The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H₂S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H₂S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2A^EC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H₂S signaling pathway. A robust reduction in endothelial MPST-dependent H₂S production followed PP2A deficiency. Exogenous H₂S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2A^EC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H₂S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.

Acute lung injury (ALI) is a significant complication of sepsis, characterized by high morbidity, mortality, and poor prognosis. Neutrophils, as critical intrinsic immune cells in the lung, play a fundamental role in the development and progression of ALI. During ALI, neutrophils generate neutrophil extracellular traps (NETs), and excessive NETs can intensify inflammatory injury. Research indicates that Taohe Chengqi decoction (THCQD) can ameliorate sepsis-induced lung inflammation and modulate immune function. This study aimed to investigate the mechanisms by which THCQD improves ALI and its relationship with NETs in sepsis patients, seeking to provide novel perspectives and interventions for clinical treatment. The findings demonstrate that THCQD enhanced survival rates and reduced lung injury in the cecum ligation and puncture (CLP)-induced ALI mouse model. Furthermore, THCQD diminished neutrophil and macrophage infiltration, inflammatory responses, and the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Notably, subsequent experiments confirmed that THCQD inhibits NET formation both in vivo and in vitro. Moreover, THCQD significantly decreased the expression of peptidyl arginine deiminase 4 (PAD4) protein, and molecular docking predicted that certain active compounds in THCQD could bind tightly to PAD4. PAD4 overexpression partially reversed THCQD's inhibitory effects on PAD4. These findings strongly indicate that THCQD mitigates CLP-induced ALI by inhibiting PAD4-mediated NETs.
Extracellular Traps/immunology* ; Acute Lung Injury/immunology* ; Animals ; Sepsis/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neutrophils/immunology* ; Male ; Protein-Arginine Deiminase Type 4/genetics* ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; Cytokines/metabolism*

Objective:To explore the clinical features and genetic etiology for a child with developmental delay, impaired growth, facial dysmorphism, and axonal neuropathy (DIGFAN).Methods:A child who was admitted to the Second Affiliated Hospital of Guangxi Medical University on March 22, 2021 was selected the study subject. Clinical data of the child was collected. Following extraction of genomic DNA, the child and his parents were subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing and bioinformatic analysis.Results:The child, a 10-year-and-9-month-old boy, had manifested with short stature, intellectual disability, delayed speech, motor and language development, and facial dysmorphism. WES and Sanger sequencing revealed that he has harbored a novel de novo c. 800T>C (p.Leu267Pro) variant of the MORC2 gene. The Leucine at position 267, which is highly conserved among various species, is located in the S5 domain of ribosome protein in the ATPase binding region of MORC2. And the Leu267Pro may affect the function of MORC2 by altering the spatial conformation and activity of ATPase. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 800T>C variant was classified as likely pathogenic (PS2+ PM2_Supporting+ PP2+ PP3). Conclusion:The MORC2: c. 800T>C (p.Leu267Pro) variant probably underlay the pathogenesis of DIGFAN syndrome in this child.

Nesfatin-1 is a neuropeptide hormone known for its biological functions,including inhibiting food intake,regulating glucose and lipid metabolism,promoting apoptosis,and providing anti-inflammatory and anti-tumor effects.Glucose metabolism is a crucial pathway for the body's energy supply.Current research has demonstrated that Nesfatin-1 can affect glucose metabolism through various mechanisms,such as inhibiting food intake,regulating enzyme activity,and improving insulin resistance,though the findings are not entirely consistent.Investigating the relationship between Nesfatin-1 and glucose metabolism may offer new insights into the diagnosis and treatment of diseases related to glucose metabolism disorders.

Objective To investigate the application of anesthesia management plan based on the concept of enhanced recovery after surgery(ERAS)in thoracoscopic surgery.Methods From December 2021 to December 2022,100 patients underwent thoracoscopic surgery were randomly divided into control group and observation group with 50 patients in each.The control group received routine anesthesia management,and the observation group received anesthesia management based on ERAS concept.The two groups were compared in terms of clinical indicators,the degree of incision pain on day 1,3,5 and 7 after surgery,the levels of inflammatory factors on day 1 and 3 after surgery.The incidence rates of pulmonary complications,nausea and vomiting,and respiratory depression in the two groups were calculated.Results Awakening and extubation time and hospital stay of observation group were shorter than those of control group,the treatment costs of observation group was less than that of control group,the visual analogue scale(VAS)of observation group at each time point after surgery were lower than those of control group,the levels of C-reactive protein(CRP)and tumor necrosis factor-α(TNF-α)of observation group on day 1 and 3 after surgery were lower than those of control group,the differences were statistically significant(P<0.05).The total incidence of pulmonary complications of observation group was lower than that of control group(6.00%vs 22.22%),the difference was statistically significant(P<0.05).The incidence rates of respiratory depression and nausea and vomiting in the observation group were 0.00%and 2.00%,respectively,while the incidence rates of respiratory depression and nausea and vomiting in the control group were 4.00%and 6.00%,respectively.There was no statistically significant difference in the total incidence rates of other complications between the two groups of patients(P>0.05).Conclusion Applying the anesthesia management plan based on ERAS concept in thoracoscopic surgery can promote postoperative recovery,reduce pain and pulmonary complications,and save treatment costs.It is worthy of clinical application.

