ObjectiveTo understand the epidemiological distribution and gene evolutionary variation of influenza A (H3N2) viruses in Fengxian District, Shanghai, in the surveillance year of 2023, and to provide a reference basis for influenza prevention and control. MethodsThe prevalence of influenza virus in Fengxian District in the 2023 influenza surveillance year (April 2023‒March 2024) was analyzed. The hemagglutinin (HA) gene, neuraminidase (NA) gene, and amino acid sequences of 75 strains of H3N2 influenza viruses were compared with the vaccine reference strain for similarity matching and phylogenetic evolutionary analysis, in addition to an analysis of gene characterization and variation. ResultsIn Fengxian District, there was a mixed epidemic of H3N2 and H1N1 in the spring of 2023, with H3N2 being the predominant subtype in the second half of the year, and Victoria B becoming the predominant subtype in the spring of 2024. A total of 75 influenza strains of H3N2 with HA and NA genes were distributed in the 3C.2a1b.2a.2a.2a.3a.1 and B.4 branches, with overall similarity to the reference strain of the 2024 vaccine higher than that of the reference strain of the 2022 and 2023 vaccine. Compared with the 2023 vaccine reference strain, three antigenic sites and one receptor binding site were changed in HA, with three glycosylation sites reduced and two glycosylation sites added; where as in NA seven antigenic sites and the 222nd resistance site changed with two glycosylation sites reduced. ConclusionThe risk of antigenic variation and drug resistance of H3N2 in this region is high, and it is necessary to strengthen the publicity and education on the 2024 influenza vaccine and long-term monitoring of influenza virus prevalence and variation levels.

BACKGROUND:Parkinson's disease is a multifactorial neurological disorder characterized by progressive loss of dopaminergic neurons,and dimethyl fumarate(DMF)has potent neuroprotective and immunomodulatory effects in neurodegenerative diseases. OBJECTIVE:To explore the neuroprotective mechanism of DMF in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease. METHODS:Twenty-four C57BL/6 mice were selected and randomly divided into control group,model group,low-dose DMF,and high-dose DMF groups.An animal model of Parkinson's disease was established in the latter three groups by intraperitoneal injection of 30 mg/kg MPTP,once a day for 5 consecutive days.Intragastric administration was given 30 minutes after each injection of MPTP.Mice in the low-dose DMF group(30 mg/kg)and high-dose DMF group(50 mg/kg)were intragastrically administered once a day for 7 consecutive days.The control and model groups were initially administered the same dose of normal saline.Behavioral testing,western blot,oxidative stress marker detection,and immunohistochemical staining were used to analyze the regulatory effects of DMF on oxidative stress and Keap1/Nrf2 signaling pathway in MPTP-induced Parkinson's disease mice,as well as the protective mechanism of DMF on degeneration of dopamine neurons. RESULTS AND CONCLUSION:Compared with the model group,mice in the low-dose DMF group exhibited significant improvements in motor retardation and postural imbalance(P<0.01),with even more remarkable improvements observed in the high-dose DMF group(P<0.01).Compared with the control group,the model group showed a significant increase in the oxidative stress marker malondialdehyde and a decrease in superoxide dismutase expression(P<0.01).Compared with the model group,the low-dose DMF group reduced malondialdehyde production and increased superoxide dismutase expression(P<0.01),and similar improvements were observed in the high-dose DMF group(P<0.01).Immunohistochemical and western blot assays demonstrated a significant decrease in the number of dopaminergic neurons and tyrosine hydroxylase protein expression in the substantia nigra of mice in the model group compared with the control group(P<0.01).However,in the low-dose DMF group,there was an increase in the number of dopaminergic neurons and tyrosine hydroxylase protein expression in the substantia nigra(P<0.01),with even more significant improvements in the high-dose DMF group(P<0.01).Western blot results revealed that the model group exhibited elevated Keap1 protein expression and decreased Nrf2 protein expression.In contrast,the DMF groups showed reduced Keap1 protein expression and increased Nrf2 protein expression compared to the model group(P<0.01).To conclude,DMF regulates the Keap1/Nrf2 pathway in the substantia nigra of mice with Parkinson's disease,and this regulatory effect is positively correlated with the dose of DMF(P<0.01).Therefore,we infer that DMF exerts neuroprotective effects through the Keap1/Nrf2 signaling pathway.

