Abstract Ring finger protein 183(RNF183) is an E3 ubiquitin ligase that catalyzes the covalent attachment of ubiquitin molecules to substrate proteins. RNF183 is expressed in tissues such as kidney and testis, and it is mainly localized to the endoplasmic reticulum, Golgi apparatus, and lysosomes in cells. As one of the components of the endoplasmic reticulum membrane, it participates in the endoplasmic reticulum stress-responsive pathway that affects cellular and protein ubiquitination. In recent years, the study of E3 ubiquitin ligase member-RNF183 with various diseases such as colorectal cancer, endometrial cancer and bladder cancer has gradually increased. In this review, the role of RNF183 in colorectal cancer, inflammatory bowel disease and other diseases, as well as biological functions such as endoplasmic reticulum stress are summarized, aiming to provide reference ideas for the study of related diseases.

Objective Exploring the diagnostic value of T-cell enzyme-linked immunospot assay(T-SPOT.TB)combined with rifampicin-resistant Mycobacterium tuberculosis real-time fluorescence quantitative nucleic acid ampli-fication detection(XpertMTB/RIF)in geriatric AIDS patients with Mycobacterium tuberculosis(MTB)infection.Methods From May 2022 to May 2024,86 elderly patients with AIDS suspected MTB in Hengshui Third People's Hospital were gathered and separated into AIDS complicated with MTB(research group)and AIDS without MTB(control group)according to the pathological examination results.MTB culture,T-SPOT.TB and XpertMTB/RIF were performed.Kappa analysis was applied to evaluate the consistency between T-SPOT.TB combined with Xpert-MTB/RIF and the gold standard for diagnosing MTB coinfection in AIDS patients.ROC curve and four grid table were plotted to analyze the value of the combination of T-SPOT.TB and XpertMTB/RIF in the diagnosis of AIDS complicated with MTB infection.Results The blood γ-interferon,the positive detection rates of T-SPOT.TB and XpertMTB/RIF in the research group were higher than those in the control group(P＜0.05).The AUC of T-SPOT.TB in diagnosing AIDS with MTB infection was 0.810,that of Xpert MTB/RIF in diagnosing AIDS with MTB infection was 0.835,and the AUC of the two in diagnosing AIDS with MTB infection was 0.910.The Kappa values of T-SPOT.TB,Xpert MTB/RIF and their combined diagnosis for AIDS with MTB infection were 0.624,0.674 and 0.825,respectively.The accuracy of T-SPOT.TB in the diagnosis of AIDS with MTB was 82.56%,the accuracy of XpertMTB/RIF in the diagnosis of AIDS with MTB was 84.88%,and the accuracy of the combined di-agnosis for AIDS with MTB was 91.86%.Conclusions T-SPOT.TB combined with XpertMTB/RIF can improve the accuracy of diagnosis of AIDS with MTB,and can be used as a clinical auxiliary diagnosis method for AIDS pa-tients complicated with MTB.

