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.

AIM:This study aims to investigate the effects and mechanisms of silent information regulator 6(SIRT6)on carbon tetrachloride(CCl4)-induced liver fibrosis in mice,as well as the expression changes in the down-stream pathways of hepatic stellate cells after SIRT6 silencing.METHODS:Thirty male C57BL/6J mice were randomly divided into a normal control group(n=6)and a model group(modeling at 2,4,8,12 weeks,n=24).A liver fibrosis model in mice was prepared by intraperitoneal injection of CCl4 twice a week for 12 weeks.Serum alanine aminotransfer-ase(ALT)and aspartate aminotransferase(AST)levels were measured to assess liver injury.Hematoxylin-eosin(HE)and Masson staining were used to observe the pathological changes in mouse liver tissues.Immunohistochemical staining was conducted to detect the expression of α-smooth muscle actin(α-SMA)in the liver,Western blot analysis was used to measure the expression of liver α-SMA,SIRT6,acetyl histone H3 at Lys9(H3K9ac),acetyl histone H3 at Lys56(H3K56ac),interleukin-1β(IL-1β),and IL-18 proteins.Hepatic stellate cells-T6(HSC-T6)underwent SIRT6 gene si-lencing,divided into NC siRNA group and SIRT6 siRNA group,with Western blot performed to detect the expression of SIRT6,H3K9ac,and H3K56ac proteins.RESULTS:Compared with the normal control group,the serum ALT and AST levels in the model group were significantly increased(P<0.05);HE and Masson staining results showed that the patho-logical changes in the liver of the model group worsened over time,with an increase in collagen fiber deposition.Both im-munohistochemistry and Western blot showed that the expression of liver α-SMA significantly increased at 8 and 12 weeks in the model group(P<0.05).Western blot results showed that the expression of SIRT6 protein in the liver of all model group mice was lower than that in the normal control group(P<0.05),and decreased gradually with the progression of liv-er fibrosis;also,the expression levels of H3K9ac,H3K56ac,IL-1β,and IL-18 in the liver of the model group mice were significantly elevated at 8 and 12 weeks(P<0.05);after SIRT6 silencing,compared with the NC siRNA group,the levels of H3K9ac and H3K56ac in the SIRT6 siRNA group significantly increased(P<0.05).CONCLUSION:The deficiency of SIRT6,by abnormally increasing H3K9ac and H3K56ac,raises the expression of IL-1β and IL-18,intensifying the in-flammatory response and promoting the progression of liver fibrosis,indicating that the aberrant expression of SIRT6 is in-volved in the development of liver fibrosis.

