ObjectiveTo investigate the key targets of Jianpi Yiqi prescription （JYP） in the treatment of hepatocellular carcinoma （HCC） based on network pharmacology and explore the effect of JYP on the invasion and proliferation of hepatocellular carcinoma cells via protein tyrosine phosphatase， non-receptor type 1 （PTPN1） by bioinformatics analysis and CRISPR/Cas9. MethodsThe potential targets of JYP in the treatment of HCC were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， SwissTargetPrediction， GeneCards， NCBI， and CTD. Additionally， the active components of JYP that could interact with PTPN1 were screened out， and then molecular docking between the targets and active components was performed in Autodock 4.0. UALCAN， HPA， and LinkedOmics were used to analyze the expression of PTPN1 in the HCC tissue， and the relationship of PTPN1 expression with the overall survival （OS） of HCC patients was discussed. CRISPR/Cas9 was used to knock down the expression of PTPN1 in HepG2 and SK-hep-1 cells， and the knockdown effect was examined by sequencing， Real-time PCR， and Western blot. HepG2 cells were classified into blank control， low-， medium-， and high-dose JYP （5.25， 10.5， 21 g·kg^-1）， and PTPN1 knockout groups. Real-time PCR and Western blot were employed to determine the mRNA and protein levels， respectively， of PTPN1 in HepG2 cells of each group. The effects of JYP and PTPN1 knockdown on the proliferation， invasion， and apoptosis of HepG2 cells were detected by Cell Counting Kit-8 （CCK-8）， Transwell， and Annexin V-FITC/PI methods， respectively. ResultsJYP had the most active components targeting PTPN1， and 31 of the active components had the binding energy less than -5.0 kcal·mol^-1 in molecular docking. The mRNA and protein levels of PTPN1 in the HCC tissue were higher than those in the normal tissue （P<0.01）. Compared with that in the normal tissue， the mRNA level of PTPN1 in the HCC tissue was up-regulated at the pathological stages Ⅰ-Ⅲ and grades G₁-G₃ （P<0.01）， and it was not significantly up-regulated at the stage Ⅳ or grade G₄. The mRNA level of PTPN1 in the TP53-mutated HCC tissue was higher than that in the TP53-unmutated HCC tissue （P<0.01）. The high mRNA level of PTPN1 was associated with the OS reduction （P<0.01）. After treatment with the JYP-containing serum or knockdown of PTPN1， HepG2 cells demonstrated decreased proliferation and invasion and increased apoptosis （P<0.01）. ConclusionPTPN1 may be one of the core targets of JYP in the treatment of HCC. It is highly expressed in the HCC tissue and cells， which is associated with the poor prognosis of patients. The expression level of PTPN1 is significantly up-regulated in the HCC tissue of the patients with TP53 mutation. However， TP53 mutation or deletion does not affect the expression of PTPN1 in HCC cells. JYP can significantly down-regulate the expression of PTPN1 to inhibit the proliferation and invasion and promote the apoptosis of HCC cells.

As an emerging artificial intelligence （AI）， the text-to-video large model Sora possesses powerful functions that previous AI did not have. In the medical field， medical staff can use the Sora model to achieve efficient medical education， patient health consultation， medical research， and other activities. Studying the innovative application scenarios， ethical issues， and governance paths of the current Sora model is of great significance for utilizing the new AI technology to promote and improve medical experience and quality， as well as to grasp the future development direction of AI in the field of healthcare.

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.

