Objective:Constructing efficacy evaluation index of TCM in treating kidney-yang deficiency syndrome based on three-dimensional hybrid method.Methods:The outcome index list of kidney-yang deficiency syndrome was preliminarily constructed through literature research, questionnaire survey and expert interview. The core indicators of kidney-yang deficiency syndrome were screened by Delphi questionnaire, and the expert consensus meeting was held to determine the core outcome of kidney-yang deficiency syndrome.Results:The TCM symptoms of kidney-yang deficiency syndrome: 7 items: frequent urination at night, waist pain, low libido, chills, fatigue, diarrhea and mental malaise. Related core indicators of kidney-yang deficiency syndrome: Level quality of life score (scale), sex life level (sexual self satisfaction, sexual life log, etc.)two entries, objective indicators in the core index and stronger correlation disease, curative effect evaluation, can be combined with clinical research involves the related diseases, used to supplement the curative effect, as recommendations, not as the main body of kidney-yang deficiency syndrome curative effect evaluation content.Conclusion:This study refers to the clinical trial of the TCM core outcome to develop technical specifications, in the development process and methods, through the "combination of qualitative and quantitative research methods" "combination of subjective and objective indicators" "combination of doctor-patient evaluation" three dimensions of mixed research methods, formation of kidney-yang deficiency syndrome curative effect evaluation of the core outcome, for the kidney-yang deficiency syndrome curative effect evaluation standard of prophase research foundation, to provide ideas and methods for the evaluation of curative effect of syndrome.

Objective: To investigate the regulatory role of Porphyromonas gingivalis(Pg) infection on the EGFR/GSK3β signaling axis, and its impact on epithelial-mesenchymal transition(EMT) and cetuximab(Ctx) resistance in esophageal squamous cell carcinoma(ESCC). Methods: Single cell RNA sequencing was employed to perform differential analysis of cellular subpopulations, identifying differentially expressed genes in ESCC tissues infected and non-infected with Pg. IHC was conducted to assess the expression of Pg and epidermal growth factor receptor(EGFR) in ESCC tissues. Western blot, RT-PCR, and IF staining were performed to evaluate EGFR expression in Pg infected ESCC cell lines KYSE70 and TE1. ESCC cells were treated with Pg and EGFR inhibitor Ctx, and divided into four groups: control(NC) group, Pg group, Ctx group, Pg+Ctx group. Cell proliferation, migration and invasion abilities were evaluated using CCK-8, plate cloning, wound healing and Transwell assay. Western blot analysis was performed to detect the expression of EMT and EGFR/GSK3β signaling pathway-associated proteins and their phosphorylation levels. Transforming growth factor-β1(TGF-β1) was used to induce EMT in ESCC cells, promoting a transition from the epithelial phenotype to mesenchymal-like phenotype. The differential effects of Ctx on these two phenotypic states were subsequently compared. Results: Epithelial cells were predominantly enriched in Pg-positive tissues, and Pg infection promoted the upregulation of EGFR expression in ESCC cells. Compared to the NC group, Pg treatment significantly enhanced the proliferation, invasion and migration capabili-ties of ESCC cells, and also increased chemoresistance to Ctx and reduced its antitumor efficacy. Pg induced EMT in ESCC cellsviathe EGFR/GSK3β signaling pathway. Notably, Ctx exhibited markedly weaker inhibitory effects on mesenchymal-like cells compared to epithelial ESCC cells. Conclusion Pg promotes ESCC cells proliferation, invasion and migration by regulating EMT through the EGFR/GSK3β signaling pathway, and enhances chemoresistance to Ctx.

