This study aimed to investigate the effects of the peptide secreted protein isthmin-1 (ISM1) on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells. ISM1 expression in NSCLC was detected by immunohistochemistry (IHC). ISM1 was overexpressed in lung cancer cell lines by transient transfection of ISM1 plasmids, or establishing ISM1 overexpression stable cell lines, or by treating cells with recombined ISM1 (rISM1). CCK-8 was used to examine cell growth. The intracellular signal transduction pathways regulated by rISM1 were analyzed by transcriptome sequencing, and verified by qRT-PCR and Western blot. The levels of intracellular ROS and apoptosis were further detected using the kit. The results showed that the expression of ISM1 was decreased in human NSCLC tissue samples compared to normal lung tissue samples. Overexpression of ISM1 or rISM1 treatment significantly suppressed the growth of lung cancer cells. RNA sequencing revealed that rISM1 mainly regulated the FoxO signaling pathway. rISM1 treatment decreased the expression of FoxO3 and FoxO1, increased reactive oxygen species (ROS) production, and induced cell apoptosis. These results suggest that ISM1 can inhibit the growth of NSCLC by regulating the FoxO signaling pathway. These findings provide new strategies for cancer therapy.

The global incidence rate of cancer is increasing yearly,and chemotherapy-induced gastrointestinal mucosal injury has become a crucial factor affecting patients'therapeutic prognosis;however,there is currently a lack of effective therapeutic drugs to address this issue.There is thus an urgent need to establish more ideal animal models of chemotherapy-induced gastrointestinal mucosal injury,to support the exploration of its pathogenesis and the development of therapeutic drugs.This review considered relevant literature published during the period from 2019 to 2024,to provide a comprehensive summary and analysis from several perspectives,including the selection of experimental animals,chemotherapeutic drugs and modeling method,evaluation indicators,and practical applications.Furthermore,we highlight several existing issues with current models,including the lack of standardized modeling method,insufficient research on models with a tumor background,and inadequate exploration of novel cell death mechanisms.This collation of the literature also revealed the gradual emergence of traditional Chinese medicine as a research hotspot,with potential for the treatment of gastrointestinal mucosal injury.Further studies of effective medicines are warranted to identify interventional strategies for chemotherapy-induced gastrointestinal mucosal injury.

Objective:To construct patient-derived xenograft (PDX) models from head and neck squamous cell carcinoma (HNSCC) patients, to explore the effect of immune reconstitution timing on the PDX modeling and immune microenvironment in humanized immune system mice (huHSC-NCG-hIL15), and to provide a reliable animal model for research on the mechanisms of head and neck squamous carcinoma and for studies on immune therapy drug interventions.Methods:This study enrolled 28 HNSCC patients (25 laryngeal carcinomas, 3 hypopharyngeal carcinomas). PDX models were established in Balb/c nude (nu) mice, NSG mice, and humanized immune system-reconstituted huHSC-NCG-hIL15 mice. Fresh HNSCC samples were transplanted into Balb/c nu and NSG mice to generate PDX models, with subsequent analysis of success-associated factors. One successfully established PDX tumor was subsequently implanted into humanized immune system-reconstituted huHSC-NCG-hIL15 mice. Tumor transplantation was performed at distinct immune reconstruction timepoints (2 vs. 7 weeks post-reconstitution), and tumor growth patterns were monitored. Flow cytometry and multiplex immunohistochemical staining were utilized to characterize immunological profiles in peripheral lymphoid organs and tumor microenvironments. Hematoxylin-eosin (HE) staining was employed to assess histomorphological concordance between primary patient tumors and PDX model tissues. Results:HNSCC PDX models were successfully established. NSG mice exhibited a higher and more stable tumor take rate compared to Balb/c nu mice (pilot study: 4/10 vs. 3/10 cases; mean take rate 60%-80% vs. 20%-60 %). The PDX success rate in NSG mice was 46.4% (13/28). In the huHSC-NCG-hIL15 mice model with immune reconstitution at 7 weeks, tumors grew significantly faster, and the PDX modeling process was shorter (617 mm3 at day 70 in 7-week cohort vs.280 mm3 in 2-week cohort). Flow cytometry analysis of the immune microenvironment showed that at 7 weeks of immune reconstitution, the proportions of B cells in the spleen and tumor tissues(2-week vs. 7-week: spleen 16.2% vs. 61.7%, tumor 26.0% vs. 38.8%) and myeloid cells in the spleen (2-week vs. 7-week: spleen 47.2% vs. 88.1 %) were significantly higher, while mice at 2 weeks post-reconstitution showed a higher proportion of T cells (2-week vs. 7-week: spleen 13.2% vs. 9.3%, tumor 4.8% vs. 2.5%). HE results demonstrated that the tumor tissues in PDX models maintained a high degree of morphological similarity to the primary tumors in both NSG and huHSC-NCG-hIL15 mouse models. Conclusion:The HNSCC PDX modeling protocol demonstrates operational feasibility and high reproducibility, establishing this model as a robust platform for mechanistic and immunotherapeutic studies.

