Activation of GABAergic neurons in the dorsal raphe nucleus alleviates hyperalgesia induced by ovarian hormone withdrawal.

ABSTRACT: Menopausal and postmenopausal women, characterized by a significant reduction in ovarian hormones, have a high prevalence of chronic pain with great pain intensity. However, the underlying mechanism of hyperalgesia induced by ovarian hormone withdrawal remains poorly understood. Here, we report that decreases in the activity and excitability of GABAergic neurons in the dorsal raphe nucleus (DRN) are associated with hyperalgesia induced by ovariectomy in mice. Supplementation with 17ß-estradiol, but not progesterone, is sufficient to increase the mechanical pain threshold in ovariectomized (OVX) mice and the excitability of DRN GABAergic (DRNGABA) neurons. Moreover, activation of the DRNGABA neurons projecting to the lateral parabrachial nucleus was critical for alleviating hyperalgesia in OVX mice. These findings show the essential role of DRNGABA neurons and their modulation by estrogen in regulating hyperalgesia induced by ovarian hormone withdrawal, providing therapeutic basis for the treatment of chronic pain in physiological or surgical menopausal women.

Ovarian-adnexal reporting and data system ultrasound evaluation and pathological characteristics of ovarian collision tumor.

BACKGROUND: Collision tumor are neoplasms, including two histologically distinct tumors that coexist in the same mass without histological admixture. The incidence of collision tumor is low and is rare clinically. AIM: To investigate ultrasound images and application of ovarian-adnexal reporting and data system (O-RADS) to evaluate the risk and pathological characteristics of ovarian collision tumor. METHODS: This study retrospectively analyzed 17 cases of ovarian collision tumor diagnosed pathologically from January 2020 to December 2023. All clinical features, ultrasound images and histopathological features were collected and analyzed. The O-RADS score was used for classification. The O-RADS score was determined by two senior doctors in the gynecological ultrasound group. Lesions with O-RADS score of 1-3 were classified as benign tumors, and lesions with O-RADS score of 4 or 5 were classified as malignant tumors. RESULTS: There were 17 collision tumors detected in 16 of 6274 patients who underwent gynecological surgery. The average age of 17 women with ovarian collision tumor was 36.7 years (range 20-68 years), in whom, one occurred bilaterally and the rest occurred unilaterally. The average tumor diameter was 10 cm, of which three were 2-5 cm, 11 were 5-10 cm, and three were > 10 cm. Five (29.4%) tumors with O-RADS score 3 were endometriotic cysts with fibroma/serous cystadenoma, and unilocular or multilocular cysts contained a small number of parenchymal components. Eleven (64.7%) tumors had an O-RADS score of 4, including two in category 4A, six in category 4B, and three in category 4C; all of which were multilocular cystic tumors with solid components or multiple papillary components. One (5.9%) tumor had an O-RADS score of 5. This case was a solid mass, and a small amount of pelvic effusion was detected under ultrasound. The pathology was high-grade serous cystic cancer combined with cystic mature teratoma. There were nine (52.9%) tumors with elevated serum carbohydrate antigen (CA)125 and two (11.8%) with elevated serum CA19-9. Histological and pathological results showed that epithelial-cell-derived tumors combined with other tumors were the most common, which was different from previous results. CONCLUSION: The ultrasound images of ovarian collision tumor have certain specificity, but diagnosis by preoperative ultrasound is difficult. The combination of epithelial and mesenchymal cell tumors is one of the most common types of ovarian collision tumor. The O-RADS score of ovarian collision tumor is mostly ≥ 4, which can sensitively detect malignant tumors.

A(H2N2) and A(H3N2) influenza pandemics elicited durable cross-reactive and protective antibodies against avian N2 neuraminidases.

Human cases of avian influenza virus (AIV) infections are associated with an age-specific disease burden. As the influenza virus N2 neuraminidase (NA) gene was introduced from avian sources during the 1957 pandemic, we investigate the reactivity of N2 antibodies against A(H9N2) AIVs. Serosurvey of healthy individuals reveal the highest rates of AIV N2 antibodies in individuals aged ≥65 years. Exposure to the 1968 pandemic N2, but not recent N2, protected against A(H9N2) AIV challenge in female mice. In some older adults, infection with contemporary A(H3N2) virus could recall cross-reactive AIV NA antibodies, showing discernable human- or avian-NA type reactivity. Individuals born before 1957 have higher anti-AIV N2 titers compared to those born between 1957 and 1968. The anti-AIV N2 antibodies titers correlate with antibody titers to the 1957 N2, suggesting that exposure to the A(H2N2) virus contribute to this reactivity. These findings underscore the critical role of neuraminidase immunity in zoonotic and pandemic influenza risk assessment.

