinoline-1-oxide(4NQO,50 mg/L).Lingual mucosa samples,being representative of normal tissue(week 0)and early(week 12)and advanced(week 28)tumorigen-esis,were harvested for microarray and methylated DNA immunoprecipitation sequencing(MeDIP-Seq).The mRNA and promoter methylation of transforming growth factor-beta-signaling protein 1(SMAD1)were evaluated with real-time quantitative reverse transcription polymerase chain reaction and Massarray in human lingual mucosa and tongue cancer cell lines.Results The cytosine guanine island(CGI)methylation level observed at 28 weeks surpassed that of both 12 weeks and 0 weeks.The promoter methylation level at 12 weeks exceeded that at 0 weeks.Notably,208 differentially expressed genes were negatively correlated to differential methylation in promoters among 0,12,and 28 weeks.The mRNA of SMAD1 was upregulated,con-current with a decrease in promoter methylation levels in cell lines compared to normal mucosa.Conclusion DNA methylation changed during lingual carcinogenesis.Overexpression of SMAD1 was correlated to promoter hypomethyl-ation in tongue cancer cell lines.

Objective To observe the effect of abdominal acupuncture in treating allergic rhinitis(AR).Methods Twenty-seven AR patients who attended Fangshan Hospital,Beijing University of Chinese Medicine from August to October 2022 were selected.They were divided into treatment group(15 cases)and control group(12 cases)according to randomized numerical table method.The treatment group received abdominal acupuncture.The control group at the same point was used one-time sterile cannula acupuncture to simulate acupuncture,but no needle was inserted into the acupoint.Two groups were treated,3 times a week for 4 weeks.The visual analogue scale(VAS),rhinoconjunctivitis quality of life questionnaire(RQLQ),Pittsburgh sleep quality index(PSQI)scores,and the histamine(HIS),leukotriene D4(LTD4),immunoglobulin E(IgE)levels were compared between two groups before and after treatment.Results At each time point after treatment,the VAS,RQLQ,PSQI scores and HIS,LTD4,IgE levels of patients in treatment group were significantly lower than those before treatment(P<0.05).There were no statistically significant differences in VAS,RQLQ,and PSQI scores,the HIS,LTD4,and IgE levels after 2-week treatment in both groups(P>0.05).After 4-week treatment and follow-up 4-week,the VAS,RQLQ,and PSQI scores,the HIS,and LTD4 levels in treatment group were significantly lower than those in control group(P<0.05).Conclusion Abdominal acupuncture has good therapeutic effect on AR and significantly improves life quality of the patients,which can reduce the levels of HIS,LTD4 and IgE.The therapy is worthy of clinical application.