Objective To investigate the clinical manifestations,molecular genetics and gonadal pathol-ogy characteristics of patients with disorders of sex development(DSD),and to summarize the clinical experi-ence of identifying rare diseases from common symptoms.Methods The clinical data of 416 patients with DSD diagnosed and treated in the multidisciplinary center of DSD of Guangzhou Women and Children's Medical Cen-ter from May 2018 to August 2023 were retrospectively analyzed,summarized and discussed.Results Accord-ing to chromosome karyotype,416 cases of DSD were classified into three types:92 cases(22.1％)of abnormal sex chromosome karyotype,285 cases(68.5％)of 46,XY karyotype and 39 cases(9.4％)of 46,XX karyotype.Among the 92 patients with abnormal sex chromosome karyotype,59 cases were raised as males,18 cases(30.5％)complained of short penis with hypospadias and cryptorchidism.The most common karyotype was 45,X/46,XY(58 cases,63.0％).Among the 285 patients with 46,XY karyotype,238 cases were raised as males,and 63 cases(26.5％)complained of short penis and hypospadias;47 cases were raised as females,and 13 ca-ses(27.7％)complained of inguinal mass.A total of 216 patients with 46,XY karyotype were subjected to whole exome gene detection,and 155 cases(71.8％)were found to have molecular pathogenesis with the clinical phe-notype.Among the 39 patients with 46,XX karyotype,19 cases were raised as males,and 8 cases(42.1％)com-plained of short penis and hypospadias.In the 18 cases of gonad biopsy,17 cases showed testicular tissue in go-nads.Whole exome sequencing was performed in 14 cases.NR5A1 gene heterozygous mutation,SRY gene muta-tion and SOX3 gene mutation were found in 2 cases,respectively(14.3％).Twenty cases were raised as females,and 14 cases(70.0％)complained of clitoral hypertrophy.Gonad biopsy was performed in 8 cases,with 7 cases of ovotestis(87.5％)and 1 case of NR5A1 gene heterozygous mutation(14.3％).Conclusions The etiologies of DSD are complex and diverse,and the clinical manifestations are various,which can be manifested as hypospa-dias,micropenis,cryptorchidism and other common symptoms of the urinary system.Different etiologies have dif-ferent treatment options.Therefore,chromosome karyotype,molecular genetic testing and gonadal pathology can be used to clarify the cause of disease,especially for rare diseases,improve the detection rate,reduce the rate of missed diagnosis,and ensure reasonable treatment,especially sex selection.

Objective To evaluate the efficacy and safety of omalizumab on the treatment of chronic spontaneous urticaria (CSU) by systemic review and meta-analysis.Methods Electronic databases,such as PubMed,Clinicaltrials.gov,the Cochrane Database of Systematic Reviews,and the Cochrane Central Register of Controlled Trials,were searched to collect randomized controlled trials (RCTs) about the efficacy and safety of omalizumab in the treatment of CSU.Two reviewers independently screened RCTs according to the inclusion and exclusion criteria,extracted data,and assessed the quality of the included RCTs.And then,a meta-analysis was carried out by using RevMan 5.3 software for comparisons of the efficacy and safety of the 75-,150-,300-,600-mg omalizumab groups versus the placebo group after 1-month treatment,as well as the total omalizumab group versus the placebo group.Results A total of 7 RCTs involving 1 365 patients were included in this meta-analysis.The results showed that the total omalizumab group and different omalizumab subgroups were superior in improving the urticaria activity score of 7 days (UAS7) and wheal number score of 7 days to the placebo group (all P ＜ 0.05).For the improvement in the itch severity score (ISS) of 7 days and complete response rate for main symptoms (UAS7 =0),the total omalizumab group,75-,150-and 300-mg omalizumab groups were superior to the placebo group (all P ＜ 0.05),but there were no significant differences between the 600-mg omalizumab group and the placebo group (P =0.07).The dermatology life quality index (DLQI) was better in the total omalizumab group,150-and 300-mg omalizumab groups than in the placebo group (all P ＜ 0.05),but no significant difference was observed between the 75-mg omalizumab group and the placebo group (P =0.50).There were no significant differences in the incidence of common adverse events or serious adverse events between the total omalizumab group as well as the 75-,150-and 300-mg omalizumab subgroups and the placebo subgroup (all P ＞ 0.05).Conclusions Omalizumab can improve clinical symptoms and life quality of patients with CSU,and is effective in improving the UAS,ISS,wheal number score,DLQI and complete response rate for main symptoms (UAS =0) with high safety.Subcutaneous injection of omalizumab at a dose of 150 or 300 mg/month shows the best efficacy in improving the clinical symptoms and life quality of patients with CSU.

