Objective Analysis of Traditional Chinese Medicine Syndrome Differentiation of Patients With Diabetes and Prediabetes: Protocol for a Nonrandomized, Exploratory, Observational Case-Control Study Using Digitalized Traditional Chinese Medicine Diagnostic Tools.

BACKGROUND: Diabetes and prediabetes are diagnosed differentially by Western and Chinese medicine. While Western medicine uses objective laboratory analysis of biochemical parameters to define the severity of diabetes and prediabetes, Chinese medicine uses a comprehensive approach that integrates observation, inquiry, pulse palpation, and tongue diagnosis. The medical information collected is then categorized into different syndromes. However, traditional methods of pulse and tongue diagnoses used to determine syndrome differentiation are highly subjective and skill dependent. OBJECTIVE: This study aims to identify the gap in conventional traditional Chinese medicine (TCM) diagnostic techniques for syndrome differentiation analysis using contemporary diagnostic devices. We devised a protocol for a nonrandomized, exploratory, observational case-control study with equal allocations in 5 arms to investigate the syndrome differentiation of diabetes and prediabetes. We hypothesize that the TCM syndrome differentiation of diabetes and prediabetes in the tropical climate may differ from that defined based on the Chinese demographic. We also speculate that the high-frequency spectral energy may reflect a difference in pulse wave intensity and density between the healthy and diabetes groups. METHODS: A total of 250 eligible participants will be equally assigned to 1 of 5 arms (healthy or subhealthy, prediabetes, diabetes, prediabetes with hypertension and dyslipidemia, and diabetes with hypertension and dyslipidemia). Participants aged 21-75 years, of any sex or race, and have been diagnosed with diabetes (fasting plasma glucose [FPG] of 7 mmol/L, or 2-hour plasma glucose [2hPG] of 11.1 mmol/L) or prediabetes (impaired FPG of 6.1-6.9 mmol/L, or impaired glucose tolerance with an 2hPG of 7.8-11 mmol/L) will be included. The Health Evaluation Questionnaire, Physical Activity Questionnaire, sugar intake assessment, Constitution in Chinese Medicine Questionnaire, radial pulse diagnosis, and tongue diagnosis will be performed in a single visit. ANOVA for continuous data and chi-square tests of independence will be used for categorical data assessments, with a level of P<.05 considered significant. RESULTS: The recruitment is in progress. We anticipate that the study will conclude in June 2025. As of July 15, 2024, we have enrolled 140 individuals. CONCLUSIONS: To the best of our knowledge, this is the first study to use contemporary TCM diagnostic instruments to map expert and empirical knowledge of TCM to its scientific equivalents for the purpose of evaluating the syndrome differentiation of diabetes. We designed this protocol with the exploratory goal to examine objectively the syndrome differentiation of patients with diabetes and those with prediabetes using TCM diagnostic technologies. The data collected and evaluated under standardized conditions using these contemporary diagnostic devices will exhibit a higher degree of stability, hence yielding dependable and unbiased results for syndrome differentiation. Thus, our findings may potentially increase the accuracy of identification, diagnosis, treatment, and prevention of diabetes and prediabetes through a system of targeted treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT05563090; https://clinicaltrials.gov/ct2/show/NCT05563090. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56024.

Unveiling the hidden link: fungi and HPV in cervical lesions.