Objective: To investigate the visual acuity and correction conditions of children and adolescents in Shanghai, so as to provide a scientific basis for developing intervention measures to prevent myopia and protect vision among children and adolescents. Methods: From October to December 2022, a stratified cluster random sampling survey was conducted, involving 47 034 students from 16 municipal districts in Shanghai, covering kindergartens (≥5 years), primary schools, middle schools, general high schools and vocational high schools. According to the Guidelines for Screening Refractive Errors in Primary and Secondary School Students, the Standard Logarithmic Visual acuity Chart was used to examine naked vision and corrected vision of students, and general information was collected. The distribution and severity of visual impairment in different age groups were analyzed, and χ 2 tests and multivariate Logistic regression were used to explore factors associated with visual impairment. Results: The detection rate of visual impairment among children and adolescents was 76.2%, with a higher rate among females (78.8%) than males ( 73.8 %), higher among Han ethic students ( 76.2 %) than minority students (71.2%), and higher among urban students (76.7%) than suburban students (75.8%), all with statistically significant differences ( χ 2=162.6, 10.4, 5.5, P <0.05). The rate of visual impairment initially decreased and then increased with age, reaching its lowest at age 7 (53.8%) and peaking at age 17 (89.6%) ( χ 2 trend = 3 467.0 , P <0.05). Severe visual impairment accounted for the majority, at 56.6%, and there was a positive correlation between the severity of visual impairment and age among children and adolescents ( r =0.45, P <0.05). Multivariate Logistic regression showed that age, BMI, gender, ethnicity and urban suburban status were associated with visual impairment ( OR =1.18, 1.01, 1.38 , 0.79, 0.88, P <0.05). Among those with moderate to severe visual impairment, the rate of spectacle lens usage was 62.8%, yet only 44.8 % of those who used spectacle lens had fully corrected visual acuity. Females (64.9%) had higher spectacle lens usage rates than males (60.6%), and general high school students had the highest spectacle lens usage (83.9%), and there were statistically significant differences in gender and academic stages ( χ 2=57.7, 4 592.8, P <0.05). Conclusions The rate of spectacle lens usage among students with moderate to severe visual impairment is relatively low, and even after using spectacle lens, some students still do not achieve adequate corrected visual acuity. Efforts should focus on enhancing public awareness of eye health and refractive correction and improving the accessibility of related health services.

ObjectiveTo identify the main chemical constituents of Anmeidan （AMD） and to explore the mechanism of AMD in regulating the extracellular signal-regulated kinase 1/2 （ERK1/2）/mitogen-activated protein kinase （MAPK）-interacting serine/threonine-protein kinase （MNK）/eukaryotic translation initiation factor 4E （eIF4E） signaling pathway to improve circadian rhythm disturbances in insomnia rats. MethodsThe main chemical constituents of AMD were identified using ultra-high-performance liquid chromatography-linear ion trap-electrostatic orbital trap mass spectrometry （UPLC-LTQ/Orbitrap/MS） in combination with reference standards. Sixty male Sprague-Dawley （SD） rats were randomly divided into control， model， melatonin， and AMD low-， medium-， and high-dose groups， with 10 rats in each group. Except for the control group， all rats were administered p-chlorophenylalanine via intraperitoneal injection to establish an insomnia model. The activity-rest rhythm of rats was assessed using the open field test and circadian rhythm test. Hematoxylin-eosin （HE） staining and Nissl staining were used to observe structural changes in hypothalamic neurons. Immunofluorescence， real-time quantitative polymerase chain reaction （Real-time PCR）， and Western blot analysis were employed to detect mRNA and protein expression levels of ERK1/2， MNK， and eIF4E in the hypothalamus. ResultsA total of 50 chemical components， including flavonoids， phenylpropanoids， triterpenoid saponins， alkaloids， and lignans， were identified in AMD. Compared with the control group， the model group exhibited significantly