Asthma is a chronic inflammatory respiratory disease involving multiple cells and cellular components， characterized by recurrent episodes of wheezing， shortness of breath， chest tightness， and coughing， significantly impacting patients' quality of life. The phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway， as a crucial hub in intracellular signaling， is widely involved in the regulation of cell growth， proliferation， survival， metabolism， and a series of pathophysiological processes. Its regulatory role in the pathological progression of asthma is particularly significant， specifically in promoting airway inflammation， mediating epithelial mesenchymal transition， accelerating airway remodeling， regulating cell autophagy， inducing mucus hypersecretion， and influencing immune response balance. This study analyzed potential molecular targets of the PI3K/Akt pathway， including activators such as cysteine proteinase inhibitor 1（CST1）， found in inflammatory zone 1（FIZZ1） and free fatty acid receptor 1（FFAR1）， and inhibitors such as human β-defensin-3（hBD-3）， disintegrins， metalloproteinase 33（ADAM33） and interleukin-27（IL-27）， and initially revealed the potential molecular mechanisms of traditional Chinese medicine（TCM） in asthma intervention. Based on this， the authors systematically summarized the efficacy and specific mechanisms of TCM monomers， compounds， and external treatments for asthma by regulating the PI3K/Akt signaling pathway through literature review and analysis， aiming at establishing a robust foundation for the wide application and advanced development of TCM in asthma treatment， offering innovative insights for clinical research and drug development of asthma.

Asthma is a chronic inflammatory respiratory disease involving multiple cells and cellular components， characterized by recurrent episodes of wheezing， shortness of breath， chest tightness， and coughing， significantly impacting patients' quality of life. The phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway， as a crucial hub in intracellular signaling， is widely involved in the regulation of cell growth， proliferation， survival， metabolism， and a series of pathophysiological processes. Its regulatory role in the pathological progression of asthma is particularly significant， specifically in promoting airway inflammation， mediating epithelial mesenchymal transition， accelerating airway remodeling， regulating cell autophagy， inducing mucus hypersecretion， and influencing immune response balance. This study analyzed potential molecular targets of the PI3K/Akt pathway， including activators such as cysteine proteinase inhibitor 1（CST1）， found in inflammatory zone 1（FIZZ1） and free fatty acid receptor 1（FFAR1）， and inhibitors such as human β-defensin-3（hBD-3）， disintegrins， metalloproteinase 33（ADAM33） and interleukin-27（IL-27）， and initially revealed the potential molecular mechanisms of traditional Chinese medicine（TCM） in asthma intervention. Based on this， the authors systematically summarized the efficacy and specific mechanisms of TCM monomers， compounds， and external treatments for asthma by regulating the PI3K/Akt signaling pathway through literature review and analysis， aiming at establishing a robust foundation for the wide application and advanced development of TCM in asthma treatment， offering innovative insights for clinical research and drug development of asthma.