Norepinephrine or phenylephrine for the prevention of post-spinal hypotension after caesarean section: A double-blinded, randomized, controlled study of fetal heart rate and fetal cardiac output.

STUDY OBJECTIVE: Spinal anesthesia often causes hypotension, with consequent risk to the fetus. The use of vasopressor agents has been highly recommended for the prevention of spinal anesthesia-induced hypotension during caesarean delivery. Many studies have shown that norepinephrine can provide more stable maternal hemodynamics than phenylephrine. We therefore tested the hypothesis that norepinephrine preserves fetal circulation better than phenylephrine when used to treat maternal hypotension consequent to spinal anesthesia. DESIGN: Prospective, randomized, double-blinded study. SETTING: Operating room. PATIENTS: We recruited 223 parturients with uncomplicated singleton pregnancies who were scheduled for elective caesarean section under combined spinal-epidural anesthesia. INTERVENTIONS: The patients received prophylactic intravenous infusion of either 0.08 µg/kg/min norepinephrine or 0.5 µg/kg/min phenylephrine for prevention of spinal anesthesia-induced hypotension. MEASUREMENTS: Changes in fetal heart rate and fetal cardiac output before and after spinal anesthesia were measured using noninvasive Doppler ultrasound. MAIN RESULTS: 90 subjects who received norepinephrine infusion and 93 subjects who received phenylephrine infusion were ultimately analyzed in the present study. The effects of norepinephrine and phenylephrine on the change of fetal heart rate and fetal cardiac output at 3 and 6 min after spinal block were similar. Although there was a statistically significant decrease in fetal cardiac output at 6 min after subarachnoid block initiation in both the norepinephrine group (mean difference 0.02 L/min; 95% CI, 0-0.04 L/min; P = 0.03) and the phenylephrine group (mean difference 0.02 L/min; 95% CI, 0-0.04 L/min; P = 0.02), it remained within the normal range. CONCLUSIONS: Prophylactic infusion of comparable doses of phenylephrine or norepinephrine has similar effects on fetal heart rate and cardiac output changes after spinal anesthesia. Neither phenylephrine nor norepinephrine has meaningful detrimental effects on fetal circulation or neonatal outcomes.

The role of gonadal hormones in regulating opioid antinociception.

Opioids are the most prescribed drugs for the alleviation of pain. Both clinical and preclinical studies have reported strong evidence for sex-related divergence regarding opioid analgesia. There is an increasing amount of evidence indicating that gonadal hormones regulate the analgesic efficacy of opioids. This review presents an overview of the importance of gonadal steroids in modulating opioid analgesic responsiveness and focuses on elaborating what is currently known regarding the underlyingmechanism. We sought to identify the link between gonadal hormones and the effect of oipiod antinociception.

Gonadal hormones contribute to the sexual dimorphism of opioid antinociception.Generally, oestradiol is a negative modulator of opioid analgesia via both non-genomic and genomic effects.Testosterone facilitates opioid analgesia mainly through the transcriptional activities of androgen receptors.Under normal physiological conditions, progestin and oestrogen exist in parallel and have a combined effect. However, progestin alone could promote opioid analgesia by increasing the expression of opioid receptors.

Association of attenuated leptin signaling pathways with impaired cardiac function under prolonged high-altitude hypoxia.

