IL-1ß and CXCR4 as Potential Therapeutic Targets for Alzheimer's Disease.

BACKGROUND: Alzheimer's Disease (AD) is a highly prevalent form of age-related dementia. However, the underlying mechanisms of AD are largely unexplored. MATERIALS AND METHODS: In this study, bioinformatics analysis was performed to identify the possible therapeutic targets for AD. The GEO database was used to screen the Differentially Expressed Genes (DEGs). Enrichment analysis, protein-protein interaction network, and LASSO model analyses were successfully performed. Furthermore, an ELISA assay was also conducted to determine the expression of principal genes within the AD and control samples. RESULTS: A total of 416 differentially expressed genes (DEGs) were recognized based on the GSE48350 and GSE28146 datasets. The IL-1ß and CXCR4 levels were markedly elevated in the AD samples relative to the control. CONCLUSION: The IL-1ß and CXCR4 genes were identified as principal AD-related genes that can be targeted for anti-AD therapy.

Clinical practice guidelines for prevention and treatment of postoperative gastrointestinal disorder with Integrated Traditional Chinese and Western Medicine (2023).

Postoperative gastrointestinal disorder (POGD) was a common complication after surgery under anesthesia. Strategies in combination with Traditional Chinese Medicine and Western medicine showed some distinct effects but standardized clinical practice guidelines were not available. Thus, a multidisciplinary expert team from various professional bodies including the Perioperative and Anesthesia Professional Committees of the Chinese Association of Integrative Medicine (CAIM), jointly with Gansu Province Clinical Research Center of Integrative Anesthesiology/Anesthesia and Pain Medical Center of Gansu Provincial Hospital of Traditional Chinese Medicine and WHO Collaborating Center for Guideline Implementation and Knowledge Translation/Chinese Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Center/Gansu Provincial Center for Medical Guideline Industry Technology/Evidence-based Medicine Center of Lanzhou University, was established to develop evidence-based guidelines. Clinical questions (7 background and 12 clinical questions) were identified through literature reviews and expert consensus meetings. Based on systematic reviews/meta-analyses, evidence quality was analyzed and the advantages and disadvantages of interventional measures were weighed with input from patients' preferences. Finally, 20 recommendations were developed through the Delphi-based consensus meetings. These recommendations included disease definitions, etiologies, pathogenesis, syndrome differentiation, diagnosis, and perioperative prevention and treatment.

Pelvic metastatic squamous cell carcinoma of unknown primary site: A case report and brief literature review.

RATIONALE: Cancer with unknown primary site is a kind of disease that is difficult to deal with clinically, accounting for 2% to 9% of all newly diagnosed cancer cases. Here, we report such a case with pelvic metastatic squamous cell carcinoma of an unknown primary site and review the relevant literature. PATIENT CONCERNS DIAGNOSES: A 43-year-old Chinese female patient was referred to our hospital and initially diagnosed as "malignant tumor of right adnexal area?, obstruction of right ureter, secondary hydronephrosis". INTERVENTIONS: Thereafter cytoreductive surgery was performed which included a total hysterectomy, left adnexectomy, partial omentum resection, pelvic lymph node dissection, and para-aortic lymph node dissection. The primary lesion could not be identified by supplementary examination and postoperative pathology. The patient was diagnosed as pelvic metastatic squamous cell carcinoma whose primary site was unknown. To prevent a recurrence, we administered adjuvant chemotherapy for the patient. OUTCOMES: The patient was followed up after treatment, complete remission has been maintained for 72 months, and no recurrence or metastasis has been found. LESSONS: Our case demonstrates that surgery combined with chemotherapy could be helpful for pelvic metastatic squamous cell carcinoma of unknown primary site.