Objective To investigate the expressions of extracellular matrix metalloproteinase inducer(EMMPRIN),matrix metalloproteinase-9(MMP-9),lysine demethylase 6B(KDM6B)proteins and their correlation with clinicopathologic features in invasive breast cancer,and analyze the correlation among the three proteins and their value in pathological diagnosis of invasive breast cancer.Methods The surgical biopsy specimens of 124 patients with invasive breast cancer who were admitted to the Department of Pathology,the Fifth Clinical Medical College of Henan University of Chinese Medicine/People's Hospital of Zhengzhou from January 2014 to December 2017 were selected as research subjects,and 20 low-grade intraductal carcinoma tissue specimens,27 high-grade intraductal carcinoma tissue specimens,and 22 adjacent tissue specimens＞1 cm away from the invasive breast cancer were selected as controls.The expressions of EMMPRIN,MMP-9 and KDM6B proteins in cancer-adjacent tissues,low-grade intraductal carcinoma tissues,high-grade intraductal carcinoma tissues and invasive breast cancer tissues were detected by immunohistochemistry.The relationship between the relative expressions of EMMPRIN,MMP-9 and KDM6B proteins and clinicopathologic features of invasive breast cancer was analyzed,Spearman correlation analysis was used to evaluate the correlation of EMMPRIN,MMP-9 and KDM6B proteins in breast cancer tissues,and receiver operating characteristic(ROC)curve was adopted to evaluate the diagnostic value of EMMPRIN,MMP-9 and KDM6B for invasive breast cancer.Results The relative expressions of EMMPRIN and MMP-9 proteins in high-grade intraductal carcinoma and invasive breast cancer tissues were significantly higher those in cancer-adjacent tissues and low-grade intraductal carcinoma tissues,and the relative expression of KDM6B protein was significantly lower than those in cancer-adjacent tissues and low-grade intraductal carcinoma tissues(P＜0.05);the relative expressions of EMMPRIN and MMP-9 proteins in invasive breast cancer tissues were significantly higher those in high-grade intraductal carcinoma tissues,and the relative expression of KDM6B protein was significantly lower than that in high-grade intraductal carcinoma tissues(P＜0.05);there was no statistically significant difference in the relative expressions of EMMPRIN,MMP-9 and KDM6B proteins between cancer-adjacent tissues and low-grade intraductal carcinoma tissues(P＞0.05).The relative expressions of EMMPRIN and KDM6B proteins were not related to the age,tumor location and tumor diameter of patients with invasive breast cancer(P＞0.05),and the relative expression of MMP-9 protein was not related to the age and tumor location of patients with invasive breast cancer(P＞0.05).Relative expressions of EMMPRIN,MMP-9 and KDM6B proteins were correlated with WHO grading,lymph node metastasis,and tumor,node and metastasis(TNM)staging of invasive breast cancer(P＜0.05),and the relative expression of MMP-9 protein was correlated with the tumor diameter(P＜0.05).In the WHO grades Ⅰ,Ⅱ,and Ⅲ of invasive breast cancer,the relative expressions of EMMPRIN and MMP-9 proteins increased sequentially,while the relative expression of KDM6B protein decreased sequentially(P＜0.05);the relative expressions of EMMPRIN and MMP-9 proteins in the lymph node metastasis group were significantly higher than those in the non-lymph node metastasis group,and the relative expression of KDM6B protein was significantly lower than that in the non-lymph node metastasis group(P＜0.05);the relative expressions of EMMPRIN and MMP-9 proteins in TNM stages Ⅲ-Ⅳ were significantly higher than those in stages Ⅰ-Ⅱ(P＜0.05),while the relative expression of KDM6B protein was significantly lower than that in stages Ⅰ-Ⅱ(P＜0.05).In the group of invasive breast cancer with diameter≤2 cm,2 to 5 cm,and＞5 cm,the relative expression of MMP-9 protein increased sequentially(P＜0.05).Spearman correlation analysis showed that the expression of EMMPRIN was positively correlated with MMP-9 protein in invasive breast cancer tissues(r=0.990,P=0.000),the expression of EMMPRIN was negatively correlated with KDM6B protein(r=-0.606,P=0.000),and the expression of MMP-9 was negatively correlated with KDM6B protein(r=-0.612,P=0.000).ROC curve analysis showed that the area under the curve(AUC)of EMMPRIN protein for diagnosing invasive breast cancer was 0.875[95％confidence interval(CI):0.823-0.926,P＜0.05],with an optimal threshold of 10.043,sensitivity of 79.0％,and specificity of 76.8％;the AUC of MMP-9 protein in diagnosing invasive breast cancer was 0.863(95％CI:0.808-0.917,P＜0.05),with an optimal threshold of 10.070,sensitivity of 74.2％,and specificity of 76.8％;the AUC of KDM6B protein in diagnosing invasive breast cancer was 0.267(95％CI:0.196-0.338,P＜0.05),with an optimal threshold of 11.003,sensitivity of 71.0％,and specificity of 98.6％.Conclusion EMMPRIN,MMP-9 and KDM6B are related to the occurrence and development of invasive breast cancer.Detection of the expressions of EMMPRIN,MMP-9 and KDM6B is helpful to the pathological diagnosis of invasive breast cancer and clinical judgment of invasion and metastasis of breast cancer.