Cardiovascular function and adipose metabolism were markedly influenced under high altitudes. However, the interplay between adipokines and heart under hypoxia remains to be elucidated. We aim to explore alterations of adipokines and underlying mechanisms in regulating cardiac function under high altitudes. We investigated the cardiopulmonary function and five adipokines in Antarctic expeditioners at Kunlun Station (4,087 m) for 20 days and established rats exposed to hypobaric hypoxia (5,000 m), simulating Kunlun Station. Antarctic expeditioners exhibited elevated heart rate, blood pressure, systemic vascular resistance, and decreased cardiac pumping function. Plasma creatine phosphokinase-MB (CK-MB) and platelet-endothelial cell adhesion molecule-1 (sPecam-1) increased, and leptin, resistin, and lipocalin-2 decreased. Plasma leptin significantly correlated with altered cardiac function indicators. Additionally, hypoxic rats manifested impaired left ventricular systolic and diastolic function, elevated plasma CK-MB and sPecam-1, and decreased plasma leptin. Chronic hypoxia for 14 days led to increased myocyte hypertrophy, fibrosis, apoptosis, and mitochondrial dysfunction, coupled with reduced protein levels of leptin signaling pathways in myocardial tissues. Cardiac transcriptome analysis revealed leptin was associated with downregulated genes involved in rhythm, Na+/K+ transport, and cell skeleton. In conclusion, chronic hypoxia significantly reduced leptin signaling pathways in cardiac tissues along with significant pathological changes, thus highlighting the pivotal role of leptin in regulation of cardiac function under high altitudes.

Gut microbiota dysbiosis contributes to depression-like behaviors via hippocampal NLRP3-mediated neuroinflammation in a postpartum depression mouse model.

Postpartum depression (PPD) is a severe mental disorder that affects approximately 10---20% of women after childbirth. The precise mechanism underlying PPD pathogenesis remains elusive, thus limiting the development of therapeutics. Gut microbiota dysbiosis is considered to contribute to major depressive disorder. However, the associations between gut microbiota and PPD remain unanswered. Here, we established a mouse PPD model by sudden ovarian steroid withdrawal after hormone-simulated pseudopregnancy-human (HSP-H) in ovariectomy (OVX) mouse. Ovarian hormone withdrawal induced depression-like and anxiety-like behaviors and an altered gut microbiota composition. Fecal microbiota transplantation (FMT) from PPD mice to antibiotic cocktail-treated mice induced depression-like and anxiety-like behaviors and neuropathological changes in the hippocampus of the recipient mice. FMT from healthy mice to PPD mice attenuated the depression-like and anxiety-like behaviors as well as the inflammation mediated by the NOD-like receptor protein (NLRP)-3/caspase-1 signaling pathway both in the gut and the hippocampus, increased fecal short-chain fatty acids (SCFAs) levels and alleviated gut dysbiosis with increased SCFA-producing bacteria and reduced Akkermansia in the PPD mice. Also, downregulation of NLRP3 in the hippocampus mitigated depression-like behaviors in PPD mice and overexpression of NLRP3 in the hippocampal dentate gyrus induced depression-like behaviors in naïve female mice. Intriguingly, FMT from healthy mice failed to alleviate depression-like behaviors in PPD mice with NLRP3 overexpression in the hippocampus. Our results highlighted the NLRP3 inflammasome as a key component within the microbiota-gut-brain axis, suggesting that targeting the gut microbiota may be a therapeutic strategy for PPD.

Regulation of CTLs/Tregs via Highly Stable and Ultrasound-Responsive Cerasomal Nano-Modulators for Enhanced Colorectal Cancer Immunotherapy.

Immunotherapy is showing good potential for colorectal cancer therapy, however, low responsive rates and severe immune-related drug side effects still hamper its therapeutic effectiveness. Herein, a highly stable cerasomal nano-modulator (DMC@P-Cs) with ultrasound (US)-controlled drug delivery capability for selective sonodynamic-immunotherapy is fabricated. DMC@P-Cs' lipid bilayer is self-assembled from cerasome-forming lipid (CFL), pyrophaeophorbid conjugated lipid (PL), and phospholipids containing unsaturated chemical bonds (DOPC), resulting in US-responsive lipid shell. Demethylcantharidin (DMC) as an immunotherapy adjuvant is loaded in the hydrophilic core of DMC@P-Cs. With US irradiation, reactive oxygen species (ROS) can be effectively generated from DMC@P-Cs, which can not only kill tumor cells for inducing immunogenic cell death (ICD), but also oxidize unsaturated phospholipids-DOPC to change the permeability of the lipid bilayers and facilitate controlled release of DMC, thus resulting in down-regulation of regulatory T cells (Tregs) and amplification of anti-tumor immune responses. After intravenous injection, DMC@P-Cs can efficiently accumulate at the tumor site, and local US treatment resulted in 94.73% tumor inhibition rate. In addition, there is no detectable systemic toxicity. Therefore, this study provides a highly stable and US-controllable smart delivery system to achieve synergistical sonodynamic-immunotherapy for enhanced colorectal cancer therapy.