Background: Cervical cancer, primarily driven by high-risk human papillomavirus (HR-HPV) infection, ranks as the second most common cancer globally. Understanding combined infections' role, including Cervical fungi, is crucial in cervical carcinogenesis. This study aims to explore the potential correlation between HR-HPV, cervical fungi, and cervical cancer, while adjusting for various factors. Methods: The study population comprised patients undergoing colposcopy and conization due to abnormal cervical screening results. Clinical data including age, gravidity, HPV (human papillomavirus) genotypes, cervical pathology, and p16/Ki67 expression were extracted. Cervical TCT (ThinPrep Pap Test) and HPV testing are utilized for screening cervical lesions, with fungal presence suggested by TCT results. 5,528 participants were included in this study. Statistical analyses investigated associations between HPV/fungi co-infection and cervical lesions, employing multinomial logistic regression and interaction analysis. Results: Co-infection with fungi and HPV may decrease the risk of cervical lesions compared to HPV infection alone. In the co-infection group, compared with HPV infection alone, the risk of low-grade squamous intraepithelial lesions (LSIL) was reduced by 27% (OR = 0.73, 95% CI: 0.59-0.90), the risk of high-grade squamous intraepithelial lesions (HSIL) was reduced by 35% (OR = 0.65, 95% CI: 0.51-0.82), and the risk of cervical cancer was reduced by 43% (OR = 0.57, 95% CI: 0.35-0.92). The interaction analysis revealed a negative interaction between fungal and HPV infections in the development of cervical cancer (RERI = -6.25, AP = -0.79, SI = 0.52), HSIL (RERI = -19.15, AP = -0.37, SI = 0.72) and LSIL (RERI = -1.87, AP = -0.33, SI = 0.71), suggesting a sub-additive effect, where the combined effect of the two infections was less than the sum of their individual effects. This indicates that fungal infection may attenuate the promoting effect of HPV on cervical lesions. In exploring the potential mechanism, we found that the co-infection group had significantly lower p16 positivity (54.6%) compared to the HPV-only group (60.2%) (p = 0.004), while there was no statistically significant difference in Ki67 positivity. Conclusion: This study unveils the intricate relationship between cervical fungi and HPV in cervical lesions. Co-infection with fungi and HPV against cervical lesions compared to HPV infection alone, indicating a novel clinical interaction. Lower p16 positivity in co-infection hints at a protective mechanism, urging further exploration.

Study on Shenbao Tablet in Treating Kidney-yang Deficiency Syndromebased on Metabolomics.

AIM: The aim of this study was to elucidate the mechanism of action of Shenbao tablets using metabolomics approach. BACKGROUND: Kidney-Yang deficiency is a common syndrome type in traditional Chinese Medicine (TCM) syndrome typology, closely related to disorders of multiple metabolic pathways and is the root cause and underlying syndrome type of many diseases. Shenbao tablets can significantly improve the main symptoms of kidney yang deficiency syndrome, but the mechanism of action of Shenbao tablets on kidney yang deficiency syndrome is still unknown. METHODS: The rats were intraperitoneally injected with hydrocortisone once a day for 40 days to simulate the syndrome. Traditional pharmacodynamic indicators (body mass, biochemical indicators and pathology) were used to evaluate the efficacy of the medicine. Serum, urine and feces were collected from rats. UPLC/MS metabolomics method was used to study the overall metabolic profile of serum, while GC/MS metabolomics method was used to study the metabolic spectrum of urine and feces. RESULTS: Results showed that the syndrome was significantly improved in the treatment group, and obvious metabolic disorders were observed in rats with the syndrome, with 47 potential biomarkers identified. Pathway analysis showed that nicotinate and nicotinamide metabolism, glycine, serine and trione metabolism, aminoacyl tRNA biosynthesis, glycoxylate and dicarboxylate metabolism were the major ways for Shenbao tablet to improve kidney-yang deficiency syndrome. CONCLUSION: The mechanism of action of Shenbao tablet in improving the syndrome involves the regulation of energy metabolism, amino acid metabolism, bile acid metabolism, fatty acid metabolism and intestinal microorganisms. This work shows that metabolomics is a promising tool for studying the essence of syndrome theory in TCM and the mechanisms of TCM.

The impact of diabetes, hypercholesterolemia, and low-density lipoprotein (LDL) on the survival of cervical cancer patients.

