This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

Objective:To evaluate the predictive value of angiopoietin-2 (Ang-2) for the prognosis in patients with acute respiratory distress syndrome (ARDS).Methods:A retrospective study was conducted, and ARDS patients admitted to the department of emergency medicine of Tongde Hospital of Zhejiang Province from December 2020 to September 2022 were enrolled. General information including gender, age, causes of ARDS, disease severity scores, plasma Ang-2 levels before treatment and at 24, 48, and 72 hours after treatment, and record the 60-day prognosis were collected. Differences in clinical data between groups were compared. Multivariate Logistic regression analysis was used to identify the independent risk factors affecting the 60-day prognosis of ARDS patients, and the receiver operator characteristic curve (ROC curve) was plotted to assess the predictive value of these risk factors for patient outcomes. Pearson correlation analysis was used to assess the correlation between Ang-2 and pulmonary vascular permeability index (PVPI) and extravascular lung water index (EVLWI).Results:A total of 132 ARDS patients were included, of which 49 patients died within 60 days and 83 patients survived. In the death group, plasma Ang-2 levels showed a gradually increasing trend, all significantly higher than before treatment (μg/L: 12.75±1.81, 12.74±1.48, 13.45±2.21 vs. 5.98±0.57, all P < 0.05), while the trend in the survival group was not significant. At 24, 48, and 72 hours after treatment, plasma Ang-2 levels in the death group were significantly higher than those in the survival group (μg/L: 12.75±1.81 vs. 7.48±1.22, 12.74±1.48 vs. 7.41±1.19, 13.45±1.41 vs. 6.88±1.41, all P < 0.05). After adjusting for confounding variables, increased plasma Ang-2 level was an independent risk factor for prognosis in ARDS patients within 60 days [odds ratio ( OR) = 0.998, 95% confidence interval (95% CI) was 0.997-0.999, P < 0.01]. ROC curve analysis demonstrated that Ang-2 levels had predictive value for prognosis in ARDS patients [area under the ROC curve (AUC) = 0.985, 95% CI was 0.971-1.000, approximate maximum Youden's index 0.867, optimal cut-off value 8.43 μg/L]. Pearson correlation analysis showed that plasma Ang-2 levels were positively correlated with PVPI and EVLWI ( r values were 0.620 and 0.712 respectively, both P < 0.01). Conclusions:Elevated level of Ang-2 is an independent risk factor for increased mortality in patients with ARDS. Higher Ang-2 levels within 72 hours after treatment may indicate poorer prognosis.

Objective:To verify the predictive value of the Second Revision of the International Staging System (R2-ISS) in newly diagnosed patients with multiple myeloma (MM) who underwent first-line autologous hematopoietic stem cell transplantation (ASCT) in a new drug era in China.Methods:This multicenter retrospective cohort study enrolled patients with newly diagnosed MM from three centers in China (Beijing Chao-Yang Hospital, Capital Medical University; the First Affiliated Hospital, Sun Yat-Sen University, and the Second Affiliated Hospital of Naval Medical University) from June 2008 to June 2018. A total of 401 newly diagnosed patients with MM who were candidates for ASCT were enrolled in this cohort, all received proteasome inhibitor and/or immunomodulator-based induction chemotherapy followed by ASCT. Baseline and follow-up data were collected. The patients were regrouped using R2-ISS. Progression-free survival (PFS) and overall survival (OS) were analyzed. The Kaplan-Meier method was used to analyze the survival curve and two survival curves were compared using the log-rank test. Cox regression analysis were performed to analyze the relationship between risk factors and survival.Results:The median age of the patients was 53 years (range 25-69 years) and 59.5% (240 cases) were men. Newly diagnosed patients with renal impairment accounted for 11.5% (46 cases). According to Revised-International Staging System (R-ISS), 74 patients (18.5 %) were diagnosed with stage Ⅰ, 259 patients (64.6%) with stage Ⅱ, and 68 patients (17.0%) with stage Ⅲ. According to the R2-ISS, the distribution of patients in each group was as follows: 50 patients (12.5%) in stage Ⅰ, 95 patients (23.7%) in stage Ⅱ, 206 patients (51.4%) in stage Ⅲ, and 50 patients (12.5%) in stage Ⅳ. The median follow-up time was 35.9 months (range, 6-119 months). According to the R2-ISS stage, the median PFS in each group was: 75.3 months for stage Ⅰ; 62.0 months for stage Ⅱ, 39.2 months for stage Ⅲ, and 30.3 months for stage Ⅳ; and the median OS was not reached, 86.6 months, 71.6 months, and 38.5 months, respectively. There were statistically significant differences in PFS and OS between different groups (both P<0.001). Multivariate Cox regression analysis showed that stages Ⅲ and Ⅳ of the R2-ISS were independent prognostic factors for PFS ( HR=2.37, 95% CI 1.30-4.30; HR=4.50, 95% CI 2.35-9.01) and OS ( HR=4.20, 95% CI 1.50-11.80; HR=9.53, 95% CI 3.21-28.29). Conclusions:The R2-ISS has significant predictive value for PFS and OS for transplant-eligible patients with MM in the new drug era. However, the universality of the R2-ISS still needs to be further verified in different populations.

