ObjectiveTo investigate the mechanism of modified Si Junzitang and Shashen Maidong Tang ［Yiqi Yangyin Jiedu prescription （YQYYJD）］ in enhancing the sensitivity of cisplatin in epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKI）-resistant lung adenocarcinoma cells based on aerobic glycolysis. MethodsThe effects of different concentrations of YQYYJD （0， 2， 3， 4， 5， 6， 7， 8 g·L^-1） and cisplatin （0， 3， 6， 9， 12， 15， 18， 21， 24， 27 mg·L^-1） on the proliferation and activity of PC9/GR cells were detected by the cell counting kit-8 （CCK-8） assay after 24 hours of intervention. The half-maximal inhibitory concentration （IC₅₀） for PC9/GR cells was calculated to determine the concentrations used in subsequent experiments. PC9/GR cells were divided into blank group （complete medium）， YQYYJD group （5 g·L^-1）， cisplatin group （12 mg·L^-1）， and combined group （YQYYJD 5 g·L^-1 + cisplatin 12 mg·L^-1）. After 24 hours of intervention， cell viability was measured using CCK-8 assay. Cell proliferation was assessed by colony formation assay， and cell migration was evaluated by scratch and Transwell assays. Glucose consumption， lactate production， and adenosine triphosphate （ATP） levels were measured by colorimetric assays. The expression levels of glycolysis-related proteins， including hexokinase 2 （HK2）， phosphofructokinase P （PFKP）， pyruvate kinase M2 （PKM2）， lactate dehydrogenase A （LDHA）， glucose transporter 1 （GLUT1）， and monocarboxylate transporter 4 （MCT4）， were determined by Western blot. ResultsBoth YQYYJD and cisplatin inhibited the viability of PC9/GR cells in a concentration-dependent manner. The IC₅₀ of PC9/GR cells for YQYYJD and cisplatin were 5.15 g·L^-1 and 12.91 mg·L^-1， respectively. In terms of cell proliferation， compared with the blank group， the cell survival rate and the number of colonies formed in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in cell survival rate and colony formation （P<0.01）. In terms of cell migration， compared with the blank group， the cell migration rate and the number of cells passing through the Transwell membrane in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group exhibited a further significant reduction in cell migration rate and the number of cells passing through the Transwell membrane （P<0.01）. In terms of glycolysis， compared with the blank group， glucose consumption， lactate production， and ATP levels in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in glucose consumption， lactate production， and ATP levels （P<0.05）. Compared with the blank group， the protein expression levels of HK2， PFKP， PKM2， and LDHA in the YQYYJD， cisplatin， and combined groups were significantly decreased （P<0.01）. The combined group showed a further significant reduction in the expression levels of these proteins compared with the YQYYJD and cisplatin groups （P<0.01）. No significant differences were observed in the protein expression levels of GLUT1 and MCT4 among the groups. ConclusionYQYYJD can synergistically inhibit the proliferation and migration of PC9/GR cells and enhance their sensitivity to cisplatin. The mechanism may be related to the downregulation of the expression of glycolysis-related rate-limiting enzymes， including HK2， PFKP， PKM2， and LDHA， thereby inhibiting glycolysis.

Objective To study the management effect of the intelligent management mode of anesthet-ic medicine box.Methods The intelligent reconstruction of the management mode of anesthesia box in the de-partment of surgical anesthesiology was carried out,and the differences in the taking and return time in 3-month before and after applying the medicine box intelligent management,error rate,and information tracking were compared,and the management effect of the medicine box was compared between the intelligent manage-ment and the traditional mode.Results The prescription modification rate,accounting error rate,discrepancy rate of person and box,and omission rate of registration had statistical differences between the traditional management mode and intelligent management mode(P<0.05).The single medicine box management work-ing time for anesthetist getting the medicine box,returning the medicine box,taking the refrigerator medicine,generating prescription and charge in intteligent management mode was shortened compared with the tradi-tional management mode,and the difference was statistically significant(P<0.05);the working time of drug management such as drug counting,prescription checking,registration records checking,drug adding and daily inventory checking in the intelligent management mode was shortened compared with the traditional manage-ment mode,and the difference was statistically significant(P<0.05).Conclusion Compared with the tradi-tional mode,the anesthetic box management intelligent mode has high efficiency and strong reliability,moreo-ver is more conducive to the standardized management of anesthetic drugs in the operating room.