BACKGROUND: Cervical cancer is a prevalent malignancy and an important health concern worldwide. Recent research has highlighted the potential impact of metabolic factors, such as hyperlipidemia and diabetes, on cancer progression, increased mortality, and patient outcomes. However, insufficient data have been reported regarding their relationship with cervical cancer. This study aimed to investigate the relationships between metabolic disorders, including dyslipidemia, dysglycemia, and metabolic syndrome, and survival in patients with cervical cancer. METHODS: We retrospectively analyzed demographic information, clinical characteristics, and metabolic health indicators of patients with cervical cancer. Patients were categorized into groups based on specific metabolic conditions: high triglyceride, high low-density lipoprotein, high cholesterol, and diabetes groups. Additionally, the presence of metabolic syndrome and other metabolic comorbidities was recorded. The log-rank test was used to compare survival rates between different patient groups and identify associated risk factors. Survival curves generated via the Cox proportional hazards model were used to evaluate the associations between metabolic parameters and survival. RESULTS: The Cox proportional hazards model was used to analyze data from 840 patients with cervical cancer between 28 and 72 years old who underwent surgery. The hazard ratio (HR) of mortality was 1.804 (95% CI 1.394-2.333, p < 0.001) in the high-density lipoprotein group, 0.758 (95% CI 0.558 to 1.030, p < 0.001) in the high-triglyceride group, 1.794 (95% CI 1.304-2.470, p < 0.001) in the high low-density lipoprotein group, and 0.011 (95% CI 0.005-0.025, p < 0.001) in the diabetes group. These factors were significantly associated with reduced survival in patients with cervical cancer, and these associations persisted after adjusting for age, cancer stage, treatment type, and the presence of metabolic syndrome or other comorbidities. CONCLUSION: This study highlights the importance of metabolic health and the significance of controlling metabolic disorders, including hyperlipidemia, diabetes, and metabolic syndrome, to improve survival outcomes in patients with cervical cancer. Future research should explore the impact of managing multiple metabolic conditions on the prognosis of these patients.

IL-18BP Therapy Ameliorates Reproductive and Metabolic Phenotypes in a PCOS Mouse Model by Relieving Inflammation, Fibrosis and Endoplasmic Reticulum Stress.

There is a chronic inflammation in PCOS patients, which is correlated with the pathogenesis of PCOS. IL-18 and IL-18BP are related with some inflammatory diseases, while less explored in PCOS. Whether IL-18BP could be a potential drug of PCOS remains unknown.IL-18 and testosterone levels were evaluated in serum of 10 non-PCOS control patients and 20 PCOS patients. Female C57/BL6 mice were gavaged with letrozole to induce PCOS mouse model and IL-18 level was evaluated in the serum of PCOS mouse model, and IL-18 is intraperitoneally injected in female mice, IL-18BP is intraperitoneally injected in the PCOS mice models. Then the body weights, estrous cycles, reproductive hormones and morphology of ovaries were analyzed. The level of ovarian chronic inflammation, fibrosis and endoplasmic reticulum (ER) stress are evaluated.IL-18 levels are increased in the serum of PCOS patients and PCOS mice models respectively. The serum DHEAS, iWAT weight and adipocyte size were increased in IL-18 group compared to the control group (P < 0.05). In the PCOS mouse model treated with IL-18BP, the body weight and serum LH/FSH ratio was decreased compared to the PCOS group (P < 0.05). The expression levels of inflammatory factors and fibrosis-related genes, the expression level of endoplasmic reticulum stress-related genes, and the ROS positive area of ovarian tissue was decreased (P < 0.05).IL-18 is involved in inducing PCOS phenotypes, while IL-18BP relieves PCOS phenotypes by alleviating ovarian chronic inflammation, fibrosis and ER stress in PCOS mice.

Prognostic patterns in invasion lymph nodes of lung adenocarcinoma reveal distinct tumor microenvironments.

Tumor-draining lymph nodes (TDLNs) are usually the first station of tumor metastasis in lung cancer. TDLNs+ have distinct pathomorphologic and tumor microenvironment (TME)-compositional patterns, which still need to be thoroughly investigated in lung adenocarcinoma (LUAD). Here, we enrolled 312 LUAD patients with TDLNs+ from our institution between 2015 and 2019. 3DHISTECH was used to scan all of the TDLNs+. Based on morphologic features, TDLNs+ patterns were classified as polarized-type or scattered-type, and TME-compositional patterns were classified as colloid-type, necrosis-type, specific-type, and common-type. Multivariate analysis revealed an increased risk of early recurrence associated with scattered-type (HR 2.37, 95% CI: 1.06-5.28), colloid-type (HR 1.95, 95% CI: 1.03-3.67), and necrosis-type (HR 2.21, 95% CI: 1.13-4.89). NanoString transcriptional analysis revealed an immunosuppression and vascular invasion hallmark in scattered and necrosis patterns and an immunoactivated hallmark in polarized and common patterns. According to imaging mass cytometry (IMC), the scattered and necrosis patterns revealed that germinal centers (GC) were compromised, GCB cell and T cell proliferation were deficient, tumor cells had the potential for proliferation, and the immune attack may be weaker. In this study, we present evidence that LUAD patients have distinct patterns and immune hallmarks of TDLNs+ related to their prognosis.