With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.

Objective: To explore the clinical manifestations and treatment plans of chronic recurrent parotitis (CRP), and to provide a reference for the clinical diagnosis and treatment of CRP. Methods: Approval was obtained from the hospital’s Medical Ethics Committee, and a retrospective analysis and summary of the clinical features, imaging characteristics, diagnosis, and treatment of 41 CRP patients with complete data were performed. Results: Among the 41 patients with CRP, 14 were male and 27 were female, with a male-to-female ratio of approximately 1:2 (14/27). The age at first-time onset ranged from 3 to 23 years, with a median age of 6 years, and there were 38 patients (92.7%, 38/41) with the first onset age of under 18 years old. The age of the first visit to our hospital ranged from 4 to 72 years old, with an average age of (41.0 ± 17.3) years; the disease duration was 0.5 to 66 years, with an average of 35.0 ± 16.1 years. Twenty-five cases had bilateral parotid gland involvement (61.0%, 25/41). The clinical manifestations of CRP are repeated swelling of one or both parotid glands, along with discomfort, and this may be accompanied by mild edema or skin flushing and pus or jelly-like secretions at the duct openings. The typical manifestations of parotid angiography are: the dominant duct and branch ducts of the parotid gland do not have specific dilation or narrowing, and the peripheral ducts show characteristic “punctate, spherical, or cavitary” dilation and delayed emptying. Of the cases, 34 had abnormal enlargement of the main duct orifice (82.9%, 34/41), and 37 presented with abnormal anterior displacement of the accessory glands (90.2%, 37/41). The treatment plan of “antibiotic perfusion + aspiration and removal of obstruction (or aspiration after obstruction dissolution)+ postprandia massage along the direction of the parotid duct (from posterior to anterior) with multiple courses for consolidation”achieved favorable outcomes. The mean follow-up period of this group was(71.1+21.9)months, and no recurrence was observed during the follow-up period. Conclusion CRP is more prevalent in young females and frequently presents with bilateral involvement. Congenital anatomical defects, such as abnormal enlargement of the main duct orifice and abnormal anterior displacement of the accessory glands, are important predisposing factors. The multi-course comprehensive therapy centered on antibiotic infusion, removal and dissolution of obstructions, and post-prandial massage along the direction of the parotid duct has significant therapeutic effects and deserves clinical application.

