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 (IC_{50, 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.

OBJECTIVE To explore the clinical efficacy and possible mechanism of the classic prescription Xinyi Powder in the treatment of allergic rhinitis with lung deficiency related cold.METHODS A total of 189 patients who met the inclusion criteria of al-lergic rhinitis with lung deficiency related cold in the otolaryngology clinic of Jiangsu Province Hospital of Chinese Medicine from Janu-ary 2023 to July 2024 were selected and randomly divided into the experimental group(n=126)and the control group(n=63).The control group was treated with oral loratadine,and the experimental group took Xinyi Powder.Before and after treatment,the TNSS,TNNSS scores and TCM syndrome scores of the two groups of patients were compared to comprehensively evaluate the clinical efficacy.The changes in the patients'quality of life were evaluated in multiple dimensions using nasal VAS and RQLQ scores.The changes in serum IL-4,IL-5,IgE,SP and CGRP expression levels were detected by ELISA.RESULTS After 14 days of treatment,the TNSS,TNNSS,VAS,RQLQ scores and TCM syndrome scores of the two groups of patients were reduced(P<0.01);the experi-mental group was better than the control group in improving the concomitant symptoms such as nasal congestion,runny nose,postnasal drip,and itchy eyes(P<0.05,P<0.01),and it could also significantly improve the symptoms of fear of wind and cold,spontaneous sweating,shortness of breath,and cough with thin sputum(P<0.01),and the total RQLQ score was significantly better than the con-trol group(P<0.01).After treatment,the serum IL-4,IL-5,IgE,SP,and CGRP levels of the two groups of patients were signifi-cantly reduced(P<0.01),and there was no statistical difference between the two groups.CONCLUSION Xinyi Powder can signifi-cantly alleviate the nasal symptoms and systemic concomitant symptoms of patients with allergic rhinitis of lung deficiency and cold type,and significantly improve the quality of life of patients.It may play a therapeutic role by inhibiting the expression of inflammatory factors and neuropeptides and regulating neuroimmunity.

Objective To explore the relevant factors affecting the efficacy of traditional Chinese medicine in treating MG,and to develop and validate a nomogram model,in order to personalize the prediction of the probability of benefits for MG patients after traditional Chinese medicine treatment,further guide clinical physicians in targeted medication,and provide guidance for the traditional Chinese medicine treatment of MG.Method Retrospective analysis of MG patients who visited the Affiliated Hospital of Changchun University of Traditional Chinese Medicine from March 2018 to June 2022,13 clinical factors were selected to evaluate the results.To acquire independent factors,univariate and multivariate Logistic analyses were performed.The area under the receiver operating characteristic curve,Harrell's concordance index,calibration curve,and decision curve analyses were used to evaluate the predictive ability,accuracy,and clinical practicability of the prediction model.Results A total of 204 cases were included,divided into derivation cohort 139 cases and temporal validation cohort 65 cases.Multivariate Logistic regression showed 4 independent predictors affecting effectiveness of traditional Chinese medicine in treating MG,including age at onset,repetitive nerve stimulation positive,oral immunosuppressant and anxiety/depression.AUC values for the model group and validation group were 0.76(95%CI:0.68-0.84)and 0.83(95%CI:0.71-0.95),respectively,and based on calibration curve and decision curve analysis,we concluded that the nomogram showed excellent performance.Conclusion MG patients may experience a decrease in short-term efficacy with age,positive RNS,concomitant emotional abnormalities,or recent history of immunosuppressive therapy.This nomogram effectively predicts the possibility of short-term effective traditional Chinese medicine treatment in MG patients.