Novel multidisciplinary cooperation model for obstetric medical quality control: A quasi-experimental study.

OBJECTIVE: To explore the impact of a novel multidisciplinary cooperation model in obstetric medical quality control. METHODS: This quasi-experimental study analyzed the quality indicators of full-term pregnant women who underwent vaginal trial labor in Zibo Maternal and Child Health Hospital between July 2021 and June 2022. The pregnant women were divided into two groups based on implementation of novel multidisciplinary cooperation: multidisciplinary and non-multidisciplinary. We compared the rate of labor analgesia, postpartum hemorrhage in vaginal delivery, transfer to cesarean section, and the 5-min Apgar score ≤7 in full-term neonates. RESULTS: A total of 3751 pregnant women were enrolled into the study, of whom 2004 were included in the non-multidisciplinary group and 1747 in the multidisciplinary group. The analgesic rate of delivery of the multidisciplinary group was higher than that of the non-multidisciplinary group (P = 0.000). We established that the rate of postpartum bleeding (P = 0.040), transfer cesarean section (P = 0.003) and the incidence of Apgar score ≤7 in 5 min of full-term neonates (P = 0.038) of the multidisciplinary group was lower than that of the non-multidisciplinary group. There was no significant difference in the mean ages (29.40 ± 3.99 vs. 29.90 ± 4.27 years; P = 0.126), mean delivery gestational ages (39.65 ± 0.87 vs. 39.64 ± 1.06; P = 0.221), mean gravidity values (1.93 ± 1.09 vs. 2.00 ± 1.18; P = 0.586) and mean parity (1.40 ± 0.56 vs. 1.42 ± 0.59; P = 0.635) of the women in the two groups. CONCLUSION: Multidisciplinary cooperation in delivery management can significantly improve some quality indicators. We established the analgesic rate of delivery can be increased and the rate of postpartum bleeding, transfer cesarean section and the incidence of Apgar score ≤7 in 5 min of full-term neonates can be decreased with the implementation of novel multidisciplinary cooperation.

SIRT6 is an epigenetic repressor of thoracic aortic aneurysms via inhibiting inflammation and senescence.

Thoracic aortic aneurysms (TAAs) develop asymptomatically and are characterized by dilatation of the aorta. This is considered a life-threating vascular disease due to the risk of aortic rupture and without effective treatments. The current understanding of the pathogenesis of TAA is still limited, especially for sporadic TAAs without known genetic mutation. Sirtuin 6 (SIRT6) expression was significantly decreased in the tunica media of sporadic human TAA tissues. Genetic knockout of Sirt6 in mouse vascular smooth muscle cells accelerated TAA formation and rupture, reduced survival, and increased vascular inflammation and senescence after angiotensin II infusion. Transcriptome analysis identified interleukin (IL)-1ß as a pivotal target of SIRT6, and increased IL-1ß levels correlated with vascular inflammation and senescence in human and mouse TAA samples. Chromatin immunoprecipitation revealed that SIRT6 bound to the Il1b promoter to repress expression partly by reducing the H3K9 and H3K56 acetylation. Genetic knockout of Il1b or pharmacological inhibition of IL-1ß signaling with the receptor antagonist anakinra rescued Sirt6 deficiency mediated aggravation of vascular inflammation, senescence, TAA formation and survival in mice. The findings reveal that SIRT6 protects against TAA by epigenetically inhibiting vascular inflammation and senescence, providing insight into potential epigenetic strategies for TAA treatment.

Reducing anxiety and improving self-acceptance in children and adolescents with osteosarcoma through group drawing art therapy.

