1.Discovery of a novel thiophene carboxamide analogue as a highly potent and selective sphingomyelin synthase 2 inhibitor for dry eye disease therapy.
Jintong YANG ; Yiteng LU ; Kexin HU ; Xinchen ZHANG ; Wei WANG ; Deyong YE ; Mingguang MO ; Xin XIAO ; Xichen WAN ; Yuqing WU ; Shuxian ZHANG ; He HUANG ; Zhibei QU ; Yimin HU ; Yu CAO ; Jiaxu HONG ; Lu ZHOU
Acta Pharmaceutica Sinica B 2025;15(1):392-408
Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC50, SMS2 = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t 1/2, cornea = 1.11 h; t 1/2, meibomian glands = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.
2.Survey on the current situation of management of sterilization and supply centers in response to emerging and outbreaks of infectious diseases in 442 hospitals and analysis of influencing factors
Jinli SHI ; Junjun MO ; Lingling LU ; Ye CHEN
Chinese Journal of Nursing 2025;60(5):589-595
Objective To investigate the current situation of emergency response management during new outbreaks of infectious diseases in central sterile supply department(CSSD)of hospitals in 18 provinces(autonomous regions and municipalities),and to provide a reference basis for the establishment of a sound emergency response management system.Methods A convenience sampling method was used to investigate and study the CSSDs in 447 hospitals from June to December 2023 using a self-developed questionnaire.The questionnaire included 3 aspects,including general information,emergency disposal management situation(including environment management,personnel management,material management,and process management),and satisfaction with emergency disposal management,and the relevant factors affecting the satisfaction with the emergency disposal management of CSSDs responding to new outbreaks of infectious disease devices were analyzed.Results A total of 447 questionnaires were recovered,with 442 valid questionnaires and a valid questionnaire recovery rate of 98.88%.In terms of environmental management,CSSDs in 88(19.91%)hospitals set up independent instrument pre-sterilization rooms for infected device disposal.In terms of material management,CSSDs in 42(9.50%)hospitals conducted daily emergency material management.In terms of personnel management,CSSDs in 236(53.39%)hospitals conducted emergency response knowledge assessments.In terms of process management,CSSDs in 225(50.90%)hospitals conducted information traceability system full-process closed-loop management.The results of multiple linear regression analysis showed that whether or not to carry out pre-treatment,emergency supplies stockpiling and management,emergency disposal knowledge assessment,establishment of standard operating procedures,and full-process closed-loop management of the traceability system were the influencing factors affecting the satisfaction of CSSD's emergency disposal management(P<0.05).Conclusion The current situation of CSSD's emergency disposal management of new outbreaks of infectious diseases needs to be improved,and the environmental management of the decontamination area should be strengthened to improve the staff's ability of emergency disposal,guarantee the reserve of emergency supplies,and strengthen the informatization of the whole process management,to reduce the risk of hospital infections and safeguard the quality of medical care.
3.EBV-positive nodal T-and NK-cell lymphoma:an analysis of 5 cases with clinico-pathological features
Yongta HUANG ; Wenwen GUO ; Xia LIU ; Ling LI ; Qiurong YE ; Xianglan MO
Chinese Journal of Clinical and Experimental Pathology 2025;41(2):186-190
Purpose To explore the clinicopathological features of EBV-positive nodal T-and NK-cell lymphoma.Methods Clinical and pathological data of 5 cases were collected.The expression of CD3,CD56,TIA-1,Granzyme B and other markers were detected by immunohistochemistry.The expression of EBER was detected by in situ hybrid-ization.The gene rearrangement and clonality were analyzed by PCR and polyacrylamide gel electrophoresis.The litera-tures were reviewed.Results The primary lesions of the 5 patients were all located in lymph nodes.All patients pres-ented with multiple lymphadenopathy,B symptoms,elevated lactate dehydrogenase(LDH)and C-reactive protein(CRP),and were in stage Ⅲ/Ⅳ.Histopathologically,the lesions show a diffuse infiltration of large to medium monot-onous tumor lymphocytes.Cell apoptosis,necrosis,and vascular invasion were not significant.Tumor cells of all cases were positive for CD3 but negative for CD56.All cases were positive for the cytotoxic markers.In situ hybridization de-tection showed that the majority of tumor cells were diffusely positive for EBER.Nevertheless,only 4 cases were posi-tive for TCR gene clonal rearrangement.Three patients received chemotherapy,2 patient declined the treatments.The median overall survival was only 3 months.Conclusions EBV-positive nodal T-and NK-cell lymphoma is an EBV-positive lymphoma of cytotoxic T-or NK-cell lineage presenting primarily with nodal disease,which is more common in elderly males.The patient has obvious symptoms and signs,rapid disease progression,and poor prognosis.Under-standing the clinicopathological features of EBV-positive nodal T-and NK-cell lymphoma can help differentiate it from other EBV-positive T-and NK-cell lymphoid proliferations and lymphomas.