Objective:To identify the characteristics of the bone marrow immune microenvironment associated with long-term survival in multiple myeloma (MM) patients.Methods:In the follow-up cohort of patients with newly diagnosed MM and who received “novel agent induction therapy and subsequent autologous stem cell transplantation and immunomodulator maintenance therapy” in the First Affiliated Hospital of Sun Yat-sen University, a cross-sectional study was carried out between August 2019 and May 2020. Using NanoString technology, the RNA expression of 770 bone marrow immune-related markers was compared between 16 patients who had progression-free survival ≥5 years and 5 patients with progressive disease. Among the 16 patients who achieved long-term survival, 9 achieved persistent minimal residual disease (MRD) negative while the other 7 had persistent positive MRD. The functional scores of each kind of immune cells were calculated based on the expression level of characteristic genes, so as to indirectly obtained the proportion of each immune cell subset. The Mann-Whitney U test and the Kruskal Wallis test were used for statistical analysis. Results:The proportion of neutrophils was significantly higher in long-surviving MM patients than in patients with progressive disease [functional scores, 13.61 (13.33, 14.25) vs. 12.93 (12.58, 13.38); Z=2.31, P=0.021]. Among long-surviving patients, those who were MRD-positive had a significantly greater number of mast cells compared with those who were MRD-negative [functional scores, 7.09 (6.49, 8.57) vs. 6.03 (5.18, 6.69); H=2.18, P=0.029]. Compared with patients with progressive disease, four genes (CTSG, IFIT2, S100B, and CHIT1) were significantly downregulated and six (C4B, TNFRSF17, CD70, IRF4, C2, and GAGE1) were upregulated in long-surviving patients. Among long-surviving patients, only gene CMA1 was significantly upgraded, 10 genes (ISG15, OAS3, MX1, IFIT2, DDX58, SIGLEC1, CXCL10, IL1RN, SERPING and TNFSF10) were significantly downregulated in the MRD-positive group compared with that in the MRD-negative group, the first 5 of which are related to the interferon response pathway. Conclusions:The increased neutrophil and mast cell numbers may be related to long-term survival in MM. Interferon signaling activation may be a key bone marrow immune profiling feature for MRD-negative, long-surviving patients with MM.

ObjectiveTo investigate the influencing factors for the clinical outcome of patients with drug-induced liver injury （DILI）， and to establish a nomogram prediction model for validation. MethodsA retrospective analysis was performed for the general information and laboratory data of 188 patients with DILI who were admitted to Heilongjiang Provincial Hospital Affiliated to Harbin Institute of Technology from January 2017 to December 2022， and according to their clinical outcome， they were divided into good outcome group with 146 patients and poor outcome group with 42 patients. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate Logistic regression analyses were used to investigate the independent influencing factors for the clinical outcome of DILI patients. R Studio 4.1.2 software was used to establish a nomogram model， and calibration curve， receiver operating characteristic （ROC） curve， and decision curve analysis （DCA） were used to perform internal validation. ResultsThe univariate Logistic regression analysis showed that liver biopsy for the diagnosis of DILI， platelet count， cholinesterase， albumin， prothrombin time activity， IgM， and IgG were associated with adverse outcomes in patients with DILI. The multivariate Logistic regression analysis showed that liver biopsy for the diagnosis of DILI （odds ratio ［OR］=0.072， 95% confidence interval ［CI］： 0.022‍ ‍—‍ ‍0.213， P<0.001）， clinical classification （OR=0.463， 95%CI： 0.213‍ ‍—‍ ‍0.926， P=0.039）， alanine aminotransferase （OR=0.999， 95%CI： 0.998‍ ‍—‍ ‍1.000， P=0.025）， prothrombin time activity （OR=0.973， 95%CI： 0.952‍ ‍—‍ ‍0.993， P=0.011）， and IgM （OR=1.456， 95%CI： 1.082‍ ‍—‍ ‍2.021， P=0.015） were independent influencing factors for clinical outcome in patients with DILI. The nomogram prediction model was established， and after validation， the calibration curve was close to the reference curve. The area under the ROC curve was 0.829， and the DCA curve showed that the model had good net clinical benefit. ConclusionThe nomogram prediction model established in this study has good clinical calibration， discriminative ability， and application value in evaluating the clinical outcome of patients with DILI.

