ObjectiveStarting from the etiology， pathogenesis， and treatment strategies of endometriosis and adenomyosis， to integrate and sort out the academic characteristics of contemporary renowned experts and schools in the field of traditional Chinese medicine gynecology. MethodsAccording to the systematic review of text and opinion （SrTO） process developed by the Joanna Briggs Institute （JBI） in Australia， this paper determined literature screening criteria by searching China National Knowledge Infrastructure （CNKI）， VIP， Wanfang， and China Biomedical Literature Database. Information was extracted after literature screening， and quality evaluation was conducted using the JBI Narrative， Text， and Opinion Systematic Review Strict Evaluation Checklist. The JBI Narrative， Opinion， Text Evaluation， and Review Tool Summary Table was used for information synthesis， and data analysis and display were conducted in the form of text and charts. ResultsThe 146 articles related to 39 renowned experts and 19 articles related to 10 schools of thought were included. Research has found that contemporary experts and schools in traditional Chinese medicine gynecology consider blood stasis as the core pathogenesis in understanding the etiology and pathogenesis of two diseases and related infertility. Their viewpoints varied from multiple aspects such as clinical symptom characteristics， meridian circulation location， pathological product evolution， disease duration， emotional psychology， lifestyle habits， preference for food and drink， innate endowment， and acquired injury. In terms of treatment， it was advocated to divide the stage， treat according to different types， adapt to the times， integrate nature and humans， and combine multiple methods to treat comprehensively when necessary. It was also recommended to skillfully use insects， make good use of classic formulas and small prescriptions， pay attention to protecting the spleen and stomach and regulating emotions， and make good use of self-formulated empirical formulas for internal or external use. Besides， individualized long-term management of patients was also advocated. ConclusionThis study applies the SrTO process to systematically summarize the academic ideas of contemporary renowned experts and schools in traditional Chinese medicine gynecology regarding the causes， mechanisms， diagnosis， and treatments of endometriosis， providing a scientific and standardized reference for future theoretical exploration.

Reactive astrocytes, which exhibit a correlation with the degeneration of dopaminergic neurons, are present in a considerable number during the progression of Parkinson's disease (PD). However, the underlying factors shaping astrocyte reactivity and neuroinflammation in PD remain inadequately elucidated. Here, we demonstrate that fibroblast growth factor 7 (FGF7)/FGF receptor 2 (FGFR2) autocrine signaling intensifies astrocyte reactivity and inflammation. Genetic deletion of Arrb2, β-Arrestin2 encoding gene, led to escalated astrocyte reactivity in MPTP-treated mice, which was further substantiated in astrocyte-specific Arrb2 knockdown mice. RNA sequencing profiling of Arrb2 knockout astrocytes identified Fgf7 as a critical effector of astrocyte reactivity. Subsequently, conditional knockdown of Fgf7 and its receptor Fgfr2 in astrocytes elicited advantageous effects for MPTP-treated mice by restraining the inflammatory phenotypic transition of reactive astrocytes. Furthermore, deletion of astrocytic Fgf7 mitigated MPTP-induced pathology in Arrb2 knockout mice. Mechanistically, STAT1 was distinguished as the transcription factor suppressing Fgf7 expression, while β-Arrestin2 counteracted the proteasomal degradation of STAT1 by binding to RNF220, an E3 ubiquitin ligase for STAT1. More importantly, selectively engaging dopamine D2 receptor (Drd2)/β-Arrestin2-biased signaling using the agonist UNC9995 exhibited therapeutic potential in MPTP-treated mice via moderation of astrocytic FGF7 production, thereby restoring balance in astrocyte reactivity. Collectively, our study bridges a crucial knowledge gap by elucidating the novel functions of FGF family members within the central nervous system, particularly within the context of PD. The autocrine signaling of FGF7/FGFR2 represents a novel mechanism and a potential druggable target for modulating astrocyte-derived inflammation.

