Objective:To investigate the impacts of Glaucocalyxin A on myocardial inflammation and immune function in dia-betes rats by regulating cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)/stimulator of interferon genes(STING)pathway.Methods:STZ was injected intraperitoneally to model diabetes in rats,after successful modeling,the rats were divided into model group,low-dose Glaucocalyxin A group[10 mg/(kg·d)],high-dose Glaucocalyxin A group[20 mg/(kg·d)]and H-151(750 nmol/d)group,control group was also set up,with 10 rats in each group,the model group and control group were given the same volume of physiological saline for 4 weeks.The fully automated biochemical analyzer was applied to detect TG,TC,HDL-C and LDL-C levels;flow cytometry was applied to detect the levels of CD4+T,CD8+T,CD4+T/CD8+T in the serum of rats in each group;ELISA was applied to detect the levels of TNF-α,IL-6 and IL-1β in myocardial tissue;HE staining was applied to observe pathologi-cal changes in rat myocardium;TUNEL staining was applied to observe the apoptosis of myocardial cells;Western blot was applied to detect the levels of Bcl-2,Bax,cGAS and STING pathway proteins.Results:The myocardial cells of rats in the control group were ar-ranged neatly and structurally intact;compared with the control group,the myocardial cells of rats in the model group were arranged in a disordered manner,with unclear nuclear structure and infiltration of inflammatory cells,the levels of serum TG,TC,CD8+T,myo-cardial tissue TNF-α,IL-6 and IL-1β,myocardial cell apoptosis rate,and the protein expression levels of Bax,cGAS and STING in rats were obviously increased,the levels of HDL-C,CD4+T,CD4+T/CD8+T,and the protein expression level of Bcl-2 were obviously reduced(P<0.05);compared with the model group,the pathological damage status of myocardial cells in the low and high doses Glau-cocalyxin A groups and H-151 group was obviously reduced,the levels of serum TG,TC,CD8+T,myocardial tissue TNF-α,IL-6 and IL-1β,myocardial cell apoptosis rate,and the protein expression levels of Bax,cGAS,and STING in rats were obviously reduced,the levels of HDL-C,CD4+T,CD4+T/CD8+T,and the protein expression level of Bcl-2 were obviously increased(P<0.05);compared with the high-dose Glaucocalyxin A group,there was no statistically obvious difference in all detection indicators in the H-151 group(P>0.05).Conclusion:Glaucocalyxin A may reduce myocardial inflammation and improve immune function in diabetes rats by inhi-biting cGAS-STING signaling pathway.

Objective:To investigate the impacts of Glaucocalyxin A on myocardial inflammation and immune function in dia-betes rats by regulating cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)/stimulator of interferon genes(STING)pathway.Methods:STZ was injected intraperitoneally to model diabetes in rats,after successful modeling,the rats were divided into model group,low-dose Glaucocalyxin A group[10 mg/(kg·d)],high-dose Glaucocalyxin A group[20 mg/(kg·d)]and H-151(750 nmol/d)group,control group was also set up,with 10 rats in each group,the model group and control group were given the same volume of physiological saline for 4 weeks.The fully automated biochemical analyzer was applied to detect TG,TC,HDL-C and LDL-C levels;flow cytometry was applied to detect the levels of CD4+T,CD8+T,CD4+T/CD8+T in the serum of rats in each group;ELISA was applied to detect the levels of TNF-α,IL-6 and IL-1β in myocardial tissue;HE staining was applied to observe pathologi-cal changes in rat myocardium;TUNEL staining was applied to observe the apoptosis of myocardial cells;Western blot was applied to detect the levels of Bcl-2,Bax,cGAS and STING pathway proteins.Results:The myocardial cells of rats in the control group were ar-ranged neatly and structurally intact;compared with the control group,the myocardial cells of rats in the model group were arranged in a disordered manner,with unclear nuclear structure and infiltration of inflammatory cells,the levels of serum TG,TC,CD8+T,myo-cardial tissue TNF-α,IL-6 and IL-1β,myocardial cell apoptosis rate,and the protein expression levels of Bax,cGAS and STING in rats were obviously increased,the levels of HDL-C,CD4+T,CD4+T/CD8+T,and the protein expression level of Bcl-2 were obviously reduced(P<0.05);compared with the model group,the pathological damage status of myocardial cells in the low and high doses Glau-cocalyxin A groups and H-151 group was obviously reduced,the levels of serum TG,TC,CD8+T,myocardial tissue TNF-α,IL-6 and IL-1β,myocardial cell apoptosis rate,and the protein expression levels of Bax,cGAS,and STING in rats were obviously reduced,the levels of HDL-C,CD4+T,CD4+T/CD8+T,and the protein expression level of Bcl-2 were obviously increased(P<0.05);compared with the high-dose Glaucocalyxin A group,there was no statistically obvious difference in all detection indicators in the H-151 group(P>0.05).Conclusion:Glaucocalyxin A may reduce myocardial inflammation and improve immune function in diabetes rats by inhi-biting cGAS-STING signaling pathway.

