Aim To investigate the biological function and molecular mechanisms of piRNA-823 in the phenotypic transformation of human umbilical vein endothelial cells(HUVEC)induced by high glucose.Methods HUVEC were incubated in high glucose(33.3 mmol/L)culture medium for 72 h.The relative expression levels of piR-NA-823 were detected by RT-qPCR,the expression changes of endothelial cell markers,mesenchymal cell markers and proteins related to transforming growth factor-β1(TGF-β1)signaling pathway were detected by Western blot,the changes of cell migration ability were evaluated by scratch and Transwell assays,the formation of new angiogenesis were assessed through angiogenesis experiments.piRNA-823 mimic(overexpression of piRNA-823)were transfected into HUVEC to analyze their effects on high glucose induced endothelial-mesenchymal transition(EndMT)and angiogenesis.Further in-tervention was performed using TGF-β1 activator(SRI011381)and inhibitor(SB525334)to verify whether piRNA-823 ex-erts its effect by regulating the TGF-β1/Smad2/3 signaling pathway.Results piRNA-823 mimic significantly inhibited the viability,proliferation,migration and angiogenesis of HUVEC induced by high glucose.The piRNA-823 mimic inhibited high glucose induced EndMT in HUVEC,characterized by upregulation of endothelial cell markers and downregulation of mesenchymal cell markers.Scratch experiments,Transwell experiments and angiogenesis experiments further confirmed that piRNA-823 mimic could effectively reverse high glucose induced HUVEC proliferation,migration a-bility enhancement,and increase in the number of new angiogenesis.Mechanistic studies revealed that the TGF-β1 acti-vator partially reversed the protective effect of piRNA-823 mimic,whereas the TGF-β1 inhibitor enhanced its effect,sug-gesting that piRNA-823 exerts its regulatory role by suppressing the activation of the TGF-β1/Smad2/3 signaling pathway.Conclusion piRNA-823 significantly inhibits high glucose induced EndMT,proliferation,migration and angiogenesis in HUVEC by suppressing the activation of TGF-β1/Smad2/3 signaling pathway.

Aim To investigate the biological function and molecular mechanisms of piRNA-823 in the phenotypic transformation of human umbilical vein endothelial cells(HUVEC)induced by high glucose.Methods HUVEC were incubated in high glucose(33.3 mmol/L)culture medium for 72 h.The relative expression levels of piR-NA-823 were detected by RT-qPCR,the expression changes of endothelial cell markers,mesenchymal cell markers and proteins related to transforming growth factor-β1(TGF-β1)signaling pathway were detected by Western blot,the changes of cell migration ability were evaluated by scratch and Transwell assays,the formation of new angiogenesis were assessed through angiogenesis experiments.piRNA-823 mimic(overexpression of piRNA-823)were transfected into HUVEC to analyze their effects on high glucose induced endothelial-mesenchymal transition(EndMT)and angiogenesis.Further in-tervention was performed using TGF-β1 activator(SRI011381)and inhibitor(SB525334)to verify whether piRNA-823 ex-erts its effect by regulating the TGF-β1/Smad2/3 signaling pathway.Results piRNA-823 mimic significantly inhibited the viability,proliferation,migration and angiogenesis of HUVEC induced by high glucose.The piRNA-823 mimic inhibited high glucose induced EndMT in HUVEC,characterized by upregulation of endothelial cell markers and downregulation of mesenchymal cell markers.Scratch experiments,Transwell experiments and angiogenesis experiments further confirmed that piRNA-823 mimic could effectively reverse high glucose induced HUVEC proliferation,migration a-bility enhancement,and increase in the number of new angiogenesis.Mechanistic studies revealed that the TGF-β1 acti-vator partially reversed the protective effect of piRNA-823 mimic,whereas the TGF-β1 inhibitor enhanced its effect,sug-gesting that piRNA-823 exerts its regulatory role by suppressing the activation of the TGF-β1/Smad2/3 signaling pathway.Conclusion piRNA-823 significantly inhibits high glucose induced EndMT,proliferation,migration and angiogenesis in HUVEC by suppressing the activation of TGF-β1/Smad2/3 signaling pathway.