16S rRNA gene sequencing reveals altered gut microbiota in young adults with schizophrenia and prominent negative symptoms.

BACKGROUND: Gut dysbiosis has been established as a characteristic of schizophrenia (SCH). However, the signatures regarding SCH patients with prominent negative symptoms (SCH-N) in young adults have been poorly elucidated. METHODS: Stool samples were obtained from 30 young adults with SCH-N, 32 SCH patients with prominent positive symptoms (SCH-P) along with 36 healthy controls (HCs). Microbial diversity and composition were analyzed by 16S rRNA gene sequencing. Meanwhile, psychiatric symptoms were assessed by the positive and negative syndrome scale (PANSS). RESULTS: There is a significant difference in ß-diversity but not α-diversity indexes among the three groups. Moreover, we found a higher abundance of Fusobacteria and Proteobacteria phyla and a lower abundance of Firmicutes phyla in SCH-N when compared with HC. Besides, we identified a diagnostic potential panel comprising six genera (Coprococcus, Monoglobus, Prevotellaceae_NK3B31_group, Escherichia-Shigella, Dorea, and Butyricicoccus) that can distinguish SCH-N from HC (area under the curve = 0.939). However, the difference in microbial composition between the SCH-N and SCH-P is much less than that between SCH-N and the HC, and SCH-N and SCH-P cannot be effectively distinguished by gut microbiota. CONCLUSION: The composition of gut microbiota was changed in the patients with SCH-N, which may help in further understanding of pathogenesis in young adults with SCH-N.

Experimental study of different dehydration methods in the process of preparing frozen brain sections.

This study aimed to provide a recommendable protocol for the preparation of brain cryosections of rats to reduce and avoid ice crystals. We have designed five different dewatering solutions (Scheme 1: dehydrate with 15%, 20%, and 30% sucrose-phosphate-buffered saline solution; Scheme 2: 20% sucrose and 30% sucrose; Scheme 3: 30% sucrose; Scheme 4: 10%, 20%, and 30% sucrose; and Scheme 5: the tissue was dehydrated with 15% and 30% sucrose polyacetate I until it sank to the bottom, followed by placement in 30% sucrose polyacetate II) to minimize the formation of ice crystals. Cryosections from different protocols were stained with Nissl staining and compared with each other by density between cells and the distance of intertissue spaces. The time required for the dehydration process from Scheme 1 to Scheme 5 was 24, 23, 24, 24, and 33 h, respectively. Density between cells gradually decreased from Scheme 1 to Scheme 5, and the distance of intertissue spaces was differentiated and irregular in different schemes according to the images of Nissl staining. We recommend the dewatering method of Scheme 4 (the brain tissues were dehydrated in 10%, 20% and 30% sucrose solution in turn until the tissue samples were completely immersed in the solution and then immersed in the next concentration solution for dehydration).

Decoding Fujian's cervical HPV landscape: unmasking dominance of non-16/18 HR-HPV and tailoring prevention strategies at a large scale.

Background: Persistent HR-HPV causes cervical cancer, exhibiting geographic variance. Europe/Americas have higher HPV16/18 rates, while Asia/Africa predominantly have non-16/18 HR-HPV. This study in Fujian, Asia, explores non-16/18 HR-HPV infections, assessing their epidemiology and cervical lesion association for targeted prevention. Methods: A total of 101,621 women undergoing HPV screening at a hospital in Fujian Province from 2013 to 2019 were included. HPV genotyping was performed. A subset of 11,666 HPV-positive women with available histopathology results were analyzed to characterize HPV genotype distribution across cervical diagnoses. Results: In 101,621 samples, 24.5% tested positive for HPV. Among these samples, 17.3% exhibited single infections, while 7.2% showed evidence of multiple infections. The predominant non-16/18 high-risk HPV types identified were HPV 52, 58, 53, 51, and 81. Single HPV infections accounted for 64.1% of all HPV-positive cases, with 71.4% of these being non-16/18 high-risk HPV infections. Age-related variations were observed in 11,666 HPV-positive patients with pathological results. Cancer patients were older. In the cancer group, HPV52 (21.8%) and HPV58 (18.6%) were the predominant types, followed by HPV33, HPV31, and HPV53. Compared to single HPV16/18 infection, non-16/18 HPV predominated in LSIL. Adjusted odds ratios (OR) for LSIL were elevated: multiple HPV16/18 (OR 2.18), multiple non-16/18 HR-HPV (OR 2.53), and multiple LR-HPV (OR 2.38). Notably, solitary HPV16/18 conferred higher odds for HSIL and cancer. Conclusion: Our large-scale analysis in Fujian Province highlights HPV 52, 58, 53, 51, and 81 as predominant non-16/18 HR-HPV types. Multiple HPV poses increased LSIL risks, while solitary HPV16/18 elevates HSIL and cancer odds. These findings stress tailored cervical cancer prevention, highlighting specific HPV impacts on lesion severity and guiding region-specific strategies for optimal screening in Asia, emphasizing ongoing surveillance in the vaccination era.

