Kynurenine pathway (KP) is a major catabolic route of tryptophan, generating a series of bioactive metabolites including kynurenine, kynurenic acid (KA), quinolinic acid, and 3-hydroxykynurenine. Beyond its fundamental role in amino acid metabolism, KP exerts critical regulatory functions in neurodevelopment, synaptic plasticity, and immune modulation. Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with onset in early childhood, characterized by persistent deficits in social communication and restricted, repetitive behaviors. Despite extensive research, the etiological mechanisms underlying ASD remain highly complex and incompletely understood, involving genetic, environmental, and immunological factors. Emerging clinical evidence has consistently revealed a significant imbalance in KP metabolites in individuals with ASD, often accompanied by altered ratios of neuroprotective versus neurotoxic byproducts. However, the primary drivers of this metabolic dysregulation and its causative contribution to ASD pathogenesis are not yet fully elucidated. In this review, we systematically review the enzymatic steps of KP and the principal physiological functions of its major metabolites, with particular emphasis on their dual roles in neuroprotection and neurotoxicity. We then analyze the potential pathogenic mechanisms through which KP dysfunction may contribute to ASD, focusing on two interconnected etiological dimensions. First, KP imbalance can promote oxidative stress, which in turn triggers chronic inflammatory responses via microglial activation and release of pro-inflammatory cytokines, thereby disrupting neuronal homeostasis. Second, aberrant KP metabolism affects neurotransmitter systems, particularly glutamatergic and dopaminergic signaling, leading to impaired neural circuit development and synaptic pruning. By integrating current findings on the KP-ASD association, this review offers a comprehensive etiological framework and a clinically relevant paradigm. Furthermore, we highlight that specific KP metabolites, such as the KA/quinolinic acid ratio, hold promise as peripheral biomarkers for early diagnosis and disease stratification. Finally, we discuss the therapeutic potential of targeting KP enzymes or receptors for personalized intervention strategies, while acknowledging the challenges in translating these findings into clinical practice.

Objective:To investigate the correlation between uterine volume and intrauterine adhesion (IUA).Methods:From June 2018 to November 2019, totally 7 007 patients who underwent hysteroscopy in outpatient operating rooms of Gynecological Minimally Invasive Center, Beijing Obstetrics and Gynecology Hospital were retrospectively analyzed . Patients of reproductive age with IUA without uterine fibroids and adenomyosis were selected as IUA group, and patients of reproductive age without uterine fibroids and adenomyosis without IUA during the same period were selected as the control group. The propensity score matching (PSM) method was used to perform 1∶1 matching for the two groups of patients, matching variables included age, height, weight, body mass index (BMI), gravidity, parity, and number of abortion curettage. Whether there was any difference in uterine volume between the two groups of patients was compared, and whether uterine volume was an influencing factor of IUA was explored. The patients in IUA group were also categorized into mild, moderate and severe to explore whether uterine volume influenced the severity of IUA. Results:(1) After inclusion and exclusion criteria, 351 patients were included in IUA group and 2 986 patients in the control group. With PSM, 327 patients in IUA group and 327 patients in the control group were finally enrolled in this study. There were no statistically significant differences in age, height, weight, BMI, gravidity, parity, and number of abortion curettage between the two groups of patients after matching (all P>0.05). (2) After PSM, there was a significant difference between the uterine volume of IUA group (median: 44.23 cm 3) and the uterine volume of the control group (median: 57.20 cm 3; P<0.001). (3) Reduced uterine volume ( OR=0.961, 95% CI: 0.952-0.970) was an independent risk factor for IUA ( P<0.001). (4) Uterine volume had a significant effect on the severity of IUA ( P<0.001), the larger the uterine volume ( B=-0.030, 95% CI: -0.044 to -0.017), the less severe the IUA. Conclusions:Reduced uterine volume is an independent risk factor for IUA, and uterine volume has a significant effect on the severity of IUA. In patients with small uterine volume size, primary and secondary prevention of IUA should be emphasized.

