Potential Mechanisms of Guizhi Fuling Wan in Treating Endometriosis: An Analysis Based on TCMSP and DisGeNET Databases.

ETHNOPHARMACOLOGICAL RELEVANCE: Guizhi Fuling Wan (GFW), is a traditional Chinese herbal formula that consists of Cinnamomi Ramulus (Guizhi), Poria Cocos(Schw.) Wolf. (Fuling), Persicae Semen (Taoren), Radix Paeoniae Rubra (Chishao), and Cortex Moutan (Mudanpi). This formula has been used in traditional Chinese medicine for more than 1800 years to treat disorders caused by stagnation of circulation and qi (air). AIM OF THE STUDY: Based on pre-clinical and clinical studies, this review aimed to reveal the potential mechanisms of GFW in inhibiting endometriosis. The enhancement of therapeutic effects of western medications on endometriosis by GFW was also shown. MATERIALS AND METHODS: A bibliographic assessment of publications on "Guizhi Fuling Wan" and "endometriosis" indexed in PubMed, Science Direct, and China National Knowledge Infrastructure (CNKI) was conducted. Five pre-clinical studies and 13 clinical studies were selected for this review. Moreover, the targeted molecules of each herb were first extracted from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform followed by obtaining the endometriosis-related genes from DisGeNET. Subsequently, pathway and gene ontology analyses using David Bioinformatics Resources explored the potential mechanisms of therapeutic effects of GFW in treating endometriosis. RESULTS: Pre-clinical and clinical studies showed that GFW might inhibit the growth of endometriotic lesion through the modulation of immunity, apoptosis-regulating molecules, and angiogenesis-associated factors, while enhancing the therapeutic effects of western medications in treating endometriosis. Furthermore, pathway and gene ontology analyses demonstrated that GFW might attenuate the disease primarily by affecting AGE-RAGE signaling pathway in diabetic complications (hsa04933) as well as pathways involved in Kaposi sarcoma-associated herpesvirus infection (hsa05167), human cytomegalovirus infection (has05163), and fluid shear stress and atherosclerosis (hsa05418). These pathways were all involved in the regulation of inflammation, angiogenesis, and apoptosis and commonly affected by all herbs. CONCLUSIONS: The current review revealed that endometriosis is highly associated with aberrant inflammatory, angiogenic, and apoptotic activities. The therapeutic effects of GFW on endometriosis are likely to act through regulating these activities.

Clinical efficacy of nirmatrelvir plus ritonavir in patients with COVID-19 and preexisting cardiovascular diseases.

BACKGROUND: This study assessed the clinical efficacy of nirmatrelvir plus ritonavir (NMV-r) in treating patients with COVID-19 who have preexisting cardiovascular diseases (CVDs). METHODS: Patients with underlying CVDs and COVID-19 were included from the TriNetX network. We employed a 1:1 propensity score matching to create two comparable cohorts: patients receiving NMV-r and those not receiving NMV-r. The primary outcome was the composite outcome of all-cause hospitalization or death within 30 days. RESULTS: Propensity score matching yielded two matched cohorts of 10,847 patients each. The composite outcomes of all-cause hospitalization or death within 30 days were 2.2% (239 patients) in the NMV-r cohort and 4.7% (512 patients) in the control cohort, indicating reduced risk in the NMV-r cohort (hazard ratio [HR], 0.475; 95% confidence interval [CI], 0407-0.533). The NMV-r cohort exhibited lower risks of all-cause hospitalization (HR, 0.525; 95% CI, 0.449-0.615) and mortality (HR, 0.113; 95% CI, 0.052-0.246) compared with the control group. A similar trend was observed across most of the subgroups. CONCLUSIONS: Our findings indicate that NMV-r to treat COVID-19 could reduce all-cause hospitalization and death in patients with CVDs.

Development of a prediction model for emergency medical service witnessed traumatic out-of-hospital cardiac arrest: A multicenter cohort study.

