ObjectiveTo investigate the potential mechanism of heat-sensitive moxibustion on chronic atrophic gastritis （CAG） through the phosphoinositide 3-kinase/protein kinase B （PI3K/Akt） signaling pathway. MethodsFifty-eight SD rats were randomly divided into blank group （n=14） and modeling group （n=44）. Rats in the blank group were fed routinely， while the rats in the modeling group received drinking water containing 1-methyl-3-nitro-1-nitrosoguanidine （MNNG） at a concentration of 140 μg/ml， combined with irregular fasting and feeding for 12 weeks to establish CAG model. After successful modeling， the rats were randomly divided into model group （n=10）， inhibitor group （n=10） and moxibustion group （n=20）. After 40 minutes of suspended moxibustion at "Zhongwan" （CV 12） daily， the rats in the moxibustion group were divided into heat-sensitive moxibustion group （n=10） and non-heat-sensitive moxibustion group （n=9） according to the change of tail temperature during moxibustion. The inhibitor group was bound for 40 minutes daily， and then administered with PI3K/Akt signaling pathway inhibitor， rapamycin solution， by gavage at a dose of 1 mg/kg. The model group received intragastric administration of 1 ml/kg normal saline after 40 minutes of restraint stress each day. All interventions were administered once daily for 28 consecutive days， while the blank group received no intervention. After the intervention finished， the body weight of rats in each group was compared. HE staining was used to observe the histopathological changes of gastric mucosa. The apoptosis-positive rate of gastric mucosal cells was detected by TUNEL assay. Immunohistochemistry was performed to determine the protein levels of matric metalloproteinase-7 （MMP7）， vascular endothelial growth factor A （VEGFA） and epidermal growth factor receptor （EGFR） in gastric mucosa. The mRNA expression levels of PI3K， Akt and mammalian target of rapamycin （mTOR） in gastric mucosal tissues were detected by qPCR. The protein levels of phosphorylated Akt （p-Akt） and phosphorylated mTOR （p-mTOR） in rat gastric mucosal tissues were measured by Western Blotting. ResultsCompared to the blank group， rats in all other groups exhibited decreased body weight， significantly increased gastric mucosal cell apoptosis-positive rates， elevated protein levels of MMP7， VEGFA and EGFR in gastric mucosa， increased mRNA expression levels of PI3K， Akt and mTOR， and enhanced protein expression levels of p-Akt and p-mTOR （P＜0.05 or P＜0.01）. Histopathological examination revealed thinning of the gastric mucosa， glandular disorganization and atrophy， accompanied by intestinal metaplasia.Compared to the model group， the heat-sensitive moxibustion group， the non-heat-sensitive moxibustion group and the inhibitor group all showed significant improvements in the above-mentioned indicators （P＜0.05 or P＜0.01）. Compared to the heat-sensitive moxibustion group， the non-heat-sensitive moxibustion group and the inhibitor group exhibited increased positive rates of gastric mucosal cell apoptosis； the non-heat-sensitive moxibustion group showed increased protein levels of MMP7， VEGFA and EGFR， as well as mRNA expression levels of PI3K， Akt and mTOR， and protein expressions of p-Akt and p-mTOR； the inhibitor group exhibited elevated protein expression level of EGFR （P＜0.05 or P＜0.01）. Histopathological examination showed that the gastric mucosal glands in the heat-sensitive moxibustion group were arranged more regularly， with an approximately normal structural appearance. ConclusionHeat-sensitive moxibustion can improve the body weight of CAG rats and repair gastric mucosal injury. Its therapeutic effects may be mediated by inhibiting excessive activation of gastric mucosal PI3K/Akt signaling pathway， thereby reducing gastric mucosal cell apoptosis.