increased total distance traveled， average speed， central area residence time， and cumulative rearing time （P<0.01）， as well as prolonged cumulative activity time and total activity time in both light and dark phases （P<0.01）. Hypothalamic neurons in the model group were sparsely arranged， reduced in number， and exhibited nuclear disappearance or nucleolar rupture， with a significantly increased apoptosis index （P<0.01）. The cytoplasm appeared turbid， Nissl body staining was lighter， and the Nissl body apoptosis index was significantly increased （P<0.01）. The mRNA expression levels of ERK1/2， MNK， and eIF4E were significantly decreased （P<0.01）， along with a significant reduction in protein expression levels of ERK1/2， phosphorylated ERK1/2 （p-ERK1/2）， MNK， phosphorylated MNK （p-MNK）， eIF4E， and phosphorylated eIF4E （p-eIF4E） （P<0.01）. Compared with the model group， the total distance， average speed， central area residence time and body upright cumulative time of the AMD high-dose group were significantly reduced （P<0.01）. The total distance， average speed and body upright cumulative time of the AMD medium-dose group were significantly reduced （P<0.01）. The cumulative time of light activity and total time of activity in each dose group of AMD were significantly shortened （P<0.01）. The cumulative time of dark activity in the high-dose group of AMD was prolonged （P<0.01）. The neurons in the middle and high dose groups of AMD were closely arranged， the number of neurons increased， and the apoptosis index of hypothalamic cells decreased significantly （P<0.05， P<0.01）. The cytoplasm of the low， middle and high dose groups of AMD was clear， the color of Nissl body became darker， and the apoptosis index of Nissl body decreased significantly （P<0.01）. The expression of ERK1/2， MNK and eIF4E mRNA and protein in the hypothalamus of the middle and high dose groups of AMD increased significantly （P<0.05， P<0.01）. ConclusionAMD primarily contains 50 chemical constituents， including flavonoids， phenylpropanoids， and triterpenoid saponins. It exhibits a "synergistic enhancement" effect through multiple components and multiple pathways to improve insomnia. AMD ameliorates circadian rhythm disturbances in p-chlorophenylalanine-induced insomnia rats by upregulating ERK1/2/MNK/eIF4E signaling pathway-related proteins.

OBJECTIVES: To investigate the efficacy of Ag₂Se nanoparticles for eliminating intracellular Porphyromonas gingivalis (P. gingivalis) in esophageal cancer and examine the effect of P. gingivalis clearance on progression of esophageal cancer. METHODS: Ag₂Se nanoparticles were synthesized via a chemical synthesis method. The effects of Ag₂Se nanoparticles on P. gingivalis viability and colony-forming ability were assessed using fluorescence staining and colony formation assays. In a mouse model bearing subcutaneous murine esophageal cancer cell allograft with P. gingivalis infection, the effect of treatment with Ag₂Se nanoparticles on the abundance of P. gingivalis in the tumor tissues was quantified using RNAscope in situ hybridization and quantitative polymerase chain reaction (qPCR), and the changes in tumor volume were monitored. The biosafety of Ag₂Se nanoparticles was assessed by examining liver and kidney functions and pathological changes in the major organs of the mice. RESULTS: Transmission electron microscopy revealed that the synthesized Ag₂Se nanoparticles were uniformly dispersed spherical particles with a diameter around 50 nm. In vitro experiments demonstrated that exposure to Ag₂Se nanoparticles significantly reduced the viability and clonal proliferation capacity of P. gingivalis in a dose-dependent manner. In the tumor-bearing mice, treatment with Ag₂Se nanoparticles significantly reduced the abundance of P. gingivalis in tumor tissues and suppressed tumor cell proliferation. No significant damages to the liver and kidney functions or the major organs were observed in Ag₂Se nanoparticle-treated mice, demonstrating good biocompatibility of Ag₂Se nanoparticles. CONCLUSIONS Ag₂Se nanoparticles exhibit significant bactericidal and inhibitory effects against P. gingivalis, and can effectively eliminate intracellular P. gingivalis to suppress the growth of esophageal cancer allograft in mice, suggesting the potential of Ag₂Se nanoparticles in the treatment of esophageal cancer.