BACKGROUND/PURPOSE: To develop a prediction model for emergency medical technicians (EMTs) to identify trauma patients at high risk of deterioration to emergency medical service (EMS)-witnessed traumatic cardiac arrest (TCA) on the scene or en route. METHODS: We developed a prediction model using the classical cross-validation method from the Pan-Asia Trauma Outcomes Study (PATOS) database from 1 January 2015 to 31 December 2020. Eligible patients aged ≥18 years were transported to the hospital by the EMS. The primary outcome (EMS-witnessed TCA) was defined based on changes in vital signs measured on the scene or en route. We included variables that were immediately measurable as potential predictors when EMTs arrived. An integer point value system was built using multivariable logistic regression. The area under the receiver operating characteristic (AUROC) curve and Hosmer-Lemeshow (HL) test were used to examine discrimination and calibration in the derivation and validation cohorts. RESULTS: In total, 74,844 patients were eligible for database review. The model comprised five prehospital predictors: age <40 years, systolic blood pressure <100 mmHg, respiration rate >20/minute, pulse oximetry <94%, and levels of consciousness to pain or unresponsiveness. The AUROC in the derivation and validation cohorts was 0.767 and 0.782, respectively. The HL test revealed good calibration of the model (p = 0.906). CONCLUSION: We established a prediction model using variables from the PATOS database and measured them immediately after EMS personnel arrived to predict EMS-witnessed TCA. The model allows prehospital medical personnel to focus on high-risk patients and promptly administer optimal treatment.

Spontaneous Pneumocephalus: A Case Report with a Literature Review.

BACKGROUND: Pneumocephalus is defined as gas in the intracranial space. Common causes include head trauma, surgery, and diagnostic/therapeutic procedures resulting from the direct disruption of the dura. Spontaneous or nontraumatic pneumocephalus is an uncommon condition, often caused by infection, either due to insidious disruption of the dura or gas-forming pathogens. CASE REPORT: Herein, we report a rare case of spontaneous pneumocephalus associated with meningitis in a patient who received conservative treatment without surgical intervention. Blood culture revealed group A streptococcus. The pneumocephalus subsided gradually with antibiotic treatment, and no neurological deficits remained. A follow-up brain computed tomography scan showed the absence of pneumocephalus, but it showed progressive hydrocephalus. The patient was discharged on the 21st day of hospitalization. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Spontaneous pneumocephalus associated with meningitis is rare. It should always raise the suspicion of meningitis and prompt suitable treatment. Emergency physicians should always be vigilant for this particular possibility on brain computed tomography.

Point-of-care testing for adult out-of-hospital cardiac arrest resuscitated at the ED to predict ROSC: Development and external validation of POC-ED-ROSC model.

BACKGROUND AND IMPORTANCE: Most prediction models, like return of spontaneous circulation (ROSC) after cardiac arrest (RACA) or Utstein-based (UB)-ROSC score, were developed for prehospital settings to predict the probability of ROSC in patients with out-of-hospital cardiac arrest (OHCA). A prediction model has been lacking for the probability of ROSC in patients with OHCA at emergency departments (EDs). OBJECTIVE: In the present study, a point-of-care (POC) testing-based model, POC-ED-ROSC, was developed and validated for predicting ROSC of OHCA at EDs. DESIGN, SETTINGS AND PARTICIPANTS: Prospectively collected data for adult OHCA patients between 2015 and 2020 were analysed. POC blood gas analysis obtained within 5 min of ED arrival was used. OUTCOMES MEASURE AND ANALYSIS: The primary outcome was ROSC. In the derivation cohort, multivariable logistic regression was used to develop the POC-ED-ROSC model. In the temporally split validation cohort, the discriminative performance of the POC-ED-ROSC model was assessed using the area under the receiver operating characteristic (ROC) curve (AUC) and compared with RACA or UB-ROSC score using DeLong test. MAIN RESULTS: The study included 606 and 270 patients in the derivation and validation cohorts, respectively. In the total cohort, 471 patients achieved ROSC. Age, initial cardiac rhythm at ED, pre-hospital resuscitation duration, and POC testing-measured blood levels of lactate, potassium and glucose were significant predictors included in the POC-ED-ROSC model. The model was validated with fair discriminative performance (AUC: 0.75, 95% confidence interval [CI]: 0.69-0.81) with no significant differences from RACA (AUC: 0.68, 95% CI: 0.62-0.74) or UB-ROSC score (AUC: 0.74, 95% CI: 0.68-0.79). CONCLUSION: Using only six easily accessible variables, the POC-ED-ROSC model can predict ROSC for OHCA resuscitated at ED with fair accuracy.

A novel therapeutic approach for endometriosis using adipose-derived stem cell-derived conditioned medium- A new hope for endometriotic patients in improving fertility.

