Objective:To analyze the epidemiological characteristics and survival rate of nasopharynx cancer (NPC) in Guangdong Province from 2011 to 2019.Methods:Based on the cancer registry data of Guangdong Province from 2011 to 2019, the crude rate, age-standardized rate (the standard population was the fifth Chinese national census of 2000) and age-specific rate of incidence and mortality of NPC were calculated, and the regional distribution characteristics were also explored. The average annual percentage change (AAPC) of the incidence and mortality rates were analyzed by using Joinpoint regression model. The observed survival rate was estimated by period survival method, and the expected survival rate was calculated by Ederer Ⅱ method.Results:The crude incidence rate and age standardized incidence rate of NPC showed a decreasing trend, and the AAPC was -1.9% and -2.1%, respectively ( P＜0.05). The crude mortality rate and age standardized mortality rate of NPC also showed a decreasing trend, and the AAPC was -4.8% and -4.6%, respectively ( P＜0.05). The incidence and mortality rates are both higher in men than those in women during the nine years. The age-specific incidence rate of NPC reached its peak in the 50-64 years old age group, and the mortality rate reached its peak in the 65-74 years old age group in Guangdong province. In 2019, the age-standardized incidence rate of NPC was 9.49/100 000 (13.89/100 000 in men and 5.19/100 000 in women). The incidence and mortality of NPC varied greatly among different areas, and the areas with highest incidence and mortality rate were both in Zhaoqing. In 2020, the five-year observed survival rate of NPC in Guangdong Province was 67.2%, the 5-year relative survival rate was 75.3% and the 5-year standardized relative survival rate was 68.9%. Conclusions:Both the incidence and mortality rates of NPC in Guangdong province show decreasing trend, and the decreasing level of the mortality rate is higher than that of the incidence rate, but the two rates are still at high levels. The prevention and control work should focus on male, middle-aged and elderly population and Zhaoqing, Zhongshan, Foshan areas.

Objective:To explore the effect of combining transcranial magnetic stimulation (rTMS) with acupuncture in the treatment of patients with vascular cognitive impairment (VCI).Methods:A total of 40 VCI patients were randomly assigned to either the control group or the experimental group ( n=20 per group) using a random number table. Both groups received routine treatment and rTMS, while the experimental group was additionally provided with acupuncture for four weeks. The rTMS was at 10Hz at 90% of the motor threshold. Before and after the treatment, both groups′ cognition was evaluated using the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE). Ability in the activities of daily living (ADL) was quantified using the modified Barthel Index (MBI). Serum levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were measured using enzyme-linked immunosorbent assays. Results:Significant improvement was observed in both groups′ average MoCA, MMSE, and MBI scores, along with reductions in peripheral serum IL-6 and TNF-α levels. The experimental group exhibited significantly higher MoCA subdomain scores in the visuospatial and executive function, attention, and delayed recall subdomains, as well as a higher total MoCA score compared to the control group. The average MMSE and MBI scores were significantly higher in the experimental group than the control group, and that group′s serum IL-6 and TNF-α levels were significantly lower, on average. Pearson correlation analysis demonstrated a positive correlation between the improvements in MoCA and MMSE scores and the reductions in IL-6 and TNF-α levels in both groups.Conclusions:rTMS combined with acupuncture effectively improves cognition and ADL ability among VCI patients. The underlying mechanism may be associated with the reduction of neuroinflammatory factors IL-6 and TNF-α.

Objective:To explore the effect of combining transcranial magnetic stimulation (rTMS) with acupuncture in the treatment of patients with vascular cognitive impairment (VCI).Methods:A total of 40 VCI patients were randomly assigned to either the control group or the experimental group ( n=20 per group) using a random number table. Both groups received routine treatment and rTMS, while the experimental group was additionally provided with acupuncture for four weeks. The rTMS was at 10Hz at 90% of the motor threshold. Before and after the treatment, both groups′ cognition was evaluated using the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE). Ability in the activities of daily living (ADL) was quantified using the modified Barthel Index (MBI). Serum levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were measured using enzyme-linked immunosorbent assays. Results:Significant improvement was observed in both groups′ average MoCA, MMSE, and MBI scores, along with reductions in peripheral serum IL-6 and TNF-α levels. The experimental group exhibited significantly higher MoCA subdomain scores in the visuospatial and executive function, attention, and delayed recall subdomains, as well as a higher total MoCA score compared to the control group. The average MMSE and MBI scores were significantly higher in the experimental group than the control group, and that group′s serum IL-6 and TNF-α levels were significantly lower, on average. Pearson correlation analysis demonstrated a positive correlation between the improvements in MoCA and MMSE scores and the reductions in IL-6 and TNF-α levels in both groups.Conclusions:rTMS combined with acupuncture effectively improves cognition and ADL ability among VCI patients. The underlying mechanism may be associated with the reduction of neuroinflammatory factors IL-6 and TNF-α.

