Drug-resistant exosome miR-99b-3p induces macrophage polarization and confers chemoresistance on sensitive cells by targeting PPP2CA.

The most frequent cancer in women to be diagnosed is breast cancer, and chemotherapy's ability to be effective is still significantly hampered by drug resistance. Tumor-derived exosomes play a significant role in drug resistance, immunological modulation, metastasis, and tumor proliferation. In this work, the differential miRNAs in the exosomes of drug-resistant and susceptible breast cancer cell lines were screened using miRNA-seq. It was demonstrated that drug-resistant human breast cancer cells and their exosomes expressed more miR-99b-3p than did susceptible cells and their exosomes. While drug-resistant cells' migration and paclitaxel resistance can be inhibited by driving down the expression of miR-99b-3p in those cells, exosomes containing miR-99b-3p from those cells can help susceptible cells migrate and become resistant. miR-99b-3p affects cell migration and paclitaxel resistance by targeting PPP2CA to promote AKT/mTOR phosphorylation. The drug-resistant cell exosome miR-99b-3p can be taken up by macrophages and affect the drug resistance and migration ability of sensitive cells by promoting the M2 polarization of macrophages. Downregulating miR-99b-3p has been shown in vivo to reverse macrophage M2 polarization, suppress tumor development, and prevent treatment resistance. The present study shows that drug-resistant cell exosomes miR-99b-3p can directly influence the migration, proliferation, and paclitaxel sensitivity of sensitive cells via PPP2CA. Additionally, the exosomes from drug-resistant cells can influence the polarization of macrophage M2 in the tumor microenvironment, which can also have an impact on the proliferation, migration, and paclitaxel sensitivity of sensitive cells.

SIRT1 in acute lung injury: unraveling its pleiotropic functions and therapeutic development prospects.

Acute lung injury (ALI) is a continuum of lung changes caused by multiple lung injuries, often associated with severe complications and even death. In ALI, macrophages, alveolar epithelial cells and vascular endothelial cells in the lung are damaged to varying degrees and their function is impaired. Research in recent years has focused on the use of SIRT1 for the treatment of ALI. In this paper, we reviewed the role of SIRT1 in ALI in terms of its cellular and molecular mechanism, targeting of SIRT1 by non-coding RNAs and drug components, as well as pointing out the value of SIRT1 for clinical diagnosis and prognosis. Based on the current literature, SIRT1 exhibits diverse functionalities and possesses significant therapeutic potential. Targeting SIRT1 may provide new therapeutic ideas for the treatment of ALI.

Adductor canal block combined with genicular nerve block versus local infiltration analgesia for total knee arthroplasty: a randomized noninferiority trial.

OBJECTIVE: This randomized controlled and double-blind study aimed to investigate whether the analgesic effect of the adductor canal block (ACB) combined with the genicular nerve block (GNB) after total knee arthroplasty is noninferior to that of the adductor canal block combined with local infiltration analgesia (LIA). METHODS: A total of 102 patients undergoing total knee arthroplasty under general anesthesia were included and randomly divided into: ACB + GNB and ACB + LIA groups; the ACB + LIA group received 80 mL of 0.2% ropivacaine with adrenaline 10 µg/mL for LIA, whereas the ACB + GNB group received 4 mL of 0.2% ropivacaine for the blockade of five peri-knee nerves. The primary outcome was the median difference in the visual analog scale scores at rest at 24 h between the two groups. Secondary outcomes involved the median differences in the pain scores at other time points. Other outcomes included the cumulative dosage of opioids calculated in morphine equivalents in the first 24 h and indicators related to knee joint functional recovery. RESULTS: In total, 36 and 38 patients were included in the ACB + GNB and ACB + LIA groups, respectively. We found that the median difference (95% confidence internal) in postoperative rest pain at 24 h (noninferiority criteria, △ = 1) was - 0.5 (- 1 to 0, p = 0.002). The median difference in cumulative opioid consumption was 1 mg (- 1 to 3, p = 0.019), meeting the noninferiority criteria, △ = 7.7 mg. CONCLUSIONS: ACB combined with GNB provides noninferior analgesia compared to ACB with LIA on the first day after total knee arthroplasty while significantly reducing local anesthetic use. TRIAL REGISTRATION: Name of the Registry: Chinese Clinical Trial Registry; Trial Registration Number: ChiCTR2300074274; Date of Registration. August 2, 2023.

