Objective To observe the clinical efficacy of Zhuanyaotang Granules for the treatment of degenerative lumbar spinal stenosis(DLSS).Methods Using a randomized double blind controlled design,104 DLSS patients were divided into an experimental group and a control group using a random number table method,with 52 patients in each group.The treatment group took oral Zhuanyaotang Granules,methylcobalamin tablets and celecoxib capsule simulants.The control group used Zhuanyaotang Granules simulants,methylcobalamin tablets and celecoxib capsules.The course of treatment was 3 weeks for both groups.The follow-ups were conducted at 1 month and 3 months after treatment.The intermittent claudication distance,visual analogue scale(VAS)score and JOA efficacy rating criteria for low back pain score were observed in both groups before treatment,1,2,3 weeks of treatment and 1 month after treatment and 3 months after treatment.Adverse reactions during treatment were recorded.Results There were 5 cases of detachment and 2 cases of exclusion in the experimental group,and 5 cases of detachment and 1 case of exclusion in the control group.Compared with before treatment,there were statistically significant differences in intermittent claudication distance,VAS score,and JOA score between the two groups of patients at various time points during treatment and follow-up(P<0.05);there was no statistically significant difference in intermittent claudication distance,VAS score,and JOA score between the experimental group and the control group before treatment and 1 and 2 weeks of treatment(P>0.05);compared with the two groups at 3 weeks of treatment and 1 and 3 months after treatment,the intermittent claudication distance and JOA score in the experimental group were lower than those in the control group(P<0.05);There was no significant difference in VAS score between the two groups and the control group after 3 weeks of treatment(P>0.05).There were 2 adverse reactions(4.4%)in the experimental group and 5 adverse reactions(10.8%)in the control group,without statistical significance(P>0.05).Conclusion Zhuanyaotang Granules can effectively relieve pain and improve lumbar function in patients with DLSS,which is more effective and safer than oral celecoxib capsules and methylcobalamin tablets.

Objective:To observe the effects of acupuncture and moxibustion on interleukin(IL)-9/IL-9 receptor(IL-9R)in the colon tissue of rats with ulcerative colitis(UC)and investigate the protective mechanism of acupuncture and moxibustion on the intestinal mucosal barrier in UC rats. Methods:Male Sprague-Dawley rats were randomly divided into a normal control(NC)group and a modeling group.UC models were prepared by giving 4%dextran sulfate sodium(DSS)water for 7 d.After the successful construction of the UC rat model,the modeling group was randomly divided into a UC group,a herb-insulated moxibustion(HM)group,and an electroacupuncture(EA)group.HM and EA interventions at bilateral Tianshu(ST25)were performed once a day for 7 d.Hematoxylin-eosin(HE)staining was used to observe the histopathological changes in the colon.The serum concentrations of IL-9,IL-6,IL-1β,and hemoglobin-H(HbH)were determined by enzyme-linked immunosorbent assay.The protein expression levels of IL-9,IL-9R,claudin-2,zonula occludens-1(ZO-1),and occludin in the colon tissue were measured by Western blotting or immuno-histochemistry.Immunofluorescence was used to detect the co-expression of PU.1 and CD4 with the IL-9 protein. Results:Compared with the NC group,the colon tissue of UC rats was severely damaged and ulcerated with congestion and edema,and the colonic histopathological score increased significantly(P<0.01).The serum HbH concentration decreased significantly(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β increased(P<0.01).The protein expression of colonic ZO-1 and occludin decreased significantly(P<0.01),while the protein expression of colonic IL-9 and IL-9R increased(P<0.05).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 increased in the colon tissue(P<0.05).Compared with the UC group,the colonic mucosal structures were gradually repaired in both HM group and EA group,and healed ulcers could be observed,the colonic histopathological score decreased significantly(P<0.05).The serum concentration of HbH increased(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β decreased(P<0.05).The protein expression levels of ZO-1 and occludin increased(P<0.05),while the protein expression levels of IL-9 and IL-9R decreased(P<0.01).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 decreased in the colon tissue(P<0.05). Conclusion:Both HM and EA can inhibit the protein expression levels of IL-9 and IL-9R in the UC colon by regulating the transcription factor PU.1,promote the repair of intestinal mucosal barrier,and down-regulate protein contents of proinflammatory factors IL-9,IL-6,and IL-1β in the serum,which may be one of the key mechanisms of acupuncture and moxibustion in reducing the inflammation of UC colonic mucosa and protecting the intestinal mucosal barrier.