Objective:To investigate the efficacy of neuromuscular electrical stimulation (NMES) combined with limb rehabilitation therapy in improving limb function of patients with hemiplegia due to stroke.Methods:A randomized controlled study was conducted on 110 patients with hemiplegia due to stroke admitted to the 987 Hospital of the PLA Joint Logistic Support Force from January 2021 to January 2023. These patients were divided into a control group and an observation group, with 55 cases each, using a random number table method. The control group received conventional rehabilitation therapy, while the observation group received NMES combined with limb rehabilitation therapy. All patients were treated for 3 months. The Trunk Impairment Scale, Brunnstrom Motor Function Scale, Surface Electromyography, Brunel Balance Scale, Simple Gait Test Scale, and Modified Ashworth Scale were used to evaluate trunk control function, limb control function, neuromuscular disorders, balance control function (forward-backward inclination angle, left-right inclination angle), gait temporal-spatial parameters, symmetry parameters, and muscle tone recovery in both groups before and after treatment.Results:After treatment, the Total Impairment Scale and Brunnstrom scores for upper and lower limbs in the observation group were higher than those in the control group [(18.31 ± 1.61) vs. (14.38 ± 1.42), (3.78 ± 0.41) vs. (3.01 ± 0.63), (3.75 ± 0.42) vs. (3.28 ± 0.63), t = 13.58, 7.60, 4.60, all P < 0.05]. Additionally, the scores for tibialis anterior, fibularis brevis, fibularis longus, medial gastrocnemius, lateral gastrocnemius muscle control were higher in the observation group compared with the control group. The scores for Berg Balance Scale, forward-backward inclination angle, left-right inclination angle, step frequency, step length, step speed, and step width in the observation group were also superior to those in the control group. All differences were statistically significant ( t = 17.88, 20.15, 24.62, 19.53, 22.80, 3.31, 8.66, 7.88, 6.08, 4.21, 7.43, 3.35, all P < 0.05). Furthermore, the deviations in step length, the ratio of support on the affected side to the unaffected side, and the ratio of swing on the affected side to the unaffected side in the observation group were lower than those in the control group [(3.53 ± 2.55) vs. (5.35 ± 3.21), (1.11 ± 0.04) vs. (1.14 ± 0.03), (1.10 ± 0.06) vs. (1.24 ± 0.09), t = 3.29, 4.45, 9.60, all P < 0.05]. Additionally, the level of muscle tone recovery in the observation group was higher than that in the control group ( Z = 2.53, P = 0.011). Conclusions:In the treatment of hemiplegia due to stroke, NMES combined with limb rehabilitation therapy can effectively improve patients' trunk and limb control, enhance balance function, and greatly promote muscle strength recovery.

