OBJECTIVE: To explore the mechanism of acupuncture on improving ovarian hypofunction in aged rats from two perspectives: the overall regulation of the hypothalamic-pituitary-ovarian (HPO) axis and the local ovarian follicle stimulating hormone (FSH)/cyclic adenosine monophosphate (cAMP) signaling pathway. METHODS: Six 3-month-old female SPF-grade Sprague-Dawley (SD) rats were selected as the blank group. Another twelve 9-month-old female SD rats were randomly divided into a model group and an acupuncture group, with six rats in each. The acupuncture group received acupuncture at "Baihui" (GV20), "Guanyuan" (CV4), and bilateral "Ciliao" (BL32) for 20 min per session, once every other day, for a total of 10 sessions. Vaginal smear tests were performed daily to observe the estrous cycle of the rats. Ovarian morphology was observed using HE staining, and follicles at various stages were counted. ELISA was used to detect levels of serum FSH, luteinizing hormone (LH), estradiol (E₂), anti-müllerian hormone (AMH), hypothalamic gonadotropin-releasing hormone (GnRH), pituitary FSH and LH, and ovarian cAMP. Immunohistochemistry and Western blot were used to detect the protein expression of ovarian cAMP protein kinase catalytic subunit, FSH receptor (FSHR), and P450. Real-time quantitative PCR was used to measure mRNA expression levels of FSHR and P450 in ovarian tissue. RESULTS: Compared with the blank group, the model group showed an increased rate of estrous cycle disorder (P<0.01), reduced granulosa cell layers with blurred boundaries and disordered arrangement, decreased numbers of developing follicles at all stages, and increased numbers of atretic follicles (P<0.01); the serum levels of FSH and LH were increased (P<0.01), while E₂ and AMH levels were decreased (P<0.01); the hypothalamic GnRH and pituitary FSH and LH levels were elevated (P<0.01), and ovarian cAMP level was decreased (P<0.01); the positive expression and protein expression of ovarian P450, cAMP protein kinase catalytic subunit, and FSHR were reduced (P<0.01), and ovarian FSHR and P450 mRNA expression was decreased (P<0.01). Compared with the model group, the acupuncture group showed a reduced rate of estrous cycle disorder (P<0.01), clear granulosa cell margins, increased numbers of primordial and secondary follicles, and decreased numbers of atretic follicles (P<0.01); the serum FSH and LH levels were decreased (P<0.01, P<0.05), while E₂ and AMH levels were increased (P<0.05, P<0.01); the hypothalamic GnRH and pituitary FSH and LH levels were decreased (P<0.01, P<0.05), and ovarian cAMP level was increased (P<0.01); the positive expression and protein expression of ovarian P450, cAMP protein kinase catalytic subunit, and FSHR were elevated (P<0.01), and ovarian FSHR and P450 mRNA expression was increased (P<0.01). CONCLUSION Acupuncture could delay ovarian hypofunction in aged rats, possibly through regulating the HPO axis and the FSH/cAMP signaling pathway.
Animals ; Female ; Rats ; Rats, Sprague-Dawley ; Follicle Stimulating Hormone/genetics* ; Acupuncture Therapy ; Ovary/metabolism* ; Signal Transduction ; Humans ; Cyclic AMP/metabolism* ; Hypothalamo-Hypophyseal System/metabolism* ; Aging/metabolism* ; Hypothalamus/metabolism* ; Pituitary Gland/metabolism* ; Gonadotropin-Releasing Hormone/metabolism*

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

Immunotherapy has been widely used in cancer treatment in recent years and functions by stimulating the immune system to kill tumor cells. Radiation therapy (RT) uses radiation to induce DNA damage and kill tumor cells. However, this activates the body's immune system, promoting the release of tumor-related antigens from inactive dendritic cells, which stimulates the recurrence and metastasis of tumors in immune system tissues. The combination of RT and immunotherapy has been increasingly evaluated in recent years, with studies confirming the synergistic effect of the two antitumor therapies. Particularly, the combination of RT by dose adjustment with different immunotherapies has positive implications on antitumor immunity as well as disease prognosis compared with respective monotherapies. This review summarizes the current research status, progress, and prospects of RT combined with immunotherapy in cancer treatment. It additionally discusses the prevalent concerns regarding the dose, time window, and toxicity of this combination therapy.
Humans ; Neoplasms/radiotherapy* ; Immunotherapy/methods* ; Combined Modality Therapy ; Radiotherapy/methods*