ObjectiveTo investigate the potential mechanism of heat-sensitive moxibustion on chronic atrophic gastritis （CAG） through the phosphoinositide 3-kinase/protein kinase B （PI3K/Akt） signaling pathway. MethodsFifty-eight SD rats were randomly divided into blank group （n=14） and modeling group （n=44）. Rats in the blank group were fed routinely， while the rats in the modeling group received drinking water containing 1-methyl-3-nitro-1-nitrosoguanidine （MNNG） at a concentration of 140 μg/ml， combined with irregular fasting and feeding for 12 weeks to establish CAG model. After successful modeling， the rats were randomly divided into model group （n=10）， inhibitor group （n=10） and moxibustion group （n=20）. After 40 minutes of suspended moxibustion at "Zhongwan" （CV 12） daily， the rats in the moxibustion group were divided into heat-sensitive moxibustion group （n=10） and non-heat-sensitive moxibustion group （n=9） according to the change of tail temperature during moxibustion. The inhibitor group was bound for 40 minutes daily， and then administered with PI3K/Akt signaling pathway inhibitor， rapamycin solution， by gavage at a dose of 1 mg/kg. The model group received intragastric administration of 1 ml/kg normal saline after 40 minutes of restraint stress each day. All interventions were administered once daily for 28 consecutive days， while the blank group received no intervention. After the intervention finished， the body weight of rats in each group was compared. HE staining was used to observe the histopathological changes of gastric mucosa. The apoptosis-positive rate of gastric mucosal cells was detected by TUNEL assay. Immunohistochemistry was performed to determine the protein levels of matric metalloproteinase-7 （MMP7）， vascular endothelial growth factor A （VEGFA） and epidermal growth factor receptor （EGFR） in gastric mucosa. The mRNA expression levels of PI3K， Akt and mammalian target of rapamycin （mTOR） in gastric mucosal tissues were detected by qPCR. The protein levels of phosphorylated Akt （p-Akt） and phosphorylated mTOR （p-mTOR） in rat gastric mucosal tissues were measured by Western Blotting. ResultsCompared to the blank group， rats in all other groups exhibited decreased body weight， significantly increased gastric mucosal cell apoptosis-positive rates， elevated protein levels of MMP7， VEGFA and EGFR in gastric mucosa， increased mRNA expression levels of PI3K， Akt and mTOR， and enhanced protein expression levels of p-Akt and p-mTOR （P＜0.05 or P＜0.01）. Histopathological examination revealed thinning of the gastric mucosa， glandular disorganization and atrophy， accompanied by intestinal metaplasia.Compared to the model group， the heat-sensitive moxibustion group， the non-heat-sensitive moxibustion group and the inhibitor group all showed significant improvements in the above-mentioned indicators （P＜0.05 or P＜0.01）. Compared to the heat-sensitive moxibustion group， the non-heat-sensitive moxibustion group and the inhibitor group exhibited increased positive rates of gastric mucosal cell apoptosis； the non-heat-sensitive moxibustion group showed increased protein levels of MMP7， VEGFA and EGFR， as well as mRNA expression levels of PI3K， Akt and mTOR， and protein expressions of p-Akt and p-mTOR； the inhibitor group exhibited elevated protein expression level of EGFR （P＜0.05 or P＜0.01）. Histopathological examination showed that the gastric mucosal glands in the heat-sensitive moxibustion group were arranged more regularly， with an approximately normal structural appearance. ConclusionHeat-sensitive moxibustion can improve the body weight of CAG rats and repair gastric mucosal injury. Its therapeutic effects may be mediated by inhibiting excessive activation of gastric mucosal PI3K/Akt signaling pathway， thereby reducing gastric mucosal cell apoptosis.