Animals ; Porphyromonas gingivalis/drug effects* ; Mice ; Esophageal Neoplasms/pathology* ; Nanoparticles ; Metal Nanoparticles ; Bacteroidaceae Infections ; Cell Line, Tumor

Objective:To investigate the effectiveness of predictive nursing based on root cause analysis in patients undergoing cesarean section.Methods:A convenience sampling method was used to select 180 women who underwent cesarean section under combined spinal-epidural anesthesia in the Affiliated Hospital of Jining Medical University from September 2021 to October 2022. According to the random number table method, they were divided into a control group ( n=90) and an observation group ( n=90). The control group received routine nursing care, while the observation group received predictive nursing based on root cause analysis. Compared the pain intensity at 24 hours after cesarean section and the incidence of postoperative complications between the two groups of parturients. Results:The Visual Analog Scale scores at 24 hours post-cesarean section and the overall incidence of postoperative complications were lower in the observation group than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Predictive nursing based on root cause analysis can effectively relieve postoperative pain and reduce the incidence of complications in patients undergoing cesarean section with combined spinal-epidural anesthesia.

Objective:To investigate the impact of Wenyang Ligong Decoction on pregnancy outcomes after transcervical resection of adhesions (TCRA) in patients with intrauterine adhesions (IUA).Methods:A retrospective cohort study was conducted to collect clinical data from 151 patients with IUA who underwent TCRA in the Reproductive Medicine Department of the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine between January 2020 and January 2023. Patients were divided into a Traditional Chinese medicine (TCM) group (79 patients) and a control group (72 patients) based on whether they received Wenyang Ligong Decoction after TCRA. The TCM group received estrogen and progesterone sequential therapy post-surgery, combined with Wenyang Ligong Decoction for 2-3 menstrual cycles. The control only received sequential treatment with estrogen and progesterone.Pregnancy outcomes one year after surgery were compared between the two groups. After adjusting for confounding factors using multivariate Cox regression analysis, the effect of Wenyang Ligong Decoction on pregnancy outcomes after TCRA in patients with IUA was observed.Results:The live birth rate [54.43%　(43/79)], the ongoing pregnancy rate [56.96% (45/79)], and the clinical pregnancy rate [52.03% (49/79)] were higher in the TCM group than in the control [26.39% (19/72), P<0.001; 30.56% (22/72), P=0.001;37.50% (27/72), P=0.003], with statistically significant differences. There were no statistically significant differences in early abortion rate and late abortion rate between the TCM group and the control (all P>0.05). According to the stratified analysis by preparation methods, in the natural conception group, the live birth rate [60.78% (31/51)], the ongoing pregnancy rate [62.75% (32/51)], and the clinical pregnancy rate [68.63% (35/51)] in the TCM group were significantly higher than those in control group [21.43% (12/56), P<0.001; 26.79% (15/56), P<0.001; 33.93% (19/56), P<0.001]; there were no statistically significant differences in early miscarriage rate and late miscarriage rate between the two groups (both P>0.05). In the assisted reproductive technology group, there were no statistically significant differences in live birth rate, ongoing pregnancy rate, clinical pregnancy rate, early miscarriage rate, and late miscarriage rate between the two groups (all P>0.05). According to the stratified analysis by age, in the <35-year-old patients, the live birth rate [66.00% (33/50)], the ongoing pregnancy rate [70.00% (35/50)], and the clinical pregnancy rate [74.00% (37/50)] in the TCM group were significantly higher than those in control group [41.30% (19/46), P=0.015; 47.83% (22/46), P=0.027; 54.35% (25/46), P=0.044]; there were no statistically significant differences in early miscarriage rate and late miscarriage rate between the two groups (both P>0.05). In the ≥35-year-old patients, the live birth rate [34.48% (10/29)], the ongoing pregnancy rate [34.48% (10/29)], and the clinical pregnancy rate [41.38% (12/29)] in the TCM group were significantly higher than those in control group [0%, P=0.001; 0%, P=0.001; 7.69% (2/26), P=0.004]; there were no statistically significant differences in early miscarriage rate and late miscarriage rate between the two groups (both P>0.05).Univariate Cox regression analysis showed that age, number of previous uterine cavity interventions, IUA score, degree of IUA, and endometrial thickness after TCRA were independent risk factors for live births, and age, IUA score, degree of IUA, intima thickness after TCRA, and treatment group were the influencing factors of persistent pregnancy (all P<0.05). After adjusting for confounding factors, multivariate Cox regression analysis showed that Wenyang Ligong Decoction significantly improved the live birth rate ( HR=3.19, 95% CI: 1.77-8.11, P=0.001) and the rate of continuous pregnancy ( HR=3.66, 95% CI: 1.80-7.48, P<0.001) in patients with IUA. Conclusion:Wenyang Ligong Decoction can significantly improve pregnancy outcomes after TCRA in patients with IUA.