Purpose: This study explored the effect of group drawing art therapy (GDAT) on anxiety and self-acceptance in children and adolescents with osteosarcoma. Methods: Using a randomized experimental study design, 40 children and adolescents with osteosarcoma who were treated in our hospital from December 2021 to December 2022 were selected as the research objects, including 20 in the intervention group and 20 in the control group. The control group received routine care for osteosarcoma, while the intervention group participated in eight sessions of GDAT, twice a week, 90-100 min each, in addition to routine care for osteosarcoma. A screening for children's anxiety disorders (SCARED) and a self-acceptance questionnaire (SAQ) were used to evaluate the patients before and after the intervention. Results: After 8 weeks of GDAT, the SCARED total score in the intervention group was 11.30 ± 8.603, and that in the control group was 22.10 ± 11.534. The difference between the two groups was statistically significant (t = -3.357, P < 0.05). In the intervention group, the SAQ total score was 48.25 ± 4.204, with self-acceptance and self-evaluation factor scores of 24.40 ± 2.521 and 23.85 ± 2.434, respectively. In the control group, the SAQ total score was 42.20 ± 4.047; the self-acceptance factor score was 21.20 ± 3.350 and that of the self-evaluation factor was 21.00 ± 2.224. The differences between the two groups were statistically significant (t = 4.637, P < 0.001; t = 3.413, P < 0.05; t = 3.866, P < 0.001, respectively). Conclusion: Group drawing art therapy can reduce anxiety and improve the levels of self-acceptance and self-evaluation in children and adolescents with osteosarcoma.

Mic60 is essential to maintain mitochondrial integrity and to prevent encephalomyopathy.

Mitochondrial encephalomyopathies (ME) are frequently associated with mutations of mitochondrial DNA, but the pathogenesis of a subset of ME (sME) remains elusive. Here we report that haploinsufficiency of a mitochondrial inner membrane protein, Mic60, causes progressive neurological abnormalities with insulted mitochondrial structure and neuronal loss in mice. In addition, haploinsufficiency of Mic60 reduces mitochondrial membrane potential and cellular ATP production, increases reactive oxygen species, and alters mitochondrial oxidative phosphorylation complexes in neurons in an age-dependent manner. Moreover, haploinsufficiency of Mic60 compromises brain glucose intake and oxygen consumption in mice, resembling human ME syndrome. We further discover that MIC60 protein expression declined significantly in human sME, implying that insufficient MIC60 may contribute for pathogenesis of human ME. Notably, systemic administration of antioxidant N-acetylcysteine largely reverses mitochondrial dysfunctions and metabolic disorders in haplo-insufficient Mic60 mice, also restores neurological abnormal symptom. These results reveal Mic60 is required in the maintenance of mitochondrial integrity and function, and likely a potential therapeutics target for mitochondrial encephalomyopathies.

Genetically Engineering Cell Membrane-Coated BTO Nanoparticles for MMP2-Activated Piezocatalysis-Immunotherapy.

Tumor immunotherapy based on immune checkpoint blockade (ICB) still suffers from low host response rate and non-specific distribution of immune checkpoint inhibitors, greatly compromising the therapeutic efficiency. Herein, cellular membrane stably expressing matrix metallopeptidase 2 (MMP2)-activated PD-L1 blockades is engineered to coat ultrasmall barium titanate (BTO) nanoparticle for overcoming the immunosuppressive microenvironment of tumors. The resulting M@BTO NPs can significantly promote the BTO's tumor accumulation, while the masking domains on membrane PD-L1 antibodies are cleaved when exposure to MMP2 highly expressed in tumor. With ultrasound (US) irradiation, M@BTO NPs can simultaneously generate reactive oxygen species (ROS) and O2 based on BTO mediated piezocatalysis and water splitting, significantly promoting the intratumoral infiltration of cytotoxic T lymphocytes (CTLs) and improving the PD-L1 blockade therapy to the tumor, resulting in effective tumor growth inhibition and lung metastasis suppression in a melanoma mouse model. This nanoplatform combines MMP2-activated genetic editing cell membrane with US responsive BTO for both immune stimulation and specific PD-L1 inhibition, providing a safe and robust strategy in enhancing immune response against tumor.

Divergent modulation of pain and anxiety by GABAergic neurons in the ventrolateral periaqueductal gray and dorsal raphe.