Pharmacokinetics and pharmacodynamics of intravenous delafloxacin in healthy subjects: model-based dose optimization.

Delafloxacin, a fluoroquinolone antibiotic to treat skin infections, exhibits a broad-spectrum antimicrobial activity. The first randomized, open-label phase I clinical trial was conducted to assess the safety and pharmacokinetics (PK) of intravenous delafloxacin in the Chinese population. A population pharmacokinetic (PopPK) model based on the clinical trial was conducted by NONMEM software. Monte Carlo simulation was performed to evaluate the antibacterial effects of delafloxacin at different doses in different Chinese populations. The PK characteristics of delafloxacin were best described by a three-compartment model with mixed linear and nonlinear clearance. Body weight was included as a covariate in the model. We simulated the AUC0-24h in a steady state at five doses in patient groups of various weights. The results indicated that for patients weighing 70 kg and treated with methicillin-resistant Staphylococcus aureus (MRSA) infections, a minimum dose of 300 mg achieved a PTA > 90% at MIC90 of 0.25 µg/mL, suggesting an ideal bactericidal effect. For patients weighing less than 60 kg, a dose of 200 mg achieved a PTA > 90% at MIC90 of 0.25 µg/mL, also suggesting an ideal bactericidal effect. Additionally, this trial demonstrated the high safety of delafloxacin in single-dose and multiple-dose groups of Chinese. Delafloxacin (300 mg, q12h, iv) was recommended for achieving optimal efficacy in Chinese bacterial skin infections patients. To ensure optimal efficacy, an individualized dose of 200 mg (q12h, iv) could be advised for patients weighing less than 60 kg, and 300 mg (q12h, iv) for those weighing more than 60 kg.

Evaluation of cutout factors with small and narrow fields using various dosimetry detectors in electron beam keloid radiotherapy.

BACKGROUND: The inherent problems in the existence of electron equilibrium and steep dose fall-off pose difficulties for small- and narrow-field dosimetry. OBJECTIVE: To investigate the cutout factors for keloid electron radiotherapy using various dosimetry detectors for small and narrow fields. METHOD: The measurements were performed in a solid water phantom with nine different cutout shapes. Five dosimetry detectors were used in the study: pinpoint 3D ionization chamber, Farmer chamber, semiflex chamber, Classic Markus parallel plate chamber, and EBT3 film. RESULTS: The results demonstrated good agreement between the semiflex and pinpoint chambers. Furthermore, there was no difference between the Farmer and pinpoint chambers for large cutouts. For the EBT3 film, half of the cases had differences greater than 1%, and the maximum discrepancy compared with the reference chamber was greater than 2% for the narrow field. CONCLUSION: The parallel plate, semiflex chamber and EBT3 film are suitable dosimeters that are comparable with pinpoint 3D chambers in small and narrow electron fields. Notably, a semiflex chamber could be an alternative option to a pinpoint 3D chamber for cutout widths≥3 cm. It is very important to perform patient-specific cutout factor calibration with an appropriate dosimeter for keloid radiotherapy.

miR-29a-5p rescues depressive-like behaviors in a CUMS-induced mouse model by facilitating microglia M2-polarization in the prefrontal cortex via TMEM33 suppression.