Objective:To investigate the expression of interleukin (IL)-22 in lung adenocarcinoma and its effect and possible mechanism for lung adenocarcinoma metastasis.Methods:The cancer tissues and paired adjacent normal tissues (>2 cm from the tumor edge) surgically removed from 27 lung adenocarcinoma patients in Tianjin Medical University Cancer Institute & Hospital from January to June 2023 were retrospectively collected. Flow cytometry was used to detect the expression levels of IL-22 in T cells of all tissues, and the expression levels of IL-22 in T cells were compared between cancer and adjacent tissues, as well as between lung cancer tissues of patients with and without lymph node metastasis. The cancer tissues and paired adjacent normal tissues were retrospectively collected from 6 patients with lung adenocarcinoma during the same period, and the expression level of IL-22 receptor IL-22RA1 in the tissues was detected by Western blotting. IL-22RA1 transcriptome data from cancer tissues of lung adenocarcinoma patients in 3 datasets in The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database were collected. Using the R software survminer package to select the optimal critical value of IL-22RA1 that reflected the survival relationship, and patients were divided into high and low IL-22RA1 groups based on this. The survival package was used to draw the overall survival curve and log-rank test was performed for inter group comparison. Recombinant IL-22 was used to treat human lung adenocarcinoma A549 cells and mouse lung adenocarcinoma LLC cells, with cells not treated with IL-22 as controls; Transwell assay was used to detect the number of migrating cells in each group; Western blotting was used to detect the expression levels of ERK, AKT and STAT signaling pathways-related proteins, matrix metalloproteinase 9 (MMP-9) and epithelial cadherin (E-cad) in each group of cells. The expression levels of these proteins in A549 cells and LLC cells were also measured after the addition of STAT3 inhibitor C188-9, AKT inhibitor MK-2206 and ERK inhibitor SCH772984. A lung metastasis model of LLC cells was constructed using 10 C57BL/6 mice, the mice were randomly divided into the experimental group and the control group using simple randomization method. IL-22 neutralizing antibody (50 μg/mouse) and non-neutralizing control antibody (50 μg/mouse) were injected once every other day. On the 10th day, the mice were euthanized and dissected to count lung metastatic nodules. The metastatic lung tissue was stained with HE and the metastatic foci were counted. Flow cytometry was used to detect the proportion of CD4 + T cells and CD8 + T cells to immune cells in single cells prepared from metastatic lung tissue. Results:The flow cytometry analysis showed that the proportion of IL-22 + CD4 + T cells in T cells (labeled with CD3 and CD45) in 27 clinically collected lung adenocarcinoma tissues [ M ( Q1, Q3)] was higher than that in adjacent normal tissues [0.28% (0.04%, 1.00%) vs. 0.01% (0.00%, 0.25%)]. The proportion of IL-22 + CD4 + T cells in lung adenocarcinoma tissues of patients with metastasis (9 cases) was higher than that of patients without metastasis (18 cases) [1.06% (0.49%, 4.72%) vs. 0.15% (0.00%, 0.35%)], and the differences were statistically significant (both P < 0.01). Western blotting analysis showed that the relative expression level of IL-22RA1 protein in lung adenocarcinoma tissues was higher than that in adjacent normal tissues (1.03±0.25 vs. 0.35±0.10), and the difference was statistically significant ( P < 0.05). The overall survival of the IL-22RA1 low expression group in lung adenocarcinoma tissues was better than that of the IL-22RA1 high expression group in the TCGA database and GEO databases GSE42127, GSE29016 and GSE26939 datasets, and the differences were statistically significant (all P < 0.001). Transwell assay showed that A549 cells [(744±40) cells, (770±64) cells vs. (403±42) cells] and LLC cells [(167±39) cells, (246±80) cells vs. (31±5) cells] treated with 100 and 200 ng/ml IL-22 for 24 hours had fewer migration numbers than the control group, and the differences were statistically significant (both P < 0.01). Western blotting analysis showed that during treatment with 100 ng/ml recombinant IL-22 for 15-1 440 minutes, the levels of p-STAT3, p-ERK and p-AKT proteins in A549 and LLC cells were higher than those in the control group, while there was no difference in the levels of E-cad and MMP-9 proteins between the two groups. After the combined treatment of recombinant IL-22 and STAT3, AKT or ERK inhibitor, the corresponding levels of p-STAT3, p-AKT and p-ERK proteins in A549 and LLC cells were similar to those in cells without inhibitor and recombinant IL-22 treatment, but significantly lower than those in cells treated with recombinant IL-22 alone. In the dissected lung tissues of mice lung metastasis models, the experimental group had fewer metastatic lung nodules than the control group (2.3±0.6 vs. 7.0±2.0), and the difference was statistically significant ( t = 3.88, P = 0.018). In the morphological observation of lung metastasis tissues, the experimental group had fewer metastatic lesions than the control group (1.8±0.8 vs. 5.4±1.1), and the difference was statistically significant ( t = 5.69, P < 0.001). Flow cytometry analysis showed that the proportion of CD8 + T cells in immune cells in the lung tissues of mice in the experimental group (labeled with CD45) was higher than that in the control group [(27±5)% vs. (15±5)%], and the difference was statistically significant ( t = 3.01, P = 0.040). There was no statistically significant difference in the proportion of CD4 + T cells in immune cells between the two groups ( P > 0.05). Conclusions:The expression levels of IL-22 and its receptor IL-22RA1 in lung adenocarcinoma tissues are higher than those in adjacent normal tissues, and the high expression level of IL-22RA1 in cancer tissues may be associated with poor prognosis of patients; on the one hand, IL-22 may promote the migration of lung adenocarcinoma cells by activating the ERK, AKT and STAT3 signaling pathways, and on the other hand, it may promote lung adenocarcinoma metastasis by reducing CD8 + T cell infiltration in the immune microenvironment of lung adenocarcinoma.

