AIM: To investigate the influence of relevant inflammatory markers in peripheral blood on the progression of neovascular glaucoma(NVG)secondary to diabetic retinopathy(DR)patients.METHODS: Retrospective case-control study. Patients were categorized into two groups based on the presence or absence of NVG: those with proliferative diabetic retinopathy(PDR)alone(PDR group, n=148)and those with NVG secondary to PDR(NVG secondary to PDR group, n=142). Peripheral blood inflammatory markers were evaluated, including white blood cell-related indices, neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio(PLR), monocyte-to-lymphocyte ratio(MLR), and systemic immune-inflammation index(SII). The distinctions in peripheral blood inflammatory markers between the two groups of patients and their relationships with NVG secondary to PDR were analyzed.RESULTS:No statistically significant differences were observed in basic characteristics between the two groups, confirming their comparability. However, significant differences were found in eosinophil percentage and MLR between the PDR group and the NVG secondary to PDR group(all P<0.05), with both values being significantly higher in the NVG secondary to PDR group. Multivariate Logistic regression analysis revealed that the eosinophil percentage and the MLR were factors influencing the development of patients with NVG secondary to PDR.CONCLUSION: Eosinophil percentage and MLR may be associated with the progression of PDR to NVG, and could serve as potential predictive markers for NVG development in PDR patients.

BackgroundCognitive function is closely related to an individual's quality of life and social functioning， with approximately 20%~35% of patients with depressive disorder experiencing some degree of cognitive impairment even after clinical symptom remission. Existing evidence suggests that tACS can improve specific cognitive domains， such as memory function， while its effects on other cognitive dimensions， such as executive functioning， attention， and information processing speed， remain unclear. ObjectiveTo explore the effects of tACS on the multidimensional cognitive functions and emotional problems of patients with depressive disorder， thus to provide references for the treatment of depressive disorder. MethodsForty-nine patients with depressive disorder who were hospitalized in the Fourth People's Hospital of Wuhu from November 2022 to October 2024 and met the diagnostic criteria for depressive disorder outlined in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）， were selected as study participants. Subjects were randomly divided into study group （n=23） and control group （n=26） based on Microsoft Excel. Both groups received sertraline treatment. The initial dose was 50 mg/day， which gradually titrated upward based on individual variability， drug tolerance， and therapeutic response， with a maintenance dose ranging from 100 to 200 mg/day. In addition， the study group underwent tACS therapy for 4 weeks， with 5 sessions per week， each lasting 20 minutes. The control group received sham stimulation， in which the stimulus was interrupted after the first 30 seconds. At baseline， the 4^th week， and the 12^th week of treatment， patients were assessed using the Hamilton Depression Scale-17 item （HAMD-17）， Hamilton Anxiety Scale （HAMA）， and MATRICS Consensus Cognitive Battery （MCCB）. ResultsRepeated measures analysis of variance indicated that both the time effect and the time×group interaction effect for HAMD-17 scores were statistically significant between the two groups （F=260.437， 25.309， P<0.01）. At week 12 of treatment， the HAMD-17 score in the study group was lower than that in the control group （t=4.236， P<0.01）. For HAMA scores， the time effect， group effect， and time×group interaction effect were all statistically significant between the two groups （F=248.082， 4.506， 9.500， P<0.05 or 0.01）. At weeks 4 and 12， study group reported lower HAMA scores compared with control group （t=4.580， 2.608， P<0.05 or 0.01）. Regarding the MCCB scores for attention/vigilance， verbal learning， and overall composite， the time effect， group effect， and time×group interaction effect were all statistically significant between the two groups （F=70.331， 27.882， 51.679， 5.560， 10.948， 7.860， 8.490， 3.874， 5.025， P<0.05 or 0.01）. After intervention， the study group showed significantly higher MCCB scores for attention/vigilance， verbal learning， and overall composite at both week 4 （t=-2.149， -3.530， -2.740， P<0.05） and week 12 （t=-3.534， -3.576， -3.838， P<0.01） when compared to the control group. ConclusionThe combined tACS and sertraline therapy may demonstrate superior efficacy to pharmacotherapy alone in the short term for improving attention/vigilance， verbal learning， overall cognitive function， and anxiety symptoms in patients with depressive disorders. Based on the 12-week outcomes， the combined tACS and sertraline therapy not only sustaine its previously observed advantages in improving cognitive domains and anxiety symptoms， but also demonstrate potentially superior efficacy over monotherapy in alleviating depressive symptoms. ［Fund by Clinical Medical Research Transformation Special Project of Anhui Province （number， 202204295107020065）］