Introduction: Endometriosis is defined as the growth of endometrial glands and stromal cells in a heterotopic location with immune dysregulation. It usually leads to chronic pelvic pain and subfertility. Although various treatments are available, the recurrence rate remains high. Adipose tissue is an abundant source of multipotent mesenchymal adipose-derived stem cells (ADSCs). ADSCs display effects on not only tissue regeneration, but also immune regulation. Thus, the current study aims to test the effects of ADSCs on the growth of endometriosis. Methods: ADSCs isolated from lipoaspiration-generated adipose tissue and their conditioned medium (ADSC-CM) were subjected to quality validation, including karyotyping as well as growth promotion and sterility tests for microbial contamination under Good Tissue Practice and Good Manufacturing Practice regulations. An autologous endometriosis mouse model was established by suturing endometrial tissue to peritoneal wall followed by treating with DMEM/F12 medium, ADSC-CM, ADSCs or ADSC-CM+ADSCs for 28 days. The area of endometriotic cysts and the degree of pelvic adhesion were measured. ICAM-1, VEGF and caspase 3 expression was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. Moreover, the mice were allowed to mate and deliver. The pregnancy outcomes were recorded. The ADSC-CM was subjected to proteomics analysis with further data mining with Ingenuity Pathway Analysis (IPA). Results: Both ADSC-CM and ADSCs passed quality validation. ADSC-CM reduced the area of endometriotic cysts. The inhibition by ADSC-CM was obliterated by adding ADSCs. The presence of ADSCs with or without ADSC-CM increased the peritoneal adhesion. ADSC-CM inhibited ICAM-1 and VEGF mRNA and protein expression, whereas the addition of ADSCs not only did not inhibit by itself, but also blocked the inhibition by ADSC-CM. The resorption rate was reduced by ADSC-CM. The number of live birth/dam and the survival rate of pup at 1 week-old were both increased by ADSC-CM in mice with endometriosis. IPA demonstrated that PTX3 was potentially critical for the inhibition of endometriosis by ADSC-CM due to its anti-inflammatory and antiangiogenic properties as well as its importance in implantation. Conclusion: ADSC-CM inhibited endometriosis development and improved pregnancy outcomes in mice. Potential translation to clinical treatment for human endometriosis is expected.

Chronic kidney disease and its association with cataracts-A cross-sectional and longitudinal study.

Introduction: We aim to explore the association between chronic kidney disease (CKD) and cataracts. Methods: A total of 121,380 participants with adequate information collected from 29 community-based recruitment centers since 2008 were analyzed. The association between CKD and self-reported diagnosed cataracts was examined in a cross-sectional cohort and was validated in a longitudinal cohort of 25,263 participants without cataracts at baseline. Results and discussion: Of all participants, cataracts occurred in 503/1,947 (26%) and 10,464/119,433 (9%) subjects in the CKD and non-CKD groups, respectively. Multivariate logistic regression showed that CKD was significantly associated with a higher prevalence of self-reported diagnosed cataracts. In the validation cohort, a higher incidence of cataracts was also noted in the CKD group (65/317, 21%) compared to the non-CKD group (1,964/24,252, 8%) during a mean 47-month follow-up. After adjusting for confounders, subjects with CKD had a 1.498-fold higher risk of incident cataracts than those without CKD (95% confidence interval = 1.114 to 2.013, p value = 0.007). We found that CKD was associated with a higher prevalence of cataracts as well as incident cataracts, which suggests CKD patients and their primary physicians should be aware of this disease and can provide a clue for further exploration of the possible mechanisms and treatments.

Habitual Tea Consumption and Risk of Cataracts: A Longitudinal Study.

We aimed to investigate the association between habitual tea consumption and the risk of developing cataracts in a large community-based cohort study. We prospectively collected volunteers from 29 recruitment centers that were ≧ 55 years old with no history of cataracts at the beginning of the study. There were 12,080 participants with available information in our study and were divided into two groups according to habitual tea consumption; non-tea-drinking and tea-drinking groups. The mean age was 59 years. Compared to the non-tea-drinking group, the tea-drinking group had a significantly lower incidence of developing cataracts (15.5% vs 12.1%) during follow-up of 46 months. In multivariate Cox proportional hazards regression analysis, the relative risk (RR) of incident cataracts was lower in the tea-drinking group than the non-tea-drinking group (RR = 0.848; 95% confidence interval [CI] = 0.751 to 0.957). Participants with ≧ 2 cups per day were associated with almost 16% reduction in the risk of developing cataracts compared with the non-tea-drinking group (RR = 0.844; 95% CI = 0.741 to 0.961). Our study suggests that habitual tea consumption can reduce the incidence of cataracts and raises the possibility that the tea content may slow the progression of cataracts.