Objective To investigate the efficacy of methylprednisolone in preventing postoperative pulmonary infections in locally advanced esophageal cancer patients undergoing neoadjuvant chemotherapy combined with immunotherapy.Methods A total of 89 patients with locally advanced esophageal cancer treated at the First Affiliated Hospital of Xinxiang Medical University from January 2022 to December 2023 were selected as the research subjects.All patients underwent thoracolaparoscopic radical esophagectomy for esophageal cancer.The patients were randomly divided into an observation group(n=45)and a control group(n=44)using a random number table method.In the observation group,one patient with intraoperative thoracotomy,two patients with extensive pleural adhesion,and one patient with preoperative upper respiratory tract infection were excluded.In the control group,one patient with extensive pleural adhesion and one patient with preoperative upper respiratory tract infection were excluded.As a result,a total of 83 patients were included in the study,with 41 in the observation group and 42 in the control group.Preoperatively,a neoadjuvant treatment regimen of paclitaxel(albumin-bound)+nedaplatin in combination with camrelizumab was given to patients in both groups for 2 cycles.Patients in the control group received conven-tional anti-infection treatment after surgery,while patients in the observation group were intravenously injected with methylpred-nisolone at a dose of 1 mg·kg-1 daily from the first to the third day after surgery.Postoperative inflammatory markers,incidence of postoperative pulmonary infections,incidence of anastomotic fistula,postoperative hospital stay,and total hospitalization costs were compared between the two groups.Results There were no statistically significant differences in leukocyte count,neutrophil ratio,procalcitonin(PCT),high-sensitivity C-reactive protein(hs-CRP),and interleukin-6(IL-6)levels of patients between the two groups before treatment(P＞0.05).On day 1 and 4 after treatment,patients in the observation group had significantly higher leu-kocyte count,neutrophil ratio,PCT,hs-CRP,and IL-6 levels compared to those before treatment(P＜0.05).On postoperative day 4,the leukocyte count,neutrophil ratio,PCT,hs-CRP,and IL-6 levels were significantly lower than those on day 1 postopera-tively(P＜0.05).On postoperative days 1 and 4,the leukocyte count,neutrophil ratio,PCT,hs-CRP and IL-6 levels of patients in the control group were significantly higher than those in the preoperative period(P＜0.05),and the leukocyte count,neutro-phil ratio and hs-CRP level were significantly lower on day 4 after surgery than on day 1 after surgery(P＜0.05);the differe-nces in PCT and IL-6 level of patients between day 4 after surgery and day 1 after surgery were not statistically significant(P＞0.05).On postoperative day 1,there were no statistically significant differences in leukocyte count,neutrophil ratio,PCT,hs-CRP,and IL-6 levels between patients in the observation group and the control group(P＞0.05).On postoperative day 4,the leukocyte count,neutrophil ratio,PCT,hs-CRP,and IL-6 levels of patients in the observation group were significantly lower than those in the control group(P＜0.05).The incidence of pulmonary infections in patients in the control group and the ob-servation group was 30.9％(13/42)and 12.2％(5/41),respectively;the incidence of pulmonary infections in patients in the observation group was significantly lower than that in the control group(x2=4.298,P＜0.05).The incidence of anasto-motic fistula in patients in the observation group and the control group was 9.76％(4/42)and 21.43％(9/42),respectively;there was no statistically significant difference between the two groups(x2=2.140,P＞0.05).The postoperative hospital stay was significantly longer in the control group than in the observation group(P＜0.05),and the total hospitalization costs were significantly higher in the control group than in the observation group(P＜0.05).Conclusion Methylprednisolone can effec-tively reduce the levels of inflammatory markers and the incidence of postoperative pulmonary infections in esophageal cancer patients undergoing neoadjuvant chemotherapy combined with immunotherapy before surgery.It is a highly safe treatment thera-py without increasing the incidence of anastomotic fistula.

Objective:To evaluate the clinical efficacy of heat-sensitive moxibustion combined with kneading and massage manipulation at pain points in treating patients with lumbar disc herniation (LDH) and chronic low back pain (LBP).Methods:Randomized controlled trial. A total of 91 patients with LDH and LBP who were admitted to Lu'an Hospital of Traditional Chinese Medicine from January 2020 to December 2022 were selected as the observation subjects. They were divided into the experimental group (46 cases) and the control group (45 cases) by random number table method. The control group was treated with conventional massage manipulation, while the experimental group was treated with heat-sensitive moxibustion combined with kneading and massage manipulation at pain points. Both groups received 4 weeks of continuous treatment. The degree of lumbar pain was evaluated with the Visual Analogue Scale (VAS), and the degree of lumbar dysfunction was evaluated with modified Oswestry Disability Index (ODI). Plasma viscosity, hematocrit, whole blood low shear viscosity and whole blood high shear viscosity were measured using a blood rheometer. Clinical efficacy was evaluated.Results:The total clinical effective rates in the experimental group and the control group were 93.48% (43/46) and 77.78% (35/45), with a statistical significance between groups ( χ2=4.58, P=0.032). After treatment, the VAS score [(3.81±0.74) vs. (4.29±0.85), t=2.88] and ODI score [(8.79±2.65) vs. (11.25±3.74), t=3.63] of the experimental group were lower than those of the control group ( P<0.01). Plasma viscosity [(1.35±0.06) mPa?s vs. (1.41±0.08) mPa?s, t=4.05], hematocrit [(37.46±2.38)% vs. (40.15±2.94)%, t=4.80], whole blood low shear viscosity [(7.41±1.53) mPa?s vs. (8.64±1.72) mPa?s, t=3.61] and whole blood high shear viscosity [(3.81±0.29) mPa?s vs. (4.07±0.31) mPa?s, t=4.13] were lower than those in the control group ( P<0.01). Conclusion:Heat-sensitive moxibustion combined with kneading and massage manipulation at pain points can effectively relieve LBP in patients with LDH and chronic LBP, improve lumbar dysfunction and hemodynamic status, and enhance clinical efficacy.