AIM:This study aims to investigate the therapeutic effects of Xiaozhen Fang(XZF)on epidermal growth factor receptor(EGFR)inhibitor,erlotinib-induced skin toxicity in mice,with a focus on the underlying functional mechanisms.METHODS:A mouse model of skin toxicity was established and divided into three groups(n=5 per group):blank,erlotinib(150 mg/kg),and erlotinib(150 mg/kg)combined with XZF(45 g/kg)groups.Skin toxicity se-verity and body weight were evaluated.Western blot was performed to detect protein levels of gasdermin D(GSDMD),caspase-1,and interleukin-1β(IL-1β)in skin tissue.Immunofluorescence was employed to analyze gasdermin E,IL-1β,caspase-1,and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)expression in skin tissue.In vitro,HacaT cells were cultured and treated with erlotinib followed by different concentrations of XZF-containing se-rum.Cell viability was assessed by MTT assay.Cell ultrastructure was observed by transmission electron microscopy,and p53-binding protein 1(53BP1)expression was analyzed by immunofluorescence staining.RESULTS:The XZF signifi-cantly alleviated erlotinib-induced skin toxicity in mouse model,as evidenced by reduced rash incidence,alleviated limb swelling,and increased body weight(P<0.05).Expression of Gasdermins,IL-1β,caspase-1,and NLRP3 was distinctly down-regulated in dorsal skin tissue(P<0.05 or P<0.01).In vitro,XZF-containing serum markedly suppressed pyropto-sis in HacaT cells(P<0.01),preserved cell membrane integrity,and significantly reduced 53BP1 fluorescence intensity(P<0.01).CONCLUSION:The XZF mitigates EGFR inhibitor,erlotinib-induced skin toxicity in mice,potentially by regulating pyroptosis through the NLRP3/caspase-1/GSDMD signaling pathway.This mechanism exerts a cytoprotective ef-fect and alleviates erlotinib-induced skin toxicity.

AIM:This study aims to investigate the therapeutic effects of Xiaozhen Fang(XZF)on epidermal growth factor receptor(EGFR)inhibitor,erlotinib-induced skin toxicity in mice,with a focus on the underlying functional mechanisms.METHODS:A mouse model of skin toxicity was established and divided into three groups(n=5 per group):blank,erlotinib(150 mg/kg),and erlotinib(150 mg/kg)combined with XZF(45 g/kg)groups.Skin toxicity se-verity and body weight were evaluated.Western blot was performed to detect protein levels of gasdermin D(GSDMD),caspase-1,and interleukin-1β(IL-1β)in skin tissue.Immunofluorescence was employed to analyze gasdermin E,IL-1β,caspase-1,and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)expression in skin tissue.In vitro,HacaT cells were cultured and treated with erlotinib followed by different concentrations of XZF-containing se-rum.Cell viability was assessed by MTT assay.Cell ultrastructure was observed by transmission electron microscopy,and p53-binding protein 1(53BP1)expression was analyzed by immunofluorescence staining.RESULTS:The XZF signifi-cantly alleviated erlotinib-induced skin toxicity in mouse model,as evidenced by reduced rash incidence,alleviated limb swelling,and increased body weight(P<0.05).Expression of Gasdermins,IL-1β,caspase-1,and NLRP3 was distinctly down-regulated in dorsal skin tissue(P<0.05 or P<0.01).In vitro,XZF-containing serum markedly suppressed pyropto-sis in HacaT cells(P<0.01),preserved cell membrane integrity,and significantly reduced 53BP1 fluorescence intensity(P<0.01).CONCLUSION:The XZF mitigates EGFR inhibitor,erlotinib-induced skin toxicity in mice,potentially by regulating pyroptosis through the NLRP3/caspase-1/GSDMD signaling pathway.This mechanism exerts a cytoprotective ef-fect and alleviates erlotinib-induced skin toxicity.

