The present study aimed to explore whether hydrogen sulfide (H₂S) improved hypoxic pulmonary hypertension (HPH) in rats by inhibiting aerobic glycolysis-pyroptosis. Male Sprague-Dawley (SD) rats were randomly divided into normal group, normal+NaHS group, hypoxia group, and hypoxia+NaHS group, with 6 rats in each group. The control group rats were placed in a normoxic (21% O₂) environment and received daily intraperitoneal injections of an equal volume of normal saline. The normal+NaHS group rats were placed in a normoxic environment and intraperitoneally injected with 14 μmol/kg NaHS daily. The hypoxia group rats were placed in a hypoxia chamber, and the oxygen controller inside the chamber maintained the oxygen concentration at 9% to 10% by controlling the N₂ flow rate. An equal volume of normal saline was injected intraperitoneally every day. The hypoxia+NaHS group rats were also placed in an hypoxia chamber and intraperitoneally injected with 14 μmol/kg NaHS daily. After the completion of the four-week modeling, the mean pulmonary artery pressure (mPAP) of each group was measured using right heart catheterization technique, and the right ventricular hypertrophy index (RVHI) was weighed and calculated. HE staining was used to observe pathological changes in lung tissue, Masson staining was used to observe fibrosis of lung tissue, and Western blot was used to detect protein expression levels of hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), pyruvate kinase isozyme type M2 (PKM2), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), GSDMD-N-terminal domain (GSDMD-N), Caspase-1, interleukin-1β (IL-1β) and IL-18 in lung tissue. ELISA was used to detect contents of IL-1β and IL-18 in lung tissue. The results showed that, compared with the normal control group, there were no significant changes in all indexes in the normal+NaHS group, while the hypoxia group exhibited significantly increased mPAP and RVHI, thickened pulmonary vascular wall, narrowed lumen, increased collagen fibers, up-regulated expression levels of aerobic glycolysis-related proteins (HK2 and PKM2), up-regulated expression levels of pyroptosis-related proteins (NLRP3, GSDMD-N, Caspase-1, IL-1β, and IL-18), and increased contents of IL-1β and IL-18. These changes of the above indexes in the hypoxia group were significantly reversed by NaHS. These results suggest that H₂S can improve rat HPH by inhibiting aerobic glycolysis-pyroptosis.
Animals ; Rats, Sprague-Dawley ; Male ; Hypertension, Pulmonary/metabolism* ; Glycolysis/drug effects* ; Hydrogen Sulfide/therapeutic use* ; Hypoxia/complications* ; Rats ; Pyroptosis/drug effects*

OBJECTIVE: To investigate the therapeutic effect of the short-penis treatment apparatus and wide-band infrared therapy apparatus on penile dysplasia (PDP) in children and establish objective parameters for assessing the severity of PDP. METHODS: This study included 252 children received in the Department of pediatric urology of the First Affiliated Hospital of Xinjiang Medical University from January to December 2023, 102 with PDP (the PDP group) and the other 150 with normal penile development (the control group), those of the former group treated with the short-penis therapeutic apparatus and wide-band infrared therapy apparatus. Before and after 30 days of treatment, we measured the flaccid penile length (FPL), stretched penile length (SPL) and penile diameters (PD) of the children, and defined the penile dysplasia index as the FPL/SPL and FPL/PD ratios. RESULTS: The penile parameters exhibited statistically significant differences between the PDP and control groups, (FPL:［1.97±0.72］cm vs ［3.25±0.51］ cm, P<0.01; SPL:［3.80±0.81］cm vs ［5.21±0.79］cm,P<0.01).The FPL remarkably increased in the PDP group after treatment(［1.97±0.72］cm vs ［2.90±1.20］ cm, P<0.01). Both FPL and SPL were notably shorter in the PDP cases than in the controls, with the cutoff values of 0.57 and 2.09, sensitivities of 80.7% and 95.3%, and specificities of 69.6% and 82.4% for FPL/SPL and FPL/PD, respectively. CONCLUSION The short-penis therapeutic apparatus and wide-band infrared therapy apparatus can promote the growth and development of the penis in children. The ratio of FPL/PD can serve as an objective indicator to effectively describe the severity of penile developmental abnormalities.