Long non-coding RNA ADAMTS9-AS1 attenuates ferroptosis by Targeting microRNA-587/solute carrier family 7 member 11 axis in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) accounts for approximately 90% of all ovarian cancer cases and is the most common cause of gynecological cancer death. Understanding the molecular mechanisms of EOC will help develop better diagnostics and more effective treatments. This study aimed to investigate whether long non-coding RNA ADAMTS9-AS1 (ADAMTS9-AS1) could regulate solute carrier family 7 member 11 (SLC7A11) expression and inhibit ferroptosis by sponging micoRNA-587 in EOC progression. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting results showed that ADAMTS9-AS1 expression was elevated in EOC cells; microRNA-587 expression was up-regulated and SLC7A11 expression was down-regulated after knocking down ADAMTS9-AS1 by transfection with siRNAs; however, microRNA-587 inhibitor reversed SLC7A11 expression in ADAMTS9-AS1 knocking down cells. Ferroptosis related marker detection and cell function assay confirmed that knocking down ADAMTS9-AS1 inhibited EOC cells proliferation and migration by promoting ferroptosis. Overexpression of micoRNA-587 also promoted ferroptosis while inhibited cells proliferation and migration in EOC cells. Additionally, micoRNA-587 inhibitor reversed the effect of ADAMTS9-AS1 silence on the ferroptosis and cell function. Moreover, dual-luciferase reporter gene assay and RNA immunoprecipitation assay confirmed that miR-587 was as a sponge for ADAMTS9-AS1 and SLC7A11. In conclusion, our study found that ADAMTS9-AS1 attenuated ferroptosis by targeting miR-587/SLC7A11 axis in EOC. Our study provides a new therapeutic target for EOC.

Factors associated with congenital syphilis: A retrospective study in Jiangxi Province, China.

BACKGROUND: There are a lack of studies about factors influencing congenital syphilis (CS) in economically underdeveloped areas, such as Jiangxi Province, China. METHODS: A retrospective study was conducted based on the information system of prevention of mother-to-child transmission of syphilis management in Jiangxi Province, China. Pregnant women with syphilis infection who delivered ≥28 gestational weeks and registered in this system from 1 January 2013 to 2030 June 2018 were enrolled. Maternal characteristics and treatment regimens associated with CS were evaluated using multivariable regression analysis. RESULTS: 1196 syphilis infected mothers and their 1207 infants were included in the analyses, and 116 infants were diagnosed with CS, providing an overall incidence of 9.61% (116/1207). Multivariable logistic regression analysis showed that increasing maternal age was barely associated with the risk of CS (adjusted odds ratio (aOR) = 0.97, 95% CI, 0.93-1.00, p = .047). Women with a high nontreponemal serum test titer (≥1:8) had a 126% increased risk of delivering an infant with CS than those with a low titer (<1:8) (aOR = 2.26, 95% CI, 1.51-3.39, p < .001). The risk for CS decreased significantly in infants born to mothers receiving adequate treatment than those receiving no treatment (aOR = 0.36, 95% CI, 0.21-0.61, p < .001). CONCLUSIONS: Adequate treatment is critical for the prevention of CS. Further strategies focusing on early diagnosis and adequate treatment among syphilis infected pregnant women, particularly among those with younger age and high nontreponemal titer, should be strengthened to prevent CS.

PATL2 regulated the apoptosis of ovarian granulosa cells in patients with PCOS.