Objective:To compare the clinical and laboratory characteristics and survival between Chinese and Western patients with myelodysplastic neoplasms (MDS) .Methods:Clinical and laboratory data were collected from 1,464 primary adult patients diagnosed with MDS at the Institute of Hematology & Blood Diseases Hospital from August 2016 to June 2024. Collected data were retrospectively analyzed and compared with 2,191 patients from the International Working Group for the Prognosis of Myelodysplastic Syndromes (IWG-PM) .Results:Chinese patients were significantly younger (median age: 56 years vs. 72 years, P<0.001) and experienced more severe hematopenia ( P<0.001) compared with patients from the IWG-PM. Further, Chinese patients exhibited a higher percentage of isolated del (20q), +8, and complex karyotypes as well as a lower percentage of normal karyotypes, del (5q), and -Y ( P<0.001). Higher U2AF1, NRAS, and NPM1 mutation rates and lower ASXL1, SF3B1, and RUNX1 mutation rates were observed in Chinese patients than in participants from the IWG-PM ( P<0.05). No significant difference in overall survival (OS) was found between the two groups (median OS: 48 [95% CI: 40 - 56]months, vs. 45[95% CI: 40 - 49] months; P=0.449). Among participants aged ≤45 years, Chinese patients demonstrated more trisomy 8 ( P=0.070) and U2AF1 mutation ( P<0.001) and higher 4-year OS rate compared with those from the IWG-PM (75.5% vs. 62.1%, P=0.001). Among participants aged ≥70 years, Chinese patients exhibited more complex karyotypes but fewer del (5q) as well as more NPM1 but less SF3B1 and TET2 compared with those from the IWG-PM ( P<0.05). Chinese patients demonstrated shorter survival (median OS: 20 [95% CI: 13 - 27] months vs. 37 [95% CI: 32 - 42] months, P<0.001) . Conclusion:Chinese and Western MDS patients differ in age of onset, clinical features, and cytogenetic or molecular genetic abnormalities, with significant differences persisting in age-matched groups. Although the OS is similar, disparities exist in survival for younger and older patients between the two populations.