Objective:To investigate the central mechanism of moxibustion in treating chronic inflammatory visceral pain(CIVP)and its analgesic effect from the perspective of the p38 mitogen-activated protein kinase(MAPK)/Ets-like transcription factor 1(ELK1)signaling pathway in the spinal cord. Methods:Clean-grade male Sprague-Dawley rats were randomly divided into a normal group,a model group,a herb-partitioned moxibustion(HPM)group,a sham-HPM group,a p38 MAPK inhibitor group,and a dimethyl sulfoxide(DMSO)group.CIVP rat models were prepared using an enema mixture of 2,4,6-trinitrobenzene sulfonic acid solution and 50%ethanol.The HPM group was treated with HPM;the sham-HPM group was treated the same as the HPM group,but the moxa cones were not ignited;rats in the p38 MAPK inhibitor group received L5-L6 intrathecal injection of p38 MAPK inhibitor(SB203580);rats in the DMSO group received L5-L6 intrathecal injection of 2%DMSO.Abdominal withdrawal reflex(AWR),mechanical withdrawal threshold(MWT),and thermal withdrawal latency(TWL)were used to observe pain-related behaviors in each group.Hematoxylin-eosin staining was used to observe the morphological changes in rat colon tissue.Western blotting and real-time quantitative reverse-transcription polymerase chain reaction were used to detect the phosphorylated protein and mRNA expression of apoptosis signal-regulating kinase 1(ASK1),MAPK kinase(MKK)3/6,p38 MAPK,ELK1,and mitogen and stress-activated protein kinase 1(MSK1)in the spinal cord. Results:Compared with the normal group,CIVP rats had severe colonic inflammatory injuries,and the pathological injury scores increased significantly,along with increased AWR scores under different colorectal distension(CRD)stimulation pressures and decreased MWT and TWL;the mRNA and phosphorylated protein expression of p38 MAPK,ELK1,MSK1,ASK1,MKK3,and MKK6 all increased in the spinal cord(P<0.01).After HPM treatment,the colon injuries were repaired,and the pathological injury scores decreased;under different CRD stimulation pressures,the AWR scores decreased,and the MWT and TWL increased;the mRNA and phosphorylated protein expression of p38 MAPK,ELK1,ASK1,and MKK3 in the spinal cord also decreased,with statistically significant differences compared with the model group and the sham-HPM group(P<0.01).There were no significant differences in the above indicators between the HPM group and the p38 MAPK inhibitor group(P>0.05),and the same was true regarding the comparisons between the model group and the DMSO group. Conclusion:HPM exerted analgesic effects via downregulating the mRNA and phosphorylated protein expression of ASK1,MKK3,p38 MAPK,and ELK1 in the spinal cord of CIVP rats.The inhibition of spinal p38 MAPK/ELK1 signaling pathway activation may be one of the mechanisms by which HPM relieves pain in CIVP.

Objective This study aims to examine the potential mechanism of Shenfu Yixin Granules on heart failure(HF)based on network pharmacology,molecular docking,and experimental verification.Methods(1)The active components of herbs in Shenfu Yixin Granules were screened and retrieved through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).PubChem database and Swiss Target Prediction platform were used to predict targets.GeneCards and OMIM databases were used to screen HF-related targets.The intersection of active ingredient targets of Shenfu Yixin Granules and HF-related targets was performed by using Venny 2.1.0 platform to obtain common targets,which were the potential targets for anti-HF effect of Shenfu Yixin Granules.The potential targets were imported into the STRING database to construct a protein-protein interaction(PPI)network and screen the core targets of Shenfu Yixin Granules for the treatment of HF.GO functional and KEGG pathway enrichment analysis of potential targets were carried out by using DAVID database.AutoDock Vina software was used for molecular docking validation of key active ingredients and core targets.(2)SD rats were randomly allocated into sham operation group,model group,Shenfu Yixin Granules(5.28 g·kg-1)group,and positive control group(sacubitril-valsartan,20.8 mg·kg-1),with eight rats in each group.A rat model of HF after myocardial infarction was established by ligating the left anterior descending coronary artery.The rats were subsequently administered orally with the corresponding drugs once daily for a period of four weeks.Cardiac function including left ventricular ejection fraction(LVEF)and left ventricular fraction shortening(LVFS)in rats was assessed by echocardiography.Additionally,the histopathological alterations in rat heart tissue were examined using hematoxylin-eosin(HE)staining and Masson staining.The serum levels of brain natriuretic peptide(BNP),artial natriuretic