AIM: PCOS often showed abnormal follicular development. Previous studies have found that the increased apoptosis of granulosa cells (GCs) is one of the key factors leading to follicular dysplasia. It has been found that the decrease or deletion of PATL2 function can significantly inhibit the development and maturation of human oocytes. We found that PATL2 was also expressed in human ovarian GCs, suggesting that PATL2 may be involved in the regulation of related biological events in GCs. This study aims to explore the function of PATL2 on regulation of GCs apoptosis, and the potential role of PATL2 in the development of PCOS-related abnormal follicles. MATERIALS AND METHODS: The follicular GCs of PCOS patients and normal ovulating female patients were collected. Moreover, human granular cell line (KGN) was used for in vitro experiments. RESULTS: (1) The maturation rate and fertilization rate of oocytes in the PCOS group were significantly lower than those in the normal control group (p＜0.05). (2) Flow cytometry and TUNEL staining showed that the apoptosis level of GCs in the PCOS group was significantly increased. (3) Immunofluorescence and Western Blot showed that the PATL2 expression level of GCs in the PCOS group was significantly reduced. (4) Knocking down the expression of PATL2 by siRNA significantly prevented the apoptosis of GCs. CONCLUSIONS: Reduced PATL2 could resulted in the increased apoptosis level of ovarian GCs, which might be closely related to the occurrence and development of abnormal follicles in PCOS.

MicroRNA miR-330-3p suppresses the progression of ovarian cancer by targeting RIPK4.

Previous studies reported that miR-330-3p was involved in the progression of several cancers, but the potential roles of miR-330-3p in ovarian cancer (OC) were unclear. In the current study, we aimed to explore the expression pattern and functions of miR-330-3p in OC. The expression level of miR-330-3p in OC tissues and cell lines was detected using RT-qPCR. The proliferation, migration and invasion of OC cells were detected using CCK-8 assay and transwell assay, respectively. Bioinformatics analysis and luciferase reporter assay were used to analyze the targeted binding site of miR-330-3p and RIPK4. The results showed that miR-330-3p was significantly downregulated in OC tissues and cell lines. Overexpression of miR-330-3p inhibited the proliferation, migration and invasion of OC cells. Mechanistically, a dual-luciferase reported assay showed that RIPK4 is a target gene of miR-330-3p. Furthermore, rescue experiments revealed that miR-330-3p suppressed the proliferation, migration and invasion of OC cells by targeting RIPK4. In summary, our findings indicated that miR-330-3p suppressed the progression of OC by targeting RIPK4. Our results indicated that miR-330-3p/RIPK4 axis might act as a novel therapeutic target for OC treatment.

[Expert consensus statement on Kangfu Xiaoyan Suppository in treatment of pelvic inflammatory in clinical practice].

Kangfu Xiaoyan Suppository is widely used in the treatment of gynecological inflammatory diseases. Long-term clinical application and a certain amount of research evidences show that Kangfu Xiaoyan Suppository can alleviate the clinical symptoms of pelvic inflammatory diseases,reduce the recurrence rate,and relieve sequelae,with a better safety and economic characteristics. As a type of nationally protected traditional Chinese medicine and type B medicine included in medical insurance,it has been selected as a Chinese patent medicine for rectal administration. It was included in the Guidelines for diagnosis and treatment of common gynecological diseases of traditional Chinese medicine published by the Chinese Academy of Traditional Chinese Medicine in 2012,the Pelvic inflammatory diseases diagnosis and treatment guidelines issued by the Infectious Diseases Collaborative Group of the Obstetrics and Gynecology Branch of the Chinese Medical Association in 2014,and the group standard of Single use of traditional Chinese medicine/combined antibiot guidelines for clinical practice-pelvic inflammatory diseases of the Chinese Academy of Traditional Chinese Medicine in 2017. To further enhance clinicians' understanding of the drug and better guide its rational clinical use,experts from the field of gynecology of traditional Chinese and Western medicine were invited to develop and compile this expert consensus. This consensus takes full account of clinical evidences and expert clinical experience,and form recommendations for clinical problems based on evidences and consensus recommendations for clinical problems without evidence by nominal grouping method. The expert consensus is mainly formed in the consideration of six factors: quality of evidence,economy,efficacy,adverse reactions,patient acceptability and others. Based on clinical research evidences and expert experience,this consensus provides a preliminary reference for the clinical use of the drug in a concise and clear format. However,evidence-based support is still required in a large number of high-quality studies,and this consensus will be revised in the future according to new clinical problems and the update of evidence-based evidence in practical application.