4.Advances in Clinical Application of Gastric Contrast-Enhanced Ultrasound for Gastric Cancer.
Guan-Mo LIU ; Hua LIANG ; Yang GUI ; Jie LI ; Xin YE ; Wei-Ming KANG
Acta Academiae Medicinae Sinicae 2025;47(5):716-724
Gastric contrast-enhanced ultrasound includes oral contrast-enhanced ultrasound (OCUS) and double contrast-enhanced ultrasound (DCEUS),which can provide valuable clinical information about tumor morphology,vascular characteristics,and treatment responses.OCUS can clearly identify the gastric wall structure and the extent and depth of lesions by applying oral contrast agents.DCEUS,based on OCUS combined with venography,can display the anatomical and perfusion characteristics of lesions.In recent years,gastric contrast agents and imaging techniques have developed rapidly.However,the clinical application of gastric contrast-enhanced ultrasound is still in the developmental stage.This article reviews the clinical status of OCUS and DCEUS in the screening,diagnosis,staging,pathological typing,and treatment evaluation of gastric cancer.Studies have shown that gastric contrast-enhanced ultrasound has high sensitivity and specificity in the assessment of diagnosis and T-staging of gastric cancer.Furthermore,gastric contrast-enhanced ultrasound has the advantages of being cost-effective,convenient,non-invasive,free from radiation exposure,real-time,and easy to repeat.In the diagnosis and treatment of gastric cancer,it is expected to become one of the important imaging assessment tools.
Humans
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Stomach Neoplasms/diagnostic imaging*
;
Contrast Media
;
Ultrasonography/methods*
5.Evaluation of the Applicability of the Dampness Syndrome Scale of Chinese Medicine(DSSCM)in Patients with Atopic Dermatitis
Li'an ZHU ; Liu ZHONG ; Yu ZHANG ; Siqi YE ; Xiumei MO
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(10):2367-2373
Objective To evaluate the applicability of the Dampness Syndrome Scale of Chinese Medicine(DSSCM)in patients with atopic dermatitis(AD).Methods A cross-sectional study was conducted 204 AD patients.Demographic data and scores of the DSSCM,Patient-Oriented Eczema Measure(POEM),Atopic Dermatitis Control Tool(ADCT),Scoring Atopic Dermatitis(SCORAD),Eczema Area and Severity Index(EASI),and Investigator's Global Assessment(IGA)were collected.SPSS and AMOS were used to analyze the reliability and validity of the DSSCM and then the correlation between dampness syndrome and clinical AD indicators was explored.Results The overall Cronbach's α coefficient of DSSCM was 0.90,and the Spearman-Brown split-half reliability coefficient was 0.81.Content validity results indicated that,except for items DSSCM 25,DSSCM 26,DSSCM 27,DSSCM 28,and DSSCM 29(with correlation coefficients<0.30),all other items showed correlation coefficients>0.40 with their respective dimensions and the total scale score.The success rates of convergent and discriminant validity tests exceeded 80%,and confirmatory factor analysis demonstrated good fit in the indices of x2/df and RMSEA.Correlation analysis revealed that DSSCM scores were significantly correlated with body mass index(BMI),Dermatology Life Quality Index(DLQI)scores,POEM scores,ADCT scores,pruritus scores,sleep scores,or SCORAD scores(P<0.05 or P<0.01).However,no significant correlations were observed between DSSCM scores and disease duration,age,IGA scores,or EASI scores(P>0.05).Conclusion The DSSCM demonstrates good reliability and validity in AD patients and its scores are correlated with clinical AD indicators,making it a suitable tool for assessing dampness syndrome in this population.