Cancer multidrug resistance (MDR) impairs the therapeutic efficacy of various chemotherapeutics. Novel approaches, particularly the development of MDR reversal agents, are critically needed to address this challenge. This study demonstrates that tenacissoside I (TI), a compound isolated from Marsdenia tenacissima (Roxb.) Wight et Arn, traditionally used in clinical practice as an ethnic medicine for cancer treatment, exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells. TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin (DOX) and paclitaxel (PAC) by downregulating ABCB1 expression and reducing ABCB1 drug transport function. Mechanistically, protein arginine methyltransferase 1 (PRMT1), whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues, was differentially expressed in TI-treated SW620/AD300 cells. SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine (aDMA) and enhanced PRMT1-EGFR interaction compared to their parental cells. Moreover, TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR, PRMT1-EGFR interaction, and EGFR downstream signaling in SW620/AD300 and KBV200 cells. These effects were significantly reversed by PRMT1 overexpression. Additionally, TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities. This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR, suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.
Humans ; Protein-Arginine N-Methyltransferases/antagonists & inhibitors* ; Drug Resistance, Neoplasm/drug effects* ; ErbB Receptors/genetics* ; Animals ; Cell Line, Tumor ; Drug Resistance, Multiple/drug effects* ; Methylation/drug effects* ; Saponins/administration & dosage* ; Mice ; Mice, Nude ; Mice, Inbred BALB C ; ATP Binding Cassette Transporter, Subfamily B/genetics* ; Doxorubicin/pharmacology* ; Paclitaxel/pharmacology* ; Female ; Repressor Proteins

Objective:To investigate the clinicopathological features and molecular characteristics of β-catenin-deficient colorectal cancer.Methods:The clinical, pathological and molecular features of 11 colorectal cancers with β-catenin protein loss diagnosed at the 960th Hospital of People′s Liberation Army of China, from January 2012 to November 2022 were analyzed.Results:Among the 11 patients, 3 were males and 8 were females. Their age ranged from 43 to 74 years, with the median age of 59 years. Six were in the left colon and 5 were in the right colon. One of the 11 cases had lymph node metastasis, 10 cases were well and moderately differentiated adenocarcinoma, and 1 was mucinous adenocarcinoma. Eight cases were of TNM stage T4, 2 of T1 stage and 1 of Tis stage. β-catenin protein was not detected using immunohistochemistry. Sanger sequencing revealed the presence of fragment-deletion mutation in exon 3 of CTNNB1 gene, resulting in loss of β-catenin protein expression.Conclusion:β-catenin deficiency is present in a small number of colorectal cancers and may be associated with exon 3 mutations of CTNNB1 gene.

Objective:To investigate the expression of latent transforming growth factor-β-binding protein (LTBP), transforming growth factor-β (TGF-β), cyclin-dependent kinase 2 (CDK2) and cyclin D2 (CCND2) in fibrillin-2 ( FBN2) interfering induced mouse retinopathy. Methods:Twenty-seven 8-week-old C57BL/6J mice were randomly divided into normal control group, empty vector group and FBN2 interference group according to the random number table method, with 9 mice in each group.The normal control group was not treated.The empty vector group and FBN2 interference group were intravitreally injected with 3 μl empty vector and 3 μl adeno-associated virus (AAV) carrying the sh-FBN2 interference plasmid in the right eye, respectively.The structural and functional changes of the retina were detected at 4 weeks after injection by optical coherence tomography (OCT) and full-field electroretinography (ERG).The expression and distribution of FBN2 protein in the retina were detected by immunofluorescence staining.The mRNA and protein expression levels of FBN2, LTBP-1, TGF-β2, CDK2 and CCND2 in mouse retina were detected by real-time fluorescence quantitative PCR and Western blot.All experiments complied with the ARVO statement.The research scheme was approved by the Experimental Animal Ethics Committee of Shandong University of Traditional Chinese Medicine (No.2019036).Results:Four weeks after injection, the results of OCT examination showed that compared with normal control and empty vector groups, the retinal pigment cortex of the FBN2 interference group was irregular with high density reflection areas.Full-field ERG results showed that compared with normal control and empty vector groups, the amplitude of Rod-a, Rod-b, Max-a and Max-b waveforms in FBN2 interference group decreased, and the differences were statistically significant (all at P<0.05).The results of immunofluorescence staining showed that FBN2 was expressed in the whole retina, and the fluorescence intensity of FBN2 was weaker in FBN2 interference group than that in normal control and empty vector groups.The fluorescence intensity of FBN2 in normal control group, empty vector group and FBN2 interference group was 16.21±2.21, 15.57±3.63 and 5.32±1.06, respectively, with a statistically significant overall difference ( F=66.03, P<0.05).The fluorescence intensity of FBN2 protein in FBN2 interference group was significantly lower than that in empty carrier group and normal control group (both at P<0.05).Compared with normal control and empty vector groups, the relative expression levels of LTBP-1 and TGF-β2 mRNA and protein were significantly increased in FBN2 interference group, while the relative expression levels of FBN2, CDK2 and CCND2 mRNA and protein were significantly decreased, and the differences were statistically significant (all at P<0.05). Conclusions:The increase of LTBP-1 and TGF-β2 and the decrease of G1/S phase related proteins CDK2 and CCND2 are involved in the development of FBN2-deficient retinopathy.