The aim of this study was to prepare a high drug-carrying capacity micellar drug delivery system(CTD@Sol)of the polymer zebra tetracycline and to preliminarily investigate the feasibility of this drug delivery system for the treatment of breast cancer.Firstly,CTD@Sol was prepared using sol as the carrier material and CTD as the model drug,and its pharmacological properties such as appearance and morphology,particle size,potential and in vitro release were evaluated.The growth inhibitory and apoptotic effects of CTD@Sol on breast cancer(4T1)cells were investigated by MTT assay and Annexin V-FITC/PI double staining assay;the uptake efficiency of 4T1 to this delivery system was investigated by flow cytometry;and the in vivo tissue distribution of the delivery system and the targeting of tumour tissues were investigated by small animal in vivo imaging technique.The results showed that CTD@Sol appeared as a light pale blue creamy white colour,with an average particle size of(159.73±1.96)nm,a PDI of 0.198±0.006,Zeta potential of-(47.60±1.77)mV,an encapsulation rate of(90.29±1.69)%and a drug loading capacity of(45.00±0.84)%;the in vitro release and haemolysis experiments showed that the drug release rate of CTD@Sol in acidic environment(pH 5.5)was significantly faster than that in neutral environment(pH 7.4),suggesting that the system is acid-sensitive and has good biosafety under endocytosed pH conditions.Cellular uptake,cytotoxicity and apoptosis experiments showed that CTD@Sol was more lethal to 4T1 cells,and the sol-gel polymer micelles as a drug delivery vehicle could significantly improve the cellular uptake efficiency of the drug;in vivo experiments showed that the delivery system had a significant targeting effect on tumour tissues.In conclusion,this study has successfully produced a CTD@Sol drug delivery system with high drug loading capacity(>45%),good pharmacological performance,strong targeting and biosafety,which has the potential to be used in the treatment of breast cancer.

Cerebral organoids are three-dimensional nerve cultures induced by embryonic stem cells(ESCs)or induced pluripotent stem cells(iPSCs)that mimic the structure and function of human brain.With the continuous optimization of cerebral organoid culture technology and the combination with emerging technologies such as organ transplantation,gene editing and organoids-on-chip,complex brain tissue structures such as functional vascular structures and neural circuits have been produced,which provides new methods and ideas for studying human brain development and diseases.This article reviews the latest advances in brain organoid technology,describes its application in neurological diseases and advances in stroke modeling and transplantation treatment.

Post-stroke cognitive impairment(PSCI)is mainly manifested as learning and memory disorders.Highly enriched RNA m6A methylation modification in mammalian brain is involved in glial cell-mediated neuroinflammation.Given that neuroinflammation is the main mechanism for neural damage and spatial and memory impairment of PSCI,it is speculated that RNA m6A methylation modification can regulate the inflammatory response of glial cells after stroke to improve PSCI.This review summarizes and analyzes the role of RNA m6A methylation modification in the development of PSCI and analyzes its detailed mechanism of regulating glial cell-mediated inflammation,which will provide reference for researchers in this field.

BACKGROUND:Long non-coding RNAs(lncRNAs),as important regulators of the inflammatory response,are involved in the immune-inflammation-brain crosstalk mechanism after ischemic stroke and have the potential to become a therapeutic agent for neurological dysfunction after ischemic stroke. OBJECTIVE:To analyze and summarize the molecular mechanism of lncRNA acting on glial cells involved in the neuroimmuno-inflammatory cascade response after ischemic stroke and the associated signaling pathways,pointing out that lncRNAs have the potential to regulate inflammation after ischemic stroke. METHODS:PubMed was searched using the search terms of"ischemic stroke,long non-coding RNA,neuroinflammation,immune function,signal pathway,microglia,astrocytes,oligodendrocyte,mechanism,"and 63 relevant documents were finally included for review. RESULTS AND CONCLUSION:In the early stage of ischemic stroke,the death of nerve cells due to ischemia and hypoxia activates the innate immune response of the brain,promoting the secretion of inflammatory factors and inducing blood-brain barrier damage and a series of inflammatory cascades responses.As an important pathogenesis factor in ischemic stroke,the neuroimmuno-inflammatory cascade has been proved to seriously affect the prognosis of patients with ischemic stroke,and it needs to be suppressed promptly in the early stage.Neuroinflammation after ischemic stroke usually induces abnormal expression of a large number of lncRNAs that mediate a series of neuro-immune-inflammatory crosstalk mechanisms through regulating the polarization of microglia,astrocytes and oligodendrocytes to exert post-stroke neuroprotective effects.LncRNAs,as important regulatory factors of the inflammatory response,inhibit the neuroimmuno-inflammatory cascade response after ischemic stroke through regulating nuclear factor-κB,lncRNA-miRNA-mRNA axis,Rho-ROCK,MAPK,AKT,ERK and other signaling pathways to effectively improve neurological impairment after ischemic stroke.Most of experimental studies on the interaction between lncRNAs and ischemic stroke are based on a middle cerebral artery occlusion model or a cerebral ischemia-reperfusion injury model,but no clinical trials have been conducted.Therefore,it remains to be further explored about whether lncRNAs can be safely applied in clinical practice.At present,there are many therapeutic drugs for the treatment of ischemic stroke,but there are relatively few studies on the application of lncRNAs,exosomes and other transplantation technologies for the treatment of ischemic stroke using tissue engineering technology,which need to be further explored.lncRNA has become an important target for the treatment of ischemic stroke with its relative stability and high specificity.In future studies,more types of inflammatory lncRNAs that function under ischemic-hypoxia conditions should continue to be explored,in order to provide new research directions for the treatment of neuroinflammation after ischemic stroke.