6.Establishment and application of ultra-fast real-time PCR for Brucella detection
Zhen-na XU ; Zhi-peng WU ; Wei-bin HONG ; Zhi-shen GUAN ; Qi-ming LIN ; Zuan-lan MO ; Yi-fei YE ; Hai-yan XIE ; Min LI ; Yan-qiu ZHU ; Xiao-jun LI ; Xian-peng ZHANG
Chinese Journal of Zoonoses 2025;41(3):278-283
This study was aimed at establishing a method of ultra-fast quantitative PCR for Brucella detection.We used an exogenous recombinant plasmid as the internal reference and targeted the T4SS secretion system,an important Brucella viru-lence factor,to design specific primers and probes.The sensitivity,specificity,and repeatability of this method were evaluated,and a standard curve was constructed.The coincidence rate of detection findings with this method versus quantitative PCR was determined.This method markedly decreased the detection time to only 10 minutes.The standard curve demonstrated a good linear relationship(Y=-3.410 7x+38.357,R2=0.998 5)with a low minimum detection limit of 10 copies/μL.The method exhibited good specificity and did not specifically amplify several common clinical bacteria other than Brucella.The de-tection of three concentrations of positive plasmids yielded coefficients of variation(CVs)of 0.20%to 0.91%,thus demonstra-ting the method's excellent repeatability.Furthermore,140 clinical samples were analyzed concurrently with the fluorescence PCR method,which yielded a 100%compliance rate and consistent results.Our findings indicated that the Brucella ultra-fast quantitative PCR was ultrafast;had high sensitivity,high specificity,and good specificity;and can be used for the clinical de-tection of Brucella and emergency investigation of epidemics.Therefore,this method is valuable for the early diagnosis of Bru-cella.
7.EBV-positive nodal T-and NK-cell lymphoma:an analysis of 5 cases with clinico-pathological features
Yongta HUANG ; Wenwen GUO ; Xia LIU ; Ling LI ; Qiurong YE ; Xianglan MO
Chinese Journal of Clinical and Experimental Pathology 2025;41(2):186-190
Purpose To explore the clinicopathological features of EBV-positive nodal T-and NK-cell lymphoma.Methods Clinical and pathological data of 5 cases were collected.The expression of CD3,CD56,TIA-1,Granzyme B and other markers were detected by immunohistochemistry.The expression of EBER was detected by in situ hybrid-ization.The gene rearrangement and clonality were analyzed by PCR and polyacrylamide gel electrophoresis.The litera-tures were reviewed.Results The primary lesions of the 5 patients were all located in lymph nodes.All patients pres-ented with multiple lymphadenopathy,B symptoms,elevated lactate dehydrogenase(LDH)and C-reactive protein(CRP),and were in stage Ⅲ/Ⅳ.Histopathologically,the lesions show a diffuse infiltration of large to medium monot-onous tumor lymphocytes.Cell apoptosis,necrosis,and vascular invasion were not significant.Tumor cells of all cases were positive for CD3 but negative for CD56.All cases were positive for the cytotoxic markers.In situ hybridization de-tection showed that the majority of tumor cells were diffusely positive for EBER.Nevertheless,only 4 cases were posi-tive for TCR gene clonal rearrangement.Three patients received chemotherapy,2 patient declined the treatments.The median overall survival was only 3 months.Conclusions EBV-positive nodal T-and NK-cell lymphoma is an EBV-positive lymphoma of cytotoxic T-or NK-cell lineage presenting primarily with nodal disease,which is more common in elderly males.The patient has obvious symptoms and signs,rapid disease progression,and poor prognosis.Under-standing the clinicopathological features of EBV-positive nodal T-and NK-cell lymphoma can help differentiate it from other EBV-positive T-and NK-cell lymphoid proliferations and lymphomas.