Diversity analyses of bacterial symbionts in four Sclerodermus (Hymenoptera: Bethylidae) parasitic wasps, the dominant biological control agents of wood-boring beetles in China.

Objective: Sclerodermus wasps are important biocontrol agents of a class of wood borers. Bacterial symbionts influence the ecology and biology of their hosts in a variety of ways, including the formation of life-long beneficial or detrimental parasitic infections. However, only a few studies have explored the species and content of the symbionts in the Sclerodermus species. Methods: Here, a high-throughput sequencing study of the V3-V4 region of the 16S ribosomal RNA gene revealed a high level of microbial variety in four Sclerodermus waps, and their diversities and functions were also predicted. Results: The three most prevalent phyla of microorganisms in the sample were Firmicutes, Bacteroides, and Proteus. The KEEG pathways prediction results indicated that the three pathways with the highest relative abundances in the S. sichuanensis species were translation, membrane transport, and nucleotide metabolism. These pathways differed from those observed in S. guani, S. pupariae, and S. alternatusi, which exhibited carbohydrate metabolism, membrane transport, and amino acid metabolism, respectively. Bacteroides were found to be abundant in several species, whereas Wolbachia was the most abundant among S. sichuanensis, with a significant negative correlation between temperature and carriage rate. Conclusions: These results offer insights into the microbial communities associated with the bethylid wasps, which is crucial for understanding how to increase the reproductive capacity of wasps, enhance their parasitic effects, and lower cost in biocontrol.

External auditory canal cholesteatoma in children: clinical manifestations.

PURPOSE: The purpose of this study was to explore the characteristics of external auditory canal cholesteatoma (EACC) among children and to describe its radiological findings on high-resolution computed tomography (CT) of the temporal bone in order to improve the diagnostic accuracy of primary EACC. METHODS: The clinical records and CT imaging features of 44 patients who were diagnosed with EACC between January 2017 and May 2022 at Shenzhen Children's Hospital were retrospectively reviewed. Clinical features, including external auditory canal wall findings, hearing damage, symptoms and physical examination findings, were analysed against the level of lesion involvement. The correlation between different types of EACC and the incidence of different clinical symptoms was analysed, and the degree of hearing impairment and the rate of bone wall destruction were examined using CT. RESULTS: The mean age at EACC onset was 9.02 ± 3.15 years, and the mean age at onset for EACC involving the right ear was older than that of EACC involving the left ear (P < 0.05). There were 44 patients (46 ears), including 10 ears with type I EACC, 23 ears with type II EACC, and 13 ears with type III EACC. Conductive hearing loss was the main type of hearing impairment observed among EACC patients. There were differences in types I, II and III EACC in terms of hearing impairment; specifically, there was a significant difference in moderate hearing impairment between type II and type III EACC patients (P < 0.05). The four most common symptoms were otorrhea, otalgia, itching and bleeding. The incidence of itching symptoms was greater in type I EACC than the incidence of otorrhea, and the incidence of otorrhea symptoms in type II and type III EACC was significantly greater than that in type I EACC(P < 0.05). There were no significant differences in the fracture rates of the anterior, posterior, superior or inferior walls of the external auditory canal within or between type II and type III EACC patients (P > 0.05). The failure rate of scute damage was significantly higher in type III EACC patients than in type II EACC patients (P < 0.05). CONCLUSION: The presence of otorrhea and hearing loss as well as the identification of granulation tissue during otoscopy suggest the need for a temporal bone CT scan. This imaging modality can aid in the early detection and accurate classification of EACC, thereby guiding the selection of appropriate surgical interventions and greatly assisting in preventing further progression of hearing impairment.

Recent Advances on Synaptotagmin-Like Mitochondrial-Lipid Binding Protein Domain Containing Lipid Transfer Proteins.

