BACKGROUND:In vitro construction of tissue-engineered intestinal models plays an important role in intestinal regeneration and intestinal disease research.The interaction of intestinal nervous system and intestinal epithelial barrier to maintain body homeostasis is a hot topic in the bionic construction of tissue-engineered intestinal tract.OBJECTIVE:To construct a bionic model that can mimic the enteric nervous system in vivo.METHODS:Using fibroin protein with villus structure as scaffold,human induced neural stem cells solidified with collagen were added to intestinal epithelial cells(Caco-2 and HT29-MTX-E12)for 3-day culture to construct a co-culture system of intestinal epithelial cells and nerve cells(co-culture group).Human induced neural stem cells or intestinal epithelial cells cultured alone that were inoculated with fibroin scaffolds were set as controls.Cell morphology was observed by scanning electron microscopy and hematoxylin-eosin staining.Cell activity was detected by Live/Dead cell staining.Human induced neural stem cell differentiation was detected by β-microtubulin immunofluorescence staining.Intestinal epithelial histological properties and barrier function were detected by microvillin,sucrase-isomaltase,tight junction protein 1,E-calmodulin,and mucin-2 immunofluorescence staining.The function of mucus secretion from intestinal epithelial cells was detected by Alcian blue staining.Alkaline phosphatase staining was performed to detect differentiation of intestinal epithelial cells,at the same time,sucrase-isomaltase,tight junction protein 1,and alkaline phosphatase mRNAs were detected by RT-qRCR.RESULTS AND CONCLUSION:The neuralized intestinal mucosal co-culture model with villi structure was successfully constructed,and neural stem cells and intestinal epithelial cells on the fibroin scaffold showed good cellular activities.After neuralization,the activity of alkaline phosphatase and sucrase-isomaltase in intestinal epithelial cells was enhanced,while the expression level of tight junction protein 1 was up-regulated.To conclude,the neuralized bionic intestinal epithelial model is beneficial to the maturation of intestinal mucosal epithelial cells and the formation of barrier function.

ObjectiveAge-related macular degeneration （AMD） is one of the leading causes of low vision and blindness in people over 50 years old， and dry AMD （dAMD） is one type for which there is currently no clear treatment. On the basis of the diagnosis and clinical characteristics of dAMD in traditional Chinese and Western medicine， this paper evaluated the fitting degrees of existing animal models of dAMD with clinical characteristics according to the evaluation methods of animal models， and put forward suggestions and prospects. MethodsLiterature on animal models of dAMD was searched against database， and the characteristics of the models were assigned according to the diagnosis criteria of diseases and syndromes of traditional Chinese and Western medicine， and the fitting degrees of the models with clinical characteristics were analyzed and evaluated. ResultsAt present， the animal models of dAMD are mainly established targeting complement factors， chemokines， oxidative damage， lipid/glucose metabolism， and natural strains. Most of the models can simulate the major pathological changes of dAMD， showing the fitting degree of 25%-50% with clinical characteristics in Western medicine. However， the evaluation of traditional Chinese medicine （TCM） syndromes， especially the evaluation of secondary syndromes， is missing， and the models present low fitting degrees with the clinical characteristics in TCM. ConclusionExisting animal models of dAMD are mostly established under the guidance of Western diagnostic standards， which reproduce the main disease characteristics of Western medicine and lack observation of TCM syndromes. Future studies can pay attention to the intervention factors and evaluation systems of spleen deficiency Qi deficiency and liver-kidney Yin deficiency syndrome and build the animal model of dAMD with integration of disease and syndrome based on clinical characteristics of traditional Chinese and Western medicine.

