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.

OBJECTIVES: To study the therapeutic mechanism of Tuihuang Mixture against cholestasis. METHODS: Forty-eight Wistar rats were randomized equally into blank group, model group, ursodeoxycholic acid group and Tuihuang Mixture group. Except for those in the blank group, all the rats were given α‑naphthylisothiocyanate (ANIT) to establish rat models of cholestasis, followed by treatments with indicated drugs or distilled water. Serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL of the rats were determined, and hepatic expressions IL-1β, IL-18, FXR, NLRP3, ASC, Caspase-1 and GSDMD were detected using q-PCR, ELISA or Western blotting. Histopathological changes of the liver tissues were observed using HE staining. RESULTS: The rat models of cholestasis had significantly increased serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL with increased mRNA and protein expressions of IL-1β and IL-18, decreased protein and mRNA expressions of FXR, and increased protein expressions of NLRP3 and Caspase-1 and mRNA expressions of NLRP3, ASC, Caspase-1 and GSDMD in the liver tissue, showing also irregular arrangement of liver cells, proliferation of bile duct epithelial cells and inflammatory cells infiltration. Treatment of the rat models with Tuihuang Mixture significantly decreased serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL, lowered IL-1β and IL-18 and increased FXR protein and mRNA expressions, and reduced NLRP3, ASC, Caspase-1 and GSDMD proteins and NLRP3, ASC and Caspase-1 mRNA expressions in the liver tissue. Tuihuang Mixture also significantly alleviated hepatocyte injury, bile duct epithelial cell proliferation and inflammatory cell infiltration in the liver of the rat models. CONCLUSIONS Tuihuang Mixture can effectively improve cholestasis in rats possibly by inhibiting NLRP3 inflammatosome-mediated pyroptosis via regulating FXR.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein ; Rats ; Receptors, Cytoplasmic and Nuclear/metabolism* ; Cholestasis/drug therapy* ; Rats, Wistar ; Inflammasomes/metabolism* ; 1-Naphthylisothiocyanate ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Interleukin-18/metabolism* ; Caspase 1/metabolism* ; Interleukin-1beta/metabolism* ; Liver/metabolism*

OBJECTIVES: To investigate the changes in blood levels of calcium and bone metabolism biochemical markers in patients with primary osteoporosis receiving treatment with denosumab. METHODS: Seventy-three patients with primary osteoporosis treated in our Department between December, 2021 and December 2023 were enrolled. All the patients were treated with calcium supplements, vitamin D and calcitriol in addition to regular denosumab treatment every 6 months. Blood calcium, parathyroid hormone (PTH), osteocalcin (OC), type I procollagen amino-terminal propeptide (PINP), and type I collagen carboxy-terminal telopeptide β special sequence (β‑CTX) data before and at 3, 6, 9, and 12 months after the first treatment were collected from each patient. RESULTS: Three months after the first denosumab treatment, the bone turnover markers (BTMs) OC, PINP, and β-CTX were significantly decreased compared to their baseline levels by 39.5% (P<0.001), 56.2% (P<0.001), and 81.8% (P<0.001), respectively. At 6, 9, and 12 months of treatment, OC, PINP, and β-CTX remained significantly lower than their baseline levels (P<0.001). Blood calcium level was decreased (P<0.05) and PTH level increased (P<0.05) significantly in these patients at months of denosumab treatment, but their levels were comparable to the baseline levels at 6, 9, and 12 months of the treatment (P>0.05). CONCLUSIONS Denosumab can suppress BTMs and has a good therapeutic effect in patients with primary osteoporosis, but reduction of blood calcium and elevation of PTH levels can occur during the first 3 months in spite of calcium supplementation. Blood calcium and PTH levels can recover the baseline levels as the treatment extended, suggesting the importance of monitoring blood calcium and PTH levels during denosumab treatment.
Humans ; Denosumab/therapeutic use* ; Calcium/blood* ; Parathyroid Hormone/blood* ; Biomarkers/blood* ; Osteoporosis/blood* ; Osteocalcin/blood* ; Procollagen/blood* ; Female ; Collagen Type I/blood* ; Peptide Fragments/blood* ; Bone Density Conservation Agents/therapeutic use* ; Bone and Bones/metabolism* ; Male ; Middle Aged ; Vitamin D ; Peptides/blood* ; Aged