OBJECTIVES: Color doppler flow imaging (CDFI) and cone-beam computed tomography (CBCT) were utilized to evaluate changes in mucosal vascular parameters and the osteogenic effects following guided bone regeneration (GBR) in the maxillary anterior region using trapezoidal or modified triangular flaps. METHODS: Patients undergoing single maxillary anterior dental implant surgery with GBR were randomly allocated into two groups: a trapezoidal flap group and a modified triangular flap group. After GBR surgery, the mucosal vascular parameters at the surgical site were assessed at various time intervals (preoperative, 2 h, 1 and 3 days, and 1, 2, and 4 weeks postoperative) using CDFI. In addition, the effects of bone augmentation were evaluated through the analysis of CBCT images obtained preoperatively, 2 h, and 6 months postoperative. RESULTS: The buccal mucosa in the edentulous area had a lower blood flow rate than the corresponding tooth in the same jaw, and the difference was statistically significant (P<0.001). The mucosal blood flow rate in the surgical area increased compared with that in the preoperative period. The peak flow rate was recorded at 2 weeks postoperatively and then decreased to levels comparable to those of the reference tooth. A statistically significant difference was observed between the two groups (P<0.05). The buccal alveolar ridge width of the implant platform was reduced by (1.3±0.9) mm in the trapezoidal flap group and (0.9±0.7) mm in the modified triangular flap group, respectively, at 6 months postoperatively, compared with 2 h postoperative. The buccal alveolar ridge width of the 5 mm from the implant platform was reduced by (0.9±0.6) mm and (0.3±0.6) mm, respectively. The buccal alveolar ridge width of the 10 mm from the implant platform was reduced by (0.6±0.8) mm and (0.2±0.6) mm, respectively. The height of the alveolar ridge was reduced by (1.9±1.4 ) mm and (1.4±1.3) mm. The change in graft volume was (136±78 ) mm³ and (114±85) mm³. However, the differences between the two groups were not statistically significant (P>0.05). CONCLUSIONS When a tooth is missing, blood flow to the buccal mucosa on the side of the missing tooth is reduced. The modified triangular flap group demonstrated superior microcirculation of blood flow in the operative area after GBR of the maxillary anterior teeth. Trapezoidal and modified triangular flaps achieved the anticipated bone augmentation during bone augmentation surgery in the maxillary anterior region, with no considerable effect on the changes in alveolar bone size parameters.
Humans ; Surgical Flaps/blood supply* ; Bone Regeneration ; Mouth Mucosa/blood supply* ; Cone-Beam Computed Tomography ; Osteogenesis ; Maxilla/surgery* ; Male ; Female ; Guided Tissue Regeneration, Periodontal/methods*

Objective: To utilize machine learning(ML) algorithms to develop accurate and effective prediction models for TAC dose/weight-adjusted trough concentration(C0/D). Methods: Data were collected on 264 TAC blood concentration monitoring data from 72 patients undergoing kidney transplantation. The effects of population statistical data, clinical features, combined medication, and ultrasound feature parameters on TAC C0/D were analyzed. Features with a significance level less than 0.05 in the univariate analysis of TAC C0/D were selected for inclusion in the random forest(RF) algorithm to identify significant features. These features were interpreted using partial dependency plots. Five ML algorithms, including RF, support vector regression(SVR), extreme gradient boosting(XGBoost), decision trees(DT) and artificial neural networks(ANN), were employed to establish the TAC C0/D prediction model. Hyper-parameter tuning was performed on the RF model that performed the best. Results : Ten characteristic variables with importance scores>5 were retained and included in the ML model: transglutaminase, red blood cell count, blood urea nitrogen, weight, serum creatinine, renal segmental arterial resistance index, renal aortic resistance index, hematocrit, renal pelvic Young′s modulus value, and time after transplantation. The partial dependence plots showed that all 10 important variables screened were positively correlated with TAC C0/D. The tuned RF model outperformed the other models with aR2of 0.81, aRMSEof 43.93, and aMAEof 29.97. Conclusion The ML models demonstrate good performance in predicting TAC C0/D and provide innovative interpretations using partial dependence plot. The optimized RF model shows optimal performance and offers a novel tool for individualized medication adjustment for TAC in renal transplant patients.