OBJECTIVE To explore the effect and mechanism of embryonic intervention with Zuogui pill on the glucose tolerance in offsprings of pregnant rats with gestational diabetes mellitus. METHODS Pregnant rats were randomly divided into blank group， model group， positive control group （insulin glargine）， Zuogui pill low-， medium- and high-dose groups （4.725， 9.45， 18.9 g/kg）. In addition to the blank group， streptozotocin was injected intraperitoneally to establish a gestational diabetes mellitus rat model. From day 6 to day 18 of pregnancy， each group was given relevant medicine and distilled water intragastrically， once a day. After 21 days of birth， the body weight and body length of offsprings were recorded， and the area under the curve （AUC） was calculated through a glucose tolerance test. After 22 days of birth， fasting blood glucose （FBG）， fasting insulin （FINS） levels in serum， insulin sensitivity index （ISI）， and homeostasis model assessment of insulin resistance （HOMA-IR） were measured， and the morphological structure of pancreatic tissue was observed. The protein spectrum of pancreatic tissue was analyzed by tandem mass tag-based proteomics， and protein and mRNA expression levels of apolipoprotein A1（ApoA1）， solute carrier family 27 member 1 （Slc27a1）， kininogen 1（Kng1） and sodium/potassium-transporting ATPase subunit alpha 2 （Atp1a2）， solute carrier family 7 member 5 （Slc7a5）， solute carrier family 3 member 2 （Slc3a2）， bile acid-coenzyme A： amino acid N- acyltransferase （Baat）， eukaryotic translation initiation factor 2 subunit gamma （Eif2s3） were detected. RESULTS Compared with the model group， the body weight， body length and ISI of offsprings in the positive control group and Zuogui pill medium-dose group were significantly increased （P＜0.05）， while the glucose tolerance and islet cell proliferation were significantly improved， and the AUC， FBG， FINS and HOMA-IR were significantly decreased （P＜0.05）. There were 88 potential target proteins for the embryonic intervention of Zuogui pill in offsprings of pregnant rats with gestational diabetes mellitus，involving multiple pathways such as peroxisome proliferator-activated receptor （PPAR）， cyclic guanosine monophosphate-protein kinase G （cGMP-PKG）， fat digestion and absorption， and bile secretion. The proteins closely related to glucose metabolism and insulin resistance mainly included ApoA1， Slc27a1， Kng1， Atp1a2， Slc7a5， Slc3a2， Baat， and Eif2s3. Among them， compared with the model group， protein and mRNA expressions of Slc7a5， Slc3a2， and Baat in the pancreatic tissues of pregnant rat offsprings in the Zuogui pill medium-dose group were significantly up-regulated （P＜0.05）； protein and mRNA expressions of ApoA1， Slc27a1， Kng1， Atp1a2 and Eif2s3 were all significantly down-regulated （P＜0.05）. CONCLUSIONS The intervention of Zuogui pill in the embryonic period on offsprings of pregnant rats with gestational diabetes mellitus can improve their blood glucose levels and pancreatic pathological morphology. The mechanism may be related to the upregulation of the expressions of Slc7a5， Slc3a2， and Baat and the down-regulation of ApoA1， Slc27a1， Kng1， Atp1a2 and Eif2s3 expressions in the PPAR， cGMP-PKG， fat digestion and absorption， and bile secretion pathways.

[Purpose]To analyze the incidence trend and age,period,cohort effects of brain and other central nervous system tumors(brain tumor)in Qidong City of Jiangsu Province from 1972 to 2021.[Methods]The incidence data of brain tumor from 1972 to 2021 were collected from the Qidong cancer registry database.The crude incidence rate(CR),age-standardized rate by Chi-nese standard population(ASRC),age-standardized rate by world standard population(ASRW)and average annual percentage change(AAPC)were calculated.The age-period-cohort(APC)model was used to analyze the age,period,and cohort effects of brain tumor incidence in Qidong City from 1972 to 2021.[Results]A total of 2 801 cases of brain tumor occurred in Qidong City from 1972 to 2021,including 1 475 male cases and 1 326 female cases.From 1972-1976 to 2017-2021,the CR increased from 1.81/10 5 to 9.28/10 5,the ASRC increased from 2.07/10 5 to 4.96/10 5,and ASRW increased from 2.00/105 to 4.98/105.From 1972 to 2021 the AAPC of CR,ASRC and ASRW were 3.97％(3.53％for male and 4.37％for female),2.02％(1.66％for male and 2.24％for female)and 2.06％(1.63％for male and 2.24％for female)(all P＜0.001).The Wald's Chi-square test of the APC model showed that there were significant differences in the trends of age,period and birth cohort effect of brain tumor risk(all P＜0.05).The age effect showed that the incidence of brain tumor increased with age,starting from the age group of 45～49 years old and reaching a peak of 25.84/10 5 in age group of 75～79 years old(95％CI:21.17/10 5～31.53/10 5).The period ef-fect showed that the risk of recent period was higher than that in the early period using 1992-1996 period as the reference,reaching the highest in 2012-2016(RR=1.64,95％CI:1.38～1.95).The birth cohort effect showed that the highest risk was in 2017-2021 births cohort(RR=11.17,95％CI:4.26～29.26)using 1952-1956 birth cohort as the reference.[Conclusion]The incidence of brain tumor in Qidong City has been rising;and age,period and cohort are the main influencing factors,suggesting that the middle-aged and elderly population should be the focus of brain tumor prevention and control.