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

OBJECTIVES: To investigate the clinical application of the digital-assisted reconstruction of the mandible and tumors with free fibula transplantation and immediate implantation via the intraoral approach. METHODS: Twelve patients with benign mandibular tumors were collected. Three-dimensional mandibular reconstruction was performed digitally before surgery to simulate mandibular tumor resection, fibula resection and reconstruction, and implant implantation. The intraoperative resection of the mandibular tumor was conducted through the intraoral approach under the guidance of a guide plate, and fibula resection, molding, reconstruction, and oral fixation were immediately performed. Implant implantation was performed during the second phase of implant surgery and denture restoration was performed 1-2 months after surgery. RESULTS: The types of mandibular defects were BrownⅠ (one case), Ⅰc (four cases), Ⅱ (one case), Ⅱc(three cases), and Ⅲ (three cases). The length of the fibular bone was 12-22 cm. The number of fibular molding amputations was as follows: two cases in two segments, six cases in three segments, three cases in four segments, and one case in five segments. All of these cases underwent folding fibular reconstruction of mandibular and alveolar bone defects. A total of 44 implants were implanted, and none failed after operation. CONCLUSIONS The intraoral approach is a reliable method for the resection of mandibular benign tumors, with few postoperative complications and the ability to position and fix accurately the reconstructed folded fibula under digital design. The immediate implantation of the transplanted fibula does not affect the blood supply and has a high success rate. It is an effective and reliable method for the resection and reconstruction of mandibular benign tumors.
Humans ; Fibula/transplantation* ; Mandibular Neoplasms/surgery* ; Mandibular Reconstruction/methods* ; Bone Transplantation/methods* ; Male ; Middle Aged ; Female ; Mandible/surgery* ; Adult ; Free Tissue Flaps ; Surgery, Computer-Assisted

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.

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 review the current research progress on pharmacoeconomics evaluation related to spinal muscular atrophy （SMA）， in order to provide valuable insights for clinical treatment， screening and medical insurance payment decision- making. METHODS A computerized search was conducted across multiple databases including PubMed， Web of Science， Embase， Scopus， Cochrane Library， EBSCOhost， CNKI， VIP， CBM and Wanfang database as well as other important health technology assessment （HTA） websites， such as National Institute for Health and Care Research，International Society of Technology Assessment in Health Care， Agency for Healthcare Research and Quality， etc. The pharmacoeconomics evaluation studies related to SMA were collected from the inception to December 31st， 2023. The literature/reports were rigorously screened based on predefined inclusion and exclusion criteria by two researchers， and the essential information from the included literature/ reports was extracted using Excel 2019. The quality of the included literature/reports was evaluated by Consolidated Health Economic Evaluation Reporting Standards 2022. RESULTS Finally， 9 articles and 15 HTA reports were included， with overall good quality of literature， but poor quality of HTA reports. There were a total of 24 studies on the pharmacoeconomics evaluation of SMA， including treatment options such as nusinersen sodium， sovaprevir， risperidone， and best supportive therapy.The review results showed that nusinersen sodium was not cost-effective in the treatment of SMA； there was no consensus on the economic viability of treatment options such as risperidone and sovaprevir； newborn/prenatal screening combined withmedication therapy was cost-effective. CONCLUSIONS newborn/prenatal screening combined with SMA medication therapy demonstrates economic advantages. It is suggested to further investigate the cost-effectiveness of new SMA drugs and SMA screening in China， taking localization parameters and medical insurance prices into account， and gradually incorporate SMA screening into the scope of neonatal genetic disease detection， in order to alleviate the financial burden of patients’ families and healthcare systems.

Objective To analyze the trends,cooperation,topics and hotspots of researches about multi-level rehabilitation service system in China. Methods The literature on multi-level rehabilitation service system in China was searched and screened in databases of CNKI from 1983 to 2023.The number of the articles was described,and the cooperation,research hotspots and changing trend were analyzed using VOSviewer. Results A total of 4 643 articles were included.The number of the articles tended to increase and developed in stages.Nine groups with five or more researchers were found,and seven of them cooperated with each other.The most frequent keywords were community-based rehabilitation(occurrence 1 251 with connection strength 1 780),stroke(occurrence 674 with connection strength 1 126),family rehabilitation(occurrence 412 with connection strength 514),rehabilitation nursing(occurrence 178 with connection strength 240)and quality of life(occur-rence 156 with connection strength 311).The researchers initially focused on disability rehabilitation,then fo-cused on community-based rehabilitation and family rehabilitation,and gradually focused on the quality of life,activities of daily living,satisfaction,mental health,negative emotion and healthcare consortium in recent years. Conclusion The researches about multi-level rehabilitation service system are developing in China,focusing on commu-nity-based rehabilitation,stroke,family rehabilitation,rehabilitation nursing and quality of life.The cooperation among scholar groups need to be strengthened.Quality of life,activities of daily living,satisfaction,mental health,negative emotion and healthcare consortium may be the hotspots in the future.