Objective:To identify the prognostic value of the Revised 15-item Myelodysplastic Syndrome-specific frailty scale (FS-15) in Chinese patients with myelodysplastic syndromes (MDS) .Methods:This retrospective study analyzed 812 patients with newly diagnosed MDS admitted to the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College from August 2016 to June 2023. Patients were assessed using the FS-15 and subsequently categorized into frail and non-frail groups. Clinical and laboratory characteristics, as well as overall survival (OS), were compared between these groups.Results:① The median patient age was 55 years ( IQR 45–64), with a median follow-up of 22.5 months (95% CI: 20.2–24.9) and a median OS of 43.3 months (95% CI: 36.8–49.8). The median FS-15 score was 0.42, with a cutoff value of 0.44. Male patients demonstrated higher median FS-15 scores than female patients (0.42 vs 0.38, P=0.006). In both the Revised International Prognostic Scoring System (IPSS-R; P=0.001) and Molecular International Prognostic Scoring System (IPSS-M; P=0.014) stratifications, FS-15 scores were significantly higher in the very high-risk group compared with the very low-risk group. ② The median OS was 54.7 months (95% CI: 47.5–NA) and 31.5 months (95% CI: 22.9–41.0) in the nonfrail ( n=452) and frail groups ( n=360), respectively ( P<0.001). The 3-year OS rates were (63.2 ± 3.2) % and (46.4 ± 3.6) % for the non-frail and frail groups, with 5-year OS rates of (49.9 ± 4.7) % and (32.0 ± 4.3) %, respectively ( P<0.001). ③Subgroup analysis revealed that nonfrail patients demonstrated significantly higher 3-year OS rates than frail patients in both the IPSS-M low-risk and very high-risk groups (all P<0.05). Similarly, nonfrail patients demonstrated superior 3-year OS rates compared with frail patients in the IPSS-R very low-risk, low-risk, and high-risk groups (all P<0.05). ④Among patients receiving hypomethylating agent therapy, the overall response rate was significantly higher in the non-frail group than in the frail group (86.7% vs 64.6%, P=0.007). Moreover, the frail group experienced higher rates of treatment-related adverse events, including febrile neutropenia (67.1% vs 47.4%, P=0.016) and liver function abnormalities (30.0% vs 14.5%, P=0.023), compared with the non-frail group. Conclusion:The FS-15 frailty score is a feasible and effective tool for assessing frailty in patients newly diagnosed with MDS in China and serves as a valuable prognostic indicator.

Objective:To investigate the clinical, laboratory, and prognostic features of myelodysplastic neoplasm (MDS) patients harboring acute myeloid leukemia (AML) -like mutations.Methods:We retrospectively analyzed clinical, molecular, and outcome data from 1 464 adults with primary MDS diagnosed at the Institute of Hematology and Blood Diseases Hospital from August 2016 to June 2024.Results:AML-like mutations were detected in 64 patients (4.4% ). Compared with patients without AML-like mutations, those with AML-like mutations were younger [median 50 ( IQR 39–60) vs 56 (45, 65) years; P=0.001], more often female (51.6% vs 35.4% ; P=0.009), had higher bone marrow blast percentage [6.5% (3.0%, 10.5% ) vs 2.5% (1.0%, 7.0% ) ; P<0.001], a higher rate of normal karyotype (75.0% vs 48.1% ; P<0.001), and lower hemoglobin levels [73 (67, 82) g/L vs 80 (66, 98) g/L; P=0.006]. The AML-like group had a higher number of gene mutations than the non-AML-like group [3 ( IQR 2–4) vs 2 (1, 3) ; P<0.001). It was enriched for mutations in NPM1, DNMT3A, WT1, PTPN11, NRAS, BCOR, FLT3, CEBPA, and MYC (all P<0.05) and had lower rates of U2AF1, ASXL1, and TP53 mutations (all P<0.05). Overall survival (OS) did not differ between groups ( P=0.730) ; however, the AML-like group had significantly shorter leukemia-free survival (LFS) [19 months (95% CI: 13–25) vs 46 months (95% CI: 38–54) ; P=0.012] and a higher 2-year cumulative incidence of AML transformation [ (41.7±9.1) % vs (10.4±1.1) % ; P<0.001]. Within the AML-like group, OS, LFS, and cumulative incidence of AML transformation did not differ between patients with low blasts and those with excess blasts (IB). Multivariable Cox regression identified age ≥60 years and PTPN11 mutations as independent adverse prognostic factors for OS, while DNMT3A, PTPN11, and FLT3 mutations independently predicted leukemic transformation. Conclusions:MDS patients harboring AML-like mutations exhibit distinct clinical and molecular features and a higher risk of progression to AML.