BACKGROUND: Lung cancer has been the leading cause of cancer-related deaths worldwide for many years. This study aimed to investigate the global patterns and trends of lung cancer. METHODS: Lung cancer incidence and mortality were derived from the GLOBOCAN 2020 database. Continuous data from Cancer Incidence in Five Continents Time Trends were used to analyze the temporal trends from 2000 to 2012 using Joinpoint regression, and average annual percent changes were calculated. The association between the Human Development Index and lung cancer incidence and mortality was assessed by linear regression. RESULTS: An estimated 2.2 million new lung cancer cases and 1.8 million lung cancer-related deaths occurred in 2020. The age-standardized incidence rate (ASIR) ranged from 36.8 per 100,000 in Demark to 5.9 per 100,000 in Mexico. The age-standardized mortality rate (ASMR) varied from 32.8 per 100,000 in Poland to 4.9 per 100,000 in Mexico. Both ASIR and ASMR were approximately twice higher in men than in women. The ASIR of lung cancer showed a downward trend in the United States of America (USA) between 2000 and 2012, and was more prominent in men. The age-specific incidence rates of lung cancer for ages of 50 to 59 years showed an upward trend in China for both men and women. CONCLUSIONS The burden of lung cancer is still unsatisfactory, especially in developing countries like China. Considering the effectiveness of tobacco control and screening in developed countries, such as the USA, there is a need to strengthen health education, accelerate the establishment of tobacco control policies and regulations, and improve early cancer screening awareness to reduce the future burden of lung cancer.
Male ; Humans ; Female ; United States ; Middle Aged ; Incidence ; Lung Neoplasms/epidemiology* ; Linear Models ; China/epidemiology*

BackgroundHome-based intervention occupies a prominent place in the treatment of autism spectrum disorder （ASD） in children， whereas previous studies on the effect of home-based early intensive behavioral intervention on verbal ability of children with ASD are somewhat inadequate. ObjectiveTo study the effects of intensive family behavioral of intervention based on Verbal Behavior Milestones Assessment and Placement Program （VB-MAPP） on the language ability of children with ASD， so as to provide references for the development of family intervention strategies for children with ASD. MethodsChildren aged 2 to 3 years old who attended the Children's Rehabilitation Department of the Second Affiliated Hospital of Shantou University Medical College from September 2020 to December 2021 and met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） diagnostic criteria for ASD were selected as the study objects. A non-randomized concurrent control trial was conducted to compare a study group （n=24） receiving home-based early intensive behavioral intervention using VB-MAPP with a control group （n=14） receiving training from other special institutions or early childhood education institutions. The intervention lasted for 6 months in both groups. Before and after the intervention， the VB-MAPP milestone assessment was performed in the two groups， and the VB-MAPP milestone score， mand， trac and listener responds were selected as the study indicators. Then the intervention effect was compared between two groups， and the multiple linear regression was performed to screen the related influencing factors. ResultsAfter intervention， the total milestone assessment score， mand， tact and listener responds scores of study group were higher than those of control group， with statistical difference （Z=-4.339~-2.195， P<0.05 or 0.01）. Multiple linear regression analysis denoted that the average weekly hours of home-based intervention in the first three months had certain effect on listener responds （β=1.029， P<0.05）. ConclusionApplication of home-based early intensive behavior intervention using VB-MAPP may contribute to the improvement of verbal abilities such as mand， tact and listener responds in children with ASD. ［Funded by 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund （number， 20200601）］