OBJECTIVES: To investigate YEATS2 expression in gastric cancer (GC), its prognostic value, and its regulatory role in epithelial-mesenchymal transition (EMT) of GC cells. METHODS: YEATS2 expression in GC was analyzed using publicly available databases. Paired GC and adjacent tissues were collected from 100 patients undergoing radical surgery for immunohistochemical detection of YEATS2 expression, and its correlations with the patients' clinicopathological parameters and Ki67 expression were analyzed. The prognostic value of YEATS2 was assessed using Kaplan-Meier analysis, Cox regression and ROC curves, and its regulatory mechanisms were analyzed using KEGG enrichment analysis. In cultured GC cell lines (HGC-27 and AGS), the effect of YEATS2 knockdown and overexpression on migration, invasion and EMT of the cells were examined with scratching assay, Transwell assay and Western blotting. RESULTS: YEATS2 was significantly overexpressed in GC tissues with a positive correlation with Ki67 (P<0.05). High YEATS2 expression was associated with elevated CEA (≥5 μg/L), CA19-9 (≥37 kU/L), T3-4 stage, and N2-3 stage (all P<0.05). Patients with high YEATS2 expression had significantly reduced 5-year survival (P<0.001); ROC analysis showed that YEATS2 expression levels had a sensitivity of 80.00% and a specificity of 66.67% for predicting patient survival (P<0.05). Cox regression identified high YEATS2 as an independent risk factor for poor postoperative 5-year survival outcome of GC patients (HR: 1.675, 95%CI: 1.013-2.771; P=0.045). KEGG enrichment analysis suggested involvement of YEATS2 in EMT in GC and Wnt/β-catenin signaling. In cultured GC cells, YEATS2 overexpression significantly promoted cell migration and invasion, upregulated the expressions of vimentin, N-cadherin, Wnt and active β-catenin, and downregulated E-cadherin expression, and these changes were obviously suppressed by treatment with XAV-939 (a Wnt/β-catenin inhibitor). CONCLUSIONS High YEATS2 expression activates Wnt/β-catenin signaling to promote EMT in GC and is correlated with poor prognosis of GC patients.
Humans ; Stomach Neoplasms/pathology* ; Epithelial-Mesenchymal Transition ; Wnt Signaling Pathway ; Cell Line, Tumor ; Prognosis ; Cell Movement ; Male ; Female ; beta Catenin/metabolism*

OBJECTIVES: To investigate the effect of hypaphorine (HYP) on Crohn's disease (CD)‑like colitis in mice and its molecular mechanism. METHODS: Thirty male C57BL/6J mice were equally randomized into WT, TNBS, and HYP groups, and in the latter two groups, mouse models of CD-like colitis were established using TNBS with daily gavage of 15 mg/kg HYP or an equivalent volume of saline. The treatment efficacy was evaluated by assessing the disease activity index (DAI), body weight changes, colon length and histopathology. The effect of HYP was also tested in a LPS-stimulated Caco-2 cell model mimicking intestinal inflammation by evaluating inflammatory responses and barrier function of the cells using qRT-PCR and immunofluorescence staining. GO and KEGG analyses were conducted to explore the therapeutic mechanism of HYP, which was validated in both the cell and mouse models using Western blotting. RESULTS: In the mouse models of CD-like colitis, HYP intervention obviously alleviated colitis as shown by significantly reduced body weight loss, colon shortening, DAI and inflammation scores, and expressions of pro-inflammatory factors in the colon tissues. HYP treatment also significantly increased the TEER values, reduced bacterial translocation to the mesenteric lymph nodes, liver, and spleen, lowered serum levels of I-FABP and FITC-dextran, increased the number of colonic tissue cup cells, and upregulated colonic expressions of MUC2 and tight junction proteins (claudin-1 and ZO-1) in the mouse models. In LPS-stimulated Caco-2 cells, HYP treatment significantly inhibited the expressions of pro-inflammatory factors and increased the expressions of tight junction proteins. Western blotting showed that HYP downregulated the expressions of the key proteins in the TLR4/MyD88 signaling pathway in both the in vitro and in vivo models. CONCLUSIONS HYP alleviates CD-like colitis in mice possibly by suppressing intestinal epithelial inflammation and improving gut barrier function.
Animals ; Male ; Mice, Inbred C57BL ; Crohn Disease/drug therapy* ; Mice ; Humans ; Caco-2 Cells ; Intestinal Mucosa/metabolism* ; Colitis/drug therapy* ; Disease Models, Animal ; Inflammation ; Toll-Like Receptor 4/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Intestinal Barrier Function