Objective:To investigate the predictive value of uterine volume for intrauterine adhesion (IUA) caused by endometrial injury, and to provide a new perspective for the primary prevention of IUA.Methods:The clinical data of 7 007 patients of reproductive age who underwent outpatient hysteroscopy in the Gynecological Minimally Invasive Center, Beijing Obstetrics and Gynecology Hospital from June 2018 to November 2019 were retrospectively analyzed. Patients of reproductive age with IUA without uterine fibroids and adenomyosis were selected as the IUA group (351 cases), and patients of reproductive age without uterine fibroids and adenomyosis and without IUA during the same period were selected as the control group (2 986 cases). The uterine volume was compared between the two groups. Multivariate binary logistic regression analysis was used to determine whether uterine volume was an independent factor for the occurrence of IUA. Ordinal multinomial logistic regression was used to analyze the correlation between uterine volume and menstrual volume in IUA patients. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of uterine volume for IUA caused by endometrial injury.Results:(1) The uterine volume of the IUA group was significantly smaller than that of the control group (median: 44.15 vs 62.59 cm 3; Z=-15.742, P<0.001). (2) Multivariate binary logistic regression analysis showed that decreased uterine volume was an independent risk factor for IUA ( OR=0.184, 95% CI: 0.139-0.245; P<0.001). (3) The area under the ROC curve of uterine volume to predict IUA was 0.756, and the optimal cut-off value of uterine volume to predict IUA was 51.49 cm 3. (4) The risk of IUA caused by endometrial injury in patients with uterine volume≤51.49 cm 3 was 4.658 times higher than that in patients with uterine volume>51.49 cm 3 (95% CI: 3.681-5.893; P<0.001). (5) The smaller the uterine volume ( β=-0.032, 95% CI:-0.046 to -0.018; P<0.001), the more likely the IUA patients were to have menorrhagia and amenorrhea. Conclusions:Uterine volume has a certain predictive value for the occurrence of IUA caused by endometrial injury. For patients with small uterine volume, it is necessary to be alert to the occurrence of IUA caused by endometrial injury and improve the awareness of primary prevention.

Objective:To evaluate the efficacy and safety of baricitinib combined with ruxolitinib cream in the treatment of progressive nonsegmental vitiligo.Methods:Clinical data were retrospectively collected from patients with progressive nonsegmental vitiligo in Boao Super Hospital. All the patients were treated with oral baricitinib daily (2 mg/day for patients weighing ≤ 50 kg; 4 mg/day for those > 50 kg) in combination with topical application of ruxolitinib cream twice daily for 24 consecutive weeks. Disease severity was assessed using the facial vitiligo area scoring index (F-VASI) and total body VASI (T-VASI) at baseline, week 12, and week 24. Adverse reactions were monitored throughout the treatment course.Results:Six patients with progressive nonsegmental vitiligo were collected, including 3 males and 3 females, aged 26 - 42 years, with the disease duration ranging from 0.5 to 25 years. At week 12, 3 patients achieved a 50% ~ < 75% improvement in facial vitiligo lesions (F-VASI 50), 1 patient achieved F-VASI 75 (75% ~ < 90% improvement), and 1 patient achieved T-VASI 50; at week 24, 4 patients achieved F-VASI 50, 1 patient achieved F-VASI 75, 1 patient achieved F-VASI 90 (≥ 90% improvement), and 3 patients achieved T-VASI 50. During the treatment, upper respiratory infection occurred in 1 patient, acne in 1 patient, pruritus in 2 patients, elevation of total cholesterol levels in 2 patients, and increase of high-density lipoprotein levels in 2 patients. No severe adverse events were observed during the treatment.Conclusion:The combination therapy with baricitinib and ruxolitinib cream may have potential efficacy and safety in the treatment of progressive nonsegmental vitiligo.