Background Occupational pneumoconiosis is the most common occupational disease in Qinghai Province and China. From the perspective of public health, it is important to assess the disease burden using disability-adjusted life years (DALY) and economic losses. Objective To evaluate the disease burden of occupational pneumoconiosis in Qinghai Province, and to provide a basis for the formulation and implementation of relevant prevention and control strategies. Methods Based on the registered data, a database of occupational pneumoconiosis cases confirmed and reported in Qinghai Province was established. The survival status and death dateof occupational pneumoconiosis patients from 2015 to 2019 were confirmed by on-site visit, telephone survey, matching search of Death Information Registration and Management System, and consulting other departments. The life loss due to occupational pneumoconiosis from 2015 to 2019 was assessed using DALY as an indicator and data from the Global Burden of Disease 2019 (GBD 2019) study. Inpatients with officially diagnosed occupational pneumoconiosis from a hospital in Qinghai Province in 2019 were selected as study subjects, the direct economic loss was evaluated with hospitalization expenses, and the indirect economic loss due to occupational pneumoconiosis in Qinghai Province in 2019 was calculated by human capital approach. Results From 2015 to 2019, 505 new cases of occupational pneumoconiosis were reported in Qinghai Province, and there were 348 death cases. Prevalent cases and years lost due to disability (YLD) due to occupational pneumoconiosis were increased, while DALY and years of life lost (YLL) due to occupational pneumoconiosis decreased firstly and then increased. In each year, there were 87% or more of the DALY, YLL, or YLD attributed to silicosis and coal workers' pneumoconiosis. In 2019, the occupational pneumoconiosis-associated DALY was 2173.55 person years. The total hospitalization expense incurred by 42 inpatients with occupational pneumoconiosis was 1256345.19 yuan. The total hospitalization expense and average daily cost of the inpatients with stageⅡand Ⅲ pneumoconiosis were higher than that of the inpatients with stageⅠ (P<0.05), and the hospitalization expense was higher in the ≥60 years age group than in the <60 years age group (P<0.05). In 2019, the indirect economic burden incurred by occupational pneumoconiosis in Qinghai Province was 44108581.65 yuan, and accounted for 0.15‰ of the gross domestic product (GDP) of the province. Conclusion The disease burden associated with occupational pneumoconiosis in Qinghai Province are outstanding. Silicosis and coal workers' pneumoconiosis are the key contributors. Targeted intervention measures including dust hazard control, enterprise management, follow-up and rehabilitation management of pneumoconiosis should be taken to prevent and control the occurrence and progression of pneumoconiosis and alleviate disease burden of pneumoconiosis.

ObjectiveTo study the correlation between Vimentin and hepatocellular carcinoma （HCC） and the mechanism of Jianpi Yiqi prescription against HCC through Vimentin. MethodCorrelation between Vimentin and HCC was analyzed based on the cancer genome atlas（TCGA）， clinical proteomic tumor analysis consortium（CPTAC）， STRING， and Cytoscape. SD rats were randomized into normal group （normal saline， ig， once/day， 4 weeks）， model group （normal saline， ig， once/day， 4 weeks）， low-dose， medium-dose， and high-dose （5.25， 10.5， 21 g·kg^-1， ig， once/day， 4 weeks） JianpiYiqi prescription groups， signal transducer and activator of transcription 3 （STAT3） inhibition group （C188-9， 4.5 mg·kg^-1， ip， once/day， 4 weeks）， and glycoprotein 130 （gp130） inhibition group （SC144， 4.5 mg·kg^-1， ip， once/day， 4 weeks）， 10 rats in each group. Diethylnitrosamine （DEN， 70 mg·kg^-1 body weight， ip） was injected in rats except the normal group to induce HCC. After the modeling， administration began. After last administration， Real-time polymerase chain reaction（Real-time PCR） was performed to determine Vimentin mRNA level in rat liver tissue. Caspase-3 activity in liver tissue was detected by colorimetry， and expression of Rho kinase （ROCK）1， ROCK2， aurora kinase B （AURKB）， Zinc-finger protein 148 （ZNF148）/zinc-binding protein-89 （ZBP-89）， STAT3， p-STAT3， total Vimentin， and phosphorylated （p）-Vimentin in liver tissue and Vimentin in liver tissue nucleus detected by Western blot. Serum Vimentin concentration was measured by enzyme-linked immunosorbent assay （ELISA）. ResultVimentin mRNA level was high in tissues from HCC patients with different cancer stages （stage Ⅰ-Ⅳ）， different pathological grades （G₁-G₃）， no regional lymph node metastasis （N0）， and different subtypes （P<0.01）. Vimentin mRNA expression was higher in tissues from patients with lymph node metastasis than in patients without lymph node metastasis and normal samples. Vimentin protein level was decreased in HCC tissues （P<0.01）. Vimentin gene has 4 mutations which can induce change in the primary structure of Vimentin protein and patients with Vimentin gene mutation had short disease free survival time （P<0.01）. The mRNA expression of Vimentin was negatively associated with HCC cell purity （P<0.01） but was positively associated with the infiltration levels of cancer-associated fibroblasts， M2 macrophages， myeloid dendritic cell and other immune cells in tumor microenvironment （P<0.01）. Association analysis results showed that the expression of Vimentin was correlated with the STAT3 expression in HCC tissues （P<0.01）. As for the animal experiment， Vimentin mRNA level and protein levels of total Vimentin and p-Vimentin in liver tssue， Vimentin protein level in liver tissue nucleus， Vimentin in rat serum， ROCK2， AURKB， STAT3 and p-STAT3 in liver tissues were up-regulated （P<0.01） and protein level of negative regulator ZBP-89 was reduced in the model group （P<0.01） compared with those in the normal group. Activity of Caspase-3 in liver tissue increased and the ROCK1 protein level was increased in the model group compared with those in the normal group. STAT3 inhibitor， gp130 inhibitor， and medium-dose and high-dose Jianpi Yiqi prescription all can reduce the secretory Vimentin protein in serum， protein levels of total Vimentin and p-Vimentin in liver tissues， and Vimentin in liver tissue nucleus， and the protein levels of STAT3/Vimentin signaling pathway-related molecules， such as STAT3， p-STAT3， ROCK2， and AURKB and up-regulate the protein level of negative regulator ZBP-89 and activity of Caspase-3 （P<0.05， P<0.01）. Effect of medium-dose or high-dose Jianpi Yiqi prescription on Vimentin mRNA expression， STAT3 protein expression， ZBP-89 protein expression， ROCK2 protein expression， AURKB protein expression and Caspase-3 activity was not significantly different from that of STAT3 inhibitor. ConclusionVimentin， an important inflammatory molecule， is closely related to the occurrence and development of HCC and its expression， subcellular location and function may be affected by cancer-associated fibroblasts， M2 macrophages， myeloid dendritic cell， and IL-6/STAT3 signaling pathway， particularly by STAT3 molecule. Jianpi Yiqi prescription may exert therapeutic effect on HCC via regulating Vimentin through the STAT3/Vimentin signaling pathway.

