The high pressure generated from urinary tract obstruction can cause damage to the tissues and cells of the urinary tract. Persistent damage can induce urinary tract fibrosis, ultimately resulting in the loss of urinary tract function and severe clinical problems. In recent years, the role of a novel mechanosensitive ion channel in urinary tract fibrosis, Piezo1, has drawn due attention. This review systematically summarizes the mechanisms of Piezo1. In upper urinary tract fibrosis, Piezo1 participates in fibrotic process through the Calcium-Calpain2-integrin β1-adhesion protein pathway and Piezo1-p38MAPK-YAP signaling pathway. In lower urinary tract fibrosis, Piezo1 mediates bladder fibrosis via the YAP1 and TGF-β1/Smad pathways, and may contribute to prostate cancer-associated urethral obstruction through the Akt/mTOR signaling pathway. This study elucidates the critical roles of Piezo1 in urinary tract fibrosis, providing a theoretical foundation for developing novel Piezo1targeted therapeutic strategies. Future research can leverage advanced technologies such as microfluidic organ-on-a-chip system to explore the precise regulatory mechanisms of Piezo1, thus offering new insights for the clinical management of urinary stricture diseases.

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

Objective:To construct a full-length infectious clone of enterovirus D68（EV-D68）expressing enhanced green fluorescent protein（EGFP）by reverse genetics in order to provide an efficient tool for studying the biological characteristics and screening antiviral drugs for EV-D68.Methods:Gene synthesis and overlap PCR techniques were used to construct the full-length clone plasmid pUC57-EV-D68 of EV-D68. The full-length viral sequence was then transferred into the pCAGGS plasmid to obtain the pCAGGS-EV-D68 plasmid. The EGFP gene was amplified and inserted into the pCAGGS-EV-D68 plasmid to construct the pCAGGS-EGFP-EV-D68 plasmid. Then，the two constructed plasmids were transfected into human rhabdomyosarcoma（RD）cells to rescue recombinant viruses RV-EV-D68 and RV-EGFP-EV-D68. The rescued viruses were identified using PCR，Western blot，and immunofluorescence techniques. The antiviral effect of doxycycline was evaluated using the rescued RV-EGFP-EV-D68. Statistical analysis was performed using the two independent samples t-test. Results:The recombinant virus RV-EGFP-EV-D68 capable of expressing EGFP was successfully rescued. Even after 15 serial passages，the virus retained EGFP expression with no significant difference in viral titers compared to the parental virus，indicating its stable passage in RD cells. Besides，the rescued strains exhibited similar replication characteristics to the parental virus. While at 24 and 36 h after infection，the titers of the rescued strains were significantly lower than that of the parental strain（both P<0.05）. This study demonstrated that doxycycline significantly reduced the fluorescence intensity of RV-EGFP-EV-D68-infected RD cells（ P<0.01）. Meanwhile，a negative correlation was observed between the doxycycline concentration and the fluorescence intensity，indicating that the rescued virus could be used for antiviral drug evaluation. Conclusions:This study successfully constructs an infectious clone of EV-D68 expressing EGFP. The rescued recombinant virus RV-EGFP-EV-D68 has been verified to be applicable for the evaluation of antiviral drugs.

Ulcerative colitis(UC)is an inflammatory disease with unclear etiology and pathogenesis.In recent years,with the continuous in-depth research on the pathology of UC,it has been discovered that there exists a new form of cell death in the pathological process of UC,namely ferroptosis.A series of pathological changes closely related to ferroptosis in the pathological tissues of UC patients.This article aims to investigate the role of ferroptosis in the pathogenesis of UC,and introduce the relationship between UC and ferroptosis from the aspects of inflammation,intestinal mucosal barrier and intestinal flora,as well as the recent research progress in this field.