BACKGROUND: Depression accounts for a high proportion of neuropsychiatric disorders and is associated with abnormal states of neurons in specific brain regions. Microglia play a pivotal role in the inflammatory state during depression development; however, the exact mechanism underlying chronic mood states remains unknown. Thus, the present study aimed to determine whether microRNAs (miRNAs) alleviate stress-induced depression-like behavior in mice by regulating the expression levels of their target genes, explore the role of neuroinflammation induced by microglial activation in the pathogenesis and progression of depression, and determine whether the role of the miR-29a-5p/transmembrane protein 33 (TMEM33) axis. METHODS: In this study, chronic unpredictable mild stress (CUMS) mouse depression model, various behavioral tests, western blotting, dual-luciferase reporter assay, enzyme-linked immunosorbent assay, real-time quantitative reverse transcription PCR, immunofluorescence and lentivirus-mediated gene transfer were used. RESULTS: After exposure to the CUMS paradigm, miR-29a-5p was significantly down-regulated. This downregulation subsequently promoted the polarization of microglia M1 by upregulating the expression of TMEM33, resulting in enhanced inflammatory chemokines affecting neurons. Conversely, the upregulation of miR-29a-5p within the prefrontal cortex (PFC) suppressed TMEM33 expression, facilitated microglia M2-polarization, and ameliorated depressive-like behavior. LIMITATIONS: Only rodent models of depression were used, and human samples were not included. CONCLUSIONS: The results of this study suggest that miR-29a-5p deficits within the PFC mediate microglial anomalies and contribute to depressive-like behaviors. miR-29a-5p and TMEM33 may, therefore, serve as potential therapeutic targets for the treatment of depression.

Anti-inflammatory and antinociceptive effects, toxicity, and phytochemical analysis of Beaumontia grandiflora Wall.

Preliminary pharmacological studies revealed that the EtOAc fraction (BGEA) might be the main active fraction with anti-inflammatory and antinociceptive effects in Beaumontia grandiflora Wall. Further assays on BGEA at doses of 200, 400, and 800 mg/kg using four animal models showed that it could inhibit the xylene-induced ear edema, carrageenan-induced paw edema, and acetic acid-induced writhing and prolong the latency time in the hot-plate test. ELISA analysis revealed that the anti-inflammatory activity of BGEA might be associated with the decrease of TNF-α, IL-1ß, and IL-6 levels and the increase of the IL-10 level. The acute toxicity test showed that except for the n-BuOH fraction, the LD50 values of the extract and other three fractions were higher than 2000 mg/kg bw. Finally, 14 compounds were identified from BGEA by LC-MS. This research provides some basis for the folk use of B. grandiflora in the treatment of inflammation and pain-related diseases.

Molecular and immunological characteristics of postoperative relapse in lymph node-positive esophageal squamous cell cancer.

BACKGROUND: The molecular and immunological characteristics of primary tumors and positive lymph nodes in esophageal squamous cell carcinoma (ESCC) are unknown and the relationship with recurrence is unclear, which this study attempted to explore. METHODS: A total of 30 ESCC patients with lymph node positive (IIB-IVA) were enrolled. Among them, primary tumor and lymph node specimens were collected from each patient, and subjected to 551-tumor-targeted DNA sequencing and 289-immuno-oncology RNA panel sequencing to identify the different molecular basis and immunological features, respectively. RESULTS: The primary tumors exhibited a higher mutation burden than lymph nodes (p < 0.001). One-year recurrent ESCC exhibited a higher Mucin16 (MUC16) mutation rate (p = 0.038), as well as univariate and multivariate analysis revealed that MUC16 mutation is independent genetic factor associated with reduced relapse-free survival (univariate, HR: 5.39, 95% CI: 1.67-17.4, p = 0.005; multivariate, HR: 7.36, 95% CI: 1.79-30.23, p = 0.006). Transcriptomic results showed non-relapse group had higher cytolytic activity (CYT) score (p = 0.025), and was enriched in the IFN-α pathway (p = 0.036), while those in the relapsed group were enriched in the TNF-α/NF-κB (p = 0.001) and PI3K/Akt pathway (p = 0.014). CONCLUSION: The difference in molecular characteristics between primary lesions and lymph nodes may be the cause of the inconsistent clinical outcomes. Mutations of MUC16 and poor immune infiltration are associated with rapid relapse of nodes-positive ESCC.

Association of levonorgestrel-releasing intrauterine device with gynecologic and breast cancers: a national cohort study in Sweden.