Objective: To investigate the relationship between depressive symptoms and frailty among middle-aged and elderly populations, so as to provide insights into the early identification and prevention of frailty. Methods: Based on the 2018 database of China Health and Retirement Longitudinal Study (CHARLS), demographic information, lifestyle and self-rated health status were collected from people aged 50 years and older. Depression symptoms were evaluated using the Short Version of Center for Epidemiological Studies Depression Scales (CES-D-10), and the frailty status was evaluated using frailty index. The relationship between depressive symptoms and frailty among middle-aged and elderly populations were using a multivariable logistic regression model, and the dose-response relationship was analyzed using a restricted cubic spline model. Results: A total of 5 172 individuals were enrolled, including 2 495 males (48.24%) and 2 677 females (51.76%), with a median age of 63.00 (interquartile range, 12.00) years, a median CES-D-10 score of 7.00 (interquartile range, 9.00) scores. There were 1 560 participants (30.16%) detected with mild depressive symptoms, 360 participants (6.96%) detected with moderate to severe depressive symptoms. Multivariable logistic regression analysis showed that after adjusting for gender, age, educational level, marital status, smoking, alcohol consumption and self-rated health status, participants who had mild depressive symptoms (OR=4.226, 95%CI: 3.625-4.928) and moderate to severe depressive symptoms (OR=10.737, 95%CI: 8.259-13.958) had a higher risk of frailty. The restricted cubic spline model showed a nonlinear relationship between depressive symptoms and frailty among middle-aged and elderly populations. When the CES-D-10 scores were greater than 7, the risk of frailty increased with higher CES-D-10 scores. Conclusion The degree of depressive symptoms in middle-aged and elderly people is associated with frailty, and there is a nonlinear relationship between the two.

Objectives:This study aimed to assess the efficacy and safety of bendamustine in combination with rituximab (BR regimen) for the treatment of newly diagnosed indolent B-cell non-Hodgkin's lymphoma (B-iNHL) and elderly mantle cell lymphoma (eMCL) .Methods:From December 1, 2020 to September 10, 2022, a multi-center prospective study was conducted across ten Grade A tertiary hospitals in Shandong Province, China. The BR regimen was administered to evaluate its efficacy and safety in newly diagnosed B-iNHL and eMCL patients, and all completed at least four cycles of induction therapy.Results:The 72 enrolled patients with B-iNHL or MCL were aged 24-74 years, with a median age of 55 years. Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1 were observed in 76.4% of patients, while 23.6% had scores of 2. Disease distribution included follicular lymphoma (FL) (51.4% ), marginal zone lymphoma (MZL) (33.3% ), eMCL (11.1% ), and the unknown subtype (4.2% ). According to the Ann Arbor staging system, 16.7% and 65.3% of patients were diagnosed with stage Ⅲ and stage Ⅳ lymphomas, respectively. Following four cycles of BR induction therapy, the overall response rate was 98.6%, with a complete response (CR) rate of 83.3% and a partial response (PR) rate of 15.3%. Only one eMCL patient experienced disease progression during treatment, and only one FL patient experienced a relapse. Even when evaluated using CT alone, the CR rate was 63.9%, considering the differences between PET/CT and CT assessments. The median follow-up duration was 11 months (range: 4-22), with a PFS rate of 96.8% and an OS rate of 100.0%. The main hematologic adverse reactions included grade 3-4 leukopenia (27.8%, with febrile neutropenia observed in 8.3% of patients), grade 3-4 lymphopenia (23.6% ), grade 3-4 anemia (5.6% ), and grade 3-4 thrombocytopenia (4.2% ). The main non-hematologic adverse reactions such as fatigue, nausea/vomiting, rash, and infections occurred in less than 20.0% of patients.Conclusion:Within the scope of this clinical trial conducted in China, the BR regimen demonstrated efficacy and safety in treating newly diagnosed B-iNHL and eMCL patients.