Objective As a signaling molecule,NO regulates key physiological processes and is closely related to periodontitis.To investigate the effect of flavonoid NO donor composite nanoparticles(G10@HAP/MSN@ZnO@COS)on osteogenic differentiation of periodontal ligament stem cells(PDLSCs)by regulating macrophage polarization.Methods The novel NO donor drug G10 was loaded on hydroxyapatite/mesoporous silicanant particles(HAP/MSN),filled with zinc oxide(ZnO),and then coated with chitosan(COS)to prepare composite nanoparticles(G10@HAP/MSN@ZnO@COS).The best concentration of G10@HAP/MSN@ZnO@COS was screened to promote cell proliferation by CCK-8 cell experiment.After the mouse mononuclear macrophages were stimulated by lipopo-lysaccharide,the mice were divided into four groups:Control group,G10 group,HAP/MSN@ZnO@COS group and G10@HAP/MSN@ZnO@COS group.Each group was cultured with fresh medium,5 μg/mL G10,5 μg/mL HAP/MSN@ZnO@COS and 5 μg/mL G10@HAP/MSN@ZnO@COS for 72 h respectively.ELISA and RT-qPCR were used to detect the expression of cytokines(TNF-α,IL-6,IL-1β,iNOS,IL-10)and mRNA expression in each group,and the phenotypic changes of M1/M2 were evaluated.The supernatant of each culture medium was used as conditioned medium to culture PDLSCs,and the osteogenic ability and cell miner-alization were evaluated by alkaline phosphatase activity test and alizarin red staining.Results CCK-8 experiment showed that G10@HAP/MSN@ZnO@COS of 5 μg/mL could significantly promote the proliferation of PDLSCs.The results of ELISA showed that compared with Control group,the expression of M1 type marker IL-1β,IL-6,TNF-α and iNOS in G10@HAP/MSN@ZnO@COS group was significantly decreased(P＜0.000 1),while the expression of M2 type marker IL-10 was significantly increased(P＜0.000 1).The results of RT-qPCR were consistent with those of ELISA,which showed that the expression of M1-related genes in G10@HAP/MSN@ZnO@COS group decreased significantly(P＜0.01).The results of alizarin red staining and alkaline phosphatase activity test showed that the number of mineralized nodules and alkaline phosphatase activity in G10@HAP/MSN@ZnO@COS-CM group were significantly higher than those in other groups(P＜0.000 1).Conclusion Composite nanoparticles(G10@HAP/MSN@ZnO@COS)can effectively inhibit the polarization of macrophages to M1 phenotype and promote it to M2 phenotypic polarization.The anti-inflammatory microenvironment regulated by G10@HAP/MSN@ZnO@COS can en-hance the osteogenic differentiation of PDLSCs.

Objective:The National Central Cancer Registry estimates the number of new cancer cases and deaths in China in 2022, using incidence and mortality data collected by the National Cancer Center.Methods:According to the data of 700 cancer registries in 2018 and the data of 106 cancer registries from 2010 to 2018, the age-period-cohort model was used to estimate the incidence rate and mortality rate of all cancers and 23 types of cancer in 2022, stratified by gender and urban and rural areas. We estimated the number of new cancer cases and deaths in China in 2022 based on the estimated rate and population data in 2022.Results:The estimated results showed that in 2022, there were approximately 4 824 700 new cancer cases in China (2 533 900 in males and 2 290 800 in females), with an age-standardized incidence rate of Chinese population (ASIR) of 208.58 per 100 000 (212.67 per 100 000 for males and 208.08 per 100 000 for females). Approximately 2 903 900 new cancer cases occurred in urban areas, with an ASIR of 212.95 per 100 000. It was estimated about 1 920 800 new cancer cases in rural areas, and the ASIR was 199.65 per 100 000. The top five cancers (lung cancer 1 060 600, colorectal cancer 517 100, thyroid cancer 466 100, liver cancer 367 700 and female breast cancer 357 200) accounted for 57.4% of all new cases. The estimated number of deaths from cancer in China in 2022 was 2 574 200 (1 629 300 in males and 944 900 in females), with an age-standardized mortality rate of Chinese population (ASMR) of 97.08 per 100 000 (127.70 per 100 000 in males and 68.67 per 100 000 in females). The number of deaths from cancer in urban and rural areas was about 1 400 600 and 1 173 400, with the ASMR of 92.37 and 103.97 per 100 000 in urban and rural areas, respectively. The top five leading cause of cancers death (lung cancer 733 300, liver cancer 316 500, gastric cancer 260 400, colorectal cancer 240 000 and esophageal cancer 187 500) accounted for 67.5% of all cancer deaths. Lung cancer ranked first in the incidence and mortality in men and women. The incidence rate in urban areas was higher than that in rural areas, while the mortality rate was lower than that in rural areas.Conclusions:The burden of cancer in China is still relatively heavy, with significant differences in cancer patterns in gender, urban-rural, and regional. The burden of cancer presents a coexistence of developed and developing countries, and the situation of cancer prevention and control is still serious in China.