OBJECTIVE To investigate the effects of the split formulas of Biyuan Heji(BYHJ)on paranasal sinus mucosal in-flammation in rats with acute rhinosinusitis(ARS)based on the pathogenesis of"wind-cold transforming into lung-heat".METHODS Unilateral nasal cavity occlusion combined with nasal dripping of Staphylococcus aureus were performed to establish a rat model of ARS.SD rats were randomly divided into blank,model,BYHJ(wind-cold removal+lung-heat removal),lung-heat removal,wind-cold removal,and positive drug groups,with 6 rats in each group.The rats were treated with the corresponding drugs for 7 d and then the samples were collected.HE staining was used to observe the pathological changes of rat paranasal sinus mucosa tissues,ELISA was employed to determine the levels of interleukin-1β(IL-1β),IL-6,IL-8,IL-9,IL-10,and IL-12 in serum,immunohistochemis-try(IHC)was adopted to measure the protein expression of tumor necrosis factor-α(TNF-α)and intercellular adhesion molecule(ICAM-1)in paranasal sinus mucosa tissues,and Western blot was used to detect the protein expression of phosphorylated p38 mito-gen-activated protein kinase(p38 MAPK),nuclear transcription factor-κB p50(NF-κB p50),and NF-κB p65 in paranasal sinus mucosa tissues.RESULTS The acute sinusitis rat inflammation model was successfully established.Compared with the model group,the water drinking,diet eating,and body weight of rats in the BYHJ group,wind-cold removal,lung-heat removal,and positive drug groups were significantly improved,the aggregation of inflammatory cells in the paranasal sinus mucosal tissue was reduced,and the levels of IL-1β,IL-6,IL-8,IL-9,and IL-12 in the serum were significantly reduced(P<0.01),IL-10 content significantly in-creased(P<0.01),the protein expression of TNF-α,ICAM-1,p38 MAPK,NF-κB p50,and NF-κB p65 in the paranasal sinus mucosa was significantly decreased(P<0.01).The comparison between various traditional Chinese medicine groups showed that the decrease of IL-1β,IL-6,IL-8,IL-9,IL-12,TNF-α,ICAM-1,p38 MAPK,NF-κB p50,and NF-κB p65 and the increase of IL-10 in the BYHJ group were better than those in the split formula groups(P<0.01),and the lung-heat removal group was better than the wind-cold removal group(P<0.01).CONCLUSION BYHJ and its split formulas can effectively inhibit the inflammatory response in rats with ARS.

OBJECTIVE To explore the clinical efficacy and possible mechanism of the classic prescription Xinyi Powder in the treatment of allergic rhinitis with lung deficiency related cold.METHODS A total of 189 patients who met the inclusion criteria of al-lergic rhinitis with lung deficiency related cold in the otolaryngology clinic of Jiangsu Province Hospital of Chinese Medicine from Janu-ary 2023 to July 2024 were selected and randomly divided into the experimental group(n=126)and the control group(n=63).The control group was treated with oral loratadine,and the experimental group took Xinyi Powder.Before and after treatment,the TNSS,TNNSS scores and TCM syndrome scores of the two groups of patients were compared to comprehensively evaluate the clinical efficacy.The changes in the patients'quality of life were evaluated in multiple dimensions using nasal VAS and RQLQ scores.The changes in serum IL-4,IL-5,IgE,SP and CGRP expression levels were detected by ELISA.RESULTS After 14 days of treatment,the TNSS,TNNSS,VAS,RQLQ scores and TCM syndrome scores of the two groups of patients were reduced(P<0.01);the experi-mental group was better than the control group in improving the concomitant symptoms such as nasal congestion,runny nose,postnasal drip,and itchy eyes(P<0.05,P<0.01),and it could also significantly improve the symptoms of fear of wind and cold,spontaneous sweating,shortness of breath,and cough with thin sputum(P<0.01),and the total RQLQ score was significantly better than the con-trol group(P<0.01).After treatment,the serum IL-4,IL-5,IgE,SP,and CGRP levels of the two groups of patients were signifi-cantly reduced(P<0.01),and there was no statistical difference between the two groups.CONCLUSION Xinyi Powder can signifi-cantly alleviate the nasal symptoms and systemic concomitant symptoms of patients with allergic rhinitis of lung deficiency and cold type,and significantly improve the quality of life of patients.It may play a therapeutic role by inhibiting the expression of inflammatory factors and neuropeptides and regulating neuroimmunity.