The Synaptotagmin-like mitochondrial-lipid binding protein (SMP) domain is found in a group of ER-resident lipid transfer proteins that are recruited to membrane contact sites (MCSs) by adaptors. Deciphering the molecular basis underlying the recruitment of SMP proteins to specific MCS sheds light not only on their cellular localization but also on their biological functions at these sites. Here we summarize recent advances in SMP domain-containing lipid transfer proteins, focusing on a recent study showing the localization, regulation and cellular function of a specific SMP protein named testis expressed protein 2 (Tex2). TMEM55, a potential PIP phosphatase on late endosome/lysosomal (LE/lys) membranes, was identified as an adaptor that enables the recruitment of Tex2 to ER- LE/lys MCS. In addition, we have summarized several important questions about the regulation and physiological functions of Tex2 that remained unanswered.

The complete mitochondrial genome and phylogenetic analysis of Cyanopterus ninghais (Hymenoptera: Braconidae).

Cyanopterus ninghais is an important gregarious ectoparasitoid during the larval stage of Monochamus alternatus, a key vector for pine wilt disease in Asia. In this study, the complete mitochondrial genome of C. ninghais was sequenced and analyzed. The mitochondrial genome of C. ninghais is 15,386 bp in length, comprising 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), and 2 ribosomal RNA genes (rRNAs). The nucleotide composition is 41.32% A, 8.29% G, 6.06% C, and 44.33% T. Phylogenetic trees of Braconidae were constructed using 13 PCG sequences via Bayesian inference (BI) and maximum likelihood (ML) analyses to determine their phylogenetic position. Both ML and BI analyses revealed that C. ninghais is closely related to Euurobracon yokahamae, Virgulibracon endoxylaphagus, and Habrobracon hebetor.

Phase separation and transcriptional regulation in cancer development.

Liquid-liquid phase separation, a novel biochemical phenomenon, has been increasingly studied for its medical applications. It underlies the formation of membrane-less organelles and is involved in many cellular and biological processes. During transcriptional regulation, dynamic condensates are formed through interactions between transcriptional elements, such as transcription factors, coactivators, and mediators. Cancer is a disease characterized by uncontrolled cell proliferation, but the precise mechanisms underlying tumorigenesis often remain to be elucidated. Emerging evidence has linked abnormal transcriptional condensates to several diseases, especially cancer, implying that phase separation plays an important role in tumorigenesis. Condensates formed by phase separation may have an effect on gene transcription in tumors. In the present review, we focus on the correlation between phase separation and transcriptional regulation, as well as how this phenomenon contributes to cancer development.

Effect of Propofol in the Cardiovascular System and its Related Mechanism Research Progress.

Propofol is the most widely used short-acting intravenous anesthetic in clinical practice. Existing studies have shown that propofol has many effects on the cardiovascular system in addition to its anesthetic effect. Propofol can antagonize a variety of tachyarrhythmias and reduce the risk of recurrence, regulate autonomic balance of the heart, modulate circulatory dynamics, thereby increasing blood perfusion to vital organs such as the kidney, intestine, and brain, and exert myocardial protection and cerebral protection during ischemia-reperfusion injury. In this paper, we review the potential mechanisms of these effects and provide and ideas for future research and novel drug development of propofol and its derivatives in cardiac electrophysiology and circulatory dynamics.

JAK activity regulates mesoderm cell fate by controlling MESP1 expression.

Cardiac development requires precise gene expression programs at each developmental stage guided by multiple signaling pathways and transcription factors (TFs). MESP1 is transiently expressed in mesoderm, and is essential for subsequent cardiac development, while the precise mechanism regulating its own transcription and mesoderm cell fate is not fully understood. Therefore, we developed a high content screen assay to identify regulators of MESP1 expression in mesodermal cells differentiated from human pluripotent stem cells (hPSCs). The screen identified CYT387, a JAK1/JAK2 kinase inhibitor, as a potent activator of MESP1 expression, which was also found to promote cardiomyocyte differentiation in vitro. Mechanistic studies found that JAK inhibition promotes MESP1 expression by reducing cytoplasmic calcium concentration and subsequently activating canonical WNT signaling. Our study identified a role of JAK signaling in early mesodermal cells, and sheds light on the connection between the JAK-STAT pathway and transcriptional regulation of MESP1, which expands our understanding of mesoderm and cardiac development.

Incomplete Histologic Healing and Diminished Biomechanical Strength of Meniscus-Bone Interface After Medial Meniscus Posterior Root Transosseous Repair in a Goat Model.