The ventrolateral periaqueductal gray (vlPAG) collaborates with the dorsal raphe (DR) in pain regulation and emotional response. However, the roles of vlPAG and DR γ-aminobutyric acid (GABA)-ergic neurons in regulating nociception and anxiety are contradictory and poorly understood. Here, we observed that pharmacogenetic co-activation of vlPAG and DR GABAergic (vlPAG-DRGABA+) neurons enhanced sensitivity to mechanical stimulation and promoted anxiety-like behavior in naïve mice. Simultaneous inhibition of vlPAG-DRGABA+ neurons showed adaptive anti-nociception and anti-anxiety effects on mice with inflammatory pain. Notably, vlPAGGABA+ and DRGABA+ neurons exhibited opposing effects on the sensitivity to mechanical stimulation in both naïve state and inflammatory pain. In contrast to the role of vlPAGGABA+ neurons in pain processing, chemogenetic inhibition and chronic ablation of DRGABA+ neurons remarkably promoted nociception while selectively activating DRGABA+ neurons ameliorated inflammatory pain. Additionally, utilizing optogenetic technology, we observed that the pronociceptive effect arising from DRGABA+ neuronal inhibition was reversed by the systemic administration of morphine. Our results collectively provide new insights into the modulation of pain and anxiety by specific midbrain GABAergic subpopulations, which may provide a basis for cell type-targeted or subregion-targeted therapies for pain management.

Comparison of the ED50 of prophylactic butorphanol in preventing morphine-induced pruritus with or without palonosetron: a prospective, double-blinded, randomized dose-response trial using an up-down sequential allocation method.

BACKGROUND: Butorphanol has been used to reduce the incidence and severity of neuraxial morphine-induced pruritus. Palonosetron is a commonly used antiemetic for the prevention of postoperative nausea and vomiting. The aim of our study was to compare the effective dose in 50% of subjects (ED50) of intravenous butorphanol infusion with or without a single intravenous bolus of palonosetron for preventing pruritus induced by epidural administration of morphine. METHODS: A total of 120 parturients were randomly assigned to receive an intravenous bolus injection of palonosetron plus continuous infusion of butorphanol (Group P + B) or an intravenous bolus of saline plus continuous infusion of butorphanol (Group B) after epidural administration of morphine. The antipruritic effect was graded as satisfactory (numerical rating scale (NRS) of pruritus ≤3) or unsatisfactory (NRS >3) within 48 h after morphine treatment. The first patient in each group received butorphanol infusion at a rate of 4 µg/kg/h. The infusion dose for each subsequent patient in the corresponding group was increased by 0.2 µg/kg/h after an unsatisfactory response or decreased by 0.2 µg/kg/h after a satisfactory response. The ED50 was calculated for each group and compared using up-down sequential analysis. RESULTS: The ED50 (mean [95% confidence interval (CI)]) of the dose of intravenous butorphanol infusion for preventing moderate to severe pruritus was lower in Group P + B (3.29 µg/kg/min [3.25-3.34 µg/kg/min]) than in Group B (3.57 µg/kg/min [3.47-3.67 µg/kg/min]) (p < 0.05). CONCLUSIONS: Under the conditions of the present study, a prophylactic use of 0.25 mg palonosetron reduced the ED50 of prophylactic infusion of butorphanol by approximately 8% to achieve a satisfactory antipruritic effect after epidural morphine for post-caesarean analgesia.

A novel link between silent information regulator 1 and autophagy in cerebral ischemia-reperfusion.

Cerebral ischemia is one of the leading causes of death and disability worldwide. Although revascularization via reperfusion combined with advanced anticoagulant therapy is currently a gold standard treatment for patients, the reperfusion itself also results in a serious dysfunction termed cerebral ischemia-reperfusion (I/R) injury. Silent information regulator 1 (sirtuin 1, SIRT1), is a classic NAD+-dependent deacetylase, which has been proposed as an important mediator in the alleviation of cerebral ischemia through modulating multiple physiological processes, including apoptosis, inflammation, DNA repair, oxidative stress, and autophagy. Recent growing evidence suggests that SIRT1-mediated autophagy plays a key role in the pathophysiological process of cerebral I/R injury. SIRT1 could both activate and inhibit the autophagy process by mediating different autophagy pathways, such as the SIRT1-FOXOs pathway, SIRT1-AMPK pathway, and SIRT1-p53 pathway. However, the autophagic roles of SIRT1 in cerebral I/R injury have not been systematically summarized. Here, in this review, we will first introduce the molecular mechanisms and effects of SIRT1 in cerebral ischemia and I/R injury. Next, we will discuss the involvement of autophagy in the pathogenesis of cerebral I/R injury. Finally, we will summarize the latest advances in the interaction between SIRT1 and autophagy in cerebral I/R injury. A good understanding of these relationships would serve to consolidate a framework of mechanisms underlying SIRT1's neuroprotective effects and provides evidence for the development of drugs targeting SIRT1.