Objective To investigate the infection status and changing trend of hepatitis C virus(HCV)infection in hospitalized patients in medical institutions,and provide reference for formulating HCV infection prevention and control strategies.Methods HCV infection surveillance results from cross-sectional survey data reported to China Healthcare-associated Infection(HAI)Surveillance System in 2020 were summarized and analyzed,HCV positive was serum anti-HCV positive or HCV RNA positive,survey result was compared with the survey results from 2003.Results In 2020,1 071 368 inpatients in 1 573 hospitals were surveyed,738 535 of whom underwent HCV test,4 014 patients were infected with HCV,with a detection rate of 68.93％and a HCV positive rate of 0.54％.The positive rate of HCV in male and female patients were 0.60％and 0.48％,respectively,with a statistically sig-nificant difference(x2=47.18,P＜0.001).The HCV positive rate in the 50-＜60 age group was the highest(0.76％),followed by the 40-＜50 age group(0.71％).Difference among all age groups was statistically signifi-cant(x2=696.74,P＜0.001).In 2003,91 113 inpatients were surveyed.35 145 of whom underwent HCV test,resulting in a detection rate of 38.57％;775 patients were infected with HCV,with a positive rate of 2.21％.In 2020,HCV positive rates in hospitals of different scales were 0.46％-0.63％,with the highest in hospital with bed numbers ranging 600-899.Patients'HCV positive rates in hospitals of different scales was statistically signifi-cant(X2=35.34,P＜0.001).In 2020,12 provinces/municipalities had over 10 000 patients underwent HCV-rela-ted test,and HCV positive rates ranged 0.19％-0.81％,with the highest rate from Hainan Province.HCV posi-tive rates in different departments were 0.06％-0.82％,with the lowest positive rate in the department of pedia-trics and the highest in the department of internal medicine.In 2003 and 2020,HCV positive rates in the depart-ment of infectious diseases were the highest,being 7.95％and 3.48％,respectively.Followed by departments of orthopedics(7.72％),gastroenterology(3.77％),nephrology(3.57％)and general intensive care unit(ICU,3.10％)in 2003,as well as departments of gastroenterology(1.35％),nephrology(1.18％),endocrinology(0.91％),and general intensive care unit(ICU,0.79％)in 2020.Conclusion Compared with 2003,HCV positive rate decreased significantly in 2020.HCV infected patients were mainly from the department of infectious diseases,followed by departments of gastroenterology,nephrology and general ICU.HCV infection positive rate varies with gender,age,and region.

Hepatocellular carcinoma （HCC） is the sixth most common cancer in the world. In recent years， the clinical early diagnosis and treatment protocols of HCC have been improved， whereas the prognosis of patients is still not satisfactory， which is due to the fact that the mechanism of HCC development has not been fully elucidated. Therefore， it is of great significance to explore the molecular mechanisms and key regulatory links of hepatocellular carcinoma development to further improve the diagnosis and treatment of HCC in China. Epigenetics has become a research hotspot because of its reversibility and easy regulation. According to relevant studies， HCC involves the accumulation of multiple genetic and epigenetic changes during the initiation， promotion， and progression stages. HCC is categorized as infantile malnutrition with accumulation， hypochondriac pain， tympan ites， and abdominal mass in traditional Chinese medicine （TCM）. In the treatment of HCC， TCM with low toxicity， multi-targets， and multi-mechanisms can inhibit tumor growth， alleviate the clinical symptoms， and enhance the quality of life of the patients. Chinese medicines and their active ingredients exert anti-HCC effects through epigenetic regulation of DNA methylation， histone modification， and non-coding RNA. Abnormal gene expression due to epigenetic regulation disorders is involved in all stages of HCC development. There are few studies on epigenetic regulation in TCM treatment of HCC， and there is still much room for development in basic and clinical trials. This paper reviews the mechanism of epigenetic regulation in HCC and summarizes the experimental results of TCM research on the related mechanism， with a view to providing a theoretical basis for future research on the mechanism of HCC development and clinical diagnosis and treatment of hepatocellular carcinoma with TCM.