Objective:To analyze the incidence trends of malignant tumors in the elderly population aged over 60 years in Qidong City from 1972 to 2021, as well as to predict the incidence rate for the next decade.Methods:Data were obtained from the Qidong Cancer Registry and Reporting System.The crude incidence rate(CR), age-standardized incidence rate using the Chinese standard population(ASRC), and age-standardized incidence rate based on Segi's world standard population(ASRW)were calculated.Joinpoint regression analysis was conducted using Joinpoint 4.9.1.0 software to determine the average annual percentage change(AAPC)in incidence.Additionally, the ARIMA model implemented in SAS 9.2 software was utilized for time series analysis to forecast incidence trends over the forthcoming 10 years.Results:In Qidong City, a total of 87, 401 malignant tumors were reported in the elderly population.The ASRW increased from 736.85 per 100, 000 in the years 1972-1976 to 1 056.33 per 100, 000 in 2017-2021.Specifically, the ASRW for males rose from 968.56 per 100, 000 to 1 332.75 per 100, 000, while the ASRW for females increased from 550.62 per 100, 000 to 825.44 per 100, 000, with AAPC values of 1.16%, 0.94%, and 1.44% over 50 years(all P<0.001).The incidence trend exhibited an upward trajectory with age, peaking in the 75-79 age group.The AAPC values for the incidence rates in the age groups of 60-64, 65-69, 70-74, 75-79, and those aged over 80 were 0.64%, 0.93%, 0.92%, 2.02%, and 2.44%, respectively(all P<0.001).Among the various cancers, lung cancer, which ranked first, saw an increase in ASRW from 100.87 per 100, 000 in 1972-1981 to 248.84 per 100, 000 in 2012-2021.In contrast, gastric cancer, ranked second, decreased from 216.23 per 100, 000 in 1972-1981 to 103.54 per 100, 000 in 2012-2021.Liver cancer, ranked third, fluctuated from 113.47 per 100, 000 in 1972-1981 to 125.13 per 100, 000 in 2012-2021.Colorectal cancer, ranked fourth, increased from 40.06 per 100, 000 in 1972-1981 to 123.47 per 100, 000 in 2012-2021, while esophageal cancer, ranked fifth, decreased from 63.42 per 100, 000 in 1972-1981 to 28.65 per 100, 000 in 2012-2021.The AAPC values over 50 years for these cancers were 2.25%, -1.89%, 0.36%, 3.13%, and -1.86%, respectively(all P<0.05).Projections indicate that by 2031, the incidence of malignant tumors among the elderly population in Qidong will reach 1 253.84 per 100, 000, with estimates of 1 566.67 per 100, 000 for males and 983.14 per 100, 000 for females. Conclusions:The incidence of malignant tumors among the elderly population in Qidong City is increasing.Common types of cancer in this demographic include lung cancer, gastric cancer, liver cancer, colorectal cancer, and esophageal cancer.Notably, lung cancer, liver cancer, and colorectal cancer are on the rise and should be prioritized in cancer prevention and control efforts.

Objective:To analyze effect of miR-532-3p on macrophage polarization in rats with chronic kidney disease(CKD)through targeted inhibition of Notch1 signal pathway.Methods:A total of 75 SD rats were divided into control group,CKD group,ago-NC group,ago-miR-532-3p group and FLI-06 group,except for control group,CKD models were constructed and corresponding plas-mids and inhibitors were injected,control group and CKD group were replaced with same amount of normal saline.Serum creatinine(Scr),blood urea nitrogen(BUN),TNF-α,IL-1β and IL-10 were measured by ELISA,HE staining and Masson staining were used to observe renal tissue pathology and renal fibrosis in rats,flow cytometry was used to detect CD11c+and CD206+of macrophages,miR-532-3p expression in rat kidney tissue was detected by qRT-PCR,Notch1 protein was detected by Western blot;target binding of miR-532-3p to Notch1 was determined by double luciferase reporter gene.Results:Structure of glomerulus,renal tubules and epithelial cells was complete,cell boundaries were clear,and cells were arranged neatly in control group;glomerular epithelial cell necrosis,mesangial matrix,glomerulosclerosis,inflammatory cell infiltration and renal fibrosis were increased in CKD group;compared with CKD group,damage degree of glomerulus and tubules,inflammatory infiltration cells and renal fibrosis degree in ago-miR-532-3p group and FLI-06 group were reduced;compared with control group,serum Scr,BUN,TNF-α,IL-1β,proportion of CD11c+,CD11c+/CD206+and Notch1 protein expression in macrophages of renal tissue were increased,serum IL-10 level,CD206+and miR-532-3p in renal tissue were decreased(P<0.05);compared with CKD group,serum Scr,BUN,TNF-α,IL-1β,proportion of CD11c+,CD11c+/CD206+and Notch1 protein expression in macrophages of renal tissue in ago-miR-532-3p group and FLI-06 group were decreased,serum IL-10 level,CD206+and miR-532-3p in renal tissue were increased(P<0.05);miR-532-3p targeted Notch1,and overexpression of miR-532-3p inhibited Notch1 protein expression.Conclusion:Promoting expression of miR-532-3p protects kidney tissue of CKD rats by inhibiting Notch1 pathway,which may be due to regulating polarization of macrophages.