peptide(ANP),and aldosterone(ALD)were determined by enzyme-linked immunosorbent assay(ELISA).Furthermore,real-time quantitative PCR and Western Blot were employed to detect mRNA and protein expressions of CAV1、F2 and MAPK1 in heart tissue.Results(1)A total of 210 active ingredients and 1 196 targets of Shenfu Yixin Granules,as well as 801 HF-related targets were obtained.Venny 2.1.0 platform was used to acquire 97 potential targets(common targets)of Shenfu Yixin Granules for the treatment of HF.Key active ingredients,such as quercetin,luteolin,arachidonic acid,kaempferol,and tanshinaldehyde were screened by"drugs-active ingredients-disease-targets"network analysis.The core targets including MAPK1、F2、CAV1、EDN1 and GJA1 were identified through PPI network analysis.The potential targets are mainly concentrated in multiple biological processes,namely,the positive regulation of gene expression,cardiac development,and the positive regulation of MAPK cascade,and involve multi key pathways including MAPK signaling pathway,HIF-1 signaling pathway and PI3K/Akt signaling pathway etc.Good binding activities were observed between MAPK1,CAV1,EDN1,F2 and quercetin,luteolin,kaempferol,tanshinaldehyde,as well as MAPK1,F2 and arachidonic acid.(2)Compared with sham operation group,LVEF and LVFS of rats significantly reduced(P＜0.01),heart mass index obviously increased(P＜0.05)in the model group.Myocardial tissue appears obvious pathological damage,and the degree of interstitial fibrosis was serious.The collagen volume fraction of the heart significantly increased(P＜0.01).The levels of serum BNP,ANP and ALD significantly increased(P＜0.01).The mRNA and protein expressions of CAV1、F2 and MAPK1 in heart tissue significantly increased(P＜0.05,P＜0.01).Compared with the model group,LVEF and LVFS of rats obviously increased(P＜0.01),but the decrease in heart mass index was not significant(P＞0.05)in Shenfu Yixin Granules group and positive control group.The pathological damage in myocardial tissues was significantly improved,the degree of interstitial fibrosis was significantly reduced.The collagen volume fraction of the heart significantly decreased(P＜0.01).The levels of serum BNP,ANP and ALD significantly decreased(P＜0.01).The mRNA and protein expressions of CAV1、F2 and MAPK1 in heart tissue significantly decreased(P＜0.05,P＜0.01).Conclusion Shenfu Yixin Granules may improve heart function and myocardial fibrosis in heart failure rats through the interaction between the active ingredients(quercetin,luteolin,arachidonic acid,kaempferol,and tanshinaldehyde)and targets(MAPK1,F2,CAV-1,and EDN1),so as to regulate MAPK signaling pathway and PI3K/Akt signaling pathway.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:To explore the efficacy and safety of domestic bortezomib in combination with lenalidomide and dexamethasone in the treatment of newly diagnosed multiple myeloma (NDMM) .Methods:This multicenter, prospective, single-arm clinical study included 126 patients with NDMM admitted to seven hospitals between December 2019 and January 2022. All patients received domestic bortezomib in combination with lenalidomide and dexamethasone (BLD regimen), and the efficacy, prognostic factors, and safety were analyzed.Results:Among the 126 patients with NDMM, 118 completed four cycles of treatment, with an overall response rate (ORR) of 93.22% (110/118) and a ≥very good partial response (VGPR) rate of 68.64% (81/118). Ultimately, 114 patients completed at least eight cycles of treatment, with an ORR of 92.98% (106/114) and a ≥VGPR rate of 77.19% (88/114). Eighteen patients underwent autologous hematopoietic stem cell transplantation after completing 6-8 cycles of the BLD regimen, with an ORR of 100% (18/18) and a ≥VGPR rate of 88.9% (16/18). The proportion of patients achieving ≥VGPR increased with the treatment duration, and factors such as staging and age did not significantly affect efficacy. Single-factor analysis showed that R2-ISS stage Ⅲ/Ⅳ, blood calcium >2.27 mmol/L, and failure to achieve VGPR after six cycles were adverse prognostic factors for progression-free survival (PFS) ( P<0.05), whereas failure to achieve VGPR after six cycles was an adverse prognostic factor for overall survival (OS) ( P<0.001). Multifactor analysis demonstrated that failure to achieve VGPR after six cycles is an independent adverse prognostic factor for PFS ( P=0.002). The incidence of hematologic adverse reactions was 16.7% (19/114), and nonhematologic adverse reactions were mainly mild to moderate, with no significant cardiac or renal adverse reactions observed. Conclusion:The BLD regimen is effective in treating NDMM, in which patients with high-risk genetic features are still achieving a high ≥VGPR rate, and the overall safety is good.

