BACKGROUND:Mitochondrial dysfunction is a key mechanism underlying the pathogenesis and progression of diabetic cystopathy.Recent studies have suggested that drugs targeting mitochondrial metabolism,oxidative stress,and apoptosis pathways can inhibit bladder tissue degeneration,offering novel therapeutic directions for diabetic cystopathy.OBJECTIVE:To explore the association between mitochondrial abnormalities and diabetic cystopathy and to summarize the mechanisms of pharmacological interventions targeting mitochondrial function.METHODS:The key words are"mitochondria,diabetes,diabetic cystopathy,diabetic bladder dysfunction,detrusor,urothelium,neuron,peripheral nerves"in Chinese and English.Relevant literature was retrieved from CNKI,WanFang,PubMed,and Web of Science.Selected articles were systematically screened and analyzed.RESULTS AND CONCLUSION:During the progression of diabetic cystopathy,mitochondria in detrusor muscle,urothelium,and peripheral nerve cells exhibit alterations in characterization,activity,function,and behavior.Under diabetic conditions,mitochondrial damage leads to increased reactive oxygen species production,increased cytochrome C release,reduced Bcl-2/Bax ratio,enhanced nuclear translocation of apoptosis-inducing factors,and activation of the poly(ADP-ribose)polymerase/c-Jun N-terminal kinase/mitochondrial apoptosis pathway.Mitochondria also act as damage-associated molecular patterns to regulate NLRP3,triggering inflammatory responses.Disrupted mitochondrial energy metabolism involves AMP-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator-1α signaling axis-mediated phenotypic changes,decreased levels of respiratory chain complexes Ⅰ,Ⅱ,andⅣ,impaired oxidative phosphorylation,inhibited tricarboxylic acid cycle,and reduced mitochondrial spare respiratory capacity.Novel therapeutic agents or formulations can ameliorate diabetic cystopathy by alleviating oxidative stress,exerting anti-inflammatory effects,and modulating energy-sensing pathways to restore mitochondrial function.Although mitochondrial roles in other diabetic complications have been extensively studied,research on their involvement in diabetic cystopathy remains insufficient and warrants further exploration.

BACKGROUND:Mitochondrial dysfunction is a key mechanism underlying the pathogenesis and progression of diabetic cystopathy.Recent studies have suggested that drugs targeting mitochondrial metabolism,oxidative stress,and apoptosis pathways can inhibit bladder tissue degeneration,offering novel therapeutic directions for diabetic cystopathy.OBJECTIVE:To explore the association between mitochondrial abnormalities and diabetic cystopathy and to summarize the mechanisms of pharmacological interventions targeting mitochondrial function.METHODS:The key words are"mitochondria,diabetes,diabetic cystopathy,diabetic bladder dysfunction,detrusor,urothelium,neuron,peripheral nerves"in Chinese and English.Relevant literature was retrieved from CNKI,WanFang,PubMed,and Web of Science.Selected articles were systematically screened and analyzed.RESULTS AND CONCLUSION:During the progression of diabetic cystopathy,mitochondria in detrusor muscle,urothelium,and peripheral nerve cells exhibit alterations in characterization,activity,function,and behavior.Under diabetic conditions,mitochondrial damage leads to increased reactive oxygen species production,increased cytochrome C release,reduced Bcl-2/Bax ratio,enhanced nuclear translocation of apoptosis-inducing factors,and activation of the poly(ADP-ribose)polymerase/c-Jun N-terminal kinase/mitochondrial apoptosis pathway.Mitochondria also act as damage-associated molecular patterns to regulate NLRP3,triggering inflammatory responses.Disrupted mitochondrial energy metabolism involves AMP-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator-1α signaling axis-mediated phenotypic changes,decreased levels of respiratory chain complexes Ⅰ,Ⅱ,andⅣ,impaired oxidative phosphorylation,inhibited tricarboxylic acid cycle,and reduced mitochondrial spare respiratory capacity.Novel therapeutic agents or formulations can ameliorate diabetic cystopathy by alleviating oxidative stress,exerting anti-inflammatory effects,and modulating energy-sensing pathways to restore mitochondrial function.Although mitochondrial roles in other diabetic complications have been extensively studied,research on their involvement in diabetic cystopathy remains insufficient and warrants further exploration.

As research delves deeper into the mechanisms of tumor immune responses,studies reveal the importance of microbial com-munities within the tumor microenvironment in tumor progression and their interactions with the host immune system.Intratumoral micro-biota could influence the tumor microenvironment,thereby promoting or inhibiting tumor growth and development.Despite this import-ance,the specific role of intratumoral microbiota impacting cancer immunotherapeutic efficacy remains largely unexplored.A deeper under-standing of the characteristics and biological functions of tumor-specific microbiota heralds a potential revolutionary innovation in cancer treatment.In this review,we introduce the discovery and sources of intratumoral microbiota,also addressing its composition,and discuss tumor tissue characteristics.Moreover,we briefly review the history of cancer immunotherapy development with a particular focus on the research progress concerning the impact of intratumoral microbiota on cancer immunotherapy.Furthermore,we explore emerging strategies that combine targeting intratumoral microbiota with immunotherapy to enhance immune efficacy,inhibit tumor progression,and improve cure rates,anticipating that this approach could represent a new direction for enhancing treatment outcomes and prospects.