Objective:To explore the structural characteristics of intestinal microflora in children with non-alcoholic fatty liver disease（NAFLD）and the relationship between intestinal microflora and the occurrence as well as development of NAFLD in children.Methods:Fifteen children with NAFLD diagnosed at the First People's Hospital of Yunnan Province from January 2022 to December 2022 were selected as subjects，and 15 healthy children who received routine physical examinations at the outpatient clinic during the same period were randomly selected as healthy control group.The height，weight，waist circumference，blood pressure，blood biochemistry of all children were collected.At the same time，the fresh fecal samples of all children were collected，and the biological information of intestinal flora was analyzed by 16S rRNA sequencing.Results:In the NAFLD group，there were eight males and seven females，with an average age of（11.13±1.77）years.In healthy control group，there were seven males and eight females，with an average age of（9.73±2.25）years.There were no significant differences in sex，age，blood pressure between two groups.Compared with the healthy control group，the levels of body mass index，waist circumference，waist-to-height ratio，alanine aminotransferase，aspartate transaminase，gamma-glutamyl transpeptidase，total bilirubin，direct bilirubin，unconjugated bilirubin，low density lipoprotein cholesterol，uric acid and serum insulin significantly increased and high density lipoprotein cholesterol significantly decreased in NAFLD group（ P<0.05）.The results of species diversity analysis showed that chaol index and observed-species index in NAFLD group were significantly higher than those in healthy control group（ P<0.05）.Species diversity analysis showed that the species with increased abundance in NAFLD group included：Proteobacteria，Gammaproteobacteria，Enterobacteriaceae，Klebsiella，Escherichia-Shigella，Escherichia-Shigella-unclassified.Differential species with increased abundance in the healthy control group included：Bifidobacterium species，Bifidobacterium，Bifidobacteriaceae，Bifidobacteriales，Actinobacteria，Actinobacteriota，Bacteroidia，Bacteroidales，Streptococcus-thermophilus. Conclusion:There are metabolic abnormalities and obvious changes in the structure of intestinal flora in children with NAFLD.Exogenous supplementation of Bifidobacterium，Streptococcus thermophilus and Bacteroides may prevent the occurrence of NAFLD，delay the progression of disease and improve fat deposition in the liver.

Despite decades of research,cancer continues to be a major global health concern.The human mouth appears to be a multiplicity of local environments communicating with other organs and causing diseases via microbes.Nowadays,the role of oral microbes in the development and progression of cancer has received increasing scrutiny.At the same time,bioengineering technology and nanotechnology is growing rapidly,in which the physiological activities of natural bacteria are modified to improve the therapeutic efficiency of cancers.These engineered bacteria were transformed to achieve directed genetic reprogramming,selective functional reorganization and precise control.In contrast to endotoxins produced by typical genetically modified bacteria,oral flora exhibits favorable biosafety characteristics.To outline the current cognitions upon oral microbes,engineered microbes and human cancers,related literatures were searched and reviewed based on the PubMed database.We focused on a number of oral microbes and related mechanisms associated with the tumor microenvironment,which involve in cancer occurrence and development.Whether engineering oral bacteria can be a possible application of cancer therapy is worth consideration.A deeper understanding of the relationship between engineered oral bacteria and cancer therapy may enhance our knowledge of tumor pathogenesis thus providing new insights and strategies for cancer prevention and treatment.