Objective To use color Doppler ultrasound to measure the hemodynamic indexes,and to es-tablish the diagnostic prediction model of inflammatory fetal distress.Methods A total of 213 pregnant women admitted to the obstetrics department of the First Affiliated Hospital of Air Force Military Medical U-niversity were collected as the research subjects and divided into the control group and case group according to whether or not fetal distress occurred,including 93 cases in the control group and 120 cases in the case group.The predictive value of PI,RI,S/D values of middle cerebral artery,umbilical artery and uterine artery for pre-dicting fetal distress was analyzed The diagnostic model was constructed by logistic regression analysis.The receiver operating characteristic(ROC)curve,calibration curve and clinical decision curve were adopted to an-alyze and evaluate the diagnostic efficiency of the model for adverse perinatal outcome and the clinical benefit of the patients.Results The univariate analysis results showed that MCA-PI,MCA-RI,MCA,S/D and CPR in the case group were lower than those in the control group,while UA-RI,UA,S/D and UtA-RI were higher than those in the control group.The multivariate regression analysis further showed that MCA-PI,MCA-RI and CPR were the independent protective factors for predicting fetal distress,while UA-R1 and UA-S/D served as the independent risk factors affecting the fetal outcome.Based on five independent influencing fac-tors,the risk prediction model was constructed,and the area under the receiver operating characteristic curve was 0.880(95％CI:0.834-0.925).The sensitivity,specificity and accuracy were 0.93,0.70 and 0.83 respec-tively,and the goodness of fit was good.Conclusion The hemodynamic indexes measured by color Doppler ul-trasound have good predictive value for the diagnosis of fetal distress.The risk prediction model established by the combined indexes has a certain reference value for the intervention in advance of pregnant women with fe-tal distress occurence.

Objective:To evaluate the effects of Huoxue Bushen Formula Granules on endometrial receptivity (ER) in patients with polycystic ovary syndrome (PCOS) in ovulation induction cycle.Methods:A randomized controlled trial was conducted. Totally 50 patients with PCOS infertility in Xiyuan Hospital of China Academy of Chinese Medical Sciences from January 2019 to January 2023 were selected as the observation objects, and were divided into observation group (29 cases) and control group (21 cases) according to the random number table method. Both groups were given oral clomiphene citrate on the 5th day of menstrual cycle or progesterone withdrawal. On this basis, the observation group was given Huoxue Bushen Formula Granules on the 5th day of menstruation, while the control group was given estradiol valerate tablets. 7 days after taking medication and injecting hCG from the 10th day of menstruation, ovulation was monitored and sexual intercourse was guided. Both groups were treated for 3 menstrual cycles and followed up for 3 months. B-ultrasound was performed on 6-8 days after ovulation to obtain uterine artery pulsatility index (PI) and blood flow resistance index (RI). TCM syndrome scores were evaluated before and after treatment, and the endometrial receptivity score (Salle score) was used to evaluate the level of ER. The pregnancy and adverse reactions during treatment were recorded in the two groups.Results:After treatment, TCM syndrome score in the observation group [14.0 (13.0, 15.0) vs. 16.0 (14.5, 19.5), Z=-3.23] was lower than that of the control group ( P<0.001). The Salle score of the observation group after treatment [12.0 (9.5.0, 13.5) vs. 10.0 (9.0, 11.0), Z=-3.84] was higher than that before treatment ( P<0.001). The PI (0.68±0.52 vs. 0.81±0.06, t=18.25), RI (1.65±0.36 vs. 2.24±0.45, t=22.78) after treatment in the observation group and the control group were lower than those before treatment ( P<0.001), without statistical significance ( t values were -0.39, -1.37, respectively, P>0.05). The total effective rate of the observation group was 75.86% (22/29), and that of the control group was 71.43% (15/21), without statistical significance ( χ2=0.12, P=0.724). The pregnancy rate of the observation group was 82.76% (24/29), and that of the control group was 57.14% (12/21), with statistical significance ( χ2=3.96, P=0.046). The incidence of adverse reactions of the observation group was 3.45% (1/29) and that of the control group was 9.52% (2/21), without statistical significance ( χ2=0.80, P=0.372). Conclusion:Huoxue Bushen Formula Granules can improve the ER of PCOS infertility patients with kidney deficiency and blood stasis syndrome, improve the pregnancy rate, reduce the TCM syndrome score, improve the quality of life of patients with high safety.