Objective:To analyze the epidemiologic characteristics of avian influenza virus and the molecular characteristics and genetic evolution of H9N2 subtype avian influenza viruses in the live poultry markets in Fujian province in 2021-2023.Methods:Six types of specimens were collected from five cities in Fujian province. The specimens were subjected to nucleic acid detection for influenza A viruses, subtypes H5, H7, and H9 by fluorescence quantitative PCR, and the results were analyzed statistically with χ2 test. Specimens with Ct value less than 31 were screened for targeted amplification and next-generation sequencing of the hemagglutinin (HA) and neuraminidase (NA) genes. Reference sequences were downloaded from the databases, and the characteristics of molecular variation and genetic evolution were analyzed by using bioinformatics softwares. Results:From 2021 to 2023, a total of 1 853 specimens were collected from five cities, with a positive rate of 50.94% for influenza A viruses, including 684 specimens of H9 subtype, 23 specimens of H5 subtype, 1 specimen of H7 subtype, 28 specimens of H5 and H9 subtype, 1 specimen of H7 and H9 subtype, and 207 specimens of unclassified A-type. There were significant differences in the positive detection rates of influenza A viruses in different cities( χ2=461.82, P<0.001). Statistically significant differences in influenza A virus positivity rates across years and quarters( χ2=12.26, P=0.002; χ2=30.12, P<0.001), with higher rates of 56.39% and 55.34% in the first and third quarters, respectively. And the differences in the positive rates of influenza A viruses in different types of specimens were statistically significant( χ2=23.05, P<0.001), with specimens on the cage surface having a positivity rate of 56.09%, which was the highest of all types of specimens. A total of 24 strains of HA and NA genes of H9N2 subtype were fully sequenced. Compared with the sequence of NCBI database, the highest identity of HA gene nucleotide sequences ranged from 97.03% to 99.87%, and the highest identity of NA gene nucleotide sequences ranged from 97.50% to 99.78%.Twenty-three strains with both HA and NA genes belonged to the G57 genotype in the Y280-like evolutionary branch of the Eurasian lineage, and one strain belonged to the Y439-like evolutionary branch of the Eurasian lineage. The cleavage sites of all the strains showed the characteristic of low pathogenicity, and most strains had receptor binding sites characterized by avian-derived and human receptors. Conclusions:The overall positive rate of avian influenza viruses in live poultry markets in Fujian province was relatively high, especially in the first and third quarters, with H9 subtype accounting for the main proportion. Most of H9N2 subtype belonged to the Y280-like G57 genotype with a small number of Y439-like evolutionary branches, suggesting the possibility of genetic recombination and the risk of human infection. Thus, surveillance of avian influenza viruses in the live poultry markets as well as mutation analysis should continue to be strengthened.

The study explored the therapeutic effect and mechanism of the compound composed of tangerine peel,plum,agrimony and hawthorn on Eimeria tenella in chicks.In the experiment,144 chicks were divided into six groups:the blank group,the model group,the diclazuril group,and the high-dose,medium-dose and low-dose traditional Chinese medicine compound groups.The 14-day-old chickens were infected,the body weight and mortality were recorded,and the samples were dis-sected at 21 days of age.The anticoccidial effect of Chenpi compound at different doses was evalua-ted by calculating anticoccidial index,feed conversion rate and detecting serum cytokine levels and related mRNA expression levels.The results showed that the anticoccidial index of the middle dose group was 172.86,and the anticoccidial index of the low dose group was 158.98.In the middle and low dose groups,the levels of IL-1β,IL-6 and MDA in serum decreased significantly,while the levels of IL-4,IL10,T-AOC,SOD,CAT and GSH-Px increased significantly,and the mRNA ex-pression levels of related inflammation and antioxidant pathways changed.Further studies found that the medium-dose compound can regulate the ChTLR15/ChMyD88/ChNF-κB/ChNLRP3/Caspase-1 inflammatory signaling pathway,activate the Nrf2/Keap1/HO-1 antioxidant signaling pathway,and enhance the body's anti-inflammatory and antioxidant capacity;at the same time,it can increase the expression of intestinal tight junction ZO-1 and Occludin,repair the damaged in-testinal barrier,and play an anticoccidial role.The results showed that the middle dose of tangerine peel compound had a good effect in the treatment of coccidiosis,and its mechanism involved the regulation of anti-inflammatory and antioxidant pathways.