Aim The effect of miR-223-3p on H9c2 cells in high glucose environments was investigated through bioinformatics and its role in the mechanism of development of diabetic cardiomyopathy was analyzed in conjunction with transcriptomic sequencing results.The objective was to identify novel therapeutic targets at the molecular level and explore the specific mechanisms of action of miR-223-3p.Methods In high glucose-cultivated H9c2 cells,miR-223-3p inhibition and control were transfected,respectively.RT-qPCR was used to detect the differences in miR-222-3p expression between the two cell groups.Differential mRNA was identified through high-throughput sequen-cing.GO functional analysis was conducted using TopGO software.DESeq2 software(v1.16.1)filtered differentially expressed genes and analyzed them using a miR-223-3p target gene database.This process predicted the target genes of miR-223-3p and validated the changes in their expression through RT-qPCR.Results The activity of H9c2 cells trea-ted with high glucose decreased significantly.Significant differences in gene expression between the control group and the inhibitor group had been indicated by transcriptomic sequencing results.GO function enrichment analysis showed that the predicted target gene set was significantly enriched in G protein-coupled receptor activity,glycerol ether monooxygenase ac-tivity,cellular anion homeostasis,and chloride ion homeostasis,among others.KEGG pathway enrichment analysis fur-ther showed that these genes were mainly involved in the TNF signaling pathway and the IL-17 signaling pathway.In ad-dition,they were related to type 1 diabetes,cytochrome P450 metabolism of exogenous drugs,and other diseases and phys-iological processes.Target gene prediction suggested that miR-223-3p may be associated with the expression changes of Cxcl10,Creb313,Mmp3,and Bc13,among others.Conclusion The prediction of miR-223-3p and its downstream target genes in high glucose induced H9c2 cell injury may provide new targets for the treatment of diabetic cardiomyopa-thy,which is of great significance for revealing the pathogenesis of diabetic cardiomyopathy and developing new treatment strategies.

Objective:To evaluate the short-term efficacy and safety of a preoperative combination of programmed cell death protein-1 (PD-1) inhibitor with either oxaliplatin + capecitabine (CapeOx) or oxaliplatin + tegafur gimeracil oteracil potassium (SOX) in the treatment of locally advanced immunotherapy-sensitive gastric cancer (LAGC) or adenocarcinoma of the esophagogastric junction (AEG).Methods:The cohort of this retrospective descriptive case series comprised patients with LAGC or AEG whose cancers had been determined to be immunotherapy- sensitive by endoscopic biopsy before treatment in the Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital and Institute from 1 August 1 2021 to 31 January 2024. Patients with any one of the following three characteristics were immunotherapy-sensitive: (i) PD-L1 combined positive score (CPS) ≥5; (ii) microsatellite instability-high (MSI-H) / mismatch repair deficiency (dMMR); or (iii) Epstein-Barr virus-encoded RNA (EBER) positivity. All study patients received PD-1 inhibitors combined with CapeOx or SOX as a neoadjuvant or conversion treatment strategy before surgery. Patients with immune system diseases, distant metastases, or human epidermal growth factor receptor 2 positivity were excluded. Factors analyzed included pathological complete response, clinical complete response, major pathological response, R0 resection rate, surgical conversion rate, and safety of the treatment, including immune-related adverse events (irAEs) and surgical complications.Results:The study cohort comprised 39 patients (28 men and 11 women) of median age 62 (range 44–79) years. After the above-described preoperative treatment, radical resection of the 14 tumors that were initially considered unresectable was achieved (surgical conversion rate: 14/14). Twenty-three of the remaining 25 patients underwent radical resection. The last two patients achieved clinical complete responses and opted for a "non-surgical strategy" (watch and wait). Overall, 37 patients (94.9%) underwent radical resection, with an R0 resection rate of 100% (37/37), pathological complete response rate of 48.6% (18/37), and major pathological response rate of 62.2% (23/37). Of the 24 patients with CPS ≥ 5 (non-MSI-H/dMMR and non-EBER positive), 11 achieved pathological complete responses and one with CPS=95 achieved a clinical complete response. Of the eight patients with MSI-H/dMMR, six achieved pathological complete responses and one a clinical complete response. Of the seven patients with EBER positivity, one achieved a pathological complete response. After excluding patients with major pathological complete responses, there was a statistically significant difference in CPS scores between preoperative biopsy specimens and postoperative surgical specimens in 13 patients (7.769±5.570 vs. 15.538±16.870, t=2.287, P=0.041). All patients tolerated preoperative immunotherapy well; nine patients (9/39, 23.1%) had Grade I–II irAEs. There were no Grade III–IV irAEs. The five patients with pyloric obstruction before treatment tolerated normal diets after treatment. The incidence of postoperative complications among all patients who underwent surgery was 18.9% (7/37), including one case of Grade IIIA anastomotic leakage, one of Grade IIIA intestinal obstruction, one of Grade II abdominal hemorrhage, two of Grade II abdominal infection, one of Grade I intestinal obstruction. Additionally, one patient developed COVID-19 postoperatively. All patients recovered with symptomatic treatment. Conclusion:We found that preoperative treatment of patients with LAGC or AEG of one of three types (CPS≥5, dMMR+MSI-H, and EBER positivity) with a PD-1 inhibitor combined with CapeOx or SOX chemotherapy achieved promising effectiveness and safety, with high surgical conversion, R0 resection, and complete response rates.