Humans ; Male ; Penis/abnormalities* ; Child ; Penile Diseases/therapy* ; Child, Preschool ; Infant

OBJECTIVE: To investigate the clinical effect of physical intervention combined with medical nutritional weight loss (PI+MNWL) in the treatment of short penis in obese children. METHODS: One hundred and twenty obese children with a short penis were included and equally divided into three groups: PI+MNWL, MNWL, and self-guided diet, who underwent PI+MNWL, MNWL intervention under the supervision of professional nutritionists in the hospital, or self-guided diet intervention at home, respectively, all for 30 days. We measured the penile parameters, including stretched penile length (SPL), flaccid penile length (FPL) and penile diameter (PD), of the children before and after treatment, and compared them among the three groups. RESULTS: After intervention, the body weight of the children was significantly decreased in all the three groups (27.1－94.1［53.59±11.88］ kg vs 23.0－85.1［49.01±11.61］ kg， P < 0.05). The weight of children in 3 groups decreased to different degrees, and the difference was statistically significant (P < 0.05). MNWL was found remarkably more effective than self-guided weight loss in reducing the body weight of the children (P < 0.05). Based on weight loss achieved through medical nutrition combined with physical intervention, the FPL in the PI+MNWL group increased from (1.93 ± 0.76) cm before treatment to (3.41 ± 1.41) cm after one course of comprehensive treatment, with a statistically significant difference (P < 0.05). Similarly, SPL increased from (3.75 ± 0.76) cm before treatment to (4.98 ± 0.64) cm, and PD increased from (1.32 ± 0.21) cm before treatment to (1.61 ± 0.66) cm, both showing statistically significant differences (P < 0.05). In the MNWL group , FPL increased from (2.01 ± 0.81) cm to (2.77 ± 0.84) cm after one course of treatment, with a statistically significant difference (P < 0.05). Additionally, SPL increased from (4.03 ± 0.84) cm before treatment to (4.40 ± 0.76) cm, also demonstrating statistical significance (P < 0.05), while PD increased from (1.37 ± 0.21) cm before treatment to (1.42 ± 0.22) cm, with statistical significance (P < 0.05). FPL and SPL increased significantly in the PI+MNWL group compared to the MNWL group (P < 0.05, P < 0.01). However, there was no significant difference in PD between the two groups following the intervention (P > 0.05). CONCLUSION MNWL is more effective than self-guided diet in controlling the body weight of children, while the combination approach of PI+MNWL is even superior to the management of short penis in obese children, with the advantages of improving the appearance and increasing the exposed length of the penis.
Humans ; Male ; Child ; Weight Loss ; Penis/abnormalities* ; Obesity/complications* ; Adolescent

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Objective To observe the effects and safety of semaglutide and saxagliptin combined with metformin in the treatment of type 2 diabetes mellitus(T2DM)with abdominal obesity(AO).Methods The data of patients with T2DM and AO were retrospectively analyzed.Patients with T2DM and AO were divided into semaglutide group and saxagliptin group according to the cohort method.Both groups were given metformin orally,0.5 g a time,tid.On this basis,the semaglutide group was injected with semaglutide,0.25 mg a time,2 weeks later,the dose was adjusted to 0.5 mg a time,qw.The saxagliptin group was given oral administration of saxagliptin on the basis of metformin,5 mg a time,qd.All patients received 3 months of treatment.Glucose metabolism indexes,pancreatic islet function indexes,adipokines and adverse drug reactions were compared between the groups.Results There were 48 cases in semaglutide group and 49 cases in saxagliptin group.After treatment,the levels of fasting plasma glucose(FPG)in the semaglutide group and the saxagliptin group were(7.45±1.22)and(7.98±1.30)mmol·L-1;the levels of 2 h plasma glucose(2 h PG)were(9.78±1.64)and(10.55±1.82)mmol·L-1;the levels of hemoglobin A1c(HbA1c)were(5.66±0.94)and(6.25±0.87)％;the