This review summarizes recent advances in neoadjuvant immunotherapy for advanced gastric cancer.Through literature search in PubMed,Web of Science,and CNKI databases from 2020 to 2023,we systematically analyzed the mechanisms,clinical applications,and bio-marker research.Programmed death-1(PD-1)inhibitors combined with chemotherapy significantly improve patient outcomes,while mi-crosatellite instability(MSI),programmed death-ligand 1(PD-L1)expression,and tumor mutational burden(TMB)have been identified as important predictive biomarkers.Multi-omics analysis shows great potential in identifying optimal responders,with pyroptosis-related gene scoring system(PRS)positively correlating with anti-tumor immune infiltration.Metabolic reprogramming and epigenetic regulation in the tumor microenvironment play key roles in immune evasion,while emerging targets such as Claudin 18.2 and combination targeting strategies further enhance therapeutic efficacy.Despite significant progress,precise patient selection and overcoming resistance mechan-isms remain major challenges.Future research should focus on biomarker validation,personalized treatment strategy development,tumor microenvironment dynamic analysis,and novel combination therapy exploration to improve clinical outcomes.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

AIM:To establish a cell model of visceral hypersensitivity and nerve hyperplasia in irritable bowel syndrome(IBS)by conducting an in vitro co-culture of mouse P815 mast cells and N2a nerve cells and explore its possible mechanism.METHODS:Enzyme-linked immunosorbent assay(ELISA)with three replicates was used to confirm the C48/80-induced P815 degranulation.The length of neurites was observed under bright field microscopy to determine the number of differentiated neurons,thereby selecting the concentration of retinoic acid(RA)for stimulating the differentia-tion of N2a cells,with four replicates.A co-culture system of P815 and N2a cells was established using Transwell cham-bers with four replicates.The following groups were established:N2a cells cultured alone,N2a cells co-cultured with P815 cells,N2a cells co-cultured with P815 cells plus C48/80,and N2a cells plus RA group.After co-culturing,the num-ber of differentiated N2a cells was observed under bright field.The expression of nerve growth factor(NGF),tyrosine ki-nase receptor A(TRKA),growth-associated protein-43(GAP43),neuron-specific enolase(NSE),synapsin(SYN),and postsynaptic density protein-95(PSD-95)at both protein and gene levels in N2a cells was detected using Western blot and polymerase chain reaction(PCR),with four replicates.RESULTS:The best condition for N2a differentiation was stimulation with 10 μmol/L RA for 24 hours,whereas the best condition for degranulation was stimulation of P815 cells with 20 mg/L C48/80 for 24 hours.Compared with N2a cells cultured alone,the differentiation ratio of the N2a+P815+C48/80 and N2a+RA groups was significantly increased(P<0.01),and the protein and mRNA expressions of NGF,TRKA,GAP43,NSE,SYN,and PSD-95 were significantly increased(P<0.05).CONCLUSION:Our results revealed that mast cell degranulation enhances the level of nerve hyperplasia in enteric nerve cells and promotes changes in nerve structure and function.Synaptic remodeling regulated by abnormal expression of key proteins such as NGF,TRKA,and GAP43 is involved in the nerve hyperplasia induced by mast cell degranulation.

The study explored the therapeutic effect and mechanism of the compound composed of tangerine peel,plum,agrimony and hawthorn on Eimeria tenella in chicks.In the experiment,144 chicks were divided into six groups:the blank group,the model group,the diclazuril group,and the high-dose,medium-dose and low-dose traditional Chinese medicine compound groups.The 14-day-old chickens were infected,the body weight and mortality were recorded,and the samples were dis-sected at 21 days of age.The anticoccidial effect of Chenpi compound at different doses was evalua-ted by calculating anticoccidial index,feed conversion rate and detecting serum cytokine levels and related mRNA expression levels.The results showed that the anticoccidial index of the middle dose group was 172.86,and the anticoccidial index of the low dose group was 158.98.In the middle and low dose groups,the levels of IL-1β,IL-6 and MDA in serum decreased significantly,while the levels of IL-4,IL10,T-AOC,SOD,CAT and GSH-Px increased significantly,and the mRNA ex-pression levels of related inflammation and antioxidant pathways changed.Further studies found that the medium-dose compound can regulate the ChTLR15/ChMyD88/ChNF-κB/ChNLRP3/Caspase-1 inflammatory signaling pathway,activate the Nrf2/Keap1/HO-1 antioxidant signaling pathway,and enhance the body's anti-inflammatory and antioxidant capacity;at the same time,it can increase the expression of intestinal tight junction ZO-1 and Occludin,repair the damaged in-testinal barrier,and play an anticoccidial role.The results showed that the middle dose of tangerine peel compound had a good effect in the treatment of coccidiosis,and its mechanism involved the regulation of anti-inflammatory and antioxidant pathways.