Objective:To analyze the differential expressions of proteins in aqueous humor in patients with exfoliation syndrome (XFS).Methods:A total of 20 patients were enrolled in the Department of Ophthalmology, People's Hospital of Hotan District from June 2020 to January 2021, including 10 patients with age-related cataract and 10 XFS patients combined with cataract, which were classified as cataract group and XFS group, respectively.A total of 50 to 100 μl aqueous humor was obtained in the middle of the anterior chamber through the intraoperative phacoemulsification channel.The proteins extracted from aqueous humor were analyzed by label-free quantitative proteomics technology.The cataract group was set as the control group, and the differentially expressed proteins (DEPs) in XFS group were screened according to P<0.05 and fold change >1.5.Gene ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis were used to explore the function and regulatory signaling pathways of DEPs in the XFS group.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2020KY[L]-21).Written informed consent was obtained from each subject. Results:In comparison with the cataract group, 25 DEPs were identified in the XFS group, primarily involved in cell adhesion, receptor, hydrolase, and molecular transport.Specifically, there were 14 down-regulated proteins including complement factor H-related protein 1 (CFHR1), endoplasmic reticulum chaperone BiP (HSPA5), biglycan (BGN), FRAS1-related extracellular matrix protein 2 (FREM2), hemoglobin subunit delta (HBD), hemoglobin subunit gamma-1 (HBG1), lysosomal thioesterase PPT2 (PPT2) etc., and 11 up-regulated proteins including latent-transforming growth factor beta-binding protein 2 (LTBP2), very low-density lipoprotein receptor (VLDLR), laminin subunit alpha-2 (LAMA2), coagulation factor Ⅸ (F9).Among them, FREM2 was the most significantly differentially expressed protein in XFS group with consistent expression levels across individual samples.GO analysis revealed that these DEPs mainly localized to the extracellular matrix of collagen, bound globin-hemoglobin complex, plasma lipoprotein particles and lysosomes.Molecular functions and biological processes showed that HBD and HBG1 were involved in cellular detoxification, PPT2 in hydrolase activity, and BGN and LTBP2 in glycosaminoglycan binding.KEGG signaling pathway analysis indicated that CFHR1 and F9 were associated with complement and coagulation cascade pathways, and FREM2 and LAMA2 were linked to the extracellular matrix interaction pathway.Conclusions:Disease progression of XFS may be associated with changes in extracellular matrix proteins, disruption of the blood-aqueous humor barrier, and potential inflammatory responses.The significant down-regulation of FREM2 protein may be a potential biomarker for XFS.

Objective:To develop an Role Adaptation Questionnaire for Nursing Assistants and test its reliability and validity.Methods:Based on Hershenson's work adaptation model, combined with relevant literature and interview results, the preliminary questionnaire was formed through research group discussion, expert content review and cognitive interview. Using the convenient sampling method, a total of 799 nursing assistants were included in the questionnaire for reliability and validity test from October to December 2022.Results:The Role Adaptation Questionnaire for Nursing Assistants consisted of 10 dimensions and 48 items. The total Cronbach's α coefficient of the questionnaire was 0.95, the split-half reliability was 0.87, the average scale-level content validity was 0.97, and the item-level content validity was 0.83-1.00. A total of 10 factors were extracted by exploratory factor analysis, and the cumulative variance contribution rate was 66.13%. The results of confirmatory factor analysis indicated that the questionnaire model was well adapted, with good convergent and discriminant validity.Conclusions:The Role Adaptation Questionnaire for Nursing Assistants has good reliability and validity, which can be used to evaluate the level of role adaptation for nursing assistants.