[Observation of preventive effect of intervention strategy based on Caprini risk evaluation model on venous thromboembolism after total knee arthroplasty].

OBJECTIVE: To observe preventive effect of Caprini based thrombosis risk evaluation model on venous thromboembolism (VTE) after total knee replacement (TKA). METHODS: Totally 257 TKA patients were admitted from May 2017 to December 2021 were selected. They were divided into conventional intervention strategies (121 patients in control group) and intervention strategies based on Caprini thrombosis risk evaluation model (136 patients in observation group), based on whether Caprini thrombosis risk evaluation model was introduced in May 2019. In normal gourp, there were 79 males and 42 females aged from 50 to 78 years old with an average of (63.10±11.86) years old;body mass index (BMI) ranged from 19 to 32 with an average of (25.21±4.95) kg/m2;55 patients on the left side and 66 on the right side. In observation group, there were 81 males and 55 females aged from 50 to 78 years old with an average of (64.35±10.54) years old;BMI ranged from 19 to 32 with an average of (24.43±5.18) kg/m2;87 patients on the left side and 49 on the right side. The incidence of VTE, visual analogue scale (VAS), Hospital for Special Surgery (HSS) score, affected limb swelling, mean velocity(Vm), peak velocity (PV), D-dimer (D-D), prothrombin time(PT), and incidence of complications were analyzed and compared. RESULTS: The incidence of VTE in observation group was 1.47%(2/136), and 9.09%(11/121) in control group, and there was statistically difference between two groups (χ2=6.976, P=0.008). At 7 days after operation, VAS, HSS score and the difference in circumference of the affected limb in observation group were significantly better than those in control group, and had statistically differences (P<0.05). Blood flow Vm and PV levels between two groups were significantly increased (P<0.001), and blood flow Vm and PV levels in observation group were significantly higher than those in control group on the 7th day after operation, and had differences (P<0.001). The serum D-D level in observation group was significantly lower than that of in control group on the 7th day after operation, and PT level was significantly higher than that of in control group, and had difference(P<0.05). There was no difference in total incidence of complications between two groups (χ2=4.488, P=0.034). CONCLUSION: Intervention strategy based on caprini thrombus risk evluation model could effectively reduce incidence of VTE and complications in TKA patients, improve swelling, hemodynamics and coagulation function of the affected limbs, and contribute to recovery of knee joint function.

Metabolism Characteristics of Mycoplasma pneumoniae Infection in Asthmatic Children.

PURPOSE: Studies have shown that Mycoplasma pneumoniae (Mp) infection can aggravate symptoms in asthmatics. However, the mechanism by which Mp infection exacerbates asthma remains unclear. Metabolomics can help identify the mechanism of Mp aggravating asthma in children, thereby providing more a potential target for improving clinical treatment programs. In this article, we analyzed the metabolic level of patients to explain how Mp aggravates asthma in children. METHODS: We divided the subjects into the asthma, Mp infection, asthma combined with Mp infection and healthy groups. Patients' peripheral blood was collected for metabolic and interaction analysis. Cytokine levels were measured via serum and exhaled breath condensate (EBC). RESULTS: A total of 150 participating subjects were divided into four groups after exclusion. We found out that there were different metabolic pathways between the healthy and disease groups. The major pathways of both asthma and asthma combined with Mp infection were valine, leucine and isoleucine biosynthesis; malate-aspartate shuttle was the main differential pathway for Mp infection. Moreover, even though three disease groups involved 81 metabolites at the same time, compared with asthma combined with Mp infection, 2 single disease groups still involved different amino acid pathways (phenylalanine, tyrosine and tryptophan biosynthesis; valine, leucine and isoleucine biosynthesis). Interaction analysis showed that Mp infection in asthmatic patients not only activated cytokines, but also activated Toll-like receptors (TLRs) 2 and 6. Finally, the levels of interleukin (IL)-4, IL-8, IL-13 and tumor necrosis factor-α in EBC with asthma combined with Mp infection were significantly higher than the 2 single disease groups. CONCLUSIONS: Mp infection in asthmatic children can cause changes in the levels of various amino acids in the body, which were enriched in the pathways such as valine, leucine and isoleucine biosynthesis. Palmitic acid can activate TLR2, and iloprost reduces IL-10 levels, ultimately leading to the increased airway inflammation.