Objective To investigate the diagnostic value of prenatal ultrasound for fetal structural abnormalities.Methods The clinical data of 3 101 fetus with structural malformations, diagnosed by prenatal ultrasound and confi rmed after induced labor, and 856 cases of missed diagnosis were analyzed. All these data were collected in Maternal and Child Health Hospital of Tangshan City from January 2010 to June 2014. The types and number of fetal structural abnormalities were recorded. The rates of detection and missed diagnosis for the fetal structural abnormalities were calculated and the reasons for missed diagnosis were analyzed.ResultsA total of 3101 cases (4 171 positions) were diagnosed as fetal structural abnormalities by prenatal ultrasound. The detection rate was 11.51‰ (3 101/269 501). There were 856 cases (947 positions) of fetal structural abnormalities were missed, and the missed diagnosis rate was 3.18‰ (856/269 501). The incidence of fetal structural abmormalities was 14.68‰ (3 957/269 501). In terms of anatomy systems, the top five were cardiovascular system abnormalities (851 cases), the central nervous system abnormalities (691 cases), facial abnormalities (562 cases), urinary system abnormalities (476 cases), and respiratory system abnormalities (134 cases). In terms of single abnormalities, the top five were cleft lip and palate (549 cases), ventricular septal defect (519 cases), hydronephrosis (331 cases), spina bifi da (212 cases), and atrial-ventricular septal defect (163 cases). The top five of missed deformities were polydactylia/symphysodactylia (285 cases), ear deformities (108 cases), hypospadias (93 cases), foot abnormalities (92cases), and ventricular septal defect (52 cases).Conclusions There is a high detection rate for fetal structural abnormalities with prenatal ultrasound. Prenatal ultrasound is an indispensable means for the diagnosis of fetal malformation, but it also has some limitations. There is a high rate of missed diagnosis for polydactylia/symphysodactylia, microtia, and hypospadias.

BACKGROUND:Tranexamic acid has been more and more used in reducing bleeding after joint replacement, but its usage method and dosage remain controversial, and become a hot focus in recent years. OBJECTIVE:To investigate the efficacy of intra-articular injection of tranexamic acid on postoperative blood loss and limb circumference changes in patients who received unilateral total knee arthroplasty. METHODS:From March to October 2013, clinical data of 90 patients undergoing primary unilateral total knee arthroplasty were randomized to the tranexamic acid group and the control group, including 19 males and 71 females. The 30 patients in the tranexamic acid group received 50 mL of 3%tranexamic acid dilute solution inside knee joint after capsule closure, and 60 patients in the control group received the same volume of physiological saline. No significant difference in age, height, body mass index, anticoagulation, the type of prosthesis, tourniquet time and preoperative diagnosis was detected between the two groups (P>0.05). The amounts of intraoperative and postoperative blood loss and blood transfusion, postoperative drainage volume, the preoperative and postoperative limb circumference 10 cm above the operated knee were recorded. Routine blood test was reviewed after the surgery. RESULTS AND CONCLUSION:There were no significant differences in total blood loss, postoperative drainage volume and limb circumference changes between tranexamic acid and control groups (P>0.05). The amount of postoperative hidden blood loss was significantly less in the tranexamic acid group than in the control group (t=-2.683, P<0.05). These data suggested that the intra-articular injection of tranexamic acid intraoperatively in patients receiving total knee arthroplasty could significantly reduce the amounts of postoperative hidden blood loss, and did not affect the postoperative limb circumference changes.

BACKGROUNDThere is no large population-based study of the distribution and changing trend of strabismus surgeries in China. This study aimed to investigate the distribution and the changing trend of strabismus surgery in a tertiary hospital of China.

METHODSA retrospective study of all the strabismus surgeries performed in Beijing Tongren Eye Center from 2003 to 2012 was carried out. Characteristics analyzed included the type of strabismus, age, and gender.

RESULTSTotally 26 524 strabismus surgeries were performed in Tongren Eye Center during the 10-year period. The number of surgeries increased steadily from 1 507 in 2003 to 3 482 in 2008 and slightly decreased to 3 124 in 2009, but there was a sharp drop to 2 569 in 2010 and then kept relatively steady at 2 760 in 2011 and 2 463 in 2012. Intermittent exotropia (30.3%) was the most common among all kinds of strabismus. The number of strabismus surgeries performed on children under 12 years of age (43.60%) was significantly higher than those of the other age groups (P < 0.05). Unilateral superior oblique paralysis was the most common subtype of paralytic strabismus (8.64%).

CONCLUSIONSThe type distribution of strabismus surgery has changed during the recent decade. The age and type distribution of different strabismus remained basically constant, among which intermittent exotropia was the most common.

Child ; Child, Preschool ; China ; Female ; Humans ; Infant ; Male ; Oculomotor Muscles ; Retrospective Studies ; Strabismus ; surgery ; Tertiary Care Centers ; statistics & numerical data