Objective:To investigate the expression of interleukin (IL)-22 in lung adenocarcinoma and its effect and possible mechanism for lung adenocarcinoma metastasis.Methods:The cancer tissues and paired adjacent normal tissues (>2 cm from the tumor edge) surgically removed from 27 lung adenocarcinoma patients in Tianjin Medical University Cancer Institute & Hospital from January to June 2023 were retrospectively collected. Flow cytometry was used to detect the expression levels of IL-22 in T cells of all tissues, and the expression levels of IL-22 in T cells were compared between cancer and adjacent tissues, as well as between lung cancer tissues of patients with and without lymph node metastasis. The cancer tissues and paired adjacent normal tissues were retrospectively collected from 6 patients with lung adenocarcinoma during the same period, and the expression level of IL-22 receptor IL-22RA1 in the tissues was detected by Western blotting. IL-22RA1 transcriptome data from cancer tissues of lung adenocarcinoma patients in 3 datasets in The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database were collected. Using the R software survminer package to select the optimal critical value of IL-22RA1 that reflected the survival relationship, and patients were divided into high and low IL-22RA1 groups based on this. The survival package was used to draw the overall survival curve and log-rank test was performed for inter group comparison. Recombinant IL-22 was used to treat human lung adenocarcinoma A549 cells and mouse lung adenocarcinoma LLC cells, with cells not treated with IL-22 as controls; Transwell assay was used to detect the number of migrating cells in each group; Western blotting was used to detect the expression levels of ERK, AKT and STAT signaling pathways-related proteins, matrix metalloproteinase 9 (MMP-9) and epithelial cadherin (E-cad) in each group of cells. The expression levels of these proteins in A549 cells and LLC cells were also measured after the addition of STAT3 inhibitor C188-9, AKT inhibitor MK-2206 and ERK inhibitor SCH772984. A lung metastasis model of LLC cells was constructed using 10 C57BL/6 mice, the mice were randomly divided into the experimental group and the control group using simple randomization method. IL-22 neutralizing antibody (50 μg/mouse) and non-neutralizing control antibody (50 μg/mouse) were injected once every other day. On the 10th day, the mice were euthanized and dissected to count lung metastatic nodules. The metastatic lung tissue was stained with HE and the metastatic foci were counted. Flow cytometry was used to detect the proportion of CD4 + T cells and CD8 + T cells to immune cells in single cells prepared from metastatic lung tissue. Results:The flow cytometry analysis showed that the proportion of IL-22 + CD4 + T cells in T cells (labeled with CD3 and CD45) in 27 clinically collected lung adenocarcinoma tissues [ M ( Q1, Q3)] was higher than that in adjacent normal tissues [0.28% (0.04%, 1.00%) vs. 0.01% (0.00%, 0.25%)]. The proportion of IL-22 + CD4 + T cells in lung adenocarcinoma tissues of patients with metastasis (9 cases) was higher than that of patients without metastasis (18 cases) [1.06% (0.49%, 4.72%) vs. 0.15% (0.00%, 0.35%)], and the differences were statistically significant (both P < 0.01). Western blotting analysis showed that the relative expression level of IL-22RA1 protein in lung adenocarcinoma tissues was higher than that in adjacent normal tissues (1.03±0.25 vs. 0.35±0.10), and the difference was statistically significant ( P < 0.05). The overall survival of the IL-22RA1 low expression group in lung adenocarcinoma tissues was better than that of the IL-22RA1 high expression group in the TCGA database and GEO databases GSE42127, GSE29016 and GSE26939 datasets, and the differences were statistically significant (all P < 0.001). Transwell assay showed that A549 cells [(744±40) cells, (770±64) cells vs. (403±42) cells] and LLC cells [(167±39) cells, (246±80) cells vs. (31±5) cells] treated with 100 and 200 ng/ml IL-22 for 24 hours had fewer migration numbers than the control group, and the differences were statistically significant (both