Objective To understand the implementation of the nursing group standards for oxygen inhalation therapy in clinical practice,and to provide a reference for improving the nursing practice of oxygen therapy.Methods A convenience sampling method was used to investigate nurses from 902 hospitals in 24 provinces and municipalities directly under the central government using a self-designed questionnaire from December 15th,2022,to January 14th,2023.The content of questionnaire included whether they had implemented the recommendations of the oxygen therapy standards,the knowledge of safety related to oxygen therapy,and the components of oxygen therapy prescriptions,the indications used for patients receiving oxygen therapy and practice status of oxygen therapy.Results A total of 10481 questionnaires were returned,of which 10447 were valid,with a valid questionnaire recovery rate of 99.68%.63.14%of the nurses indicated that the hospital had organized training on oxygen therapy standards.Only 47.82%of nurses know the correct use of the Venturi mask.41.90%of nurses could indicate the correct indicator of flow adjustment.31.88%of the nurses stated that they will adjust the oxygen flow rate based on the oxygenation status of carbon dioxide storage patients.Only 19.56%of nurses indicated that humidification is applied in oxygen therapy based on the oxygen flow and duration.Conclusion Even though nurses had received training related to oxygen therapy standards,the level of knowledge of oxygen therapy standards was still low;therefore continuous systematic training was needed,and the implementation of the content of oxygen therapy standards needed to be further standardized.Healthcare institutions would focus on organizing systematic training and maintaining the training effect,enhancing infrastructure and providing support for implementation.Recommendation to the nursing administration is to explore how to comprehensively and continuously implementing the oxygen therapy nursing standards with the ultimate goal of providing patients safer and more accurate oxygen therapy.

Objective To evaluate the policy of human organ transplantation in China, aiming to provide theoretical basis for further optimizing the policy of human organ transplantation. Methods Based on text mining and statistical analysis, seven normative policies of human organ transplantation formulated by national government from 2000 to 2022 were quantitatively evaluated by constructing policy modeling consistency (PMC) with 10 first-level variables and 35 second-level variables. Results Among the seven policies, six were graded as excellent policies and one as perfect policy, with an average PMC index of 8.476. Except X₈ policy audience, the scores of other second-level variables of P5 were higher than or equal to the mean. The scores of all second-level variables of P1 were lower than or equal to the mean. P1 and P5 significantly differed in X₃ policy timeliness, X₄ policy norms and X₆ policy tools. P5 was more specific and relatively comprehensive in these aspects, and its score was significantly higher than that of P1. Conclusions Human organ transplantation policies in China are generally excellent, scientific and rational. Health administrative departments at all levels should pay attention to the grasp of policy timeliness, the combination of policy tools, and fully mobilize the initiative and enthusiasm of all policy audience to participate in organ transplantation management when formulating organ transplantation policies.

Objective:To compare the efficacy of intraluminal microwave ablation with radiofrequency ablation in the treatment of varicose veins of the lower extremities.Methods:The clinical data of 520 patients (522 affected limbs) who underwent lower extremity varicose vein surgery at the Department of Vascular Surgery of the First Affiliated Hospital of Anhui Medical University from Jun 2021 to Sep 2022 were collected. Patients were divided into endovenous microwave ablation group (EMWA group, n = 201) and radiofrequency ablation group (RFA group, n = 321). Follow-up was performed at 1 week, 1 , 6 and 12 months after surgery. The primary efficacy endpoint was the occlusion rate of the treated segment vein, the primary safety endpoint was the incidence of surgery-related and/or device-related complications, and the secondary endpoints were the venous clinical severity score (VCSS) and chronic venous insufficiency quality of life questionnaire (CIVIQ) scores at follow-up. Results:The technique success rate and the occlusion rate of the affected segment vein was 100% in both groups evaluated one week after surgery; Six and 12 months after surgery, the occlusion rate in the RFA group was 98.9%, and that in the EMWA group was 99.3% and respectively 97.8%, 97.2% ,without statically significant difference.During the follow-up period, there were no cases of reoperation due to vein recanalization. no serious events such as deep vein thrombosis, pulmonary embolism or death occurred in either group. The incidence of adverse events (induration, ecchymosis, skin burn, incision infection, limb numbness, hematoma, thrombotic superficial phlebitis, endovenous heat induced thrombosis, etc.) in both groups was compared, and the difference was not statistically significant. VCSS and CIVIQ scores improved significantly in both groups at 1 ,6 and 12 months after treatment, and the difference was statistically significant(all P < 0.01). Conclusion:EMWA and RFA have the advantages of simple operation, good clinical efficacy and high degree of improvement in quality of life.