Objective To explore the relevant factors affecting the efficacy of traditional Chinese medicine in treating MG,and to develop and validate a nomogram model,in order to personalize the prediction of the probability of benefits for MG patients after traditional Chinese medicine treatment,further guide clinical physicians in targeted medication,and provide guidance for the traditional Chinese medicine treatment of MG.Method Retrospective analysis of MG patients who visited the Affiliated Hospital of Changchun University of Traditional Chinese Medicine from March 2018 to June 2022,13 clinical factors were selected to evaluate the results.To acquire independent factors,univariate and multivariate Logistic analyses were performed.The area under the receiver operating characteristic curve,Harrell's concordance index,calibration curve,and decision curve analyses were used to evaluate the predictive ability,accuracy,and clinical practicability of the prediction model.Results A total of 204 cases were included,divided into derivation cohort 139 cases and temporal validation cohort 65 cases.Multivariate Logistic regression showed 4 independent predictors affecting effectiveness of traditional Chinese medicine in treating MG,including age at onset,repetitive nerve stimulation positive,oral immunosuppressant and anxiety/depression.AUC values for the model group and validation group were 0.76(95%CI:0.68-0.84)and 0.83(95%CI:0.71-0.95),respectively,and based on calibration curve and decision curve analysis,we concluded that the nomogram showed excellent performance.Conclusion MG patients may experience a decrease in short-term efficacy with age,positive RNS,concomitant emotional abnormalities,or recent history of immunosuppressive therapy.This nomogram effectively predicts the possibility of short-term effective traditional Chinese medicine treatment in MG patients.

OBJECTIVE To investigate the effects of the split formulas of Biyuan Heji(BYHJ)on paranasal sinus mucosal in-flammation in rats with acute rhinosinusitis(ARS)based on the pathogenesis of"wind-cold transforming into lung-heat".METHODS Unilateral nasal cavity occlusion combined with nasal dripping of Staphylococcus aureus were performed to establish a rat model of ARS.SD rats were randomly divided into blank,model,BYHJ(wind-cold removal+lung-heat removal),lung-heat removal,wind-cold removal,and positive drug groups,with 6 rats in each group.The rats were treated with the corresponding drugs for 7 d and then the samples were collected.HE staining was used to observe the pathological changes of rat paranasal sinus mucosa tissues,ELISA was employed to determine the levels of interleukin-1β(IL-1β),IL-6,IL-8,IL-9,IL-10,and IL-12 in serum,immunohistochemis-try(IHC)was adopted to measure the protein expression of tumor necrosis factor-α(TNF-α)and intercellular adhesion molecule(ICAM-1)in paranasal sinus mucosa tissues,and Western blot was used to detect the protein expression of phosphorylated p38 mito-gen-activated protein kinase(p38 MAPK),nuclear transcription factor-κB p50(NF-κB p50),and NF-κB p65 in paranasal sinus mucosa tissues.RESULTS The acute sinusitis rat inflammation model was successfully established.Compared with the model group,the water drinking,diet eating,and body weight of rats in the BYHJ group,wind-cold removal,lung-heat removal,and positive drug groups were significantly improved,the aggregation of inflammatory cells in the paranasal sinus mucosal tissue was reduced,and the levels of IL-1β,IL-6,IL-8,IL-9,and IL-12 in the serum were significantly reduced(P<0.01),IL-10 content significantly in-creased(P<0.01),the protein expression of TNF-α,ICAM-1,p38 MAPK,NF-κB p50,and NF-κB p65 in the paranasal sinus mucosa was significantly decreased(P<0.01).The comparison between various traditional Chinese medicine groups showed that the decrease of IL-1β,IL-6,IL-8,IL-9,IL-12,TNF-α,ICAM-1,p38 MAPK,NF-κB p50,and NF-κB p65 and the increase of IL-10 in the BYHJ group were better than those in the split formula groups(P<0.01),and the lung-heat removal group was better than the wind-cold removal group(P<0.01).CONCLUSION BYHJ and its split formulas can effectively inhibit the inflammatory response in rats with ARS.