Objective:To construct patient-derived xenograft (PDX) models from head and neck squamous cell carcinoma (HNSCC) patients, to explore the effect of immune reconstitution timing on the PDX modeling and immune microenvironment in humanized immune system mice (huHSC-NCG-hIL15), and to provide a reliable animal model for research on the mechanisms of head and neck squamous carcinoma and for studies on immune therapy drug interventions.Methods:This study enrolled 28 HNSCC patients (25 laryngeal carcinomas, 3 hypopharyngeal carcinomas). PDX models were established in Balb/c nude (nu) mice, NSG mice, and humanized immune system-reconstituted huHSC-NCG-hIL15 mice. Fresh HNSCC samples were transplanted into Balb/c nu and NSG mice to generate PDX models, with subsequent analysis of success-associated factors. One successfully established PDX tumor was subsequently implanted into humanized immune system-reconstituted huHSC-NCG-hIL15 mice. Tumor transplantation was performed at distinct immune reconstruction timepoints (2 vs. 7 weeks post-reconstitution), and tumor growth patterns were monitored. Flow cytometry and multiplex immunohistochemical staining were utilized to characterize immunological profiles in peripheral lymphoid organs and tumor microenvironments. Hematoxylin-eosin (HE) staining was employed to assess histomorphological concordance between primary patient tumors and PDX model tissues. Results:HNSCC PDX models were successfully established. NSG mice exhibited a higher and more stable tumor take rate compared to Balb/c nu mice (pilot study: 4/10 vs. 3/10 cases; mean take rate 60%-80% vs. 20%-60 %). The PDX success rate in NSG mice was 46.4% (13/28). In the huHSC-NCG-hIL15 mice model with immune reconstitution at 7 weeks, tumors grew significantly faster, and the PDX modeling process was shorter (617 mm3 at day 70 in 7-week cohort vs.280 mm3 in 2-week cohort). Flow cytometry analysis of the immune microenvironment showed that at 7 weeks of immune reconstitution, the proportions of B cells in the spleen and tumor tissues(2-week vs. 7-week: spleen 16.2% vs. 61.7%, tumor 26.0% vs. 38.8%) and myeloid cells in the spleen (2-week vs. 7-week: spleen 47.2% vs. 88.1 %) were significantly higher, while mice at 2 weeks post-reconstitution showed a higher proportion of T cells (2-week vs. 7-week: spleen 13.2% vs. 9.3%, tumor 4.8% vs. 2.5%). HE results demonstrated that the tumor tissues in PDX models maintained a high degree of morphological similarity to the primary tumors in both NSG and huHSC-NCG-hIL15 mouse models. Conclusion:The HNSCC PDX modeling protocol demonstrates operational feasibility and high reproducibility, establishing this model as a robust platform for mechanistic and immunotherapeutic studies.

Objective To analyze acupoint selection law of Professor Fu Wenbin in using acupuncture for the treatment of insomnia based on data mining technology;To provide references for the formulation and optimization of clinical treatment plans.Methods The cases of insomnia treated by acupuncture in the Acupuncture and Moxibustion Department of Guangdong Provincial Hospital of Traditional Chinese Medicine from January 1,2020 to December 31,2021 and in the Acupuncture and Moxibustion Department of Shenzhen Bao'an Hospital of Traditional Chinese Medicine from August 1,2018 to December 31,2021 were collected.A database of prescription information for acupuncture treatment for insomnia was established.The law of acupoint selection frequency,meridians,specific acupoints,correlation analysis and hidden structure analysis for acupuncture treatment of insomnia was mined.Results A total of 517 prescriptions were collected.Acupoints were mainly taken from Baihui(DU20,516 times),Yintang(DU29,499 times),Zhongwan(RN12,482 times)and Taichong(LR3,410 times),and meridians were mainly from Conception Vessel(2 120 times,11 acupoints),Governor Vessel(1 074 times,5 acupoints),liver meridian(410 times,1 acupoint),stomach meridian(401 times,8 acupoints)and kidney meridian(300 times,6 acupoints).The main specific acupoints were the Jiaohui(2 723 times,20 acupoints),Mu(892 times,4 acupoints),and Yuan(746 times,8 acupoints).The core acupoint combination based on Zhongwan-Baihui,Yintang(RN12-DU20-DU29)was formed by the correlation analysis of high-frequency acupoints,and the hidden structure of high-frequency acupoints was analyzed to obtain four comprehensive clustering models corresponding to the evidence of heart-kidney disharmony,liver depression and kidney deficiency,liver depression and kidney deficiency,and heart and gallbladder dysregulation.Conclusion Professor Fu Wenbin uses acupuncture to treat insomnia,with balancing yin and yang,regulating Conception Vessel and Conception Vessel as the basic treatment principle,dredging the liver to regulate the spirit,harmonizing the stomach to calm the spirit,communicating with the heart and kidney,and treating the heart and gallbladder as the treatment method.

Game-based psychological assessment utilizes game mechanisms and elements to enhance partic-ipants'motivation and improve measurement accuracy,but similar to traditional methods,it mainly focuses on static results.By integrating game-based psychological assessment with artificial intelligence technology,this paper propo-ses the paradigm of intelligent psychological assessment based on interactive environment.With analyzing dynamic process data within the game,this paradigm can accurately depict the participants'actions and results in the interac-tive context,more effectively representing individual psychological states and behavioral characteristics.This new paradigm demonstrates advancements and significant potential for development in terms of demand,data collection,and analysis techniques.