This review summarizes recent advances in neoadjuvant immunotherapy for advanced gastric cancer.Through literature search in PubMed,Web of Science,and CNKI databases from 2020 to 2023,we systematically analyzed the mechanisms,clinical applications,and bio-marker research.Programmed death-1(PD-1)inhibitors combined with chemotherapy significantly improve patient outcomes,while mi-crosatellite instability(MSI),programmed death-ligand 1(PD-L1)expression,and tumor mutational burden(TMB)have been identified as important predictive biomarkers.Multi-omics analysis shows great potential in identifying optimal responders,with pyroptosis-related gene scoring system(PRS)positively correlating with anti-tumor immune infiltration.Metabolic reprogramming and epigenetic regulation in the tumor microenvironment play key roles in immune evasion,while emerging targets such as Claudin 18.2 and combination targeting strategies further enhance therapeutic efficacy.Despite significant progress,precise patient selection and overcoming resistance mechan-isms remain major challenges.Future research should focus on biomarker validation,personalized treatment strategy development,tumor microenvironment dynamic analysis,and novel combination therapy exploration to improve clinical outcomes.

AIM:To establish a cell model of visceral hypersensitivity and nerve hyperplasia in irritable bowel syndrome(IBS)by conducting an in vitro co-culture of mouse P815 mast cells and N2a nerve cells and explore its possible mechanism.METHODS:Enzyme-linked immunosorbent assay(ELISA)with three replicates was used to confirm the C48/80-induced P815 degranulation.The length of neurites was observed under bright field microscopy to determine the number of differentiated neurons,thereby selecting the concentration of retinoic acid(RA)for stimulating the differentia-tion of N2a cells,with four replicates.A co-culture system of P815 and N2a cells was established using Transwell cham-bers with four replicates.The following groups were established:N2a cells cultured alone,N2a cells co-cultured with P815 cells,N2a cells co-cultured with P815 cells plus C48/80,and N2a cells plus RA group.After co-culturing,the num-ber of differentiated N2a cells was observed under bright field.The expression of nerve growth factor(NGF),tyrosine ki-nase receptor A(TRKA),growth-associated protein-43(GAP43),neuron-specific enolase(NSE),synapsin(SYN),and postsynaptic density protein-95(PSD-95)at both protein and gene levels in N2a cells was detected using Western blot and polymerase chain reaction(PCR),with four replicates.RESULTS:The best condition for N2a differentiation was stimulation with 10 μmol/L RA for 24 hours,whereas the best condition for degranulation was stimulation of P815 cells with 20 mg/L C48/80 for 24 hours.Compared with N2a cells cultured alone,the differentiation ratio of the N2a+P815+C48/80 and N2a+RA groups was significantly increased(P<0.01),and the protein and mRNA expressions of NGF,TRKA,GAP43,NSE,SYN,and PSD-95 were significantly increased(P<0.05).CONCLUSION:Our results revealed that mast cell degranulation enhances the level of nerve hyperplasia in enteric nerve cells and promotes changes in nerve structure and function.Synaptic remodeling regulated by abnormal expression of key proteins such as NGF,TRKA,and GAP43 is involved in the nerve hyperplasia induced by mast cell degranulation.