PURPOSE: To enhance the understanding of histologic healing after repairing medial meniscal posterior root tears (MMPRTs) at an early stage, utilizing a goat model. METHODS: Eighteen adult goats, totaling 36 knee joints, were allocated into 3 groups (n = 12): sham group (Sham), root tear group (RT), and root tear with transosseous suture group (RTS). At 12- and 24-week intervals postsurgery, all the knees were harvested for imaging, macroscopic, histologic, and biomechanical assessments. RESULTS: The intact root served as a meniscus-bone interface that connected the tibial and circular fibers of the meniscus with a bony insertion and a root-meniscus transition. A direct fibrous connection was displayed at the bony insertion proximal to the synovium in the RTS group, while the remaining regions of the root displayed indirect fibrous healing. The healing in the RT group was disjointed and reminiscent of scar tissue. The RTS group exhibited a more pronounced coronal extrusion compared to the Sham group (0.42 ± 0.09 vs 0.19 ± 0.02, P = .0012) but was improved relative to that of the RT group (0.49 ± 0.02, P = .0028). The failure load and stiffness of the RTS group were notably higher than those of the RT group, with a strength of 42.67% and a stiffness of 83.75% of the intact root. All the samples ruptured at the root-meniscus transitions. CONCLUSIONS: The incomplete healing may be attributed to the histologic factors underlying the low healing rate and persistent medial meniscal extrusion. Notably, the region attached to the posterior cruciate ligament exhibited superior healing compared to other regions of the bony insertion in the repaired group. Conversely, the root-meniscus transition displayed discontinuity, representing a mechanical weakness in the healing process. CLINICAL RELEVANCE: Modifications of bone tunnel positioning and suture placement could be undertaken in subsequent studies to enhance the healing of the root-meniscus transition.

Mild hypothermia pretreatment improves hepatic ischemia-reperfusion injury: A systematic review and meta-analysis of animal experiments.

BACKGROUND AND AIM: Mild hypothermia in hepatic ischemia-reperfusion injury is increasingly being studied. This study aimed to conduct a systematic evaluation of the effectiveness of mild hypothermia in improving hepatic ischemia-reperfusion injury. METHODS: We systematically searched CNKI, WanFang Data, PubMed, Embase, and Web of Science for original studies that used animal experiments to determine how mild hypothermia(32-34°C) pretreatment improves hepatic ischemia-reperfusion injury(in situ 70% liver IR model). The search period ranged from the inception of the databases to May 5, 2023. Two researchers independently filtered the literature, extracted the data, and assessed the risk of bias incorporated into the study. The meta-analysis was performed using RevMan 5.4.1 and Stata 15 software. RESULTS: Eight randomized controlled trials (RCTs) involving a total of 117 rats/mice were included. The results showed that the ALT levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [Standardized Mean Difference (SMD) = -5.94, 95% CI(-8.09, -3.78), P<0.001], and AST levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [SMD = -4.45, 95% CI (-6.10, -2.78), P<0.001]. The hepatocyte apoptosis rate in the mild hypothermia pretreatment group was significantly lower than that in the normothermic control group [SMD = -6.86, 95% CI (-10.38, -3.33), P<0.001]. Hepatocyte pathology score in the mild hypothermia pretreatment group was significantly lower than that in the normothermic control group [SMD = -4.36, 95% CI (-5.78, -2.95), P<0.001]. There was no significant difference in MPO levels between the mild hypothermia preconditioning group and the normothermic control group [SMD = -4.83, 95% CI (-11.26, 1.60), P = 0.14]. SOD levels in the mild hypothermia preconditioning group were significantly higher than those in the normothermic control group [SMD = 3.21, 95% CI (1.27, 5.14), P = 0.001]. MDA levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [SMD = -4.06, 95% CI (-7.06, -1.07) P = 0.008]. CONCLUSION: Mild hypothermia can attenuate hepatic ischemia-reperfusion injury, effectively reduce oxidative stress and inflammatory response, prevent hepatocyte apoptosis, and protect liver function.

Lateral quadratus lumborum block vs acupuncture for postcesarean analgesia: a randomized clinical trial.