Objective     To investigate the current status of esophageal cancer surgery-related researches using bibliometric methodologies and identify the trend and hotspots. Methods     The Chinese and English literature was collected from Web of Science and CNKI from inception of each database to April 1, 2022. VOSviewer 1.6.18 and CiteSpace 6.1 were applied to cluster the authors, institutions, and keywords. For social network and time series analysis, Excel, GraphPad, and R 4.0.3 were used to visualize the literature on esophageal cancer surgery. Results     Finally, 19 566 English literature and 19 872 Chinese literature was included. The results demonstrated that the annual publishing of both Chinese and English literature increased over time, with English literature increasing rapidly and Chinese literature maintaining an average number of above 1 000 per year from 2011 to 2019. Researches were predominantly centered in Europe, the United States, Japan, South Korea, and China. China's researches in the field of surgical treatment in esophageal cancer lacked international collaboration, which began later than East Asian countries such as Japan and South Korea and had less influence. From the keyword perspective, previous researches on surgical treatment of esophageal cancer mostly focused on surgical techniques, complications, and comprehensive perioperative therapy. Both Chinese and English literature showed that the prevalence of keywords such as minimally invasive surgery, comprehensive treatment, and clinical trials increased dramatically during the recent years, indicating that these fields may represent the future directions and research trends. Conclusion     Compared to East Asia countries, such as Japan and South Korea, Chinese esophageal cancer surgery-related researches are relatively lacking. The research direction and field are similar to those in developed countries such as the United States and Europe. Future attention may be focused on minimally invasive treatment, comprehensive treatment, and clinical trials associated with surgical treatment of esophageal cancer.