8.Survey on the current situation of management of sterilization and supply centers in response to emerging and outbreaks of infectious diseases in 442 hospitals and analysis of influencing factors
Jinli SHI ; Junjun MO ; Lingling LU ; Ye CHEN
Chinese Journal of Nursing 2025;60(5):589-595
Objective To investigate the current situation of emergency response management during new outbreaks of infectious diseases in central sterile supply department(CSSD)of hospitals in 18 provinces(autonomous regions and municipalities),and to provide a reference basis for the establishment of a sound emergency response management system.Methods A convenience sampling method was used to investigate and study the CSSDs in 447 hospitals from June to December 2023 using a self-developed questionnaire.The questionnaire included 3 aspects,including general information,emergency disposal management situation(including environment management,personnel management,material management,and process management),and satisfaction with emergency disposal management,and the relevant factors affecting the satisfaction with the emergency disposal management of CSSDs responding to new outbreaks of infectious disease devices were analyzed.Results A total of 447 questionnaires were recovered,with 442 valid questionnaires and a valid questionnaire recovery rate of 98.88%.In terms of environmental management,CSSDs in 88(19.91%)hospitals set up independent instrument pre-sterilization rooms for infected device disposal.In terms of material management,CSSDs in 42(9.50%)hospitals conducted daily emergency material management.In terms of personnel management,CSSDs in 236(53.39%)hospitals conducted emergency response knowledge assessments.In terms of process management,CSSDs in 225(50.90%)hospitals conducted information traceability system full-process closed-loop management.The results of multiple linear regression analysis showed that whether or not to carry out pre-treatment,emergency supplies stockpiling and management,emergency disposal knowledge assessment,establishment of standard operating procedures,and full-process closed-loop management of the traceability system were the influencing factors affecting the satisfaction of CSSD's emergency disposal management(P<0.05).Conclusion The current situation of CSSD's emergency disposal management of new outbreaks of infectious diseases needs to be improved,and the environmental management of the decontamination area should be strengthened to improve the staff's ability of emergency disposal,guarantee the reserve of emergency supplies,and strengthen the informatization of the whole process management,to reduce the risk of hospital infections and safeguard the quality of medical care.
9.Establishment and application of ultra-fast real-time PCR for Brucella detection
Zhen-na XU ; Zhi-peng WU ; Wei-bin HONG ; Zhi-shen GUAN ; Qi-ming LIN ; Zuan-lan MO ; Yi-fei YE ; Hai-yan XIE ; Min LI ; Yan-qiu ZHU ; Xiao-jun LI ; Xian-peng ZHANG
Chinese Journal of Zoonoses 2025;41(3):278-283
This study was aimed at establishing a method of ultra-fast quantitative PCR for Brucella detection.We used an exogenous recombinant plasmid as the internal reference and targeted the T4SS secretion system,an important Brucella viru-lence factor,to design specific primers and probes.The sensitivity,specificity,and repeatability of this method were evaluated,and a standard curve was constructed.The coincidence rate of detection findings with this method versus quantitative PCR was determined.This method markedly decreased the detection time to only 10 minutes.The standard curve demonstrated a good linear relationship(Y=-3.410 7x+38.357,R2=0.998 5)with a low minimum detection limit of 10 copies/μL.The method exhibited good specificity and did not specifically amplify several common clinical bacteria other than Brucella.The de-tection of three concentrations of positive plasmids yielded coefficients of variation(CVs)of 0.20%to 0.91%,thus demonstra-ting the method's excellent repeatability.Furthermore,140 clinical samples were analyzed concurrently with the fluorescence PCR method,which yielded a 100%compliance rate and consistent results.Our findings indicated that the Brucella ultra-fast quantitative PCR was ultrafast;had high sensitivity,high specificity,and good specificity;and can be used for the clinical de-tection of Brucella and emergency investigation of epidemics.Therefore,this method is valuable for the early diagnosis of Bru-cella.
10.Research progress on origin of abnormal aorta in coronary artery
Mingtang YE ; Yang WANG ; Di YU ; Jirong QI ; Xuming MO
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(2):117-123
Anomalous aortic origin of the coronary artery(AAOCA) refers to the abnormal initiation, route, or distribution of coronary arteries, which is generally believed to be caused by abnormal or incomplete development of embryonic coronary arteries, and is a rare congenital cardiovascular malformation. It can exist independently without other congenital heart disease. With the development of medical science and people's understanding of AAOCA, more and more AAOCA has been detected, and its clinical significance has attracted more and more attention. Based on abnormal coronary artery opening, malignant or potential contorts can cause long-term blood flow dynamic change, appear abnormal blood vessel hardening of the arteries, at the same time due to walk in the pulmonary artery and the ascending aorta between two vessels, vulnerable to the extrusion of large blood vessels, which caused a temporary blood flow in coronary artery interruption, can cause acute angina pectoris, myocardial infarction, arrhythmia, exercise-induced cardiac syncope. This review focuses on the anatomy, diagnosis and treatment of coronary artery abnormalities arising from aorta.

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