Objective: To explore the efficacy of transcystoscopic holmium laser sieve-shaped fenestration in the treatment of ureteral cysts in children. Methods: The clinical data of 41 children with ureteral cysts treated in our hospital during Jan.2019 and Dec.2023 were retrospectively analyzed.All children received this surgery.The perioperative indicators and postoperative outcomes were recorded. Results: All operations were successful, the average operation time being (32.20±11.49) min.During the 12-month follow-up, the cysts were reduced or the obstructive symptoms were relieved in 31 cases, and the cysts completely disappeared in 6 cases.Vesicoureteral reflux (VUR) developed in 4 cases, 1 of which had grade Ⅱ VUR with no obvious symptoms and received conservative treatment.Repeated urinary tract infections developed in 2 cases; obstructive symptoms remained unchanged in 1 case; these 3 cases received vesicoureteral replantation.Two days before operation and 3 months after operation, the ureter diameter was (9.95±2.38) mm and (7.41±3.39) mm (t=3.16, P＜0.05), the anteroposterior diameter of the renal pelvis was (13.32±2.63) mm and (9.07±3.02) mm (t=6.86, P＜0.01). Conclusion: Transcystoscopic holmium laser sieve-shaped fenestration for children with ureteral cysts has good efficacy, little trauma and few complications.It can quickly relieve obstructive symptoms and can be used as the initial treatment of ureteral cysts.

Sexual dimorphism in the brain underlies behavioral differences between sexes. The bed nucleus of the stria terminalis (BNST) is a complex nucleus that differs between males and females, but the sexual dimorphism in cytoarchitecture and the connectome of its oval subdivision (ovBNST) remains largely unexplored. By combining snRNA-seq and transgenic labeling, we found a higher density of ovBNST proenkephalin (ovBNST^PENK) neurons in male than female mice. Anatomically, we virally mapped the efferents and afferents of ovBNST^PENK neurons, finding reciprocally dimorphic connections with the hypothalamus and striatum. Gene enrichment analysis suggests that ovBNST^PENK neurons are modulated by the upstream dopamine pathway. Functionally, by applying caspase-3-mediated depletion of ovBNST^PENK neurons, we found that loss of these neurons enhanced locomotor activity in male but not female mice, without altering the anxiety-like phenotypes in either sex. Our study may pave the way for a better understanding of the anatomical and functional profiles of ovBNST^PENK neurons from a sexually dimorphic perspective.
Animals ; Male ; Female ; Septal Nuclei/physiology* ; Sex Characteristics ; Neurons/physiology* ; Enkephalins/metabolism* ; Mice ; Mice, Transgenic ; Protein Precursors/metabolism* ; Mice, Inbred C57BL ; Neural Pathways/physiology*

Frostbite is the most common cold injury and is caused by both immediate cold-induced cell death and the gradual development of localized inflammation and tissue ischemia. Delayed healing of frostbite often leads to scar formation, which not only causes psychological distress but also tends to result in the development of secondary malignant tumors. Therefore, a rapid healing method for frostbite wounds is urgently needed. Herein, we used a mouse skin model of frostbite injury to evaluate the recovery process after frostbite. Moreover, single-cell transcriptomics was used to determine the patterns of changes in monocytes, macrophages, epidermal cells, and fibroblasts during frostbite. Most importantly, human-induced pluripotent stem cell (hiPSC)-derived skin organoids combined with gelatin-hydrogel were constructed for the treatment of frostbite. The results showed that skin organoid treatment significantly accelerated wound healing by reducing early inflammation after frostbite and increasing the proportions of epidermal stem cells. Moreover, in the later stage of wound healing, skin organoids reduced the overall proportions of fibroblasts, significantly reduced fibroblast-to-myofibroblast transition by regulating the integrin α5β1-FAK pathway, and remodeled the extracellular matrix (ECM) through degradation and reassembly mechanisms, facilitating the restoration of physiological ECM and reducing the abundance of ECM associated with abnormal scar formation. These results highlight the potential application of organoids for promoting the reversal of frostbite-related injury and the recovery of skin functions. This study provides a new therapeutic alternative for patients suffering from disfigurement and skin dysfunction caused by frostbite.
Animals ; Organoids/metabolism* ; Mice ; Humans ; Wound Healing ; Frostbite/metabolism* ; Skin/pathology* ; Induced Pluripotent Stem Cells/cytology* ; Cicatrix/pathology* ; Fibroblasts/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Extracellular Matrix/metabolism* ; Male