Objective To explore the similarities and differences in clinical efficacy and mRNA transcriptomics characteristics between acupuncture and shallow needling at non-acupoints and to provide a basis for determining whether shallow needling at non-acupoints is suitable as a sham acupuncture control in acupuncture clinical trials.Methods Eighty patients with chronic spontaneous urticaria(CSU)who visited the Dermatology Department of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine between July 8,2018 and to July 29,2019,were included.The patients were randomly divided into the acupuncture group(n=41)and the sham acupuncture group(n=39)using a computerized complete random design.Additionally,12 healthy individuals were included as the healthy control group.For patients in the acupuncture group,"Baihui(GV20),""Shenting(GV24),""Zhongwan(CV12),"and bilateral"Quchi(LI11),""Tianshu(ST25),""Xuehai(SP10),""Zusanli(ST36),"and"Sanyinjiao(SP6)"were selected for regular acupuncture.The sham acupuncture group received non-acupoint shallow needling at eight non-acupoints on the head,upper limbs,lower limbs,and abdomen.Both groups underwent daily treatment,with five consecutive days constituting one treatment course followed by a two-day interval.A total of two courses were administered.The urticaria activity score(UAS)was used to evaluate wheals and pruritus,whereas the visual analog scale(VAS)score was used to evaluate the degree of pruritus.Blinding effectiveness was also evaluated.Based on clinical evaluation and sample quality,serum samples from six patients in each treatment group before and after the intervention,along with those from six healthy individuals,were selected for RNA sequencing using the BGISEQ-500 sequencer.Differentially expressed mRNAs were identified using the"DEGseq"software package,and the similarities and differences in mRNA expression between the two groups were analyzed.Results UAS and VAS scores decreased in both groups at 1,2,3,and 4 weeks of treatment compared with before treatment(P＜0.01).The decrease in UAS and VAS scores in both groups was time-dependent(P＜0.01)but not related to the grouping or the interaction between grouping and time(P＞0.05).By the end of the second week of treatment,the number of patients in both groups who believed they had received true acupuncture was similar between the two groups,with no significant difference.mRNA transcriptomic sequencing revealed that,before and after treatment,the enrichment types and degrees of differentially expressed mRNA were similar between the acupuncture and sham acupuncture groups at the biological process,cellular component,and molecular function levels.In terms of biological processes,both groups were commonly enriched in coagulation,hematoma,oxygen transport,and gas transport.In terms of cellular components,both groups exhibited enrichment in hemoglobin complexes,platelet alpha granules,extracellular exosomes,extracellular organelles,and extracellular vesicles.At the molecular function level,both groups were commonly enriched in actin filament-binding substances,haptoglobin,peroxidase activity,and oxygen blood binding.In the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,both groups showed common enrichment in multiple entries such as cytokine-cytokine receptor interaction,ECM-receptor interaction,microRNAs in cancer,proteoglycans in cancer,bladder cancer,and malaria.Conclusion Acupuncture and sham acupuncture exhibited similar clinical treatment effects and mRNA transcriptomics profiles.In the design of acupuncture clinical trials,disease specificity should be carefully considered.Sham acupuncture control using non-acupoint shallow needling may not be suitable for skin diseases such as urticaria.

Objective To evaluate the value of multimodal brain function monitoring using quantitative electroencephalography(QEEG)and transcranial Doppler(TCD)in predicting hematoma enlargement and prognosis in patients with acute hypertensive intracerebral hemorrhage.Methods A retrospective analysis was conducted on the clinical data of 120 patients with acute hypertensive intracerebral hemorrhage from October 2019 to October 2022.All patients underwent QEEG and TCD examinations within 24 hours of admission,and were divided into hematoma enlargement group(79 cases)and hematoma stabilization group(41 cases)based on whether the hema-toma had expanded.By comparing the parameter differences of QEEG and TCD between two groups,explore the correlation between these monitoring indicators and hematoma enlargement and patient prognosis.Results The patients in the hematoma enlargement group had a higher average age and a higher smoking rate.The initial neuro-logical damage in the hematoma enlargement group was more severe.The DAR and DTABR values of the hematoma enlargement group were significantly higher than those of the stable group at different time points after cerebral hemorrhage(P<0.05).Correlation analysis shows that DAR,DTABR,and P1 have significant positive correla-tions with hematoma enlargement,with DAR and DTABR showing particularly strong correlations(r values of 0.774 and 0.738,respectively,P<0.05),while P1 has relatively weak correlations(r=0.213,P<0.05).ROC curve analysis shows that DAR,DTABR,and P1 parameters have high sensitivity and specificity in predicting hematoma enlargement,with an AUC value of up to 0.970 for DAR.During the follow-up period,the MRS scores of the stable hematoma group were significantly better than those of the hematoma expansion group at all time points(P<0.05).Conclusion QEEG and TCD are helpful in early identification of high-risk patients,enabling more targeted treatment measures and improving clinical outcomes for patients.