P < 0.01). Western blotting analysis showed that during treatment with 100 ng/ml recombinant IL-22 for 15-1 440 minutes, the levels of p-STAT3, p-ERK and p-AKT proteins in A549 and LLC cells were higher than those in the control group, while there was no difference in the levels of E-cad and MMP-9 proteins between the two groups. After the combined treatment of recombinant IL-22 and STAT3, AKT or ERK inhibitor, the corresponding levels of p-STAT3, p-AKT and p-ERK proteins in A549 and LLC cells were similar to those in cells without inhibitor and recombinant IL-22 treatment, but significantly lower than those in cells treated with recombinant IL-22 alone. In the dissected lung tissues of mice lung metastasis models, the experimental group had fewer metastatic lung nodules than the control group (2.3±0.6 vs. 7.0±2.0), and the difference was statistically significant ( t = 3.88, P = 0.018). In the morphological observation of lung metastasis tissues, the experimental group had fewer metastatic lesions than the control group (1.8±0.8 vs. 5.4±1.1), and the difference was statistically significant ( t = 5.69, P < 0.001). Flow cytometry analysis showed that the proportion of CD8 + T cells in immune cells in the lung tissues of mice in the experimental group (labeled with CD45) was higher than that in the control group [(27±5)% vs. (15±5)%], and the difference was statistically significant ( t = 3.01, P = 0.040). There was no statistically significant difference in the proportion of CD4 + T cells in immune cells between the two groups ( P > 0.05). Conclusions:The expression levels of IL-22 and its receptor IL-22RA1 in lung adenocarcinoma tissues are higher than those in adjacent normal tissues, and the high expression level of IL-22RA1 in cancer tissues may be associated with poor prognosis of patients; on the one hand, IL-22 may promote the migration of lung adenocarcinoma cells by activating the ERK, AKT and STAT3 signaling pathways, and on the other hand, it may promote lung adenocarcinoma metastasis by reducing CD8 + T cell infiltration in the immune microenvironment of lung adenocarcinoma.

Objective To explore the relationships between headache and pulmonary function,chronic lung disease(CLD)in middle-aged and elderly people in China.Methods This cross-sectional study collected data from participants aged 45 and above in the 2015 China Health and Retirement Longitudinal Study(CHARLS).Headache was diagnosed based on self-report,and CLD and asthma were defined by self-reported doctor diagnoses or a combination of health assessments and medication use.Peak expiratory flow(PEF)was used as an indicator of pulmonary function.Multivariable logistic regression model was used to analyze the correlations between PEF,asthma,CLD,and headache.Relationship between PEF and headache was analyzed by restricted cubic spline(RCS)analysis and subgroup analysis.Results Among 12 661 middle-aged and elderly participants,the prevalence of headache was 14.42%(1 826/12 661),with a prevalence of 9.07%(558/6 151)in males and 19.48%(1 268/6 510)in females.After full adjustment for covariates,each 1 L/s increase in PEF was associated with a 7%reduction in the risk of headache(odds ratio[OR]=0.93,95%confidence interval[CI]0.90-0.96,P＜0.001).Categorizing PEF into quartiles(Q1-Q4),as the increase of PEF,the risk of headache significantly decreased(ORs for Q2,Q3,and Q4 were 0.92,0.82,and 0.72,respectively,Ptrend＜0.001).Additionally,asthma(OR=1.78,95%CI 1.43-2.20,P＜0.001)and CLD(OR=2.21,95%CI 1.92-2.53,P＜0.001)were positively associated with the risk of headache.RCS analysis indicated a negative linear correlation between PEF and the risk of headache(Poverall＜0.001,Pnon-linear=0.57).Subgroup analysis revealed that a history of hypertension had a significant impact on the negative association between PEF and headache(Pinteraction＜0.001).Conclusion There is a significant negative correlation between PEF and headache among middle-aged and elderly people in China,while asthma and CLD are positively associated with headache.Improving lung function in middle-aged and elderly populations may be an effective strategy for preventing or alleviating headache.