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

A 52-year-old female patient was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA), asthma and allergic rhinitis and was treated with mepolizumab (100 mg, once every 4 weeks). Three days after the second administration, the patient developed dark yellow urine, and abnormal liver function indicators were found on day 6 after administration. Laboratory tests showed total bilirubin (TBIL) of 22 μmol/L, direct bilirubin (DBIL) of 14.9 μmol/L, alanine aminotransferase (ALT) of 461 U/L, aspartate aminotransferase (AST) of 129 U/L, and alkaline phosphatase (ALP) of 296 U/L. After a comprehensive assessment, it was considered that mepolizumab may caused liver injury in the patient. Magnesium isoglycyrrhizinate, glutathione, and ursodeoxycholic acid were used for liver protection. Five days later, the urine color became lighter and liver function indicators improved (TBIL 17.4 μmol/L, DBIL 9.8 μmol/L, ALT 214 U/L, AST 85 U/L, ALP 226 U/L). After about 2 weeks of continued liver protection treatment, liver function returned to normal. Mepolizumab treatment was suspended and during the follow-up for about half a year, the patient did not experience liver function abnormalities or other discomforts again.

Damage to organelles plays a significant role in myocardial ischemia/reperfusion injury,which results in the dysfunction of mitochondria and other related organelles.The communication between mitochondria and other organ-elles can also affect the development of myocardial ischemia/reperfusion injury.For instance,the mitochondria-associated endoplasmic reticulum membrane provides a"seamless connection"and regulates the exchange of organelles and metabolites(such as ions,lipids and proteins)between the mitochondria and the endoplasmic reticulum,which subse-quently affects myocardial ischemia/reperfusion injury.However,there is a lack of studies regarding the interaction be-tween mitochondria and related organelles,which is a critical component in triggering myocardial ischemia/reperfusion inju-ry.Therefore,this article describes the role of mitochondrial crosstalk with endoplasmic reticulum,lysosomes and nuclei in myocardial ischemia/reperfusion injury,and aims to provide a theoretical basis for targeting mitochondrial crosstalk with other organelles in the treatment of myocardial ischemia/reperfusion injury.

Objective:To analyze clinical efficacy, failure mode and prognostic factors of nasopharyngeal carcinoma (NPC) patients undergoing intensity modulated radiation therapy (IMRT).Methods:Clinical data of 951 locally advanced NPC patients who were newly-treated with IMRT in Hunan Cancer Hospital from January 2018 to January 2019 were retrospectively analyzed. The patients' general data, overall survival (OS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), local recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) were analyzed. Comparison among different groups was performed by one-way ANOVA. Survival rate was calculated by Kaplan-Meier method. Survival difference was compared by log-rank test. Univariate and multivariate analyses were performed by Cox regression model.Results:The median follow-up time was 62.0 months (IQR, 58.0-65.0 months). The 5-year OS, LRFS, RRFS, LRRFS, DMFS, and PFS were 85.4%, 94.0%, 97.7%, 92.6%, 85.7% and 76.9%, respectively. According to the 8th edition staging of American Joint Committee on Cancer (AJCC), there were 10 cases (1.1%) of stage I, 76 cases (8.0%) of stage II, 445 cases (46.8%) of stage III, and 420 cases (44.2%) of stage IVA, respectively. Among them, the OS rates of stage I, II, III and IVA patients were 100%, 97.2%, 88.8% and 79.2%, respectively ( P<0.001); LRRFS rates were 100%, 90.4%, 94.7% and 90.4%, respectively( P=0.104); DMFS rates were 90.0%, 95.9%, 88.0% and 81.1%, respectively ( P<0.001); PFS rates were 90.0%, 89.1%, 80.9% and 70.1% respectively ( P<0.001). There were 183 cases of treatment failure, including 52 cases (5.5%) of local failure, 19 cases (2.0%) of regional failure, 130 cases (13.7%) of distant metastasis, 16 cases of local combined with regional failure (1.7%), 16 cases (1.7%) of local failure combined with distant metastasis, 13 cases (1.4%) of regional failure combined with distant metastasis, and 9 cases (0.9%) of local regional failure combined with distant metastasis, respectively. Multivariate regression analysis suggested that EB virus DNA copy number before treatment, T stage and N stage were the independent prognostic factors affecting OS, DMFS and PFS. Conclusions:Compared with two-dimensional radiotherapy, IMRT has improved the overall therapeutic effect for NPC, especially the local control rate. Distant metastasis is still the main failure mode. Clinical staging, prognostic risk stratification and prognostic biomarkers can be combined to deliver stratified and precise treatment, which may further improve clinical efficacy and reduce treatment-related side effects.