Objective:To analyze the epidemiological characteristics and survival rate of nasopharynx cancer (NPC) in Guangdong Province from 2011 to 2019.Methods:Based on the cancer registry data of Guangdong Province from 2011 to 2019, the crude rate, age-standardized rate (the standard population was the fifth Chinese national census of 2000) and age-specific rate of incidence and mortality of NPC were calculated, and the regional distribution characteristics were also explored. The average annual percentage change (AAPC) of the incidence and mortality rates were analyzed by using Joinpoint regression model. The observed survival rate was estimated by period survival method, and the expected survival rate was calculated by Ederer Ⅱ method.Results:The crude incidence rate and age standardized incidence rate of NPC showed a decreasing trend, and the AAPC was -1.9% and -2.1%, respectively ( P＜0.05). The crude mortality rate and age standardized mortality rate of NPC also showed a decreasing trend, and the AAPC was -4.8% and -4.6%, respectively ( P＜0.05). The incidence and mortality rates are both higher in men than those in women during the nine years. The age-specific incidence rate of NPC reached its peak in the 50-64 years old age group, and the mortality rate reached its peak in the 65-74 years old age group in Guangdong province. In 2019, the age-standardized incidence rate of NPC was 9.49/100 000 (13.89/100 000 in men and 5.19/100 000 in women). The incidence and mortality of NPC varied greatly among different areas, and the areas with highest incidence and mortality rate were both in Zhaoqing. In 2020, the five-year observed survival rate of NPC in Guangdong Province was 67.2%, the 5-year relative survival rate was 75.3% and the 5-year standardized relative survival rate was 68.9%. Conclusions:Both the incidence and mortality rates of NPC in Guangdong province show decreasing trend, and the decreasing level of the mortality rate is higher than that of the incidence rate, but the two rates are still at high levels. The prevention and control work should focus on male, middle-aged and elderly population and Zhaoqing, Zhongshan, Foshan areas.

Objective:To investigate the clinicopathological features, diagnosis and differential diagnosis of adrenal cortical carcinoma (ACC) in children.Methods:Twenty-five children with ACC diagnosed in the Department of Pathology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from March 2014 to August 2022 were retrospectively analyzed. The related literature was reviewed.Results:A total of 25 children with ACC were collected, including 11 males and 14 females, with a male to female ratio of 1.0∶1.3. The patient ages ranged from 8 months to 14 years (median, 4 years). Eighteen cases with clinical data had functional tumors (18/22, 81.8%) presenting with virilization or precocious puberty (15/18), symptoms related to hypercortisolism (8/18) or endocrine symptoms mixed with both (5/18), while 3 cases (3/22, 13.6%) had unknown clinical data. The clinical manifestations of four patients with nonfunctional tumors were an abdominal mass and/or abdominal pain, walking instability and others. Grossly, the average maximum diameter of the tumor was 9.4 cm. Most of the tumors were nodular and partially encapsuled. The cut surfaces were gray or gray brown, soft with hemorrhage. Histologically, the tumor cells were diffusely distributed, separated by a vascular-rich network. The tumor cells were large, with distinct nucleoli, abundant eosinophilic or clear cytoplasm, and round or oval nuclei. The mitotic index was high, and atypical mitoses were common. Necrosis, calcification, capsule invasion or/and venous invasion were present. In some cases, the tumor invaded the surrounding soft tissues or kidneys. Immunohistochemically, the tumor cells were diffusely positive for syn and SF1 and focally positive for α-inhibin, Melan A and Calretinin, but negative for CgA. Ki-67 proliferation index ranged from 2%-90%. TP53 gene status was examined in 7 cases, in which mutations were detected in 4 cases. Follow-up data was obtained in 21 patients, among whom 18 received chemotherapy and 3 received radiotherapy. Distant metastasis occurred in 13 patients. Median progression-free survival (PFS) was 11.2 months and median overall survival (OS) was 54.7 months. Patients aged less than 5 years had a better prognosis for OS ( P<0.05) than the older ones (≥5 years), but a similar PFS ( P>0.05). Male patients and Ki-67 proliferation index <15% had a better prognosis tendency for OS, but there was no statistically significant difference ( P>0.05). Conclusions:ACC in children is a rare, often functional tumor associated with Li-Fraumeni genetic syndrome and has a poor prognosis. Diagnosis and differential diagnosis require a combination of morphological, phenotypic and clinical analysis.