ObjectiveAge-related macular degeneration （AMD） is one of the leading causes of low vision and blindness in people over 50 years old， and dry AMD （dAMD） is one type for which there is currently no clear treatment. On the basis of the diagnosis and clinical characteristics of dAMD in traditional Chinese and Western medicine， this paper evaluated the fitting degrees of existing animal models of dAMD with clinical characteristics according to the evaluation methods of animal models， and put forward suggestions and prospects. MethodsLiterature on animal models of dAMD was searched against database， and the characteristics of the models were assigned according to the diagnosis criteria of diseases and syndromes of traditional Chinese and Western medicine， and the fitting degrees of the models with clinical characteristics were analyzed and evaluated. ResultsAt present， the animal models of dAMD are mainly established targeting complement factors， chemokines， oxidative damage， lipid/glucose metabolism， and natural strains. Most of the models can simulate the major pathological changes of dAMD， showing the fitting degree of 25%-50% with clinical characteristics in Western medicine. However， the evaluation of traditional Chinese medicine （TCM） syndromes， especially the evaluation of secondary syndromes， is missing， and the models present low fitting degrees with the clinical characteristics in TCM. ConclusionExisting animal models of dAMD are mostly established under the guidance of Western diagnostic standards， which reproduce the main disease characteristics of Western medicine and lack observation of TCM syndromes. Future studies can pay attention to the intervention factors and evaluation systems of spleen deficiency Qi deficiency and liver-kidney Yin deficiency syndrome and build the animal model of dAMD with integration of disease and syndrome based on clinical characteristics of traditional Chinese and Western medicine.

BACKGROUND:In vitro construction of tissue-engineered intestinal models plays an important role in intestinal regeneration and intestinal disease research.The interaction of intestinal nervous system and intestinal epithelial barrier to maintain body homeostasis is a hot topic in the bionic construction of tissue-engineered intestinal tract.OBJECTIVE:To construct a bionic model that can mimic the enteric nervous system in vivo.METHODS:Using fibroin protein with villus structure as scaffold,human induced neural stem cells solidified with collagen were added to intestinal epithelial cells(Caco-2 and HT29-MTX-E12)for 3-day culture to construct a co-culture system of intestinal epithelial cells and nerve cells(co-culture group).Human induced neural stem cells or intestinal epithelial cells cultured alone that were inoculated with fibroin scaffolds were set as controls.Cell morphology was observed by scanning electron microscopy and hematoxylin-eosin staining.Cell activity was detected by Live/Dead cell staining.Human induced neural stem cell differentiation was detected by β-microtubulin immunofluorescence staining.Intestinal epithelial histological properties and barrier function were detected by microvillin,sucrase-isomaltase,tight junction protein 1,E-calmodulin,and mucin-2 immunofluorescence staining.The function of mucus secretion from intestinal epithelial cells was detected by Alcian blue staining.Alkaline phosphatase staining was performed to detect differentiation of intestinal epithelial cells,at the same time,sucrase-isomaltase,tight junction protein 1,and alkaline phosphatase mRNAs were detected by RT-qRCR.RESULTS AND CONCLUSION:The neuralized intestinal mucosal co-culture model with villi structure was successfully constructed,and neural stem cells and intestinal epithelial cells on the fibroin scaffold showed good cellular activities.After neuralization,the activity of alkaline phosphatase and sucrase-isomaltase in intestinal epithelial cells was enhanced,while the expression level of tight junction protein 1 was up-regulated.To conclude,the neuralized bionic intestinal epithelial model is beneficial to the maturation of intestinal mucosal epithelial cells and the formation of barrier function.

Objective To understand the experience of fall alertness in elderly patients with rheumatoid arthritis and to provide references for the development of targeted nursing intervention strategies.Methods 13 elderly patients with rheumatoid arthritis,who were admitted to the Department of Rheumatology and Immunology of a tertiary hospital in Guizhou Province from February to April 2024,were selected through purposive sampling.Phenomenological qualitative research methods were used,with semi-structured in-depth interviews.Data were analyzed using Colaizzi's seven-step method,and themes were extracted.Results 3 main themes and 9 sub-themes were identified:the process of fall risk perception(reshaping fall risk cognition,establishing emotional coping mechanism,enhancing fall alertness effect),behavioral responses to fall alertness(creating a safe living environment,regularizing daily routine plan),and needs for fall prevention support(need for fall prevention knowledge,home rehabilitation care needs,intelligent device usage needs,psychosocial support needs).Conclusion Clinical medical staff should pay attention to the transformation process of fall risk perception in elderly rheumatoid arthritis patients,accurately identify patients'fall support needs in practice,and guide patients to adopt appropriate fall alert response behaviors through innovative fall demand support interaction paths and the construction of social support network systems,in order to improve patients'fall alertness and reduce their fall risk.