OBJECTIVE To improve the quality evaluation method of Platycodonis Radix, to study the differences in the quality of three-years-old Platycodonis Radix under different harvesting periods, and to determine the optimal harvesting period of Platycodonis Radix. METHODS The leachate, ash, moisture, refractive index and the content of six saponins were used as the quality evaluation indexes. The differences between the herbs of Platycodonis Radix at different harvesting periods were characterized with the help of mathematical and statistical methods. And link the entropy weight method, gray correlation analysis and TOPSIS method were combined to obtain the statistical analysis of the relevant indexes and the quality ranking information of the herbs in different harvesting periods. RESULTS There were significant differences between the quality evaluation indexes of three-years-old Platycodonis Radix at different harvesting periods. The added multi-indicator testing had improved the quality evaluation system of Platycodonis Radix and enhanced the "Drug properties-Effectiveness" linkage of the herbs. And the results of the comprehensive quality evaluation model showed that the herbs harvested around October 21 (Frost’s Descent) were ranked best in terms of comprehensive index. CONCLUSION In order to ensure the quality of Platycodonis Radix, the best harvesting period for three-years-old Platycodonis Radix is determined around the "Frost’s Descent" season, taking into account the characteristics of the herbs' appearance and the material basis of herbs.

ObjectiveTo investigate the therapeutic effects and difference in the effects of Arisaematis Rhizoma （AR） before and after processing （i.e.， Arisaematis Rhizoma Preparatum， ARP） with Zingiberis Rhizoma Recens-Alumen on allergic asthma in rats and to provide a basis for the theory of processing improving the efficacy. MethodA rat model of allergic asthma was established in 70 SD rats by intraperitoneal injection of ovalbumin （OVA）-aluminum hydroxide. The rats were administrated with the aqueous extracts of AR （1.2， 0.3 g∙kg^-1） and ARP （1.2， 0.3 g∙kg^-1） aqueous extracts by gavage， and montelukast sodium （0.001 g∙kg^-1） was used as the positive drug. The T helper cell type 1/type 2 （Th1/Th2） ratio in the serum and bronchoalveolar lavage fluid （BALF） and percentages of inflammatory cells in BALF were determined. Polymerase chain reaction （PCR） was employed to determine the mRNA level of mucin 5AC （MUC5AC） in the lung tissue. The pathological changes in the lung tissue were observed by hematoxylin-eosin （HE） staining and PAS staining. Immunohistochemical assay was employed to measure the expression of c-Jun amino-terminal kinase （JNK）， extracellular signal regulated protein kinase （ERK）， and p38 mitogen-activated protein kinase （p38 MAPK） in rat lung tissue. Western blot was employed to determine the protein levels of ERK， p-ERK， JNK， p-JNK， p38， p-p38 in the lung tissue. The effects of AR and ARP were compared based on overall desirability. ResultCompared with the blank group， the levels of interleukin-12 （IL-12） and γ interferon （IFN-γ） in serum and BALF of rats in the model group were significantly lower （P<0.05， P<0.01）， and the levels of interleukin-4 （IL-4）， interleukin-5 （IL-5） and interleukin-13 （IL-13） were significantly higher （P<0.05， P<0.01）. Compared with the model group， the serum and BALF contents of IL-12 and IFN-γ in rats in the montelukast sodium group， high-dose AR group and high-dose ARP group were significantly higher （P<0.05， P<0.01）， and the contents of IL-4， IL-5 and IL-13 were significantly lower （P<0.05， P<0.01）， and the serum contents of IFN-γ in rats in the low-dose AR group and low-dose ARP group were in BALF was significantly higher （P<0.05） and IL-4 and IL-13 were significantly lower （P<0.05， P<0.01）， the percentages of macrophages， lymphocytes， neutrophils， and eosinophils were reduced in BALF， and the expression of JNK/ERK/p38 MAPK signaling pathway and MUC5AC protein was inhibited in lung tissues. Overall assessment of the normalized analysis revealed that the ARP group was slightly more potent than the AR group after administration of the same dose. ConclusionAR and ARP can effectively treat allergic asthma by inhibiting JNK/ERK/p38 MAPK signaling pathway， and the effect is better after concoction， which can provide data support for its "concoction efficiency".