Objective: To observe the root and root canal morphology of mandibular second molars in Western Guangxi by CBCT, to provide a reference for clinical diagnosis and treatment. Methods: In total, 564 patients′ 1 128 mandibular second molars that satisfy the inclusion criteria were analyzed with a planmecaromexis CBCT machine and its own image analysis software. The patients′ gender, age and ethnic differences in the root and canal morphology and the symmetry of the bilateral root and canal were statistically analyzed. Results: Among the 1 128 mandibular second molars, 662 were the Zhuang ethnic group and 384 were the Han ethnic group, and 82 were other ethnic groups; the double root type and C-shaped root type accounted for a relatively high proportion: 73.94% and 24.47%, respectively. The detection rates of the double root type were higher in males than in females (P < 0.05); the detection rates of the C-shaped root type were higher in females than in males (P <0.05); the root type of the teeth was mainly double-rooted in the Zhuang ethnic group (P<0.01). The incidence of type IV in the mesial root of the double root type mandibular second molar was the highest (P < 0.01), and the incidence of type I in the distal root was the highest (P < 0.01). The C-shaped root canal is more continuous at the mouth of the root canal, more downward corresponds to a worse continuity: in three different levels of root canal orifice, root middle and root apex, the root canal orifice is dominated by the C1 type, and both root middle and root apex are mainly C3-type (P < 0.01). The difference in symmetry of bilateral roots and root canals was statistically significant among different gender groups, age groups, and ethnic groups (P < 0.05): there were more males than females, the results in the 18-35-year-old group and the Zhuang ethnic group were higher. Conclusion The root and root canal morphology of mandibular second molars in western Guangxi people are complex and changeable. The roots are mainly double root type in the Han ethnic group and the Zhuang ethnic group. C-shaped roots are also common. The detection rate of C-shaped roots in the Zhuang ethnic group was higher, and the symmetry rate of bilateral roots and that of bilateral root canals was higher in the Zhuang ethnic group than in the Han ethnic group.

Objective:To investigate the clinicopathological characteristics, diagnosis, differential diagnosis and prognostic factors of SMARCB1 (INI1)-deficient sinonasal carcinoma (SDSC).Methods:Sixteen cases of SDSC diagnosed in the Department of Pathology, Beijing Tongren Hospital from January 2016 to September 2020 were enrolled. Ninety-nine cases of small round cell malignant tumors of the head and neck were selected as the control, including poorly-differentiated squamous cell carcinoma ( n=10), poorly-differentiated adenocarcinoma ( n=5), undifferentiated carcinoma (SNUC, n=4), NUT carcinoma ( n=5), neuroendocrine carcinoma ( n=10), and other non-epithelial tumors [olfactory neuroblastoma ( n=10), rhabdomyosarcoma ( n=10), NK/T-cell lymphoma ( n=10), malignant melanoma ( n=10), Ewing′s sarcoma/primitive neuroectodermal tumor (EWS/PNET, n=5)] and non-keratinizing undifferentiated nasopharyngeal carcinoma ( n=20). The clinical and pathologic characteristics of SDSC, and immunohistochemical (IHC) expression of broad-spectrum CKpan, CK7, CK8/18, CK5/6, p63, p40, p16, INI1, NUT and neuroendocrine markers (Syn, CgA, CD56) were evaluated. In situ hybridization (ISH) was used to detect EBER and fluorescence in situ hybridization (FISH) to detect INI1 gene deletion. Results:The 16 cases of SDSC accounted for 1.3% (16/1 218) of all malignant sinonasal tumors in the author′s unit during this time period, and 2.4% (16/657) of all malignant epithelial tumors. Microscopically, there was no clear squamous and adenomatous differentiation, but "rhabdoid-like" cells, are often seen. All SDSC cases were positive for CKpan and CK8/18, negative for INI1; Epstein-Barr virus was not detected by ISH; and INI1 gene deletion was observed in all 11 SDSC patients with FISH. Twelve cases were followed up for 3-47 months. One died of tumor-related diseases half a year after diagnosis, and the remaining patients were alive with tumor, the longest survival time was 47 months.Conclusion:SDSC should be differentiated from a variety of poorly-differentiated tumors in the sinonasal area. Histologically, SDSC has no clear differentiation, but the tumor cells are characteristically basal-like or rhabdoid-like, with non-specific vacuoles, translucent or vacuolar nuclei, prominent nucleoli and necrotic foci. They are negative for INI1 IHC staining, and FISH demonstrates INI1 gene deletion. The clinical prognosis is still unclear, further studies on its biologic behavior and treatment methods are warranted.