Objective:To evaluate the short-term efficacy and safety of a preoperative combination of programmed cell death protein-1 (PD-1) inhibitor with either oxaliplatin + capecitabine (CapeOx) or oxaliplatin + tegafur gimeracil oteracil potassium (SOX) in the treatment of locally advanced immunotherapy-sensitive gastric cancer (LAGC) or adenocarcinoma of the esophagogastric junction (AEG).Methods:The cohort of this retrospective descriptive case series comprised patients with LAGC or AEG whose cancers had been determined to be immunotherapy- sensitive by endoscopic biopsy before treatment in the Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital and Institute from 1 August 1 2021 to 31 January 2024. Patients with any one of the following three characteristics were immunotherapy-sensitive: (i) PD-L1 combined positive score (CPS) ≥5; (ii) microsatellite instability-high (MSI-H) / mismatch repair deficiency (dMMR); or (iii) Epstein-Barr virus-encoded RNA (EBER) positivity. All study patients received PD-1 inhibitors combined with CapeOx or SOX as a neoadjuvant or conversion treatment strategy before surgery. Patients with immune system diseases, distant metastases, or human epidermal growth factor receptor 2 positivity were excluded. Factors analyzed included pathological complete response, clinical complete response, major pathological response, R0 resection rate, surgical conversion rate, and safety of the treatment, including immune-related adverse events (irAEs) and surgical complications.Results:The study cohort comprised 39 patients (28 men and 11 women) of median age 62 (range 44–79) years. After the above-described preoperative treatment, radical resection of the 14 tumors that were initially considered unresectable was achieved (surgical conversion rate: 14/14). Twenty-three of the remaining 25 patients underwent radical resection. The last two patients achieved clinical complete responses and opted for a "non-surgical strategy" (watch and wait). Overall, 37 patients (94.9%) underwent radical resection, with an R0 resection rate of 100% (37/37), pathological complete response rate of 48.6% (18/37), and major pathological response rate of 62.2% (23/37). Of the 24 patients with CPS ≥ 5 (non-MSI-H/dMMR and non-EBER positive), 11 achieved pathological complete responses and one with CPS=95 achieved a clinical complete response. Of the eight patients with MSI-H/dMMR, six achieved pathological complete responses and one a clinical complete response. Of the seven patients with EBER positivity, one achieved a pathological complete response. After excluding patients with major pathological complete responses, there was a statistically significant difference in CPS scores between preoperative biopsy specimens and postoperative surgical specimens in 13 patients (7.769±5.570 vs. 15.538±16.870, t=2.287, P=0.041). All patients tolerated preoperative immunotherapy well; nine patients (9/39, 23.1%) had Grade I–II irAEs. There were no Grade III–IV irAEs. The five patients with pyloric obstruction before treatment tolerated normal diets after treatment. The incidence of postoperative complications among all patients who underwent surgery was 18.9% (7/37), including one case of Grade IIIA anastomotic leakage, one of Grade IIIA intestinal obstruction, one of Grade II abdominal hemorrhage, two of Grade II abdominal infection, one of Grade I intestinal obstruction. Additionally, one patient developed COVID-19 postoperatively. All patients recovered with symptomatic treatment. Conclusion:We found that preoperative treatment of patients with LAGC or AEG of one of three types (CPS≥5, dMMR+MSI-H, and EBER positivity) with a PD-1 inhibitor combined with CapeOx or SOX chemotherapy achieved promising effectiveness and safety, with high surgical conversion, R0 resection, and complete response rates.