levels of fasting insulin(FINS)were(29.12±2.46)and(34.34±7.15)pmol·L-1;the levels of fasting C-peptide(FC-P)were(292.66±67.53)and(319.03±77.92)pmol·L-1;homeostatic model assessment-insulin resistance(HOMA-IR)were 2.51±0.78 and 2.94±0.89;homeostatic model assessment-β(HOMA-β)were 51.74±15.31 and 43.72±14.56;levels of Irisin were(4.56±0.32)and(4.17±0.54)ng·L-1;the levels of spexin(SPX)were(0.71±0.15)and(0.64±0.17)ng·mL-1;the levels of asprosin(ASP)were(1.22±0.16)and(1.34±0.25)μg·L-1.The above indexes were significantly different between semaglutide group and saxagliptin group(all P＜0.05).The total incidence rates of adverse drug reactions in semaglutide group and saxagliptin group were 10.42％(5 cases/48 cases)and 2.04％(1 case/49 cases),without statistically significant difference(P＞0.05).Conclusion The combination of semaglutide and metformin can lower blood glucose and in patients with T2DM and AO more significantly,and improve pancreatic function and adipokines,with good safety.

Objective To evaluate the bioequivalence of metronidazole tablet and reference formulation in Chinese healthy subjects.Methods A single-dose,two-cycle,randomized,open,self-crossover trial was designed with 48 healthy subjects randomly assigned to fasting or postprandial group.For each group,a single oral dose of metronidazole tablet(200 mg)or a reference preparation(200 mg)per cycle were enrolled.The concentration of metronidazole in plasma was measured by high performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS).The non-compartmental model was applied to calculate the pharmacokinetic parameters for bioequivalence analysis via SAS 9.3 software.Results The main pharmacokinetic parameters of test and reference metronidazole tablets in the fasting group were as follows,the Cmax were(4 855.00±1 383.97)and(4 799.13±1 195.32)ng·h·mL-1;the AUC0-t were(54 834.68±12 697.88)and(55 931.35±11 935.28)ng·h·mL-1;the AUC0-∞ were(56 778.09±13 937.76)and(57 922.83±13 260.54)ng·h·mL-1;the Tmax were respectively 1.17 and 1.00 h;t1/2 were(8.99±1.76)and(9.11±1.73)h,respectively.The ratio of the geometric mean and its 90％confidence intervals(CI)of Cmax,AUC0-t and AUC0-∞ were all within the equivalent interval of 80.00％-125.00％.As for postprandial conditions,the main pharmacokinetic parameters of test and reference metronidazole tablets were as follows,the Cmax were(4 057.08±655.08)and(4 044.17±773.98)ng·h·mL-1;the AUC0-t were(55 956.42±12 228.12)and(55 121.04±11 784.55)ng·h·mL-1;the AUC0-∞ were(58 212.83±13 820.00)and(57 350.38±13 229.46)ng·h·mL-1;the Tmax were 2.50 and 2.25 h;the t1/2 were(9.37±1.68)and(9.37±1.79)h,respectively.The ratio of the geometric mean and 90％CI of Cmax,AUC0-t and AUC0-∞ were all within the equivalent interval of 80.00％-125.00％.Conclusion The two preparations were bioequivalent to Chinese healthy adult volunteers under both fasting and fed conditions.

AIM To prepare the soluble microneedles of Aconitum brachypodum Diels alkaloids.METHODS Centrifugal molding method was adopted in the preparation of soluble microneedles.With chondroitin sulfate consumption,PVP K120 consumption and 40%ethanol consumption as influencing factors,piercing rate as an evaluation index,the formulation was optimized by Box-Behnken response surface method,after which the morphology,piercing performance,drug content and in vitro transdermal performance were investigated.RESULTS The optimal formulation was determined to be 123 mg for chondroitin sulfate consumption,298 mg for PVP K120 consumption,and 2.4 mL for 40%ethanol consumption,the piercing rate was 98.3%.The soluble microneedles were yellow and square patch with conoid needle,which could pierce aluminum foil and rat skin,along with the drug content of(0.94±0.025)mg.The soluble microneedle group demonstrated the accumulative permeability rate of 91.4%within 24 h,which was higher than that in the gel ointment group,and the permeability accorded with Higuchi equation.CONCLUSION The soluble microneedles of A.brachypodum alkaloids exhibit good mechanical strength,which can achieve effective transdermal delivery of drugs.