Objective:To retrospectively analyze the current status of consultation, clinical characteristics, and treatment status of patients with IgG4-related disease (IgG4-RD) in order to provide assistance and a basis for early and standardized diagnosis and treatment.Methods:IgG4-RD cases admitted to our hospital from June 2015 to October 2023 were collected. The details of patients' basic information, initial symptoms, department visits, laboratory and imaging findings, histopathological examination results, and treatment plans were recorded. A statistical descriptive analysis was performed on the data.Results:A total of 105 patients with IgG4-RD were included, with a median age of 59.0 (18.0, 78.0) years. The main departments visited were clinical immunology and gastroenterology (83.8%, 88/105). The median diagnostic duration was eight months, with a maximum of 300 months, and 33.3% (35/105) of patients needed over one year for diagnosis. 92 cases underwent histopathological examinations and IgG4 staining, with a total positivity rate of 87.0% (80/92). Among these, sixteen cases underwent pathological examination after surgery, with a positivity rate of 100%; the remaining 76 cases out of 92 underwent liver biopsy, with a positivity rate of 76.1%. Out of these, there were 22 cases from the pancreas, 21 from the submaxillary gland, nine from the labial gland, and seven each from the duodenal papilla and liver, with positivity rates of 81.8%, 81.0%, 55.6%, 85.7%, and 85.7%, respectively. Eleven cases (10.5%) with normal serum IgG4 were diagnosed based on multi-organ involvement and pathological results. 94 cases (89.5%) had elevated IgG4, with a predominance of＞2.70 g/L. The median follow-up period for the 87 cases was 14 months. Two cases had poor response, twelve patients relapsed, five cases relapsed without combined drug treatment after surgery, five cases relapsed due to drug withdrawal, and two cases relapsed while tapering off steroids.Conclusions:As a multisystem disease, IgG4-RD still faces the difficulties of time-consuming diagnosis and inappropriate treatment. Therefore, it is necessary to rely on a multidisciplinary collaboration model to improve the awareness level and promote the early and standardized diagnosis and treatment of patients with IgG4-RD.

Objective To explore the predictive value of quantitative parameters of dual-layer detector spectral CT(DLCT)for Ki-67 expression in solid lung adenocarcinoma.Methods The data of 103 patients were retrospectively collected,and the patients were divided into Ki-67 high expression and Ki-67 low expression groups according to Ki-67 proliferation index.The quantitative parame-ters of DLCT were measured and calculated,and the differences in these parameters between the two groups were compared.The parameters with statistically significant differences were assessed for correlation with Ki-67 expression.The efficacy of DLCT param-eters and combined parameters in predicting Ki-67 expression in solid lung adenocarcinoma were evaluated by receiver operating character-istic(ROC)curve and compared by DeLong test.Results Long diameter,short diameter and smoking history were positively corre-lated with the Ki-67 expression in solid lung adenocarcinoma(r>0,P<0.05).Gender and quantitative parameters of DLCT were nega-tively correlated with the Ki-67 expression in solid lung adenocarcinoma(r<0,P<0.05).The combined parameters of convention and spectral CT had the highest prediction efficiency.Conclusion The quantitative parameters of DLCT can be used to evaluate the Ki-67 expres-sion in solid lung adenocarcinoma.