BACKGROUND: Improved pain control after cesarean section remains a challenging objective. Although both the lateral quadratus lumborum block (L-QLB) and acupuncture have been reported to provide superior postoperative analgesia after cesarean section when compared to placebo, the efficacy of these techniques has never been compared head-to-head. OBJECTIVE: This study was conducted to investigate the comparative analgesic efficacy of L-QLB and acupuncture following elective cesarean section. STUDY DESIGN: In this prospective, randomized, controlled clinical trial, a total of 190 patients with singleton-term pregnancies scheduled for cesarean section under spinal-epidural anesthesia were enrolled. Patients were randomized 1:1 to acupuncture group or L-QLB group. L-QLB group received bilateral L-QLB with 0.33% ropivacaine and sham acupuncture, acupuncture group received transcutaneous electrical acupoint stimulation and press needle therapy, and sham L-QLB. All patients received the standard postoperative pain treatment. The primary outcome was pain scores on movement at 24 hours. Secondary endpoints included pain scores in the first 48 hours postoperatively, patient-controlled intravenous analgesia (PCIA) demands, analgesia-related adverse effects, postoperative complications, QoR-15, the time to mobilization, and gastrointestinal function. RESULTS: Median (interquartile range [range]) pain scores at 24 hours on movement were similar in patients receiving acupuncture or L-QLB (3 [2-4] vs 3 [2-4], respectively; P=.40). PCIA consumption and pain scores within 48 hours postoperatively also showed no difference between the two groups. The acupuncture improved QoR-15 scores at 24 and 48 hours postoperatively (P<.001), as well as shortened the time to first flatus (P=.03) and first drinking (P<.001) compared to L-QLB. In addition, the median time to mobilization in the L-QLB group was markedly prolonged compare with acupuncture group (17.0 [15.0-19.0] hours vs 15.3 [13.3-17.0] hours, estimated median difference, 1.5; 95% CI, 1-2; P<.001). CONCLUSION: As a component of multimodal analgesia regimen after cesarean section, acupuncture did not lower postoperative pain scores or reduce analgesic medication consumption compared to L-QLB.

Neurofibromin 2 modulates Mammalian Ste2-like kinases1/2 and large tumor suppressor gene1 expression in A549 lung cancer cell line.

AIM: To explore the impact of up- or down-regulation of Neurofibromin 2 (NF2) on the expression of downstream Hippo pathway genes, large tumor suppressor gene1 (LATS1), and phosphorylation of Mammalian Ste2-like kinases1/2 (MST1/2), in lung cancer cells. METHODS: A549 lung cancer cells were used. The NF2 was down-regulated by si-RNA interference and upregulated by lentiviral vector mediated overexpression. The LATS1 and MST1/2 expressions were evaluated by real-time PCR and western blot. RESULTS: Down-regulation of NF2 decreased LATS1 and MST1/2 level (P<0.05). Overexpression of NF2 increased LATS1 (P<0.05) and Mammalian Ste2-like kinases1 (MST1) (P<0.05), suggesting LATS1 and MST1 are modulated by NF2 in a lung cancer cell line. CONCLUSIONS: NF2 mediates the downstream LATS1 and MST1/2 expressions in a lung cancer cell line.

[Effect of polymethoxylated flavonoids on glucose and lipid metabolism in rat model of obesity induced by a high-fat diet].