Plant-derived nanovesicles have gained attention given their similarity to mammalian exosomes and advantages such as low cost,sustainability,and tissue targeting.Thus,they hold promise for disease treatment and drug delivery.In this study,we proposed a time-efficient method,PEG 8000 combined with sucrose density gradient centrifugation to prepare ginger-derived nanovesicles(GDNVs).Subse-quently,curcumin(CUR)was loaded onto GDNV by ultrasonic incubation.The optimum conditions for ginger-derived nanovesicles loaded with curcumin(CG)were ultrasound time of 3 min,a carrier-to-drug ratio(GDNV:CUR)of 1∶1.The study achieved a high loading capacity(94.027％±0.094％)and encapsu-lation efficiency(89.300％±0.344％).Finally,the drugs'in vivo distribution and anti-colitis activity were investigated in mice.CG was primarily distributed in the colon after oral administration.Compared to CUR and GDNV,CG was superior in improving disease activity,colon length,liver and spleen coefficients,myeloperoxidase activity,and biochemical factor levels in ulcerative colitis(UC)mice.In addition,CG plays a protective role against UC by modulating serum metabolite levels and gut flora.In summary,our study demonstrated that GDNV can be used for CUR delivery with enhanced therapeutic potential.

Plant-derived nanovesicles have gained attention given their similarity to mammalian exosomes and advantages such as low cost, sustainability, and tissue targeting. Thus, they hold promise for disease treatment and drug delivery. In this study, we proposed a time-efficient method, PEG 8000 combined with sucrose density gradient centrifugation to prepare ginger-derived nanovesicles (GDNVs). Subsequently, curcumin (CUR) was loaded onto GDNV by ultrasonic incubation. The optimum conditions for ginger-derived nanovesicles loaded with curcumin (CG) were ultrasound time of 3 min, a carrier-to-drug ratio (GDNV:CUR) of 1:1. The study achieved a high loading capacity (94.027% ± 0.094%) and encapsulation efficiency (89.300% ± 0.344%). Finally, the drugs' in vivo distribution and anti-colitis activity were investigated in mice. CG was primarily distributed in the colon after oral administration. Compared to CUR and GDNV, CG was superior in improving disease activity, colon length, liver and spleen coefficients, myeloperoxidase activity, and biochemical factor levels in ulcerative colitis (UC) mice. In addition, CG plays a protective role against UC by modulating serum metabolite levels and gut flora. In summary, our study demonstrated that GDNV can be used for CUR delivery with enhanced therapeutic potential.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

The minimal persistent inflammation(MPI)of allergic rhinitis(AR)is asymptomatic inflammation that occurs locally in the nasal mucosa after exposure to low doses of allergens.With the study of MPI,researchers have realized that this local sub-clinical inflammation in patients with AR not only causes chronic damage to the nasal mucosa,but also increases the hypersensitivity and hyperresponsiveness of allergic airway disease.The concept of MPI has changed our strategy for the treatment of AR,which re-quires that we should not only intervene in the symptomatic exacerbation period,but also intervene in the asymptomatic MPI period.This article systematically reviews the immunological mechanism,adverse effects,and treatment strategies of the MPI,to provide bet-ter treatment for the MPI of AR and reduce the recurrence of AR.

Purpose To investigate the expression of Clau-din18.2 and its relationship with clinicopathological parameters and prognosis in Epstein-Barr virus-associated gastric cancer(EBVaGC),and also to analyze the correlation between the ex-pression of Claudin18.2 and PD-L1,ARID1A,and HER2.Methods Tissue samples of 694 patients received radical gas-trectomy,and 25 cases of EBVaGC were selected according to EBER results and matched one by one.Immunohistochemistry was employed to assess the expression levels of Claudin18.2,PD-L1,ARID1A and HER2 in EBVaGC and non-EBVaGC.Ka-plan-Meier survival analysis was performed for analyzing the re-lationship between the expression of Claudin18.2,PD-L1 and ARID1A and the prognosis of gastric cancer patients,and the survival curve was drawn.Spearman correlation analysis was used to assess the respective relationships between Claudin18.2 and PD-L1,ARID1A,and HER2.Results The positive/high expression rates of Claudin18.2 in EBVaGC were 76％and 64％respectively.Furthermore,the positive/high expression rates of Claudin18.2 in non-EBVaGC were 32％and 20％,respective-ly.Claudin18.2 expression showed positively correlations with the tumor site(proximal stomach)in gastric cancer patients.In addition,compared with non-EBVaGC,PD-L1 CPS score was higher in EBVaGC(P＜0.001),and the deletion rate of AR-ID1A expression was also higher in EBVaGC(P=0.012).But there was no significant difference,and so did not the expression level of HER2 between EBVaGC and non-EBVaGC.Survival a-nalysis revealed that positive/high expression of Claudin18.2 did not show a significant correlation with prognosis.Sperman corre-lation analysis indicated a positive correlation between Clau-din18.2 and PD-L1(r=0.338 4,P=0.016 2),while the ex-pression of Claudin18.2 was negatively correlated with ARID 1A(r=-0.354 5,P=0.011 5).Finally,there was no signifi-cant correlation between Claudin18.2 and HER2.Conclusion Claudin18.2 is highly expressed in EBVaGC,which is correla-ted with PD-L1 and ARID1A.It provides more options of combi-nation therapies for patients with advanced gastric cancer.