[Purpose]To analyze the trend of incidence rates of gallbladder cancer in Qidong City of Jiangsu Province from 1972 to 2021.[Methods]The incidence data of gallbladder cancer from 1972 to 2021 were collected from the Qidong Tumour Registry database,the crude incidence rate(CR),age-standardized rate by Chinese standard population(ASRC),age-standardized rate by world standard population(ASRW)of gallbladder cancer were calculated.Trend analysis was per-formed using Joinpoint 4.9.1.0 software to calculate the average annual percentage change(AAPC)of gallbladder cancer incidence rates,and time trend analysis was performed on the overall inci-dence rate by sex and age.[Results]A total of 1 369 cases of gallbladder cancer occurred in Qi-dong City from 1972 to 2021,accounting for 0.93％of all malignant tumors.The overall CR of gallbladder cancer was 2.44/105 in 50 years,ASRC was 0.88/105 and ASRW was 1.45/105.The truncated rate of 35～64 years old was 1.98/105,the cumulative incidence of gallbladder cancer at 0～74 years old was 0.16％,and the risk of cumulative incidence of gallbladder cancer was 0.16％.CR was slightly higher in women than that in men,but after standardization it was slightly higher in men than that in women.The sex ratio of CR,ASRC and ASRW was 0.89,1.07 and 1.06,respectively.With the increase of age,the incidence of gallbladder cancer was also increased.The age of onset was slightly increased in last 50 years.In last 50 years,there was an upward trend in the overall incidence of gallbladder cancer,the incidence both for men and women,and the inci-dence of each age group.[Conclusion]The incidence of gallbladder cancer in Qidong City has increased considerably during the past 50 years,and continuing attention should be paid to the prevention and treatment of gallbladder cancer especially for the key populations.

[Purpose]To analyze the survival rate of breast cancer in Qidong City of Jiangsu Province from 1972 to 2019 and to predict the trend in the next 10 years.[Methods]The data of breast cancer collected from Qidong Cancer Registry from 1972 to 2019 were extracted.Observed survival rate(OSR),relative survival rate(RSR),age-adjusted relative survival(ARS)and average annual percentage change(AAPC)of breast cancer were calculated.ARIMA model was used to predict the trend of breast cancer survival rate.[Results]The 5-year RSR increased from 57.30％during 1972-1977 to 89.01％during 2014-2019,and the uptrend of RSR in the 8 periods was statistically significant(P＜0.001).The 5-year ARS increased from 48.12％during 1972-1977 to 85.64％during 2014-2019 with an AAPC of 1.85％(t=10.113,P＜0.001).The 5-year RSR during 1972-2019 for males was 85.22％,and for females was 74.51％.For females,the 5-year RSR in-creased from 56.44％during 1972-1977 to 88.93％during 2014-2019 with an AAPC of 1.29％(t=13.087,P＜0.001),and the 5-year ARS increased from 46.14％during 1972-1977 to 85.23％during 2014-2019 with an AAPC of 1.90％(t=10.369,P＜0.001).The 5-year RSR in the age groups of 25～34,35～44,45～54,55～64,65～74,and over 75 years old were 66.91％,74.69％,76.97％,75.52％,73.44％and 66.40％,respectively;the corresponding AAPCs of 5-RSR in above age groups were 1.02％(t=3.816,P=0.009),1.03％(t=4.936,P=0.003),1.23％(t=5.826,P=0.001),1.86％(t=5.997,P=0.001),2.13％(t=10.245,P＜0.001),and 1.44％(t=6.405,P=0.001),respectively.ARIMA modeling of survival trend prediction showed that 5-RSR and 5-ARS for breast cancer will be ascended to 98.76％and 98.33％by 2028,respectively.[Conclusion]The overall survival rate of registered breast cancer cases in Qidong City has been greatly improved and will be further improved in the future,more attention should be paid to the prevention and treatment of breast cancer.