Therapeutic effect of daphnetin on the autoimmune arthritis through demethylation of proapoptotic genes in synovial cells.

BACKGROUND: We have previously reported that dephnetin is therapeutically effective in the treatment of rheumatoid arthritis (RA) in collagen-induced arthritis (CIA) rat model. However, the molecular mechanism and the effect of daphnetin on demethylating proapoptotic genes in the synovial cells remains further clarified. This study may provide a deeper insight into the medicinal application of daphnetin as a treatment for RA. METHODS: (1) The proliferation inhibition of CIA rat synovial cells was determined by an MTT (3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenyterazoliumromide) assay; (2) Methylation specific PCR (MSP) was used to measure the methylation of the proapoptotic genes DR3 (death receptor 3), PDCD5 (programmed cell death 5), FasL and p53; (3) Real time-PCR was performed to determine the mRNA expression of DR3, PDCD5, FasL, p53 and DNA methyltransferases (DNMTs) DNMT1, DNMT3a and DNMT3b; (4) Flow cytometry was applied to detect the protein expression of the DR3, PDCD5, FasL and p53; (5) The apoptotic rate of synovial cells was assessed by flow cytometry with Annexin V and propidium iodide (PI); (6) Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to observe the changes of CIA rat synovial cell structure. RESULTS: (1) In the range of 1.25 µg/mL to 40 µg/mL, daphnetin and 5-aza-dc had a dose-dependent and time-dependent degree of inhibition to the CIA rat synovial cells. (2) Daphnetin and 5-aza-dc had a demethylating role on the proapoptotic genes DR3, PDCD5, FasL and p53 of CIA rat synovial cells. (3) Daphnetin and 5-aza-dc decreased the gene expression of methyltransferases DNMT1, DNMT3a and DNMT3b, and increased expression of proapoptotic genes DR3, PDCD5, FasL and p53, which translated into an increased protein expression of DR3, PDCD5, FasL and p53. (4) Daphnetin and 5-aza-dc changed the structure of CIA rat synovial cells to show apoptotic changes and increased the rate of apoptosis. CONCLUSIONS: Daphnetin can reduce the expression of DNMT1, DNMT3a and DNMT3b, which could result in the proapoptotic genes DR3, PDCD5, FasL and p53 being demethylated. Therefore, daphnetin can increase proapoptotic gene and protein expression resulting in structural apoptotic changes and an increase in early and late CIA rat synovial cell apoptosis.

Expression of DJ-1 in endometrial cancer: close correlation with clinicopathological features and apoptosis.

OBJECTIVES: DJ-1 was originally cloned as a putative oncogene capable of transforming NIH3T3 cells in cooperation with H-Ras or c-Myc, which has been implicated in the pathogenesis of some solid tumors. The aim of this study was to investigate the expression and clinical significance of DJ-1 in endometrial cancer and study its effect on cell proliferation and apoptosis in endometrial cancer Ishikawa cells. METHODS: Reverse transcription polymerase chain reaction and Western blotting were performed to determine the DJ-1 expression in 100 surgical specimens of endometrial cancer tissues, paired tumor-adjacent tissues, and 30 surgical specimens of normal endometrium tissues. The proliferation variety of endometrial cancer Ishikawa cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay after transfecting the interference plasmid pGPU6/GFP/neo-DJ-1-shRNA into Ishikawa cells. Real-time polymerase chain reaction and Western blotting were used to evaluate the effect of interference plasmid on target gene expression. Apoptosis rate was determined by flow cytometry. RESULTS: DJ-1 expression in endometrial cancer tissues was higher than in tumor-adjacent tissues and normal endometrial tissues. At the same time, it was associated with signs of cancer progression, including differentiation, myometrial invasion depth, and presence of lymph node metastasis. Knocking down DJ-1 promoted the apoptosis of Ishikawa cells. CONCLUSIONS: High DJ-1 expression seems to be negatively correlated with apoptosis. Meanwhile, it may be part of the mechanisms for the development, invasion, and metastasis in endometrial cancer.