Objective:To analyze the value of 68Ga-fibroblast activation protein inhibitor (FAPI)-04 PET/CT in the detection of myocardial injury in patients treated with anti-tumor therapy. Methods:A retrospective study was conducted on 164 patients who underwent 68Ga-FAPI-04 PET/CT to evaluate the efficacy of anti-tumor therapy in Renji Hospital, School of Medicine, Shanghai Jiao Tong University between August 2021 and March 2024. The patients were divided into 68Ga-FAPI-04-positive group ( n=63, 36 males, 27 females, age (66.7±9.6) years) and 68Ga-FAPI-04-negative group ( n=101, 42 males, 59 females, age (55.2±14.1) years) based on the uptake of left ventricular myocardium (LVM). Moreover, FAPI-04 uptake was analyzed based on different types and locations, and the corresponding SUV max differences were analyzed by Kruskal-Wallis rank sum test. The differences of SUV max between 68Ga-FAPI-04-positive group and 68Ga-FAPI-04-negative group were analyzed by Mann-Whitney U test. The clinical factors such as gender, age, body mass index (BMI), previous history of coronary heart disease, left ventricular ejection fraction (LVEF), smoking history, hypertension, diabetes, cancer types and immune checkpoint inhibitors (ICIs) treatment were collected, and their predictive values for LVM 68Ga-FAPI-04 uptake were investigated by the binary logistic regression analysis. Results:Fifty patients of the 68Ga-FAPI-04-positive group (79.4%, 50/63) showed focal uptake of LVM, 7 patients (11.1%, 7/63) showed multifocal myocardial uptake, and 6 patients (9.5%, 6/63) showed diffuse myocardial uptake. A total of 127 uptake lesions were found, and most of them were located in the septum (37.8%, 48/127). The SUV max of LVM in 68Ga-FAPI-04-positive group and 68Ga-FAPI-04-negative group were 4.00(3.10, 5.40) and 1.31(1.20, 1.40) respectively ( z=-10.82, P<0.001). Differences of the SUV max among focal uptake group, multifocal myocardial uptake group, and diffuse myocardial uptake group were not significantly different (4.00(3.00, 5.10) vs 7.60(3.60, 9.30) vs 3.95(3.05, 5.05); H=3.81, P=0.149). There is no statistically significant difference either in FAPI uptake among different sites of LVM ( H=1.51, P=0.825). Age, previous history of coronary heart disease, BMI, LVEF and ICIs treatment were independent predictive factors for positive 68Ga-FAPI-04 uptake in the LVM (odds ratio ( OR) values: 0.87-10.43, all P<0.05). Conclusion:68Ga-FAPI-04 PET/CT is a potential new imaging method for the visualization of myocardial injury in patients with anti-tumor therapy.

Objective To establish an artificial intelligence (AI)-assisted platform for detection of parasite eggs, and to evaluate its detection efficiency and accuracy, so as to provide technical supports for elimination of parasitic diseases. Methods A total of 1 003 slides of Enterobius vermicularis, horkworm, Trichuris trichiura, Clonorchis sinensis, Taenia, Ascaris lumbricoides, Schistosoma japonicum, Paragonimus westermani and Fasciolopsis buski eggs were collected, and converted into digital images with an automatated scanning microscope to create a dataset. Based on the Object Detection platform on the Baidu Easy DL model, an AI-assisted platform for detection of parasite eggs was created through procedures of uploading, labeling, training, evaluation and optimization. Then, 70% of the datasets were randomly selected for model training, and the precision, recall and average accuracy were calculated to evaluate the effectiveness of platform for recognition of parasite eggs. In addition, the platform was deployed on the computer and smart phone terminals for use. Results An AI-assisted platform for detection of parasite eggs was successfully created. If the platform was deployed using the public cloud application programming interface (API), the average accuracy, precision and recall of the platform were 93.42%, 92.55% and 89.32% for recognition of parasite eggs. If the platform was deployed using the offline software development kit (SDK), the average accuracy, precision and recall of the platform were 92.97%, 94.78% and 87.63% for recognition of parasite eggs. In addition, the precision of the platform was 97.00% and 96.23% for identification of Taenia and C. sinensis eggs, respectively. Conclusions The AI-assisted platform for detection of parasite eggs has been successfully created, which is high in the accuracy for recognition of parasite eggs and convenient in use. This platform may provide a powerful technical support for parasitic disease diagnosis.

ABSTRACT:Objective To report the data of 4 cases of Trocar-assisted ureteroscopy in the treatment of transplanted renal ureteral stones,to analyze the effectiveness of this therapy,and provide a reference for the treatment of such patients.Methods Clinical data of 4 patients with ureteral stones of transplanted kidney treated at the Affiliated Hospital of Guizhou Medical University during Jan.2016 and Jul.2023 were retrospectively analyzed.All patients received auxiliary ureteral soft/rigid endoscopic combined with holmium laser lithotripsy after Trocar-assisted bladder fistula.Renal function was rechecked after surgery and all patients were followed up regularly.Results All 4 cases had upper ureteral stones.During the follow-up of 24-68(average 38)months,no residual or recurrent stones were observed.Renal function and creatinine level returned to normal(79.0 μmol,95.0 μmol,60.6 μmol,82.0 μmol,respectively).Conclusion The treatment of ureteral stones of transplanted kidney should be individualized.Bladder fistula with Trocar-assisted ureteroscopy can effectively protect the function of transplanted kidney,which is worthy of promotion and application.