Objective To understand the prevalence and risk factors of hyperuricemia in electronics factory workers in Wuhan, and to provide evidence for the health protection of electronics factory workers. Methods A total of 1 415 employees in an electronics factory in Wuhan were selected as the research subjects, and the physical examination and determination of various biochemical indicators, as well as questionnaire survey were carried out. Results The detection rate of hyperuricemia among workers in the electronics factory in Wuhan was 32.43%, with 36.33% for men and 14.11% for women, and the difference was statistically significant ( χ²＝46.077，P＜0.001). The detection rate of hyperuricemia was the highest (33.77%) among those with university or college education, followed by graduate students and above (31.50%). Compared with subjects with good lifestyle habits, people with drinking habits had higher hyperuricemia detection rate (49.38%), and the difference was statistically significant (P =0.001). The detection rates of hyperuricemia in those with central obesity and elevated alanine aminotransferase were 48.23% and 61.29%, respectively, which were significantly higher than those in the subjects without the above diseases (26.91% and 27.21%, respectively), and the differences were statistically significant (P <0.001). Obese people had the highest detection rate of hyperuricemia (66.95%), followed by overweight people (43.75%), and the difference was statistically significant (P <0.001). Multivariate logistic analysis showed that alcohol drinking (OR=1.836, 95% CI=1.139-2.961, P =0.013) and body mass index ≥ 24 kg/m² (OR=2.175, 95% CI=1.686 -2.806, P <0.001) were risk factors for hyperuricemia in electronic factory workers. Elevated alanine aminotransferase (ALT) was significantly correlated with hyperuricemia (OR=2.964, 95%CI=2.146-4.095 , P <0.001). Female gender was a protective factor for hyperuricemia in workers in the electronics factory (OR=0.441, 95%CI=0.297-0.653 , P <0.001). Conclusion The detection rate of hyperuricemia among workers in an electronics factory in Wuhan is high, and the detection rate of hyperuricemia in men is higher than that in women. Alcohol consumption, overweight and obesity will increase the risk of hyperuricemia. Elevated ALT is associated with hyperuricemia. Maintaining an ideal body mass index and establishing a good lifestyle play an important role in preventing hyperuricemia.

ObjectiveTo investigate the clinical efficacy of Gandouling tablet （GDL） on abnormal lipid metabolism in Wilson's disease （WD） and the correlation between the prediction model of hepatic steatosis and the related indexes of lipid metabolism in WD. MethodA total of 86 patients with abnormal lipid metabolism in WD were selected. The 24-hour urine copper， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， serum triglyceride （TG）， total cholesterol （TC）， apolipoprotein B （ApoB）， low density lipoprotein cholesterol （LDL-C）， bile acid （BA）， γ-glutamyl transferase （GGT）， prediction model of hepatic steatosis ［hepatic steatosis index （HSI） and Zhejiang University index （ZJU index）］， ultrasonic attenuation coefficient imaging （ATT）， and traditional Chinese medicine （TCM） syndrome score were statistically analyzed before treatment. Pearson correlation test was used to analyze the correlation between TG， TC， LDL-C， ApoB， ALT， AST， ALT/AST， BA， GGT， TCM syndrome score， ATT， and HIS and ZJU. The patients were divided into an observation group and a control group by random number table method， with 43 cases in each group. The observation group was treated with GDL combined with sodium dimercaptopropane sulfonate （DMPS）， while the control group was only treated with DMPS as a control. After six courses of treatment， 24-hour urine copper， TC， TG， LDL-C， ApoB， HSI， ZJU， ATT， TCM syndrome score， and clinical efficiency before and after treatment were observed and compared between the two groups. The correlation between HSI and ZJU and serum TC， TG， LDL-C， ApoB， ALT， AST， ALT/AST， BA， GGT， TCM syndrome scores， and ATT was analyzed. ResultPearson correlation analysis showed that serum TC （r = 0.811）， TG （r = 0.826）， LDL-C （r = 0.802）， ApoB （r = 0.820）， ALT （r = 0.497）， ALT/AST （r = 0.826）， TCM syndrome score （r = 0.716）， and ATT （r = 0.736） were positively correlated with HSI （P<0.01）， while AST， BA， and GGT had no significant correlation with HSI. TC （r = 0.718）， TG （r = 0.765）， LDL-C （r = 0.667）， ApoB （r = 0.699）， ALT/AST （r = 0.403）， TCM syndrome score （r = 0.666）， and ATT （r = 0.684） were positively correlated with ZJU （P<0.01）. ALT， AST， BA， and GGT had no significant correlation with ZJU. The total effective rate of the observation group was 86.05 （37/43）， and that of the control group was 72.09% （31/43）. The total effective rate of the observation group was higher than that of the control group （Z = -2.301， P<0.05）. After treatment， the 24-hour urine copper of the two groups increased significantly. The levels of TC， TG， LDL-C， and ApoB were significantly decreased， and the HSI， ZJU， and ATT were significantly decreased （P<0.01）. Compared with those in the control group after treatment， the above indexes improved better in the observation group （P<0.05， P<0.01）. ConclusionGDL can effectively improve the level of copper and lipid metabolism in patients with WD， with high clinical safety and good clinical application value. The prediction model of hepatic steatosis can effectively reflect the degree of abnormal lipid metabolism in WD.