Objective:To investigate the clinical efficacy and safety of ibrutinib in treatment of chronic lymphocytic leukemia (CLL).Methods:The clinical data of 68 patients with CLL in Fujian Medical University Union Hospital from May 1998 to October 2019 were retrospectively analyzed, including 39 cases receiving ibrutinib as the first therapy, 20 cases receiving ibrutinib as the second therapy, and 9 cases receiving ibrutinib as the second and above therapy. The clinical characteristics, IGHV gene mutation, the short-term therapeutic efficacy and survival of patients with stratified chromosomal karyotype were analyzed; the adverse events were also analyzed.Results:The median follow-up time was 53.2 months until May 2020. The objective remission rate (ORR) was 83.8% (57/68), including 8 cases (11.8%) of complete remission, 49 cases (72.1%) of partial remission, 5 cases (7.4%) of the stable disease, 6 cases (8.8%) of progression of the disease. The ORR of patients without IGHVmutation was higher than that of those with IGHV mutation [93.3% (28/30) vs. 76.3% (29/38), χ2=33.656, P<0.05]; the ORR of patients with low risk and low-moderate risk International Prognostic Index (IPI) score was higher than that of those with moderate-high risk and high risk [90.6% (29/32) vs. 77.8% (28/36), χ2=7.248, P = 0.007], and differences in the ORR of patients stratified by other factors were not statistically significant (all P > 0.05). Among 68 patients, 31 cases (45.6%) had adverse reactions and they insistently received the treatment; 26 cases (38.2%) had grade1-2 adverse reactions, 5 cases (7.4%) had grade 3 and above adverse reactions; 2 cases (2.9%) had drug withdrawal because of adverse reactions. The median progression-free survival (PFS) time and overall survival (OS) time of CLL patients treated with ibrutinib had not been reached. The 5-year PFS rate of patients with IGHV mutation was higher than that of patients with IGHV non-mutation (100.0% vs.72.1%, P = 0.020), the 5-year PFS rate of patients with normal chromosome karyotype was higher than that of those with abnormal chromosome karyotype (100.0% vs.74.3%, P = 0.019). Conclusion:Ibrutinib is effective and safe in treatment of CLL patients.

OBJECTIVE：To explore the therap eutic effects and its mech anism of Jianpi yiqi decoction on diethylnitrosamine （DEN）induced liver cancer model rats. METHODS ：Totally 80 male SD rats were divided into normal group ，model group ， Nod-like receptor family 3（NLRP3）inhibition group （MCC950，4.5 mg/kg），caspase-1 inhibitory group （VX-765，4.5 mg/kg）， Jianpi yiqi decoction low-dose ，medium-dose and high-dose groups （5.25，10.5，21 g/kg），with 10 rats in each group except for 20 rats in model group （10 of them were only used to judge whether modeling was successful ）. Rats in each group were intraperitoneally injected with DEN （70 mg/kg）to induce liver cancer model ，except for the rats in normal group which were replaced by normal saline. After modeling ，normal group and model group were given normal saline intragastrically ；inhibitor groups were given relevant medicine intraperitoneally ；Jianpi yiqi decoction groups were given relevant medicine intragastrically ， once a day ，for consecutive 4 weeks. After last administration ，histopathological morphology of liver tissue was observed. The contents of serum inflammatory factors TNF-α and IL-1β were detected. The expression of NLRP3 and programmed cell necrosis associated protein （ASC，pro-caspase-1，RIP1，RIP3 and MLKL ）in liver tissue were detected. RESULTS ：Compared with the normal group ，the hepatocytes of model group showed varying， degrees of steatosis ，enlarged nuclei ，lumpy，bleeding and necrosis，accompanied by proliferative foci and nodules. Liver 198086， tissue injury index ，serum content of TNF-α and IL-1β as well as the protein expression of NLRP 3，ASC，pro-caspase-1，RIP1，RIP3 and MLKL in liver tissue were significantly increased （P＜0.05 or P＜0.01）. Compared with model 防治。E-mail：sherwin_zhuo@126.com group，there were still a large number of inflammatory cell infiltration in the liver tissue of rats in Jianpi yiqi decoction low-dose and medium dose groups ，while the inflammatory cell infiltration of rats in high-dose group and inhibitor groups decreased significantly ；the liver tissue injury index and above indexes levels in serum and liver tissue were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS ：Jianpi yiqi decoction shows therapeutic effect on liver cancer model rats ，the mechanism of which may be associated with down-regulating the expression of NLRP3 inflammasome and inhibiting programmed cell necrosis.