Background::Breast cancer is ranked among the most prevalent malignancies in the Chinese female population. However, comprehensive reports detailing the latest epidemiological data and attributable disease burden have not been extensively documented.Methods::In 2018, high-quality cancer surveillance data were recorded in 700 population-based cancer registries in China. We extracted data on female breast cancers (International Classification of Diseases, Tenth Revision [ICD-10]: C50) and estimated the incidence and mortality in 2022 according to the baseline data and corresponding trends from 2010 to 2018. Pathological types were classified according to the ICD for Oncology, 3rd Edition codes. Disability-adjusted life years (DALYs) were calculated as the sum of the years of life lost (YLLs) and years lived with disability (YLDs).Results::In 2022, approximately 357,200 new female breast cancer cases and 75,000 deaths occurred in China, accounting for 15.59% and 7.94% of total new cancer cases and deaths, respectively. The age-standardized incidence rate (ASIR) was 33.04 per 100,000. When analyzed by pathological type, the ASIRs for papillary neoplasms, invasive breast carcinoma, rare and salivary gland-type tumors, and other types were 1.13, 29.79, 0.24, and 1.88 per 100,000, respectively. The age-standardized mortality rate (ASMR) was 6.10 per 100,000. A total of 2,628,000 DALYs were found to be attributable to female breast cancer in China, comprising 2,278,300 YLLs and 349,700 YLDs. The ASIR, ASMR, and age-standardized rate (ASR) for DALYs in urban areas were consistently higher than those in rural areas. We observed a four-fold increase in the ASIR and ASR for DALYs and an eight-fold increase in the ASMR among females over 55 years compared with those aged under 55 years.Conclusion::These data provide invaluable insights into the latest epidemiology of female breast cancer in China and highlight the urgency for disease prevention and control strategy formulation.

Objective:The National Central Cancer Registry estimates the number of new cancer cases and deaths in China in 2022, using incidence and mortality data collected by the National Cancer Center.Methods:According to the data of 700 cancer registries in 2018 and the data of 106 cancer registries from 2010 to 2018, the age-period-cohort model was used to estimate the incidence rate and mortality rate of all cancers and 23 types of cancer in 2022, stratified by gender and urban and rural areas. We estimated the number of new cancer cases and deaths in China in 2022 based on the estimated rate and population data in 2022.Results:The estimated results showed that in 2022, there were approximately 4 824 700 new cancer cases in China (2 533 900 in males and 2 290 800 in females), with an age-standardized incidence rate of Chinese population (ASIR) of 208.58 per 100 000 (212.67 per 100 000 for males and 208.08 per 100 000 for females). Approximately 2 903 900 new cancer cases occurred in urban areas, with an ASIR of 212.95 per 100 000. It was estimated about 1 920 800 new cancer cases in rural areas, and the ASIR was 199.65 per 100 000. The top five cancers (lung cancer 1 060 600, colorectal cancer 517 100, thyroid cancer 466 100, liver cancer 367 700 and female breast cancer 357 200) accounted for 57.4% of all new cases. The estimated number of deaths from cancer in China in 2022 was 2 574 200 (1 629 300 in males and 944 900 in females), with an age-standardized mortality rate of Chinese population (ASMR) of 97.08 per 100 000 (127.70 per 100 000 in males and 68.67 per 100 000 in females). The number of deaths from cancer in urban and rural areas was about 1 400 600 and 1 173 400, with the ASMR of 92.37 and 103.97 per 100 000 in urban and rural areas, respectively. The top five leading cause of cancers death (lung cancer 733 300, liver cancer 316 500, gastric cancer 260 400, colorectal cancer 240 000 and esophageal cancer 187 500) accounted for 67.5% of all cancer deaths. Lung cancer ranked first in the incidence and mortality in men and women. The incidence rate in urban areas was higher than that in rural areas, while the mortality rate was lower than that in rural areas.Conclusions:The burden of cancer in China is still relatively heavy, with significant differences in cancer patterns in gender, urban-rural, and regional. The burden of cancer presents a coexistence of developed and developing countries, and the situation of cancer prevention and control is still serious in China.