Objective To investigate the prevalence and influencing factors associated with frailty among institutional older adults and to provide evidence for intervention study.Methods A total of 237 older adults living in four welfare homes from Chengdu in Sichuan Province were recruited by convenience sampling.A cross-sectional survey was conducted,and frailty was assessed by the frailty phenotype;general information was collected by selfmade general information questionnaire;functional capacity was assessed by Barthel questionnaire;depressive status was assessed by GDS-15;cognitive function was assessed by clock drawing test and nutritional status was assessed by short form mini nutritional scale questionnaire (MNA-SF).Results The reported rate of frailty was 55.69％ among institutional older adults,and 44.31％ reported no frailty;grip weakness (207,87.3％),slow walking speed (172,72.6％) and low physical activity(131,55.3％) were the main frailty problems.Univariate analysis showed that the elderly'frailty conditions were different in the pre-retirement occupations,smoking,alcohol consumption,physical exercise,chronic diseases,medication,acute events (last year),self-reported health,using assisted walking devices,ability of daily life,depression,cognitive ability and nutritional status,and the differences were statistically significant(P＜0.05).Conclusion The status of frailty is not optimistic among institutional older adults and many factors are associated with frailty.Healthcare providers should pay more attention to the frailty issue and take timely intervention strategies to prevent or delay the frailty.

Objective: To describe the cytologic features of adenoid cystic carcinoma (ADCC) of salivary glands, and to identify distinguishing cytologic features of ADCC and basal cell adenoma (BCA). Methods: A retrospective review of cytology smears of 30 cases of ADCC and 12 cases of BCA of salivary glands were performed. All cases were collected from Beijing Tongren Hospital, Capital Medical University from January 2010 to January 2017. Except for 2 aspirate smears of ADCC, all were touch imprint smears. All cases had further histological confirmation. Results: Neoplastic ductal cells of ADCC were arranged in three-dimensional clusters, sheets and singles. Hyaline globules were found in most cases (20/30, 66.7%). The nuclei were round to oval, showing varying degrees of nuclear atypia. These included (1) the nuclei were hyperchromatic, demonstrating coarse or slightly coarse, irregularly distributed chromatin; (2) the nuclei were slightly large and vary in size; (3) appearance of the nuclei had a different degree of irregularity (often mild). Nucleoli were common seen (21/30, 70.0%), and were prominent in some cases. Mitosis and necrosis were rare. Cytologically, BCA showed cell arrangements and nuclear features overlapped with those of ADCC. The cytologic difference between these two tumors included: (1) the tumor cells presented rarely in singles; (2) hyaline globules were very uncommon (1/12) in BCA; (3) nuclei of BCA were hypochromatic or slightly hyperchromatic, homogeneous and uniform in appearance and size, overall without nuclear atypia and they were smaller and slender then those of ADCC and (4) individual cells of BCA showed relatively abundant cytoplasm. Conclusions The cytologic features of ADCC and BCA both overlap and different from each other. Most cases can be diagnosed by cytologic examination. The presence of hyaline globules is an important diagnostic clue of ADCC, although not pathognomonic. Nuclear atypia of neoplastic ductal cells is an essential cytological feature in the diagnosis of ADCC, and is the most reliable point for differential diagnosis of ADCC and BCA.