This study established a rat model of obesity by using a high-fat diet(HFD) to explore the effect of polymethoxylated flavonoids on glucose and lipid metabolism in the model rats and decipher the role and mechanism of polymethoxylated flavonoids in mitigating obesity. Thirty normal SD rats were selected and randomized into normal, model, ezetimibe(0.1 mg·kg~(-1)), and polymethoxylated flavonoids(62.5 mg·kg~(-1) and 125 mg·kg~(-1)) groups based on the body weight. Except the normal group receiving a conventional diet, the other groups received a HFD. Rats were administrated with corresponding doses of drugs by gavage. During the administration period, the body weight of each group of rats was regularly weighed, and the serum lipid and glucose levels were measured by a fully automated biochemical analyzer. Islet homeostasis and serum levels of obesity factors were measured by ELISA. The 16S rRNA high-throughput sequencing was employed to study the gut microbiota. Hematoxylin-eosin staining was employed to observe the histomorphology of white fat, brown fat, and pancreas. After the wet weights of white fat and brown fat were measured, the organ index was calculated. Immunohistochemistry and Western blot were employed to determine the protein levels. The results showed that polymethoxylated flavonoids reduced the body weight and Lee's index and improved blood lipid levels of the model rats. Polymethoxylated flavonoids reduced blood glucose and insulin secretion, increased insulin responsiveness, and alleviated insulin resistance. In addition, polymethoxylated flavonoids regulated the serum levels of obesity factors and reduced the weights and indexes of white fat and brown fat, the diameter of white adipocytes, and the number of fat vacuoles in brown fat and pancreatic islet cells. The intervention with polymethoxylated flavonoids increased the diversity of gut microbiota in the model rats, increasing the beneficial bacteria associated with glucose and lipid metabolism and reduced the harmful bacteria at the genus level. In addition, polymethoxylated flavonoids up-regulated the protein levels of glucose transporter 4(GLUT4), phosphorylated AMP-activated protein kinase(p-AMPK), peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α), and uncoupling protein 1(UCP1). In summary, polymethoxylated flavonoids may increase the body utilization of glucose and lipids by regulating the homeostasis of insulin, the serum levels of obesity factors, the diversity of gut microbiota, and the expression of mitochondrial metabolism-related proteins in brown adipocytes, thereby mitigating obesity in rats.

Ultrastructure and distribution of antennal sensilla of parasitic wasp, Cotesia gregalis (Hymenoptera: Braconidae).

Cotesia gregalis Yang et Wei (Hymenoptera: Braconidae) is a gregarious koinobiont endoparasitic wasp attacking the larvae of fall webworm, Hyphantria cunea, an important invasive insect pest in China. To better understand the parasitic wasps' mating and parasitic behaviors, we examined the morphology of the antennae of adult C. gregalis, as well as the type, number, and distribution of antennal sensilla, via scanning electron microscopy. The antennae of female and male C. gregalis are filiform and comprise a scape, pedicel, and 16 flagellomeres. The female antennae are significantly shorter than those of male. A total of nine morphological types of antennal sensilla (mechanoreceptor and chemoreceptor) are presented in both sexes, including four mechanoreceptors (sensilla chaetica [two subtypes], sensilla trichodea and Böhm bristles); five chemoreceptors (sensilla basiconica [two subtypes], sensilla placodea, sensilla styloconica, and sensilla coelocapitula). There is no difference in the type and distribution of antennal sensilla between males and females, but the number and length of some antennal sensilla show sexual dimorphism. The functional morphology of the sensilla of C. gregalis is discussed by comparison with other parasitic wasps. These findings provide foundation for further research on the chemical communication and host localization mechanisms of C. gregalis. RESEARCH HIGHLIGHTS: The first report of morphology and distribution pattern of the antennal sensilla in C. gregalis is discussed. A total of seven main types and nine antennal sensilla subtypes are observed in male and female C. gregalis. The type and distribution of antennal sensilla in males and females are identical; however, the number and length of certain antennal sensilla show sexual dimorphism.

The complete mitochondrial genome of Sigara lateralis (Leach, 1817) (Nepomorpha: Corixidae).

The Sigara lateralis (Leach, 1817) is a small aquatic insect belonging to the family Corixidae. The study aims to reveal the genomic data of the mitochondrial genome of S. lateralis. The length of its circular mitochondrial genome is 15,725 bp long with an A + T bias (75.96%). The mitogenome comprises 37 genes, including 13 protein-coding genes (PCGs), 22 transfer RNA genes, and two rRNA genes. The phylogenetic analyses showed that the S. lateralis is the closest to S. septemlineata. These findings will help the conservation of Corixidae from the perspective of genetic evolution.