BACKGROUND: The levonorgestrel-releasing intrauterine device (LNG-IUD) is widely used for the treatment of menorrhagia, dysmenorrhea, and for contraception. However, the association between the use of LNG-IUD and the risk of site-specific gynecologic and breast cancers remains inconclusive. OBJECTIVE: We aim to address this knowledge gap by investigating whether the use of LNG-IUD is associated with a significant risk of site-specific gynecologic and breast cancers. This will be achieved by accessing the nationwide Swedish Registers, with consideration given to the influence and potential interaction of family history of cancer. STUDY DESIGN: A total of 514,719 women aged 18 to 50 years who have used LNG-IUD between July 2005 and December 2018 were identified from the Swedish Prescribed Drug Register and randomly matched with 1,544,157 comparisons who did not use LNG-IUD at a ratio of 1:3. The propensity score was calculated and matched among women who used LNG-IUD and the matched comparisons. The follow-up period started from the date of the first prescription of LNG-IUD for users as well as for their matched comparisons and ended at the date of diagnosis of gynecologic and breast cancers, date of death from any cause, and the end of the study period, whichever came first. The Cox proportional hazard model with a competing risk analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Additive interaction was calculated as the relative excess risk for interaction, while multiplicative interaction was calculated by including a product term in the regression model. RESULTS: The use of LNG-IUD was associated with a 13% higher risk of breast cancer (adjusted HR, 1.13; 95% CI, 1.10-1.17), a 33% lower risk of endometrial cancer (adjusted HR, 0.67; 95% CI, 0.56-0.80), a 14% lower risk of ovarian cancer (adjusted HR, 0.86; 95% CI, 0.75-0.99), and a 9% reduced risk of cervical cancer (adjusted HR, 0.91; 95% CI, 0.84-0.99) compared to women who did not use LNG-IUD. A significant additive interaction between LNG-IUD use and family history of cancer was observed in breast cancer, indicating a relative 19% excess risk for interaction (P<.002), and 1.63 additional cases per 10,000 person-years. CONCLUSION: The risk of gynecologic and breast cancers exhibits a site-specific effect among LNG-IUD users. It is important to note that the observed effect is small for breast cancer and the results are limited by the observational study design. Clinical recommendations regarding the use of LNG-IUD should carefully weigh its potential benefits and risks. Close monitoring is advisable for the potential development of breast cancer, particularly among women with a family history of breast cancer.

To identify important MRI features to differentiate hepatic mucinous cystic neoplasms from septated hepatic cysts based on random forest.

OBJECTIVE: To identify important MRI features to differentiate hepatic mucinous cystic neoplasms (MCN) from septated hepatic cysts (HC) using random forest and compared with logistic regression algorithm. METHODS: Pathologically diagnosed hepatic cysts and hepatic MCNs with pre-operative contrast-enhanced MRI in our hospital from 2010 to 2023 were collected and only septated lesions on enhanced MRI were enrolled. A total of 21 septated HC and 18 MCNs were included in this study. Eighteen MRI features were analyzed and top important features were identified based on random forest (RF) algorithm. The results were evaluated by the prediction performance of a RF model combining the important features and compared with the performance of the logistic regression (LR) algorithm. Finally, for each identified feature, diagnostic probability, sensitivity, and specificity were calculated and compared. RESULTS: Four variables, i.e., the septation arising from wall without indentation, multiseptate, intracapsular cyst sign, and solitary lesion were extracted as top important features with significance for MCNs by the random forest algorithm. The RF model using these variables had an AUC of 0.982 (0.95CI, 0.950-1.000), compared with the LR model based on two identified features with AUC of 0.931 (0.95CI, 0.846-1.000), p = 0.202. Among the four important features, multiseptate had the highest specificity (95.2%) and good sensitivity (72.2%, lower than the septation from wall without indentation, 94.4%) to diagnose MCNs. CONCLUSION: Four out of 18 MRI features were extracted as reliably important factors to differ hepatic MCNs from septated HC. The combination of these four features in a RF model could achieve satisfactory diagnostic efficacy.

The gut microbiome from middle-aged women with depression modulates depressive-like behaviors and plasma fatty acid metabolism in female middle-aged mice.