Objective To investigate the clinical effect of Sansheng Decoction combined with Chinese herbal medicine fumigation on patients with lumbar disc herniation after percutaneous endoscopic lumbar discectomy(PELD).Methods Sixty-six patients with lumbar disc herniation of liver and kidney deficiency complicated with blood-stasis syndrome who were planning to take PELD were randomly divided into control group and treatment group,33 cases in each group.Both groups were treated with PELD.After PELD,the control group was routinely treated with anti-inflammatory,analgesic,neurotrophic and anti-infective treatment.On the basis of treatment for the control group,the treatment group was treated with modified Sansheng Decoction(composed of Eucommiae Cortex,Atractylodis Macrocephalae Rhizoma,Corni Fructus,Notoginseng Radix et Rhizoma,Acanthopanacis Cortex,etc.)orally combined with Chinese herbal medicine fumigation(consists of Achyranthis Bidentatae Radix,Angelicae Sinensis Radix,Spatholobi Caulis,Taxilli Herba,Kadsurae Coccineae Radix,etc.).Before and after treatment,the changes of Visual Analogue Scale(VAS)score of lumbar pain,Japanese Orthopedic Association(JOA)score and Oswestry Disability Index(ODI)score of lumbar function in the two groups were observed.Moreover,the postoperative complications and recurrence in the two groups were compared.Results(1)After 1 month,3 months and 6 months of treatment,except that there was no significant difference between the post-6-month VAS scores and the post-3-month VAS scores in the control group(P＞0.05),the VAS scores of lumbar pain in the two groups were all significantly lowered compared with those at the previous observation time point(P＜0.05),and the decrease in the treatment group after 1 month,3 months and 6 months of treatment was significantly superior to that in the control group(P＜0.05 or P＜0.01).(2)After 1 month,3 months and 6 months of treatment,except that the JOA scores of lumbar function in the control group after 6 months of treatment did not differ from those after 3 months of treatment(P＞0.05),the JOA scores of the two groups were all significantly increased compared with those at the previous observation time point(P＜0.05),and the increase in the treatment group after 1 month,3 months and 6 months of treatment was significantly superior to that in the control group(P＜0.01).(3)After 1 month,3 months and 6 months of treatment,the ODI score of lumbar function in the two groups were all significantly decreased compared with those at the previous observation time point(P＜0.05),and the decrease in the treatment group after 1 month,3 months and 6 months of treatment was significantly superior to that in the control group(P＜0.01).(4)In terms of the complications,no injury of nerve root and dura mater or other adverse reactions occurred in the two groups after operation.(5)During the trial,there was one patient lost from each group,and the remaining patients were followed up for 3 years.Within the 3 years,4 patients in the control group relapsed,and one patient in the treatment group relapsed,and all of the relapsed patients did not receive reoperation.Conclusion Sansheng Decoction combined with Chinese herbal medicine fumigation exerts certain effect in the treatment of patients with liver and kidney deficiency complicated with blood-stasis syndrome after PELD for lumbar disc herniation.The therapy can effectively relieve postoperative pain and promote the recovery of postoperative lumbar function.

Objective To propose a lead attention network-based ST-T change recognition algorithm to detect ECG ST-T changes accurately.Methods Firstly,heartbeat signals were extracted through R-wave localization,and a 12-lead heartbeat matrix was generated by correlation-based screening and merging to realize data augmentation.Secondly,a lead attention module was constructed by combining depthwise convolution(DWConv)with the channel attention squeeze-and-excitation block(SE-block)structure to perceive the differences in ST-T status among electrocardiogram leads.Thirdly,the mapping output by two independent attention modules was fused and splicing with the original signal residual was carried out,so that attention information extraction and original information transfer were enhanced effectively.Finally,SE-ResNet was used as the backbone network to extract signal features to complete the classification and identification of ST-T changes.To validate the recognition performance of the proposed algorithm for ST-T changes in ECG,the 12-lead ECG data of 97 472 patients containing different ECG rhythms were collected for ablation and comparison experiments at the First Affiliated Hospital of Army Medical University.Results The proposed algorithm achieved an AUC of 0.965 with a sensitivity of 90.51%,specificity of 90.23%,positive predictive value of 89.24%and overall accuracy of 90.36%on an independent test set.Comparative analysis demonstrated superior performance to four benchmark architectures,including VGG16,ResNet18,MobileNetV3-Small and ShuffleNet,in terms of both classification accuracy and computational efficiency.Conclusion The algorithm designed can accurately detect ST-T changes and can be used for wearable ECG automatic analysis to assist in the early warning of cardiovascular diseases in both acute and chronic patients and highland residents.[Chinese Medical Equipment Journal,2025,46(7):1-11]