Objective:To investigate the efficacy and safety of a combination of programmed death receptor 1 (PD-1) inhibitor and multi-target tyrosine kinase inhibitor anlotinib in second-line treatment of non-small cell lung cancer (NSCLC).Methods:A prospective randomized controlled study was conducted. Using the random number table method, 118 NSCLC patients who were admitted to Shaanxi Provincial Cancer Hospital from June 2021 to June 2023 were randomly divided into the control group and the observation group, with 59 patients in each group. The observation group was treated with PD-1 inhibitor combined with anlotinib, while the control group was treated with PD-1 inhibitor. There were 36 males and 23 females in the observation group, with an age of (56±5) years; there were 34 males and 25 females in the control group, with an age of (56±5) years. There was no statistically significant difference in general clinicopathological data between the two groups (all P > 0.05). The short-term clinical efficacy [objective response rate (ORR) and disease control rate (DCR)], tumor-related factor levels [vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP-2), tissue inhibitor of matrix metalloproteinase (TIMP), and tumor necrosis factor β1 (TNF-β1)], inflammatory status [plasma fibrinogen-to-albumin ratio (FAR)], lung function [forced vital capacity (FVC) and peak expiratory flow (PEF)] before and after treatment, the European Organization for Research and Treatment on Cancer (EORTC) core questionnaire for quality of life assessment (QLQ-C30) score, and occurrence of adverse reactions were compared between two groups of patients. Results:The ORR and DCR of the observation group were 33.90% (20/59) and 69.49% (41/59), respectively; the ORR and DCR of the control group were 10.17% (6/59) and 44.07% (26/59), respectively; the comparison of ORR and DCR between the two groups showed statistically significant differences ( χ2 values were 9.67 and 7.77, both P < 0.05). There was no statistically significant difference in the levels of tumor-related factors between the observation group and the control group before treatment (all P > 0.05); after 4 cycles of treatment, the levels of VEGF and MMP-2 in the observation group were lower than those in the control group, while the levels of TIMP and TNF-β1 were higher than those in the control group, and the differences were statistically significant (all P < 0.001). The FAR of the observation group and the control group before treatment were (0.15±0.06) g/L and (0.16±0.06) g/L, respectively, with no statistically significant difference ( t = 0.90, P = 0.367); after 4 cycles of treatment, the FAR were (0.07±0.01) g/L and (0.11±0.04) g/L, respectively, with statistically significant difference ( t = 7.45, P < 0.001). Before treatment, there was no statistically significant difference in FVC and PEF between the observation group and the control group (both P > 0.05); after 4 cycles of treatment, the FVC and PEF in the observation group were higher than those in the control group, and the differences were statistically significant (both P < 0.001). There were no statistically significant differences in the EORTC QLQ-C30 scores of functional dimension, symptom dimension and global health status/quality of life dimension between the observation group and the control group before treatment (all P > 0.05); after 4 cycles of treatment, the scores of functional dimension and global health status/quality of life dimension in the observation group were higher than those in the control group, while the symptom dimension score was lower than that in the control group, and the differences were statistically significant (all P < 0.001). The incidence of adverse reactions in the observation group was 6.78% (4/59), while in the control group it was 10.17% (6/59), and the difference was not statistically significant ( P = 0.741). Conclusions:The combination of PD-1 inhibitor and anlotinib in second-line treatment of NSCLC has good clinical efficacy, it can reduce the inflammatory response, improve the lung function and quality of life, and has good safety.