The global incidence rate of cancer is increasing yearly,and chemotherapy-induced gastrointestinal mucosal injury has become a crucial factor affecting patients'therapeutic prognosis;however,there is currently a lack of effective therapeutic drugs to address this issue.There is thus an urgent need to establish more ideal animal models of chemotherapy-induced gastrointestinal mucosal injury,to support the exploration of its pathogenesis and the development of therapeutic drugs.This review considered relevant literature published during the period from 2019 to 2024,to provide a comprehensive summary and analysis from several perspectives,including the selection of experimental animals,chemotherapeutic drugs and modeling method,evaluation indicators,and practical applications.Furthermore,we highlight several existing issues with current models,including the lack of standardized modeling method,insufficient research on models with a tumor background,and inadequate exploration of novel cell death mechanisms.This collation of the literature also revealed the gradual emergence of traditional Chinese medicine as a research hotspot,with potential for the treatment of gastrointestinal mucosal injury.Further studies of effective medicines are warranted to identify interventional strategies for chemotherapy-induced gastrointestinal mucosal injury.

Objective:To investigate the efficacy of neuromuscular electrical stimulation (NMES) combined with limb rehabilitation therapy in improving limb function of patients with hemiplegia due to stroke.Methods:A randomized controlled study was conducted on 110 patients with hemiplegia due to stroke admitted to the 987 Hospital of the PLA Joint Logistic Support Force from January 2021 to January 2023. These patients were divided into a control group and an observation group, with 55 cases each, using a random number table method. The control group received conventional rehabilitation therapy, while the observation group received NMES combined with limb rehabilitation therapy. All patients were treated for 3 months. The Trunk Impairment Scale, Brunnstrom Motor Function Scale, Surface Electromyography, Brunel Balance Scale, Simple Gait Test Scale, and Modified Ashworth Scale were used to evaluate trunk control function, limb control function, neuromuscular disorders, balance control function (forward-backward inclination angle, left-right inclination angle), gait temporal-spatial parameters, symmetry parameters, and muscle tone recovery in both groups before and after treatment.Results:After treatment, the Total Impairment Scale and Brunnstrom scores for upper and lower limbs in the observation group were higher than those in the control group [(18.31 ± 1.61) vs. (14.38 ± 1.42), (3.78 ± 0.41) vs. (3.01 ± 0.63), (3.75 ± 0.42) vs. (3.28 ± 0.63), t = 13.58, 7.60, 4.60, all P < 0.05]. Additionally, the scores for tibialis anterior, fibularis brevis, fibularis longus, medial gastrocnemius, lateral gastrocnemius muscle control were higher in the observation group compared with the control group. The scores for Berg Balance Scale, forward-backward inclination angle, left-right inclination angle, step frequency, step length, step speed, and step width in the observation group were also superior to those in the control group. All differences were statistically significant ( t = 17.88, 20.15, 24.62, 19.53, 22.80, 3.31, 8.66, 7.88, 6.08, 4.21, 7.43, 3.35, all P < 0.05). Furthermore, the deviations in step length, the ratio of support on the affected side to the unaffected side, and the ratio of swing on the affected side to the unaffected side in the observation group were lower than those in the control group [(3.53 ± 2.55) vs. (5.35 ± 3.21), (1.11 ± 0.04) vs. (1.14 ± 0.03), (1.10 ± 0.06) vs. (1.24 ± 0.09), t = 3.29, 4.45, 9.60, all P < 0.05]. Additionally, the level of muscle tone recovery in the observation group was higher than that in the control group ( Z = 2.53, P = 0.011). Conclusions:In the treatment of hemiplegia due to stroke, NMES combined with limb rehabilitation therapy can effectively improve patients' trunk and limb control, enhance balance function, and greatly promote muscle strength recovery.

Lung cancer is a serious pulmonary tumor,with exacerbation of chronic lung inflammation being a precursor to the development of lung cancer.Relevant animal models are widely used in experimental research,to gain a deeper understanding of the pathogenesis of lung cancer and to develop preventive treatment strategies.Induced lung cancer animal models are of particular importance for understanding the transition from chronic lung inflammation to lung cancer.Early intervention is crucial for the prevention and treatment of lung cancer.Here we review the recent literature regarding the inducing factors for lung cancer,including carcinogens(e.g.nicotine-derived nitrosamine ketone,benzopyrene,diethylnirtosamine atmospheric fine particulate matter(PM2.5),coal smoke,heavy metal ions,radiation,and biological infections).We also summarize animal models of lung inflammation and cancer transformation induced by these factors,discuss the mechanisms by which relevant carcinogens induce lung cancer,analyze the advantages and limitations of the animal models,and consider future development directions.This review aims is to provide a valuable reference for the future establishment of relevant models.