Mitochondrial DNA release via the mitochondrial permeability transition pore activates the cGAS-STING pathway, exacerbating inflammation in acute Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is an immune vasculitis of unknown origin, characterized by transient inflammation. The activation of the cGAS-STING pathway, triggered by mitochondrial DNA (mtDNA) release, has been implicated in the onset of KD. However, its specific role in the progression of inflammation during KD's acute phase remains unclear. METHODS: We measured mtDNA and 2'3'-cGAMP expression in KD patient serum using RT-qPCR and ELISA. A murine model of KD was induced by injecting Lactobacillus casei cell wall extract (LCWE), after which cGAS-STING pathway activation and inflammatory markers were assessed via immunohistochemistry, western blot, and RT-qPCR. Human umbilical vein endothelial cells (HUVECs) were treated with KD serum and modulators of the cGAS-STING pathway for comparative analysis. Mitochondrial function was evaluated using Mitosox staining, mPTP opening was quantified by fluorescence microscopy, and mitochondrial membrane potential (MMP) was determined with JC-1 staining. RESULTS: KD patient serum exhibited increased mtDNA and 2'3'-cGAMP expression, with elevated levels of pathway-related proteins and inflammatory markers observed in both in vivo and in vitro models. TEM confirmed mitochondrial damage, and further studies demonstrated that inhibition of mPTP opening reduced mtDNA release, abrogated cGAS-STING pathway activation, and mitigated inflammation. CONCLUSION: These findings indicate that mtDNA released through the mPTP is a critical activator of the cGAS-STING pathway, contributing significantly to KD-associated inflammation. Targeting mtDNA release or the cGAS-STING pathway may offer novel therapeutic approaches for KD management.

Evaluating effectiveness and safety of combined percutaneous transhepatic gallbladder drainage and laparoscopic cholecystectomy in acute cholecystitis patients: Meta-analysis.

BACKGROUND: Acute cholecystitis (AC) is a common disease in general surgery. Laparoscopic cholecystectomy (LC) is widely recognized as the "gold standard" surgical procedure for treating AC. For low-risk patients without complications, LC is the recommended treatment plan, but there is still controversy regarding the treatment strategy for moderate AC patients, which relies more on the surgeon's experience and the medical platform of the visiting unit. Percutaneous transhepatic gallbladder puncture drainage (PTGBD) can effectively alleviate gallbladder inflammation, reduce gallbladder wall edema and adhesion around the gallbladder, and create a "time window" for elective surgery. AIM: To compare the clinical efficacy and safety of LC or PTGBD combined with LC for treating AC patients, providing a theoretical basis for choosing reasonable surgical methods for AC patients. METHODS: In this study, we conducted a clinical investigation regarding the combined use of PTGBD tubes for the treatment of gastric cancer patients with AC. We performed searches in the following databases: PubMed, Web of Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Database. The search encompassed literature published from the inception of these databases to the present. Subsequently, relevant data were extracted, and a meta-analysis was conducted using RevMan 5.3 software. RESULTS: A comprehensive analysis was conducted, encompassing 24 studies involving a total of 2564 patients. These patients were categorized into two groups: 1371 in the LC group and 1193 in the PTGBD + LC group. The outcomes of the meta-analysis revealed noteworthy disparities between the PTGBD + LC group and the LC group in multiple dimensions: (1) Operative time: Mean difference (MD) = 17.51, 95%CI: 9.53-25.49, P < 0.01; (2) Conversion to open surgery rate: Odds ratio (OR) = 2.95, 95%CI: 1.90-4.58, P < 0.01; (3) Intraoperative bleeding loss: MD = 32.27, 95%CI: 23.03-41.50, P < 0.01; (4) Postoperative hospital stay: MD = 1.44, 95%CI: 0.14-2.73, P = 0.03; (5) Overall postoperative complication rate: OR = 1.88, 95%CI: 1.45-2.43, P < 0.01; (6) Bile duct injury: OR = 2.17, 95%CI: 1.30-3.64, P = 0.003; (7) Intra-abdominal hemorrhage: OR = 2.45, 95%CI: 1.06-5.64, P = 0.004; and (8) Wound infection: OR = 0. These findings consistently favored the PTGBD + LC group over the LC group. There were no significant differences in the total duration of hospitalization [MD = -1.85, 95%CI: -4.86-1.16, P = 0.23] or bile leakage [OR = 1.33, 95%CI: 0.81-2.18, P = 0.26] between the two groups. CONCLUSION: The combination of PTGBD tubes with LC for AC treatment demonstrated superior clinical efficacy and enhanced safety, suggesting its broader application value in clinical practice.