OBJECTIVE: To evaluate the clinical value of lidocain in the treatment of tinnitus through three routes of administration (intravenous, intratympanic and acupoint injection) by analyzing literatures. METHOD: Articles were collected through Hownet, Wanfang, VIP, Pubmed, SciVerse ScienceDirect, Springer and OVID, etc. The articles were strictly evaluated based on their quality. The Meta-analysis was performed to evaluate the outcomes by RevMan 5. 2 software. RESULT: A total of 16 articles with 1203 patients were enrolled in the analysis. Their tinnitus history ranged from 7 hours to 20 years. Assessment methods include tinnitus loudness levels, severity scales and subjective feelings. None of articles refer to maintaining time, instead of "short-term", "short" and so on. A total of 133 cases received intravenous injection and the effective rate was 73.4% (98 cases). 50 cases and 332 cases received intratympanic and acupoint injection respectively and their effective rates were 74.0% and 87.7%, respectively. The effective rate ranged from 42.4% to 58.3% in control group. Meta-analysis results indicate that all three routes of lidocaine administrations are more effective than conventional methods (P < 0.05). CONCLUSION Different routes of lidocaine administration have a good but short time effects on the tinnitus control. It can effectively reduce the time of tinnitus habituation as a complementary treatment. But its value still needs further evaluation.
Humans ; Lidocaine ; administration & dosage ; therapeutic use ; Tinnitus ; drug therapy

OBJECTIVETo develop a method for determination of 2, 4-dichlorophenoxyacetic acid (2, 4-D) in the air of workplace by high-performance liquid chromatography.

METHODS2, 4-D was collected by ultrafine glass filters, desorbed by methanol, separated by a C18 column, and detected by a UV detector. Identification and quantification of 2, 4-D were performed by retention time and peak areas, respectively.

RESULTSThe linear range of the test was 2∼200 µg/ml; the elution efficiency was 94.6%- 95.9%; the limit of detection (S/N = 3) was 0.034 µg/ml (injection volume of 20 µl eluant); the lower limit of quantification (S/N = 10) was 0.11 µg/ml; the minimum detectable concentration was 0.011 mg/m(3); the minimum quantifiable concentration was 0.037 mg/m(3) (with sampled air volume of 45 L).

CONCLUSIONThis method is convenient and simple in sample collection and preparation, and satisfies all methodological requirements. Therefore, this method is useful for the determination of 2, 4-D in the air of workplace.

2,4-Dichlorophenoxyacetic Acid ; analysis ; Air ; analysis ; Air Pollutants, Occupational ; analysis ; Chromatography, High Pressure Liquid ; methods ; Workplace

Objective To observe the effects of electro-acupuncture and functional training on gross motor function of children with cerebral palsy. Methods 137 children with cerebral palsy were divided into observation group (n=81) and control group (n=56). The observation group received electro-acupuncture and functional training, and the control group received functional training only. Results The scores of Gross Motor Function Measure (GMFM) increased in both group after treatment (P<0.01), and it was significantly higher in the observation group than in the control group (P<0.01). Conclusion Electro-acupuncture and functional training is superior to functional training in gross motor function.

Objective: To establish the quality standard of Fushukang Granules (Radix Astragali, Radix Angelicae sinensis, Rhizoma Chuanxiong, Radix Paeoniae Alba, etc.). Methods: TLC was used in qualitative identification of the Radix Astragali, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Radix Paeoniase Alba. And TLC-scanning was used for assay of astragaloside I in the preparation. Results: Radix Astragali, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Radix Paeoniae Alba could be detected by TLC. Astragaloside I had a good linear relationship within the range of 1.001～5.005?g(r=0.9998). The average recovery was 92.46%, and the RSD was 2.82%, respectively. Conclusion: The method established is stable and reliable. It can be used for quality control of the preparation.