Purpose To investigate the expression of C1GALT1 in gastric cancer and its effect on the biological be-havior of BGC-823 in gastric cancer cells.Methods The ex-pression of C1GALT1 mRNA and protein in gastric cancer tis-sues and normal gastric mucosa,gastric cancer cells and normal gastric mucosal cells was analyzed by bioinformatics,qRT-PCR and Western blot;the transient transfection of siRNA into BGC-823 cells was designed with C1GALT1 cDNA sequence as the target.Transwell assay was used to detect the effect of C1GALT1-siRNA on the migration and invasion ability of BGC-823 cells in gastric cancer.Western blot method detected the expression of epithelial-mesenchymal transition(EMT)-related proteins in BGC-823 after transfection of C1GALT1-siRNA.Re-sults C1GALT1 was highly expressed in gastric cancer tissues and cell lines BGC-823,SGC-7901 and MGC-803,and the ex-pression levels were positively correlated with gastric cancer pathological stages Ⅰ and Ⅱ(P＜0.05).After interfering with C1GALT1 in BGC-823 cells,the ability of migration and inva-sion decreased(P＜0.05),epithelial cell markers E-cadherin and Claudin-1 protein expression increased,while mesenchymal cell markers vimentin and Slug protein expression decreased(P＜0.05).Conclusion C1GALT1 is highly expressed in gastric cancer tissues and cells,silencing of C1GALT1 can inhibit mi-gration and invasion ability of gastric cancer,the mechanism may be related to EMT.

Photon Counting Detector(PCD)is a device used to detect X-ray photons,which can directly convert the energy of photons into electrical signals to achieve photon counting and measurement.PCD-based energy spectrum computed tomography(PCD-CT)technology can provide additional energy spectral imaging information,and improve imaging quality while reducing radiation dose.Compared with energy integrating detectors(EID),PCD has advantages of high energy conversion efficiency,good imaging quality,exquisite structural design,and wide application range.It has broad application prospects in ultra-low-dose CT,specific disease diagnosis,and industrial inspection.The application of PCD-CT in spectral CT imaging was reviewed to provide a useful reference for its application in clinical medical diagnosis and industrial applications.

Objective:To investigate the prognosis of newly diagnosed multiple myeloma (MM) patients with t (14;16) abnormality.Methods:Clinical data from 564 patients diagnosed with initial MM from January 2018 to November 2020 at Beijing Chaoyang Hospital affiliated with Capital Medical University and the First Affiliated Hospital of Sun Yat-sen University were collected and retrospectively analyzed. The prognoses of patients with t (14;16) were analyzed and compared with the prognoses of patients with normal FISH, and those with t (4;14) and del (17p) .Results:Among 564 newly diagnosed MM patients, 19 (3.4%) exhibited t (14;16) abnormalities, with 14 cases diagnosed with 1q21+ and three cases with del (17p). Progression-free survival (PFS) and overall survival (OS) of patients with t (14;16) were significantly shorter compared with patients with normal FISH (the median PFS: 14 months vs not reached, P<0.001; the median OS: 42 months vs not reached, P=0.002). No statistically significant difference was detected in PFS and OS between the 15 patients with t (14;16) and the 15 with t (4;14) after propensity score matching (the median PFS: 13.0 months vs not reached, P=0.247; the median OS: 42 months vs not reached, P=0.609). Similarly, no statistically significant difference was observed in PFS and OS between 15 patients with t (14;16) and 15 with del (17p) (the median PFS: 13 months vs 31 months, P=0.939; the median OS: 42 months vs 37.3 months, P=0.557). Propensity score matching indicated that when combined with 1q21+, no statistically significant differences were present in PFS and OS between patients with t (14;16) and patients with t (4;14) or patients with del (17p) (all P>0.05). Whether or not the patients with t (14;16) had undergone auto-HSCT did not significantly impact the PFS and OS (all P>0.05) . Conclusion:t (14;16) is often associated with high-risk cytogenetic abnormalities in newly diagnosed MM patients, and its adverse prognostic value is similar to that of t (4;14) and del (17p) .