AIM:To investigate the effect of cryptotanshinone(CPT)on myocardial hypertrophy induced by isoprenaline(ISO)in rats and explore its potential mechanism.METHODS:The experimental design consisted of two parts.The first aimed to investigate the effects of CPT on cardiac function,pathological manifestations,and the Janus ki-nase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway in rats with myocardial hyper-trophy.The rats were divided into six groups,namely the control,CPT control,and model groups and low-(15 mg·kg-1·d-1),medium-(30 mg·kg-1·d-1),and high-dose(60 mg·kg-1·d-1)CPT treatment groups,with six rats per group.The sec-ond part aimed to validate the role of the JAK2/STAT3 signaling pathway in the CPT-mediated myocardial hypertrophy treatment.Rats were divided into four groups,namely the control,model,high-dose CPT treatment,and coumermycin A1(CA1,a JAK2/STAT3 agonist)intervention(rats received ISO injection followed by 60 mg·kg-1·d-1 of high-dose CPT and 1 mg·kg-1·d-1 of CA1 for 15 d)groups,with five rats per group.Myocardial hypertrophy was induced in rats via intra-peritoneal injection of ISO(5 mg/kg),and CPT intervention lasted for 15 days.Cardiac function-related parameters were assessed using echocardiography,and pathological changes were evaluated through hematoxylin-eosin,Masson,and wheat germ agglutinin staining.Protein expression levels of atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),β-myosin heavy chain(β-MHC),and JAK2/STAT3 signaling pathway-related proteins were detected by Western blot analysis.RESULTS:Compared with the model group,CPT administration improved cardiac dysfunction-related ul-trasound markers and significantly reduced ISO-induced cardiomyocyte hypertrophy and myocardial fibrosis in rats with hy-pertrophy in a dose-dependent manner(P<0.05).Additionally,CPT decreased the levels of ANP,BNP,and β-MHC in-duced by ISO modeling(P<0.05),and inhibiting the phosphorylation of JAK2 and STAT3(P<0.05).Furthermore,a partial reversal of the therapeutic effect on myocardial hypertrophy induced by ISO modeling was observed when CA1 was administered(P<0.05).CONCLUSION:The CPT exhibits potential as a therapeutic agent for cardiac hypertrophy by effectively attenuating ISO-induced cardiac hypertrophy in rats through JAK2/STAT3 signaling inhibition.

Objective:To analyze the guiding value of index of consciousness 1(IoC1) and index of consciousness 2(IoC2) in anesthesia management of laparoscopic surgery.Methods:A total of 100 elderly patients undergoing laparoscopic surgery under general anesthesia in the Beijing Coal Group General Hospital from June 2022 to October 2023 were prospectively selected as research objects, and they were divided into the observation group and the control group according to random number table method, with 50 cases in each group. The observation group used IoC1 and IoC2 to monitor and guide anesthesia management, while the control group used bispectral index (BIS) to monitor the depth of anesthesia, and combined with the experience of anesthesiologists to guide anesthesia management. The changes of vital signs of patients in the two groups were compared after calm entry (T 0), induction of anesthesia (T 1), implantation of laryngeal mask 1 min (T 2), carbon dioxide (CO 2) pneumoperitoneum 1 min (T 3), and removal of laryngeal mask 1 min (T 4). The time of resuscitation extubation, dosage of anesthetic drugs, dosage of vasoactive drugs, IoC1, IoC2 and BIS were compared between the two groups. Results:The pneumoperitoneum time and incidence of circulatory instability between the two groups had no statistical differences ( P>0.05). The time of resuscitation and extubation in the observation group was shorter than that in the control group : (8.16 ± 6.08) min vs. (13.10 ± 7.09) min, the dosage of propofol and remifentanil were lower than those in the control group : (382.10 ± 201.90) mg vs. (465.48 ± 213.51) mg, (0.81 ± 0.62) mg vs. (1.17 ± 0.55) mg, there were statistical differences ( P<0.05). The amount of ephedrine and atropine between the two groups had no statistical differences ( P>0.05). The dosage of norepinephrine in the observation group was lower than that in the control group: (106.42 ± 46.12) μg vs. (147.04 ± 51.38) μg, there was statistical difference ( P<0.05). The heart rate, mean arterial pressure (MAP) and IoC1/BIS between the two groups had no statistical differences ( P>0.05). The IoC2 values of T 0, T 1, T 2, T 3 and T 4 in the observation group were 97.46 ± 2.46, 45.28 ± 5.08, 48.64 ± 4.51, 50.44 ± 4.21 and 96.08 ± 2.69, respectively. The IoC2 value of T 3 was higher than that of T 1 and T 2 in the observation group, there were statistical differences ( P<0.05). Conclusions:The application of IoC1 and IoC2 to monitor and guide the anesthesia management of laparoscopic patients under general anesthesia makes the application of anesthetic drugs more quantitative and precise, the perioperative vital signs more stable, and the recovery time faster.