OBJECTIVE To explore the correlation between changes in intestinal toxicity and changes in component composition of the Mongolian medicine Euphorbiae pekinensis Radix(EPR)before and after processing with milk.METHODS Mice were given 95%ethanol extract of raw EPR,milk-processed EPR and water-processed EPR by gavage.The purgative effect and intestinal inflam-matory toxicity changes of EPR before and after milk processing were investigated using the fecal water content and the levels of inflam-matory factors TNF-α and IL-1β in each intestinal segment of mice as indicators;LC-MS/MS was used to analyze the composition changes of the 95%alcohol extract of EPR before and after milk processing.RESULTS Compared with the blank group,the raw and water processed products of EPR could significantly increase the water content of mouse feces and the levels of TNF-α and IL-1β in each intestinal segment(P＜0.05);compared with the raw product group,all indicators in the milk processing group were significantly reduced(P＜0.05),while there was no significant difference in the water processing group,indicating that water processing cannot at-tenuate toxicity,and the auxiliary material milk is the key auxiliary material to reduce the toxicity of EPR.Mass spectrometry analysis results showed that a total of 50 components were identified in EPR,including 38 terpenoid components,6 phenolic acid components,and 6 other components.The content of each component decreased to varying degrees after milk processing.Principal component analy-sis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)were performed on the mass spectrum data of raw ma-terials and products,and it was found that the components of raw materials and products can be obviously clustered into 2 categories.13 differential components of raw materials and products were screened through t test,and 11 of which were terpene compo-nents,indicating that the composition of terpene components changed significantly after milk processing.17 components derived from EPR were detected in the residual liquid of milk excipients after processing,of which 16 were terpenoids,indicating that the terpenoid components of EPR were transferred to the excipient milk during the soaking and processing processes.CONCLUSION The toxicity of EPR is reduced and the purgative effect is alleviated after milk processing.The attenuation mechanism may be that during the milk soaking and processing processes,terpenoid components are transferred to the milk,and the content of toxic components in the decoc-tion pieces is reduced,thereby reducing the toxicity.

Objective:To investigate the clinical and pathological features of congenital hepatic fibrosis (CHF).Methods:The clinical and pathological findings of 20 patients diagnosed with CHF from 2017 to 2023 were retrospectively analyzed.Results:Among the 20 patients, 8 were males and 12 were females with a median age of 21.5 years. Mostly patients were admitted to the hospital with cirrhosis, portal hypertension and upper gastrointestinal bleeding. Pathological features were diffuse fibrosis in the portal area, formation of fibrous septa of varying width, segmentation of the liver parenchyma, with hyperplasia of small bile ducts. Among them, 1 case (5%) was complicated with Caroli's disease, and 1 case (5%) was HNF1α hepatocellular adenoma. IHC GS showed that was positively expressed in acinar region 3 in 75% cases.Conclusion:CHF is mainly manifested by portal hypertension and its complications. Histopathology is the gold standard for diagnosis. The possibility of CHF should be considered first in children and adolescents with portal hypertension but no history of hepatitis, and complicated kidney disease. The positive pattern of acinus-3 region of GS in IHC is helpful for the diagnosis of CHF.

Hip fracture is considered as the most severe osteoporotic fracture characterized by high disability and mortality in the elderly. Improved surgical techniques and multidisciplinary team play an active role in alleviating prognosis, which places higher demands on perioperative nursing. Dysfunction, complications, and secondary impact of anaesthesia and surgery add more difficulties to clinical nursing. Besides, there still lack clinical practices in perioperative nursing for elderly patients with hip fracture in China. In this context, led by the Orthopedic Nursing Committee of Chinese Nursing Association, the Expert consensus on clinical practice in perioperative nursing for elderly patients with hip fracture ( version 2023) is developed based on the evidence-based medicine. This consensus provides 11 recommendations on elderly patients with hip fracture from aspects of perioperative health education, condition monitoring and inspection, complication risk assessment and prevention, and rehabilitation, in order to provide guiding advices for clinical practice, improve the quality of nursing and ameliorate the prognosis of elderly patients with hip fracture.