L-citrulline is a nonprotein amino acid that plays an important role in human health and has great market demand. Although microbial cell factories have been widely used for biosynthesis, there are still challenges such as genetic instability and low efficiency in the biosynthesis of L-citrulline. In this study, an efficient, plasmid-free, non-inducible L-citrulline-producing strain of Escherichia coli BL21(DE3) was engineered by combined strategies. Firstly, a chassis strain capable of synthesizing L-citrulline was constructed by block of L-citrulline degradation and removal of feedback inhibition, with the L-citrulline titer of 0.43 g/L. Secondly, a push-pull-restrain strategy was employed to enhance the L-citrulline biosynthesis, which realized the L-citrulline titer of 6.0 g/L. Thirdly, the NADPH synthesis and L-citrulline transport were strengthened to promote the synthesis efficiency, which achieved the L-citrulline titer of 11.6 g/L. Finally, fed-batch fermentation was performed with the engineered strain in a 3 L fermenter, in which the L-citrulline titer reached 44.9 g/L. This study lays the foundation for the industrial production of L-citrulline and provides insights for the modification of other amino acid metabolic networks.
Citrulline/biosynthesis* ; Escherichia coli/genetics* ; Metabolic Engineering/methods* ; Fermentation ; NADP/biosynthesis*

Objective To study the effects of monomers in Lagotis brachystachya Maxim including quercetin,echinacoside,and apigenin on the p38MAPK/JNK,TLR4/MyD88/NF-κB,and NLRP3 signaling through establishing a rat model of chronic alcoholic liver injury combined with gouty arthritis,and to explore the mechanism of the above-mentioned monomers in the treatment of chronic alcoholic liver injury combined with gouty arthritis.Methods Eighty rats were randomly divided into normal group,model group,bifendate group(100 mg·kg-1),colchicine group(0.3 mg·kg-1),and different dose groups of quercetin(50,25 mg·kg-1),echinacoside(50,25 mg·kg-1),and apigenin(50,25 mg·kg-1).The rats were administered at a dose of 10 mL·kg-1 per day in the morning and administered with 56-degree Red Star Erguotou at a dose of 4 mL·kg-1 in the afternoon,with gradual increasement of 2 mL·kg-1 per week until a final dose of 10 mL·kg-1.The rats were continuously fed by gavage for 8 weeks.Gouty arthritis model was induced at the 53th day of alcohol-based feeding.Toe volume was measured at difference time.At the end of the 8th week,blood was collected after the last administration.Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP)levels,total cholesterol(TC)and triglycerides(TG)were measured.Enzyme-Linked Immunosorbent Assay(ELISA)was used to detect interleukin-1β(IL-1β)in rat serum.Western Blot was used to detect the expression of p38 mitogen-activated protein kinase(p38MAPK),phosphorylated p38MAPK(p-p38MAPK),c-Jun N-terminal kinase(JNK),phosphorylated JNK(p-JNK),Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),nuclear factor-κB(NF-κB),phosphorylated NF-κB(p-NF-κB),and NOD-like receptor protein domain containing 3(NLRP3)in liver and synovial tissues.Results Compared with the normal group,the toe swelling degree in the model group was significantly increased at difference time(P＜0.05,P＜0.01).The levels of ALT,AST,ALP,TC,TG,and IL-1β in serum were significantly increased(P＜0.01).The protein expression levels of p-p38MAPK,p-JNK,MyD88,p-NF-κB,TLR4,and NLRP3 in liver and synovial tissues were all increased to varying degrees(P＜0.01).Compared with the model group,the toe swelling degree in all treatment groups significantly decreased after 24 hours(P＜0.01).The levels of ALT and TC in the bifendate group and different dose groups of monomers decreased to varying degrees(P＜0.05,P＜0.01).Except for the low dose group of echinacoside,the levels of AST and ALP in other treatment groups decreased to varying degrees(P＜0.01).Except for the high dose group of quercetin,the levels of TG in other treatment groups decreased to varying degrees(P＜0.01).The protein expression levels of p-p38MAPK,p-JNK,MyD88,p-NF-κB,TLR4,and NLRP3 in liver and synovial tissues of rats in all treatment groups were down-regulated(P＜0.05,P＜0.01).Conclusion The monomers in Lagotis brachystachya Maxim show certain therapeutic effects of treating different diseases with same treatment on the rat model of chronic alcoholic liver injury combined with gouty arthritis,and their therapeutic effects may be mediated through p38MAPK/JNK,TLR4/MyD88/NF-κB,and NLRP3 signaling pathways.