Objective:To compare the differences of three-dimensional computed tomography(3DCT),four-dimensional computed tomography(4DCT),and multi-parametric magnetic resonance(MR)sequences of the radiotherapy for liver cancer in delineation for target area,and analyze which MR sequence was more accurate in assisting CT image to delineate the target area,and design respectively reverse intensity modulated radiotherapy plan,and compare the dosimetric parameters of the target areas of receiving radiotherapy and normal liver tissue.Methods:This retrospective study was conducted to analyze radiotherapy data from case data of 18 patients with hepatocellular carcinoma(HCC)who admitted to the First Affiliated Hospital of Bengbu Medical University between August 2023 and June 2024.These data included 10 respiratory phases in 3DCT and 4DCT,and free-breathing sequence(MR-FB),diaphragm navigation sequence(MR-NAVI),and breath-hold(MR-BH)sequence of multi-parametric MRI,and the gross tumor volumes(GTVs)of them were delineated,which were respectively 5 modal images and liver contours included GTV3D,GTV4D,GTVMR-FB,GTVMR-NAVI,and GTVMR-BH.Pinnacle3 9.8 treatment plan system(TPS)was applied to conduct registration and fusion for image by using mutual information method.The 3DCT(GTV3D)was used as reference image to compare the volume of target area,and the displacement of mass center with other 4 kinds of images.The volume difference(VD),overlap ratio(OR),Dice similarity coefficient(DSC),and Jaccard index(JAC)were used to assess the differences among different target area.The indicators of plan evaluation included conformity index(CI),homogeneity index(HI),GTV doses(D2%,D98%,Dmean),and the exposure dose of normal tissue of liver.Results:In images of five modalities,the GTV median volumes were respectively 28.83,33.10,26.75,25.05,and 22.65 cm3.In images of five modalities,the median volume of liver were respectively 1293.46,1483.09,1213.81,1195.69,and 1141.02 cm3.Compared with other 3 target areas,the displacement of GTVMR-BH was the smallest on head-foot direction,with statistically significant differences among them(Z=-2.305,-2.307,-2.134,P<0.05).The OR,DSC,and JAC values of GTV4D were significantly better than these of GTVMR-FB,GTVMR-NAVI,and GTVMR-BH(ZOR=-2.911,-3.006,-3.195,ZDSC=-2.726,-2.215,-2.556,ZJAC=-2.556,-2.704,-2.953,P<0.05).The VD value of GTVMR-FB was better than that of GTV4D,GTVMR-NAVI,and GTVMR-BH,with statistically significant(Z=-2.675,-2.817,-2.580,P<0.05).Additionally,the OR,DSC,and JAC values of GTVMR-FB and GTVMR-NAVI were better than those of GTVMR-BH,with statistically significant(ZOR=-2.859,-2.817,ZDSC=-2.184,-2.783,ZJAC=-2.385,-2.783,P<0.05).All five plans met clinical dose requirements.Friedman test showed there was no statistically significant differences in dosimetric parameters of target area among different plans(P>0.05).However,compared to the PTV3D plan,the PTVMR-FB,PTVMR-NAVI,and PTVMR-BH plans resulted in lower levels in mean dose(Dmean)of liver and volume parameters(V5,V10,V20,V30)of various doses,with statistically significant differences(Dmean:Z=-2.433,-2.307,-2.807,ZV5=-2.512,-2.433,-2.652,ZV10=-2.433,-2.536,-2.968,ZV20=-2.536,-2.652,-2.807,ZV30=-2.611,-2.652,-2.968,P<0.05).Conclusion:In actually clinical application,MR-NAVI and 4DCT also can be adopted to assist 3DCT to delineate target area besides MR-FB sequence that is conventionally used in MR location,thus can enhance precision of delineation,and optimize radiotherapy plan,and decrease exposure dose of normal liver tissue.

Objective To compare the effectiveness between ultrasound-guided paravertebral block(PVB)and general anesthesia in percutaneous nephrolithotomy(PCNL).Methods Clinical data of 284 patients who underwent PCNL in our hospital from January 2023 to March 2024 were collected.These were 78 cases of PVB(PVB group)and 206 cases of general anesthesia(general anesthesia group).A total of 61 cases in each of the two groups were matched with propensity score,and the operative time,intraoperative fluid infusion volume,postoperative haemoglobin changes,postoperative visual analogue scale(VAS),hospital stay,hospital costs,and incidence of postoperative complications were compared.Results The operations were completed in both groups of patients successfully,with stable vital signs during the operation and no intraoperative anesthetic complications such as bradycardia,respiratory depression,or hypotension.There were significant differences between the two groups in heart rate(HR)before the start of surgery[(66.5±10.4)beats/min vs.(77.5±11.7)beats/min,t=-5.471,P=0.000],HR at the end of surgery[(60.5±8.4)beats/min vs.(71.0±12.3)beats/min,t=-5.472,P=0.000],mean arterial pressure(MAP)before the start of surgery[(97.2±11.9)mm Hg vs.(103.1±12.3)mm Hg,t=-2.694,P=0.008],MAP at the end of surgery[(85.2±8.8)mm Hg vs.(94.3±11.6)mm Hg,t=-4.892,P=0.000],pulse oxygen saturation(SpO2)before the start of surgery[(99.0±1.1)％vs.(99.6±0.6)％,t=-3.347,P=0.001]and SpO2 at the end of surgery[(99.2±1.1)％vs.(99.8±0.4)％,t=-4.122,P=0.000].The operative time was significantly shorter in the PVB group than that in the general anesthesia group[55.0(41.5,75.5)min vs.95.0(65.0,130.0)min,Z=-5.173,P=0.000].The postoperative haemoglobin changes[5(2,11)g/L vs.8(4,11)g/L,Z=-2.099,P=0.036],postoperative VAS score[1(1,1)points vs.1(1,2)points,Z=-3.342,P=0.001],postoperative hospital stay[3(2,3)dvs.4(3,6)d,Z=-6.016,P=0.000]and hospital costs[(14 499.4±2141.0)yuan vs.(19 634.2±3846.8)yuan,t=-9.109,P=0.000]were statistically lower in the PVB group than those in the general anesthesia group.Comparison of intraoperative fluid infusion volume[600(600,600)ml vs.600(600,1100)ml,Z=-1.800,P=0.072],postoperative venting time[1(1,1)d vs.1(1,1)d,Z=-1.045,P=0.296],and phase Ⅰ stone removal rate[88.5％(54/61)vs.82.0％(50/61),x2=1.043,P=0.307]showed no significant differences between the two groups.The incidence of postoperative complications in the PVB group was significantly lower than that in the general anesthesia group[6.6％(4/61)vs.19.7％(12/61),x2=4.604,P=0.032].Conclusion Ultrasound-guided PVB in PCNL maintains stable intraoperative vital signs,reduces operative time and bleeding,alleviates postoperative pain,reduces postoperative complications and postoperative hospital stay,and saves medical costs,having a good safety and efficacy.