Objective To investigate the expression of long non-coding RNA(lncRNA),surfactant associated 1 pseudogene(SFTA1P)in lung squamous carcinoma and its effect on the biological functions of SFTA1P in lung squamous carcinoma cell lines.Methods Based on the cancer genome atlas(TCGA)database,the differential expression of SFTA1P in tumor and normal tissues were compared in patients diagnosed with lung squamous cell carcinoma.Then,the expression of SFTA1P was detected in human normal lung epithelial cell line BEAS-2B and lung squamous cell lines SK-MES-1 and H520 with real-time quantitative polymerase chain reaction(RT-qPCR).SK-MES-1 and H520 cells with overexpression and/or knockdown of SFTA1P were constructed by transfecting the overexpression plasmids(pcDNA3.1-SFTA1P)and small interfering RNAs(si-SFTA1P-1 and si-SFTA1P-2).CCK-8 assay and Transwell assay were used to investigate the effect of SFTA1P on biological functions in lung squamous carcinoma cells.Differential gene expression analysis,correlation analysis and functional enrichment analysis were employed to explore the potential mechanism that SFTA1P may affect biological functions of lung squamous cells.Results Analysis of TCGA showed that the expression of SFTA1P was significantly lower in lung squamous cell carcinoma tissue than adjacent normal tissue(P＜0.05).RT-PCR results showed that the expression of SFTA1P was obviously lower in lung squamous carcinoma cells than the human normal lung epithelial cells(P＜0.05).And the expression level of SFTA1P was relatively lower in the SK-MES-1 cells than the H520 cells(P＜0.05).Overexpression of SFTA1P suppressed the proliferation,migration and invasion of lung squamous carcinoma cells(P＜0.05),while its knockdown promoted these abilities(P＜0.05).Differential gene expression analysis,correlation analysis and functional enrichment analysis indicated that SFTA1P may inhibit MYC,G2m checkpoints and E2f signaling pathways in lung squamous cell carcinoma.Conclusion SFTA1P shows anti-cancer function in lung squamous cell carcinoma,and it may affect the biological functions of lung squamous cell carcinoma cells through down-regulating MYC,G2m checkpoints and E2f signaling pathways.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To study the risk factors for embolism in children with refractory Mycoplasma pneumoniae pneumonia(RMPP)and to construct a nomogram model for prediction of embolism.Methods This retrospective study included 175 children diagnosed with RMPP at Children's Hospital Affiliated to Zhengzhou University from January 2019 to October 2023.They were divided into two groups based on the presence of embolism:the embolism group(n=62)and the non-embolism group(n=113).Multivariate logistic regression analysis was used to screen for risk factors of embolism in children with RMPP,and the R software was applied to construct the nomogram model for prediction of embolism.Results Multivariate logistic regression analysis indicated that higher levels of D-dimer,interleukin-6(IL-6)and neutrophil to lymphocyte ratio(NLR),lung necrosis,and pleural effusion were risk factors for embolism in children with RMPP(P＜0.05).The area under the curve of the nomogram model for prediction of embolism constructed based on the aforementioned risk factors was 0.912(95％CI:0.871-0.952,P＜0.05).The Hosmer-Lemeshow goodness-of-fit test showed that the model had a good fit with the actual situation(P＜0.05).Calibration and decision curve analysis indicated that the model had high predictive efficacy and clinical applicability.Conclusions Higher levels of D-dimer,IL-6 and NLR,lung necrosis,and pleural effusion are risk factors for embolism in children with RMPP.The nomogram model based on these risk factors has high clinical value for predicting embolism in children with RMPP.