Objective To assess the influences of self-and interviewer-administered methods on the scores of anxiety and depression questionnaires among the patients with sports injuries.Methods A total of 532 participants with sports injuries treated in the Sports Medicine Center of West China Hospital,Sichuan University from November 2022 to May 2023 were included.They were randomly assigned to either the interviewer-administered group(n=270)or the self-administered group(n=262)to complete the generalized anxiety disorder(GAD-7)and the patient health questionnaire(PHQ-9)scales.The total scores and prevalence rates of anxiety and depres-sion were compared between the two groups.Results There was no statistically significant difference in gender,occupation,or surgical site between the two groups(all P＞0.05).The self-administered group had higher scores of GAD-7 and PHQ-9 scales than the interviewer-administered group(P＜0.001,P＜0.001).A greater proportion of participants in the self-administered group than in the interview-administered group met the criteria for mild to moderate anxiety and depression(P＜0.001,P=0.002).The prevalence rates of moderate to se-vere anxiety(GAD-7 ≥10)and depression(PHQ-9 ≥10)showed no statistically significant difference between the two groups(P=0.761,P=0.086).Conclusion This study demonstrates that the participants in the self-administered group are more likely to report mild to moderate symptoms of anxiety and depression than those in the interviewer-administered group.

Objective To observe the value of deep learning(DL)models for automatic classification of echocardiographic views.Methods Totally 100 patients after heart transplantation were retrospectively enrolled and divided into training set,validation set and test set at a ratio of 7∶2∶1.ResNet18,ResNet34,Swin Transformer and Swin Transformer V2 models were established based on 2D apical two chamber view,2D apical three chamber view,2D apical four chamber view,2D subcostal view,parasternal long-axis view of left ventricle,short-axis view of great arteries,short-axis view of apex of left ventricle,short-axis view of papillary muscle of left ventricle,short-axis view of mitral valve of left ventricle,also 3D and CDFI views of echocardiography.The accuracy,precision,recall,F1 score and confusion matrix were used to evaluate the performance of each model for automatically classifying echocardiographic views.The interactive interface was designed based on Qt Designer software and deployed on the desktop.Results The performance of models for automatically classifying echocardiographic views in test set were all good,with relatively poor performance for 2D short-axis view of left ventricle and superior performance for 3D and CDFI views.Swin Transformer V2 was the optimal model for automatically classifying echocardiographic views,with high accuracy,precision,recall and F1 score was 92.56％,89.01％,89.97％and 89.31％,respectively,which also had the highest diagonal value in confusion matrix and showed the best classification effect on various views in t-SNE figure.Conclusion DL model had good performance for automatically classifying echocardiographic views,especially Swin Transformer V2 model had the best performance.Using interactive classification interface could improve the interpretability of prediction results to some extent.

Objective:To investigate the effect of intraoperative protection of the supraclavicular nerve on the healing of clavicular 1/3 mid-shaft fracture.Methods:A retrospective study was conducted to analyze the 83 patients who had been treated for clavicular 1/3 mid-shaft fractures at Department of Orthopaedics, The First Central Hospital of Baoding from June 2021 to March 2022. There were 57 males and 26 females with an age of (48.1±12.8) years. The patients were divided into 2 groups according to whether the supraclavicular nerve was protected or not during operation. There were 39 cases in the observation group (the supraclavicular nerve was protected during operation) and 44 cases in the control group (the supraclavicular nerve was not protected during operation). The incision length, operation time, intraoperative blood loss, hospital stay, visual analogue scale (VAS) pain scores before operation and 3, 6 and 12 months after operation, fracture healing at 3, 6 and 12 months after operation, and postoperative complications were recorded and compared between the 2 groups. Additionally, the number of microvessels in the middle clavicle was recorded and compared between the affected and healthy sides in 8 patients in the observation group at 6 weeks after operation.Results:There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). The operation time for the observation group [(72.2±5.4) min] was significantly longer than that for the control group [(61.1±4.7) min]. The VAS scores at postoperative 3 and 6 months for the observation group [2.7 (2.4, 3.1) and 2.1 (1.9, 2.6) points] were significantly lower than those for the control group [3.5 (3.2, 3.8) and 2.7 (2.4, 2.9) points] ( P<0.05). The fracture healing rates at postoperative 3 and 6 months in the observation group [97.4% (38/39) and 100% (39/39)] were significantly higher than those in the control group [81.8% (36/44) and 86.4% (38/44)] ( P<0.05), but there was no significant difference in the fracture healing between the 2 groups at 12 months after operation ( P>0.05). At 6 weeks after operation, the number of microvessels in the middle clavicle was respectively 85.3±0.7 and 87.1±0.8 in the 8 patients in the observation group, showing no significant difference ( P>0.05). After operation, delayed incision healing occurred in 3 cases in the observation group and in 4 cases in the control group, and abnormal sensation of the skin around the incision occurred in 9 cases in the observation group and in 26 cases in the control group, showing a significant difference between the 2 groups ( P<0.05). Conclusion:Intraoperative protection of the supra-clavicular nerve is beneficial for reduction of early postoperative pain and improvement of early fracture healing, and may have a positive effect on the postoperative reconstruction of microvascular network.