Objective To study the applicability and optimization of computer simulation methods during the allocation of health care providers for medical evacuation on board medical trains.Methods Using Anylogic as a simulation modeling tool,the process of mass evacuation of the injured by means of medical trains was simulated.The simulated process of rescue involved the generation,categorization,treatment and surgery of the injured individuals.The allocation of health care resources was assessed based on the different rates at which the injured arrived.Results In the carriage for mild to moderate patients,24 doctors and 36 nurses could meet the need of treatment.In the carriage for critically ill ones,4 doctors and 6 nurses could meet the need when the rate at which the injured arrived was 100-200 people/an hour.When the injured arrived at the rate of 300-476 people/an hour,4 doctors and 8 nurses were needed.Conclusion Computer simulation can be feasibly used to study the allocation of human resources for health care,which can facilitate decision-making about mass evacuation of injured personnel by means of medical trains.

Objective To explore the diagnostic value of energy spectrum CT quantitative parameters combined with serum thy-roid stimulating hormone receptor-messenger ribonucleic acid(TSHR-mRNA)for papillary thyroid microcarcinoma(PTMC).Methods A total of 105 patients with thyroid micronodules confirmed by surgery and pathology were collected,61 of whom were PTMC(PTMC group),and 44 patients with micronodular goiter(MNG)(MNG group).Energy spectrum CT quantitative parameters and serum TSHR-mRNA expression were compared between the two groups.The diagnostic value of energy spectrum CT quantitative parame-ters alone and combined with serum TSHR-mRNA for PTMC was analyzed by receiver operating characteristic(ROC)curve.Results The iodine concentration and slope of energy spectrum CT quantitative parameters between PTMC group and MNG group were signifi-cantly different in plain scan,arterial and venous phases(P＜0.05).The mean serum TSHR-mRNA expression in the PTMC group was higher than that in MNG group(P＜0.05).The area under the curve(AUC)for diagnosing PTMC using quantitative parame-ters of energy spectrum CT combined with serum TSHR-mRNA was 0.913,and the accuracy,sensitivity,and negative predictive value of diagnosing PTMC were significantly higher than those of quantitative parameters of energy spectrum CT or serum TSHR-mRNA(P＜0.05).Conclusion Both energy spectrum CT quantitative parameters and serum TSHR-mRNA can be used to diagnose PTMC alone,and the combination of both is more accurately.

Objective:To investigate the improvement effect of cognitive psychotherapy on negative emotions and shame in patients with cancer and depression.Methods:A total of 114 patients with cancer and depression who received treatment at Shaoxing 7 th People's Hospital from February 2022 to May 2023 were included in this randomized controlled study. The patients were randomly divided into two groups: group A and group B, with 57 patients in each group. Group A received routine western medicine treatment, while group B received routine western medicine combined with cognitive psychotherapy. Both groups received treatment for 8 weeks. Various measures were evaluated at the end of the treatment period, including negative emotions (Hamilton Depression Scale score, Hamilton Anxiety Scale score), shame (Social Impact Scale score), self-efficacy (Breastfeeding Self-Efficacy Scale score), sleep quality (Pittsburgh Sleep Quality Index score), and clinical efficacy. Results:After treatment, the Hamilton Depression Scale score and Hamilton Anxiety Scale score in group B were (7.83 ± 2.01) points and (9.78 ± 1.94) points, respectively, which were significantly lower than those in group A [(12.15 ± 2.37) points, (13.06 ± 2.32) points, t = 10.50, 8.19, both P < 0.001). The Social Impact Scale score in group B was significantly lower than that in group A [(44.72 ± 4.93) points vs. (51.63 ± 6.10) points, t = 6.65, P < 0.001]. The Breastfeeding Self-Efficacy Scale score in group B was significantly higher than that in group A [(121.65 ± 11.44) points vs. (100.24 ± 10.73) points, t = -10.31, P < 0.001]. The Pittsburgh Sleep Quality Index score in group B was significantly lower than that in group A [(7.00 ± 0.85) points vs. (9.83 ± 1.10) points, t = 15.37, P < 0.001]. The overall response rate in group B was significantly higher than that in group A [94.74% (54/57) vs. 80.70% (46/57), χ2 = 5.21, P = 0.022]. Conclusion:Cognitive psychotherapy has a significant impact on patients with cancer and depression, effectively alleviating negative emotions and shame, enhancing self-efficacy, and improving sleep quality. Therefore, it deserves clinical promotion.