Objective To propose a lead attention network-based ST-T change recognition algorithm to detect ECG ST-T changes accurately.Methods Firstly,heartbeat signals were extracted through R-wave localization,and a 12-lead heartbeat matrix was generated by correlation-based screening and merging to realize data augmentation.Secondly,a lead attention module was constructed by combining depthwise convolution(DWConv)with the channel attention squeeze-and-excitation block(SE-block)structure to perceive the differences in ST-T status among electrocardiogram leads.Thirdly,the mapping output by two independent attention modules was fused and splicing with the original signal residual was carried out,so that attention information extraction and original information transfer were enhanced effectively.Finally,SE-ResNet was used as the backbone network to extract signal features to complete the classification and identification of ST-T changes.To validate the recognition performance of the proposed algorithm for ST-T changes in ECG,the 12-lead ECG data of 97 472 patients containing different ECG rhythms were collected for ablation and comparison experiments at the First Affiliated Hospital of Army Medical University.Results The proposed algorithm achieved an AUC of 0.965 with a sensitivity of 90.51%,specificity of 90.23%,positive predictive value of 89.24%and overall accuracy of 90.36%on an independent test set.Comparative analysis demonstrated superior performance to four benchmark architectures,including VGG16,ResNet18,MobileNetV3-Small and ShuffleNet,in terms of both classification accuracy and computational efficiency.Conclusion The algorithm designed can accurately detect ST-T changes and can be used for wearable ECG automatic analysis to assist in the early warning of cardiovascular diseases in both acute and chronic patients and highland residents.[Chinese Medical Equipment Journal,2025,46(7):1-11]

Objective:To construct a full-length infectious clone of enterovirus D68（EV-D68）expressing enhanced green fluorescent protein（EGFP）by reverse genetics in order to provide an efficient tool for studying the biological characteristics and screening antiviral drugs for EV-D68.Methods:Gene synthesis and overlap PCR techniques were used to construct the full-length clone plasmid pUC57-EV-D68 of EV-D68. The full-length viral sequence was then transferred into the pCAGGS plasmid to obtain the pCAGGS-EV-D68 plasmid. The EGFP gene was amplified and inserted into the pCAGGS-EV-D68 plasmid to construct the pCAGGS-EGFP-EV-D68 plasmid. Then，the two constructed plasmids were transfected into human rhabdomyosarcoma（RD）cells to rescue recombinant viruses RV-EV-D68 and RV-EGFP-EV-D68. The rescued viruses were identified using PCR，Western blot，and immunofluorescence techniques. The antiviral effect of doxycycline was evaluated using the rescued RV-EGFP-EV-D68. Statistical analysis was performed using the two independent samples t-test. Results:The recombinant virus RV-EGFP-EV-D68 capable of expressing EGFP was successfully rescued. Even after 15 serial passages，the virus retained EGFP expression with no significant difference in viral titers compared to the parental virus，indicating its stable passage in RD cells. Besides，the rescued strains exhibited similar replication characteristics to the parental virus. While at 24 and 36 h after infection，the titers of the rescued strains were significantly lower than that of the parental strain（both P<0.05）. This study demonstrated that doxycycline significantly reduced the fluorescence intensity of RV-EGFP-EV-D68-infected RD cells（ P<0.01）. Meanwhile，a negative correlation was observed between the doxycycline concentration and the fluorescence intensity，indicating that the rescued virus could be used for antiviral drug evaluation. Conclusions:This study successfully constructs an infectious clone of EV-D68 expressing EGFP. The rescued recombinant virus RV-EGFP-EV-D68 has been verified to be applicable for the evaluation of antiviral drugs.

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin ( 1) and variecolactone ( 2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues ( 5- 7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

Sarcopenia, which is characterized by progressive and generalized loss of skeletal muscle mass and strength, has been well described to be associated with numerous poor postoperative outcomes, such as increased perioperative mortality, postoperative sepsis, prolonged length of stay, increased cost of care, decreased functional outcome, and poorer oncological outcomes in cancer surgery. Multimodal prehabilitation, as a concept that involves boosting and optimizing the preoperative condition of a patient prior to the upcoming stressors of a surgical procedure, has the purported benefits of reversing the effects of sarcopenia, shortening hospitalization, improving the rate of return to bowel activity, reducing the costs of hospitalization, and improving quality of life. This review aims to present the current literature surrounding the concept of sarcopenia, its implications pertaining to colorectal cancer and surgery, a summary of studied multimodal prehabilitation interventions, and potential future advances in the management of sarcopenia.