BACKGROUND: Intestinal dysbacteriosis has frequently been involved in the context of depression. Nonetheless, only scant information is available about the features and functional changes of gut microbiota in female middle-aged depression (MAD). OBJECTIVE: This study aims to explore whether there are characteristic changes in the gut microbes of female MAD and whether these changes are associated with depressive-like behaviors. Meanwhile, this study observed alterations in the lipid metabolism function of gut microbes and further examined changes in plasma medium- and long-chain fatty acids (MLCFAs) in mice that underwent fecal microbiota transplantation (FMT). METHODS: Stool samples obtained from 31 MAD, along with 24 healthy individuals (HC) were analyzed by 16 S rRNA gene sequencing. Meanwhile, 14-month-old female C57BL/6J mice received antibiotic cocktails and then oral gavage of the microbiota suspension of MAD or HC for 3 weeks to reconstruct gut microbiota. The subsequent depressive-like behaviors, the composition of gut microbiota, as well as MLCFAs in the plasma were evaluated. RESULTS: A noteworthy disruption in gut microbial composition in MAD individuals compared to HC was observed. Several distinct bacterial taxa, including Dorea, Butyricicoccus, and Blautia, demonstrated associations with the demographic variables. A particular microbial panel encompassing 49 genera effectively differentiated MAD patients from HC (AUC = 0.82). Fecal microbiome transplantation from MAD subjects led to depressive-like behaviors and dysfunction of plasma MLCFAs in mice. CONCLUSIONS: These findings suggest that microbial dysbiosis is linked to the pathogenesis of MAD, and its role may be associated with the regulation of MLCFAs metabolism.

Revealing genes associated with cervical cancer in distinct immune cells: A comprehensive Mendelian randomization analysis.

Human papillomavirus can be contracted by sexually active women. However, only a small proportion of these infections persist and have the potential to progress into cervical cancers, indicating a significant involvement of the immune system in cervical cancer development. Despite this, our understanding of the precise contributions of genes from different immune cell types in cervical cancers remains limited. Therefore, the primary objective of our study was to investigate the potential causal relationships between specific immune cell genes and the development of cervical cancers. By accessing expression quantitative trait loci datasets of 14 distinct immune cell types and genome wide association study of cervical cancers, we employed the summary data-based Mendelian randomization (SMR) along with multi-single nucleotide polymorphism (SNP)-based SMR to identify significant genes associated with cervical cancers. Colocalization analysis was further conducted to explore the shared genetic causality. A total of 10 genes across 11 immune cell types (26 significant gene-trait associations) were found to be associated with cervical cancers after false discovery rate correction. Notably, the ORMDL3, BRK1 and HMGN1 gene expression levels showed significant association with cervical cancer in specific immune cell types, respectively. These associations were supported by strong evidence of colocalization analyses. Our study has identified several genes in different immune cells that were associated with cervical cancer. However, further research is necessary to confirm these findings and provide more comprehensive insights into the association between these gene expressions and cervical cancer risk.

A novel clinical nomogram for predicting cancer-specific survival in patients with non-serous epithelial ovarian cancer: A real-world analysis based on the Surveillance, Epidemiology, and End Results database and external validation in a tertiary center.

BACKGROUND: Currently, there is a lack of prognostic evaluation methods for non-serous epithelial ovarian cancer (EOC). METHOD: We collected patients with non-serous EOC diagnosed between 2010 and 2017 from the Surveillance, Epidemiology, and End Results (SEER) database into a training cohort (n = 2078) and an internal validation cohort (n = 891). Meanwhile, patients meeting the criteria were screened from the Fujian Provincial Maternal and Child Health Hospital from 2013 to 2022 as an external validation cohort (n = 56). Univariate and multivariable logistic regression were used to determine the independent prognostic factors of cancer-specific survival (CSS) to construct the nomogram. The nomogram was validated by the concordance index (C-index), receiver operating characteristics (ROC) curve and calibration curves. RESULT: Age, laterality, preoperative CA125 status, histologic type, tumor grade, AJCC stage, surgery lesion, number of lymph nodes examined, residual lesion size, and bone metastasis were identified as independent prognostic factors to construct the nomogram. The nomogram showed better predictive ability than FIGO stage through internal and external cohorts validation. The C-index of the nomogram in the training cohort, validation cohort, and external validation cohort were 0.831, 0.835 and 0.944 higher than those of the Federation International of Gynecology and Obstetric (FIGO) stage, P<0.05. The Area Under Curve (AUC) values results indicated great clinical usefulness of the nomogram. The calibration curve indicated good agreement between the nomogram prediction and actual survival. CONCLUSION: We developed a nomogram with high predictive accuracy to predict survival in patients with non-serous EOC.