Objective To investigate the effect of intravitreal injection of fibrillin-2(FBN2)recombinant protein on FBN2-deficient retinopathy.Methods Thirty-two SPF-grade C57BL/6J mice were randomly divided into 4 groups:nor-mal control group,negative control group,FBN2 knockdown group,and FBN2 recombinant protein group,with 8 mice in each group.The right eyes were taken as the experimental eyes.Mice in the normal control group did not receive any inter-vention,mice in the negative control group were intravitreally injected with 3 μL empty vector(1 mg·L-1),and mice in the FBN2 knockdown group and FBN2 recombinant protein group were intravitreally injected with 3 μL adeno-associated vi-rus(1 mg·L-1).After 4 weeks,mice in the FBN2 recombinant protein group were intravitreally injected with 3 μL FBN2 recombinant protein(1 mg·L-1).Then,electroretinogram(ERG)and optical coherence tomography(OCT)were used to measure the amplitude of Rod-b and Max-a waves and the changes in the retinal structure.Real-time quantitative poly-merase chain reaction(RT-PCR)and Western blot were used to detect changes in FBN2,microfibril-associated glycopro-tein 2(MAGP-2),collagen I(COL1)mRNA and protein expression in the mouse retina.Results The ERG findings showed that compared with the negative control group and normal control group,the amplitude of Rod-b and Max-a waves in the retina of mice in the FBN2 knockdown group and FBN2 recombinant protein group decreased(all P＜0.05);com-pared with the FBN2 knockdown group,the amplitude of Rod-b and Max-a waves in the retina of mice in the FBN2 recom-binant protein group significantly increased(both P＜0.05).The OCT findings showed that compared with the FBN2 knock-down group,the structure of the retinal pigment epithelium and the light reflex in the FBN2 recombinant protein group be-came more regular.The RT-PCR detection results showed that compared with the FBN2 knockdown group,the expression of FBN2 mRNA in the retinal tissue of mice in the FBN2 recombinant protein group significantly increased,while the ex-pression of COL1 and MAGP-2 mRNA significantly decreased(all P＜0.05).Western blot assay results showed that com-pared with the FBN2 knockdown group,the expression of FBN2 protein in the retinal tissue of mice in the FBN2 recombi-nant protein group increased significantly,while the expression of COL1 and MAGP-2 proteins decreased significantly(all P＜0.05).Conclusion Intravitreal injection of FBN2 recombinant protein can compensate for the endogenous deficiency of FBN2 in mice with FBN2-deficient retinopathy and achieve therapeutic effects by regulating COL1 and MAGP-2 expres-sion.