Background: Cardiopulmonary resuscitation (CPR) strategies in COVID-19 patients differ from those in patients suffering from cardiogenic cardiac arrest. During CPR, both healthcare and non-healthcare workers who provide resuscitation are at risk of infection. The Working Group for Expert Consensus on Prevention and Cardiopulmonary Resuscitation for Cardiac Arrest in COVID-19 has developed this Chinese Expert Consensus to guide clinical practice of CPR in COVID-19 patients. Main recommendations: 1) A medical team should be assigned to evaluate severe and critical COVID-19 for early monitoring of cardiac-arrest warning signs. 2) Psychological counseling and treatment are highly recommended, since sympathetic and vagal abnormalities induced by psychological stress from the COVID-19 pandemic can induce cardiac arrest. 3) Healthcare workers should wear personal protective equipment (PPE). 4) Mouth-to-mouth ventilation should be avoided on patients suspected of having or diagnosed with COVID-19. 5) Hands-only chest compression and mechanical chest compression are recommended. 6) Tracheal-intubation procedures should be optimized and tracheal-intubation strategies should be implemented early. 7) CPR should be provided for 20-30 min. 8) Various factors should be taken into consideration such as the interests of patients and family members, ethics, transmission risks, and laws and regulations governing infectious disease control. Changes in management: The following changes or modifications to CPR strategy in COVID-19 patients are proposed: 1) Healthcare workers should wear PPE. 2) Hands-only chest compression and mechanical chest compression can be implemented to reduce or avoid the spread of viruses by aerosols. 3) Both the benefits to patients and the risk of infection should be considered. 4) Hhealthcare workers should be fully aware of and trained in CPR strategies and procedures specifically for patients with COVID-19.

Objective:To evaluate the efficacy of acrivastine alone or in combination with loratadine in the treatment of chronic refractory urticaria.Methods:From March 2017 to December 2018, a multicenter, randomized, controlled clinical study was conducted in 4 centers. Patients with chronic refractory urticaria were randomly divided into two groups, i.e., combined treatment group receiving oral acrivastine capsules 8 mg thrice a day plus oral loratadine tablets 10 mg once a day, and acrivastine alone group receiving oral acrivastine capsules 8 mg thrice a day plus a placebo 10 mg once a day. The course of treatment was 4 weeks. Visits were scheduled at baseline and after 1, 2 and 4 weeks of treatment. At the same time, clinical data were collected, and adverse events were recorded. Symptom scores were evaluated based on degree of itching, number and size of wheals, duration of each attack and number of attacks per week, and symptom score reduce index (SSRI) was used to evaluate the efficacy. Repeated measures analysis of variance and chi-square test were used to evaluate the efficacy and safety.Results:Fifty-three patients in the combined treatment group and 59 in the acrivastine alone group were included in the efficacy analysis. Before treatment, there was no significant difference in symptom score or visual analogue score between the two groups. After 2 weeks of treatment, 19 patients were cured and 10 achieved marked improvement in the combined treatment group, with a response rate of 54.72%; 15 were cured and 6 achieved marked improvement in the acrivastine alone group, with a response rate of 35.59%. After 4 weeks of treatment, 23 patients were cured and 9 achieved marked improvement in the combined treatment group, with a response rate of 60.38%; 20 were cured and 2 achieved marked improvement in the acrivastine alone group, with a response rate of 37.29%. After 2 and 4 weeks of treatment, the response rates were significantly higher in the combined treatment group than in the acrivastine alone group ( χ2 = 4.13, 5.96 respectively, both P < 0.05) . The SSRI significantly differed among different follow-up time points, as well as between the 2 groups ( F = 8.62, 4.38 respectively, both P < 0.05) . Multivariate analysis of variance showed that SSRI was significantly higher in the combined treatment group (0.63 ± 0.05, 0.68 ± 0.05, respectively) than in the acrivastine alone group (0.47 ± 0.05, 0.51 ± 0.05, respectively) after 2 and 4 weeks of treatment (both P < 0.05) . Drug-related adverse reactions, including drowsiness, stomach upsets, headache and liver function abnormality, occurred in 7 patients in the combined treatment group, as well as in 3 in the acrivastine alone group. Conclusion:Acrivastine is safe and effective for the treatment of chronic refractory urticaria, and acrivastine combined with loratadine can markedly improve the efficacy.