Researchers commonly use cyclization recombination enzyme/locus of X-over P1 (Cre/loxP) technology-based conditional gene knockouts of model mice to investigate the functional roles of genes of interest in Sertoli and Leydig cells within the testis. However, the shortcomings of these genetic tools include high costs, lengthy experimental periods, and limited accessibility for researchers. Therefore, exploring alternative gene silencing techniques is of great practical value. In this study, we employed adeno-associated virus (AAV) as a vector for gene silencing in Sertoli and Leydig cells. Our findings demonstrated that AAV serotypes 1, 8, and 9 exhibited high infection efficiency in both types of testis cells. Importantly, we discovered that all three AAV serotypes exhibited exquisite specificity in targeting Sertoli cells via tubular injection while demonstrating remarkable selectivity in targeting Leydig cells via interstitial injection. We achieved cell-specific knockouts of the steroidogenic acute regulatory ( Star ) and luteinizing hormone/human chorionic gonadotropin receptor (Lhcgr) genes in Leydig cells, but not in Sertoli cells, using AAV9-single guide RNA (sgRNA)-mediated gene editing in Rosa26-LSL-Cas9 mice. Knockdown of androgen receptor ( Ar ) gene expression in Sertoli cells of wild-type mice was achieved via tubular injection of AAV9-short hairpin RNA (shRNA)-mediated targeting. Our findings offer technical approaches for investigating gene function in Sertoli and Leydig cells through AAV9-mediated gene silencing.
Animals ; Male ; Leydig Cells/metabolism* ; Mice ; Dependovirus/genetics* ; Sertoli Cells/metabolism* ; Gene Silencing ; Genetic Vectors ; Testis/cytology*

Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures. Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS, but the application of hydrogen has flammable and explosive safety concerns. Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance, thus improving ARDS in patients and animal models. Coral calcium hydrogenation (CCH) is a new solid molecular hydrogen carrier prepared from coral calcium (CC). Whether and how CCH affects acute lung injury in ARDS remains unstudied. In this study, we observed the therapeutic effect of CCH on lipopolysaccharide (LPS) induced acute lung injury in ARDS mice. The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable, demonstrating a significant improvement compared to the untreated ARDS model group. CCH treatment significantly reduced pulmonary hemorrhage and edema, and improved pulmonary function and local microcirculation in ARDS mice. CCH promoted mitochondrial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2 (Trx2), improved lung mitochondrial dysfunction induced by LPS, and reduced oxidative stress damage. The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

Acute respiratory distress syndrome(ARDS)is a common respiratory emergency,but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures.Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS,but the application of hydrogen has flammable and explosive safety concerns.Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance,thus improving ARDS in patients and animal models.Coral calcium hydrogenation(CCH)is a new solid molecular hydrogen carrier prepared from coral calcium(CC).Whether and how CCH affects acute lung injury in ARDS re-mains unstudied.In this study,we observed the therapeutic effect of CCH on lipopolysaccharide(LPS)induced acute lung injury in ARDS mice.The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable,demonstrating a significant improvement compared to the untreated ARDS model group.CCH treatment significantly reduced pulmonary hemorrhage and edema,and improved pulmonary function and local microcirculation in ARDS mice.CCH promoted mitochon-drial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2(Trx2),improved lung mitochondrial dysfunction induced by LPS,and reduced oxidative stress damage.The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.