ObjectiveTo describe the differences in imported malaria cases before and after the COVID-19 pandemic in Pudong New Area， Shanghai， to explore the possible impact of isolation measures during the pandemic on malaria， and to provide a basis for formulation of malaria control strategies during the prevention and control of major infectious diseases in the future. MethodsInformation on malaria cases reported in Pudong New Area from 2017 to 2022 was collected and divided into two groups： cases before the COVID-19 pandemic （2017‒2019） and cases after the COVID-19 pandemic （2020‒2022）. Analysis was conducted on information such as gender， age， parasite species， country of infection， place of onset， time of onset， time of first diagnosis， time of confirmed diagnosis， hospitalization， and duration of treatment for both groups. ResultsThe pre-COVID group consisted of 21 cases， and post-COVID group consisted of 28 cases， with male and falciparum malaria predominating in both groups. There were statistically significant differences between the two groups in terms of Shanghai residency status， use of preventive measures， and adherence to standardized treatment （P<0.05）. The time interval from symptom onset to first diagnosis was longer in the pre-COVID group than that in the post-COVID group （Z=-2.617， P<0.05 ）. The interval from the first diagnosis to the confirmed diagnosis and duration of treatment were shorter in the pre-COVID group than that in the post-COVID group （Z=-3.381， P<0.05； Z=-4.148， P<0.05）. There was no significant difference in gender， age， malaria classification， source of infection， onset area， length of hospital stay， complications， severe cases， and interval between onset and diagnosis between the two groups （P>0.05）. ConclusionAfter the outbreak of COVID-19， the medical priority plan prolongs the treatment time of malaria patients， increasing the risk of severe illness and death.

ObjectiveTo investigate the population and chigger mite infection of rodents in Pudong District， Shanghai， so as to provide the scientific basis for the prevention and control of rodents and chigger transmitted diseases. MethodsThe monitoring work was conducted in four points including Xuanqiao， Hangtou， Laogang and Nanhui New Town with night trapping method from 2020 to 2022. Habitats as farmland， wasteland， rural residential areas， and parks were selected. The rodent species were identified and rodent density was calculated. All chigger mites were collected from the earlaps and auricular fossae of the rodents. The species of chigger mites were identified and the chigger mite index was calculated. ResultsA total of 222 rodents were captured. They belonged to 5 species， 4 genera， 2 families and 2 orders， including 4 species， 3 genera， and 1 family of Rodentia and 1 species of Insectivora. M. musculus was the dominant species， with a composition ratio of 54.05%. Total 80 chigger mites were captured， with a detection rate of 36.03%. The total chigger index was 0.36 and Rattus tanezumi held the highest （6.00）， followed by M. musculus （0.48）. There were 3 species of chigger mites， L.deliense， L.scutellare， and L.gaohuense. L.deliense was the dominant specie， accounting for 55.00%. ConclusionThere is a risk of chigger-borne disease transmission in Pudong New Area with M. musculus as the dominant host and L. deliense as the dominant species.

The CRISPR-Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated) system is an "adaptive immune system" found in the genomes of bacteria and archaea which is mediated by RNA and resists foreign nucleic acid invasion.Take advantage of specific recognition of target nucleic acid, CRISPR-Cas system can efficiently edit their target site or accurately regulate gene expression, and now have been developed into a powerful tool for gene editing.According to the different compositions of the effector complex, the system has been divided into two categories: class 1 (type I, type IV, and type III) and class 2 (type II, type V, and type VI).Class 2 system, like the CRISPR-Cas9, is widely used in basic research due to the earliest discovery and best research.However, class 1 has not been maturely developed and utilized though it makes up 90% of the entire CRISPR-Cas system.In this essay, the classification of subtype, the assembly of Cascade complex, the cleavage and degradation mechanism of Cas3, and the application in gene editing of class 1 type I CRISPR-Cas system will be discussed and summarized to provide new ideas and methods for further mechanism studying and application of this category.