Focus on the cGAS-STING Signaling Pathway in Sepsis and Its Inflammatory Regulatory Effects.

Sepsis is a severe systemic inflammatory response commonly occurring in infectious diseases, caused by infection with virulent pathogens. In the pathogenesis of sepsis, the cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase-stimulator of interferon genes (cGAS-STING) signaling pathway serves a crucial role as a fundamental immunoregulatory mechanism. This signaling pathway activates STING upon recognizing intracellular DNA damage and pathogen-derived DNA, subsequently inducing the production of numerous inflammatory mediators, including interferon and inflammatory cytokines, which in turn trigger an inflammatory response. The aim of this paper is to explore the activation mechanism of the cGAS-STING signaling pathway in sepsis and its impact on inflammatory regulation. By delving into the mechanism of action of the cGAS-STING signaling pathway in sepsis, we aim to identify new therapeutic strategies for the treatment and prevention of sepsis.

Primary lymphoma of the female genital tract masquerading as gynecological malignancy.

BACKGROUND: Primary lymphoma of the female genital tract (PLFGT) is a rare malignant tumor in the female reproductive system, with a low incidence and few clinical reports. The aim of this study is to report our institutional experience with this rare malignancy and emphasize the need for increasing the awareness about PLFGT presenting with gynecologic symptoms. METHODS: The medical records of patients diagnosed with PLFGT from March 2014 to November 2022 in the First Affiliated Hospital of Wannan Medical College were reviewed. Histological classification and staging were based on the World Health Organization and Ann Arbor systems, respectively. RESULTS: There were 13 patients with diagnosis of PLFGT and the median length of follow-up was 31 months (0-102 months). The main clinical symptoms included postmenopausal vaginal bleeding, pelvic mass and abdominal pain. Serum LDH increased in 10 patients and serum CA125 elevated in 2 patients. The tumor of ovarian or uterine presented as solid masses in CT or MRI, and ascites was rare. The histological subtypes were diffuse large B-cell (n = 12) and follicular (n = 1) lymphoma. Tumors were located in ovary (n = 8), uterus (n = 3), and cervix (n = 2). According to the Ann Arbor staging system, 6 cases were classified as stage II and 7 cases were classified as stage IV, respectively. A total of 10 patients underwent surgery. Combination chemotherapy was used in 10 patients. Eight patients had tumor-free survival, 1 patient had recurrent disease, 3 patients died and 1 patient lost to follow-up. The median survival time was 32 months (1-102 months). CONCLUSION: PLFGT usually presents as gynecological symptoms and solid masses in pelvis. Surgery or biopsy was the way to obtain the pathologic diagnosis, and combination chemotherapy is the efficient method for PLFGT. Making an accurate preoperative diagnosis is of paramount importance to avoid radical gynecologic surgery.

Thymalfasin therapy accelerates COVID-19 pneumonia rehabilitation through anti-inflammatory mechanisms.

INTRODUCTION: Thymosin drugs are commonly used for the treatment of viral infections due to their immunomodulatory effects. The comprehensive clinical efficacy of Thymalfasin therapy for COVID-19 associated pneumonia is not yet fully researched, another issue, whether the use of thymosin drugs can reduce the rate of COVID-19 progression to severe pneumonia has not been well documented. The aim of the present study was to multi-angle evaluate the clinical efficacy of Thymalfasin therapy for COVID-19 pneumonia by retrospective review of the clinical data of 338 inpatients with common COVID-19 infection who received treatment in our hospital. METHODS: The primary index of observation was whether progression to severe pneumonia occurred within a week after admission, and the secondary indexes were the length of hospital stay, time of negative conversion of COVID-19 antigen, the number of peripheral lymphocytes and white blood cells (WBC), and C-reactive protein (CRP) and procalcitonin (PCT) levels,and the control of pneumonia related symptoms, for example, fever, listlessness, inflammatory exudate area shown on lung CT (%). RESULTS: The length of hospital stay of patients in Thymalfasin group was significantly shorter than that of patients in the control group (p < 0.01). The proportion of relief of pneumonia related symptoms (fever, fatigue) in the Thymalfasin therapy group was significantly higher than that in the control group, and the inflammatory exudate area shown on CT was significantly lower than that in the control group (p < 0.05). Multivariate logistic regression analysis showed that the use of Thymalfasin was an independent protective factor affecting the progression to severe pneumonia. Multifactorial Cox model analysis indicated that negative conversion of COVID-19 antigen was significantly faster in patients using Thymalfasin and younger patients. CONCLUSION: Thymalfasin therapy has shown excellent clinical efficacy in the treatment of COVID-19 pneumonia, it can reduce inflammatory reactions, promote the relief of COVID-19 pneumonia related symptoms such as fever and fatigue, facilitate effusion absorption, and accelerate COVID-19 pneumonia recovery. Thymalfasin can prevent progression of common COVID-19 infection to severe pneumonia via multiple immunity-enhancing and anti-inflammatory protective mechanisms.