[Concurrent chemoradiotherapy versus radiotherapy in advanced cervical carcinoma].

BACKGROUND & OBJECTIVE: Cisplatin-based concurrent chemoradiotherapy has become the standard treatment modality for locally advanced cervical cancer. However, the optimal chemotherapy regimen combined with radiotherapy remains controversial. This study was to compare the therapeutic efficacy and toxicity of concurrent chemoradiotherapy with those of radiotherapy, and those among different regimens of concurrent chemoradiotherapy for stage IIB-IIIB cervical cancer. METHODS: From Jan. 2003 to Dec. 2004, 285 patients with stage IIB-IIIB cervical cancer treated in Maternal and Child Health Hospital of Jiangxi Province were randomly assigned to receive radiotherapy alone or concurrent chemoradiotherapy. According to different chemotherapy regimens, patients in the concurrent chemoradiotheapy group were randomly chosen to receive radiotherapy with chemotherapy of bleomycin and cisplatin (RT+BP), radiotherapy with chemotherapy of taxol and carboplatin (RT+TP), and radiotherapy with chemotherapy of 5-fluorouracil and cisplatin (RT+FP). The 3-year survival rates and toxicity of different groups were compared. RESULTS: After a median follow-up of 42 months, the 3-year survival was higher in the concurrent chemoradiotheray group (75%) than in the radiotherapy group (65%) (P=0.042). Acute treatment-related toxicity (grade III and IV) was higher in the concurrent chemoradiotherapy group than in the radiotherapy group (P<0.001); while the delayed treatment-related toxicity was similar in the two groups (P=0.613). The 3-year survival rates of BP, TP and FP chemoradiotherapy groups were 74%, 80% and 71%, without significant differences (P=0.792). Acute toxicities (grade III and IV) and delayed toxicities were similar among the three groups. CONCLUSIONS: Concurrent chemoradiotherapy significantly improves the survival for patients with stage IIB-IIIB cervical cancer compared to radiotherapy alone. Among the three chemoradiotherapy regimens, radiotherapy combined with taxol and carboplatin exerts a slightly higher 3-year survival than the other two regimens with tolerable toxicity.

[Clinical analysis of 48 patients with vaginal enlarged amputation of cervix].

OBJECTIVE: To evaluate the feasibility and safety of vaginal enlarged amputation of cervix to treat patients with cervical cancer of stage Ia1 and cervical intraepithelial neoplasia grade III (CIN III) who were unfit for conization surgery. METHODS: From July 2002 to May 2007, patients with cervical cancer at stage Ia1, diagnosed by pathology after loop electrosurgical excision procedure (LEEP), large area CIN III (the area of lesion>or=3/4 on colposcopy), CIN III coexisted with vaginal intraepithelial neoplasia (VAIN) in the superior segment of vagina, CIN II-III recurrence or with residual lesion, positive margin after conization of cervix, who wanted to preserve fertility and (or) corpus uteri were selected to receive vaginal enlarged amputation of cervix. RESULTS: Forty-eight cases including 5 with cervical cancer in stage Ia1, 38 with large area CIN III (9 with gland involvement), 2 with residual lesion and 2 with positive margin after LEEP, 1 recurrence after cold knife conization, received the procedure successfully. The median age was 34 years (range 27-40), median operation time was 60 minutes (range 30-100), median blood loss was 40 ml (range 5-300), and median hospital stay was 10 days (range 7-17). After follow-up 1-39 months, no patient had postoperative complications and recurrence, and all patients resumed normal menstrual cycle and sexual life. CONCLUSION: Vaginal enlarged amputation of cervix appears to be a safe and feasible procedure for patients with cervical cancer at stage Ia1 and CIN III who are unfit for conization surgery.