Objective:To investigate the iodine nutrition status of pregnant women in Zhejiang Province, explore the impact of salt industry system reform on iodine nutrition level of pregnant women, and provide scientific basis for prevention and treatment of iodine deficiency disorders.Methods:From 2016 to 2021, a multi-stage stratified sampling method was used to select 100 pregnant women from 90 counties (cities, districts) in Zhejiang Province each year as survey subjects. Salt samples were collected from pregnant women's families, and one random urine sample was taken for salt iodine and urinary iodine level testing, respectively.Results:A total of 56 581 samples of household edible salt were collected from pregnant women, with a median salt iodine level of 23.20 mg/kg. Among them, 7 961 were non iodized salt, 45 803 were qualified iodized salt, and 2 817 were unqualified iodized salt. The iodized salt coverage rate was 85.93% (48 620/56 581), and the qualified iodized salt consumption rate was 80.95% (45 803/56 581). The proportion of non iodized salt increased from 10.05% (897/8 928) in 2016 to 15.09% (1 461/9 679) in 2021 (χ 2trend = 95.16, P < 0.001). A total of 56 581 urine samples were collected from pregnant women, with a median urinary iodine level of 130.50 μg/L. Among them, the proportions of urinary iodine levels < 150, 150 - 249, 250 - 499, and ≥500 μg/L were 58.32% (32 996/56 581), 27.24% (15 410/56 581), 12.24% (6 926/56 581), and 2.21% (1 249/56 581), respectively. The median urinary iodine level of pregnant women in inland areas was significantly higher than that in coastal areas ( Z = 19.15, P < 0.001). Furthermore, urinary iodine levels exhibited a non-linear decline as age increased (χ 2regression = 12.65, P < 0.001; χ 2partial = 22.65, P < 0.001) and as pregnancy progressed (χ 2regression = 37.28, P < 0.001; χ 2partial = 18.89, P < 0.001). Conclusions:The overall iodine nutrition status of pregnant women in Zhejiang Province is in a state of iodine deficiency (< 150 μg/L), and there is a greater risk in coastal areas compared to inland areas. However, in the context of the reform of the salt industry system, it is still necessary to strengthen the quality supervision of iodized salt, provide scientific iodine supplementation education, promote specialized iodized salt for pregnant women, and strengthen interventions for prevention and control of iodine deficiency disorders.

Objective:To investigate the effects of Vibrio vulnificus ( Vv) quorum-sensing protein LuxS on the homeostasis of pulmonary innate immune cells in sepsis-induced acute lung injury. Methods:This study constructed luxS knockout and complemented Vv strains. The time required for wild type, luxS knockout, and complemented Vv strains to grow to an absorbance of 600 nm in liquid medium was measured using a spectrophotometer. Iron-overloaded mice were intraperitoneally infected with 1×10 5 CFU of the above three kinds of Vv strains, respectively. Clinical scoring for sepsis-induced dyspnea was used to evaluate the respiratory quality in mice. At 7 h after infection, the pathological changes in lung tissues were observed by HE staining; the bacterial loads in lung tissues were measured; the single-cell suspension of lung tissues was analyzed by flow cytometry. Uniform manifold approximation and projection (UMAP) was used to reduce the dimension of the distribution of CD45 + immune cells in lung tissues of mice in the PBS control group and infection groups with different strains. The frequency and absolute number of innate immune cells in lung tissues were analyzed by multicolor flow cytometry. One-way analysis of variance and t test were used for statistical analysis. Results:There was no significant difference in the growth rate of wild type, luxS knockout, and complemented Vv strains in liquid medium. Compared with the mice infected with the wild type or complemented strain, the mice infected with the luxS knockout strain exhibited overall alleviated respiratory difficulty, decreased inflammatory cell infiltration in lung tissues, and reduced bacterial load in lung tissues ( P<0.05). Besides, there was no significant difference in clinical respiratory scores, inflammatory cell infiltration, or bacterial loads between the mice infected with the complemented strain and wild type strain. UMAP analysis showed that compared with the mice infected with the luxS knockout strain, the mice infected with the wild type or complemented strain showed increased proportions of neutrophils and eosinophils in lung tissues. Results of multicolor flow cytometry analysis further verified that the proportions of neutrophils and eosinophils were significantly lower in the mice infected with the luxS knockout strain than in the mice infected with wild type or complemented strain ( P<0.01, P<0.000 1), while the proportion of alveolar macrophages was significantly higher as compared with that in the mice infected with wild type or complemented strain ( P<0.01). Conclusion:During Vv infection, LuxS may promote acute lung injury by affecting the homeostasis of neutrophils, eosinophils and resident macrophages in lung tissues.