Identification and Characterization of Novel ACE Inhibitory and Antioxidant Peptides from Sardina pilchardus Hydrolysate.

Sardina pilchardus is a valuable source of bioactive peptides with potential applications in functional foods. In this study, we investigated the angiotensin-converting enzyme (ACE) inhibitory activity of Sardina pilchardus protein hydrolysate (SPH) produced using dispase and alkaline protease. Our results showed that the low molecular mass fractions (<3 kDa) obtained through ultrafiltration exhibited more effective ACE inhibition, as indicated by screening with ACE inhibitory activity. We further identified the low molecular mass fractions (<3 kDa) using an LC-MS/MS rapid screening strategy. A total of 37 peptides with potential ACE inhibitory activity were identified based on high biological activity scores, non-toxicity, good solubility, and novelty. Molecular docking was used to screen for peptides with ACE inhibitory activity, resulting in the identification of 11 peptides with higher -CDOCKER ENERGY and -CDOCKER INTERACTION ENERGY scores than lisinopril. The sequences FIGR, FILR, FQRL, FRAL, KFL, and KLF were obtained by synthesizing and validating these 11 peptides in vitro, all of which had ACE inhibitory activity, as well as zinc-chelating capacity. All six peptides were found to bind to the three active pockets (S1, S2, and S1') of ACE during molecular docking, indicating that their inhibition patterns were competitive. Further analysis of the structural characteristics of these peptides indicated that all six peptides contain phenylalanine, which suggests that they may possess antioxidant activities. After experimental verification, it was found that all six of these peptides have antioxidant activities, and we also found that the SPH and ultrafiltration fractions of SPH had antioxidant activities. These findings suggest that Sardina pilchardus may be a potential source of natural antioxidants and ACE inhibitors for the development of functional foods, and using LC-MS/MS in combination with an online database and molecular docking represents a promising, effective, and accurate approach for the discovery of novel ACE inhibitory peptides.

True hermaphroditism with sex cord tumor with annular tubules (SCTAT): a rare case report and review of the literature.

BACKGROUND: True hermaphroditism is a rare condition. It is defined as the presence of both testicular and ovarian tissues in the same individual. Sex cord tumour with annular tubules (SCTAT) is a rare stromal tumour of the sex cord that occurs mostly in the ovaries. CASE PRESENTATION: A 16-year-old girl presented to the gynaecology department with primary amenorrhea. Gynaecological examination revealed an enlarged clitoris that looked like a small penis. The chromosome karyotype was chimaera. The postoperative pathology confirmed true hermaphroditism with SCTAT. The patient underwent hormonal replacement after an operation and had no evidence of recurrence for 6 months. CONCLUSION: Cases of true hermaphroditism with SCTAT are extremely rare conditions. Surgery and hormonal replacement are important for improving the prognosis of such patients.

Establishment of ultrasound-guided stellate ganglion block in rats.

Background: A novel protocol for accurate stellate ganglion block under ultrasound guidance was designed in rats. This technique raises the success rate of stellate ganglion block and reduces the incidence of brachial plexus and vagus nerve block. Methods: Fifty-six Sprague-Dawley were randomly divided into an ultrasound-guided group (n = 28) and a blind technique group (n = 28). The rats in the blind technique group were injected with 1.5% lidocaine mixed with methylene blue after signs of brachial plexus stimulation were elicited. The lateral side of the cephalic brachial vein was located under the first rib, where lidocaine was injected into the rats in the ultrasound-guided group. The up-and-down sequential method of Dixon was used to determine the minimum effective volume for stellate ganglion block in rats. Furthermore, we calculated the required operative duration of the two methods and observed the difference in the lidocaine diffusion range between the two groups. Results: The minimum effective volume for stellate ganglion block in the ultrasound-guided group was 0.040 ml, and the 95% CI was 0.026-0.052 ml. In the blind technique group, the minimum effective volume was 0.639 ml, and the 95% CI was 0.490-0.733 ml. Within the 95% CI of the lowest effective volume, the incidence of brachial plexus block as a complication of stellate ganglion block under ultrasound guidance was 10.00%. Conclusion: Stellate ganglion block under ultrasound guidance is more accurate than blind detection, which the incidence of complications of stellate ganglion block under ultrasound guidance was significantly lower than under blind detection; the rate of methylene blue staining in the vagus nerve was significantly lower under ultrasound guidance.