[Purpose]To analyze the trend of incidence rates of gallbladder cancer in Qidong City of Jiangsu Province from 1972 to 2021.[Methods]The incidence data of gallbladder cancer from 1972 to 2021 were collected from the Qidong Tumour Registry database,the crude incidence rate(CR),age-standardized rate by Chinese standard population(ASRC),age-standardized rate by world standard population(ASRW)of gallbladder cancer were calculated.Trend analysis was per-formed using Joinpoint 4.9.1.0 software to calculate the average annual percentage change(AAPC)of gallbladder cancer incidence rates,and time trend analysis was performed on the overall inci-dence rate by sex and age.[Results]A total of 1 369 cases of gallbladder cancer occurred in Qi-dong City from 1972 to 2021,accounting for 0.93％of all malignant tumors.The overall CR of gallbladder cancer was 2.44/105 in 50 years,ASRC was 0.88/105 and ASRW was 1.45/105.The truncated rate of 35～64 years old was 1.98/105,the cumulative incidence of gallbladder cancer at 0～74 years old was 0.16％,and the risk of cumulative incidence of gallbladder cancer was 0.16％.CR was slightly higher in women than that in men,but after standardization it was slightly higher in men than that in women.The sex ratio of CR,ASRC and ASRW was 0.89,1.07 and 1.06,respectively.With the increase of age,the incidence of gallbladder cancer was also increased.The age of onset was slightly increased in last 50 years.In last 50 years,there was an upward trend in the overall incidence of gallbladder cancer,the incidence both for men and women,and the inci-dence of each age group.[Conclusion]The incidence of gallbladder cancer in Qidong City has increased considerably during the past 50 years,and continuing attention should be paid to the prevention and treatment of gallbladder cancer especially for the key populations.

[Purpose]To analyze the survival rate of breast cancer in Qidong City of Jiangsu Province from 1972 to 2019 and to predict the trend in the next 10 years.[Methods]The data of breast cancer collected from Qidong Cancer Registry from 1972 to 2019 were extracted.Observed survival rate(OSR),relative survival rate(RSR),age-adjusted relative survival(ARS)and average annual percentage change(AAPC)of breast cancer were calculated.ARIMA model was used to predict the trend of breast cancer survival rate.[Results]The 5-year RSR increased from 57.30％during 1972-1977 to 89.01％during 2014-2019,and the uptrend of RSR in the 8 periods was statistically significant(P＜0.001).The 5-year ARS increased from 48.12％during 1972-1977 to 85.64％during 2014-2019 with an AAPC of 1.85％(t=10.113,P＜0.001).The 5-year RSR during 1972-2019 for males was 85.22％,and for females was 74.51％.For females,the 5-year RSR in-creased from 56.44％during 1972-1977 to 88.93％during 2014-2019 with an AAPC of 1.29％(t=13.087,P＜0.001),and the 5-year ARS increased from 46.14％during 1972-1977 to 85.23％during 2014-2019 with an AAPC of 1.90％(t=10.369,P＜0.001).The 5-year RSR in the age groups of 25～34,35～44,45～54,55～64,65～74,and over 75 years old were 66.91％,74.69％,76.97％,75.52％,73.44％and 66.40％,respectively;the corresponding AAPCs of 5-RSR in above age groups were 1.02％(t=3.816,P=0.009),1.03％(t=4.936,P=0.003),1.23％(t=5.826,P=0.001),1.86％(t=5.997,P=0.001),2.13％(t=10.245,P＜0.001),and 1.44％(t=6.405,P=0.001),respectively.ARIMA modeling of survival trend prediction showed that 5-RSR and 5-ARS for breast cancer will be ascended to 98.76％and 98.33％by 2028,respectively.[Conclusion]The overall survival rate of registered breast cancer cases in Qidong City has been greatly improved and will be further improved in the future,more attention should be paid to the prevention and treatment of breast cancer.