Objective:To investigate the clinical features and prognosis of testicular relapse in pediatric acute lymphoblastic leukemia (ALL).Methods:Clinical data including the age, time from initial diagnosis to recurrence, relapse site, and therapeutic effect of 37 pediatric ALL with testicular relapse and treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between November 2011 and December 2022 were analyzed retrospectively. Patients were grouped according to different clinical data. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis.Results:The age at initial diagnosis of 37 pediatric testicular relapse patients was (5±3) years and the time from initial diagnosis to testicular recurrence was (37±15) months. The follow-up time was 43 (22, 56) months. Twenty-three patients (62%) were isolated testis relapse. The 5-year OS rate and EFS rate of the 37 relapsed children were (60±9) % and (50±9) % respectively. Univariate analysis showed that the 2-year EFS rate in the group of patients with time from initial diagnosis to testicular recurrence >28 months was significantly higher than those ≤28 months ((69±10)% vs. (11±11)%, P<0.05), 2-year EFS rate of the isolated testicular relapse group was significantly higher than combined relapse group ((66±11)% vs. (20±13) %, P<0.05), 2-year EFS rate of chimeric antigen receptor T (CAR-T) cell treatment after relapse group was significantly higher than without CAR-T cell treatment after relapse group ((78±10)% vs. (15±10)%, P<0.05). ETV6-RUNX1 was the most common genetic aberration in testicular relapsed ALL (38%, 14/37). The 4-year OS and EFS rate of patients with ETV6-RUNX1 positive were (80±13) % and (64±15) %, respectively. Multivariate analysis identified relapse occurred≤28 months after first diagnosis ( HR=3.09, 95% CI 1.10-8.72), combined relapse ( HR=4.26, 95% CI 1.34-13.52) and CAR-T cell therapy after relapse ( HR=0.15,95% CI 0.05-0.51) were independent prognostic factors for 2-year EFS rate (all P<0.05). Conclusions:The outcome of testicular relapse in pediatric ALL was poor. They mainly occurred 3 years after initial diagnosis. ETV6-RUNX1 is the most common abnormal gene.Patients with ETV6-RUNX1 positive often have a favorable outcome. Early relapse and combined relapse indicate unfavorable prognosis, while CAR-T cell therapy could significantly improve the survival rate of children with testicular recurrence.

Objective To detect the expression profile of heme oxygenase-1(HO-1)during the process of wound repair in radiation-wound combined injury(R-W-CI),and evaluate its wound healing improving effects of R-W-CI by HO-1 knockdown with siRNA.Methods A total of 36 male C57BL/6J mice(8 weeks old)were randomly and equally divided into a simple skin wound group(W group)and a skin wound group combined with whole-body radiation(6 Gy)injury(R-W-CI group).During the wound healing process,the wounds were photographed and recorded,and the residual areas were quantified by Image J.Wound tissues were sampled and stained with HE staining for pathological and histological observation,and the damage to the hematopoietic system was assessed by dynamic examination of the peripheral blood.The expression and changes of HO-1 in wound tissues were detected by q-PCR and Western blotting.Then,26 male C57BL/6J mice(8 weeks old)were randomly and equally divided into siRNA knockdown HO-1 group(si-HO-1 group)and siRNA negative control group(si-NC group).After radiation combined injury was inflicted,60 μL of F127 gel loaded with si-HO-1(5 μm/L)was applied to each wound in the si-HO-1 group,and an equal amount of F127 gel loaded with negative control si-NC was applied to the wound in the si-NC group.The knockdown of HO-1 in wound tissues was detected by Western blotting,and the changes in wound area were observed.In the wound tissues harvested in 3 d after wounding,the expression of cytokines IL-1β,IL-6 and TNF-α was examined by q-PCR and the proliferation of granulation tissues was evaluated by Ki67 immunohistochemical staining.HE staining was performed on wound tissues on day 3 and day 9 post-injury to assess the improvement effect of knockdown of HO-1 on wound healing of radiation combined injuries.Results Compared with the W group,semi-quantitative analysis of the residual wound area showed that healing was significantly delayed in the R-W-CI group on days 7 and 10 post-injury(P＜0.01).HE staining on day 7 showed that in the R-W-CI group,the re-epithelialization was delayed,and the growth of granulation tissues was poor;and at the same time,peripheral blood leukocytes and their classified counts showed a significant decrease in the early period after injury(P＜0.05).Further tests indicated that the expression of HO-1 protein was slightly higher in the wound of the R-W-CI group than that of the W group in 3 and 7 d after injury,though no significant difference(P＞0.05),whereas statistical difference was seen in 10 d(P＜0.05),accompanied by the distribution of the full-length and truncated forms of HO-1 protein.Quantitative PCR obtained similar results in the mRNA expression of HO-1 in wounds in both 7 and 10 d after injury(P＜0.05).siRNA intervention could effectively knock down the HO-1 protein level of the wounds(P＜0.05),promote wound contraction(P＜0.05),reduce the width of the wound(P＜0.01),up-regulate the inflammatory cytokines IL-6 and TNF-α in 3 d,enhance the proliferation of repair cells in wound margin,and improve the growth of the granulation tissue in the R-W-CI model when compared with the conditions after si-NC intervention.Conclusion There exists a sustained high expression level of HO-1 during wound repair,and wound knockdown of HO-1 by siRNA can improve the lack of inflammation status and promote wound healing in R-W-CI mice.

Objective:To comprehensively retrieve and summarize the best evidence on the prevention of position-related nerve injury in adult patients undergoing general anesthesia, in order to provide evidence-based guidance for standardized position management during general anesthesia surgery in adults.Methods:Clinical decision-making, guidelines, evidence summaries, best practice, practice advisories, systematic reviews, expert consensuses were systematically search in UpToDate, BMJ Best Practice, Guidelines International Network (GIN), Canadian Medical Association: Clinical Practice Guideline(CMA Infobase), National Guideline Clearinghouse (NGC), National Institute for Health and Care Excellence(NICE), Cochrane Library, PubMed, CNKI, Wanfang, and related websites. The literature retrieval period was from the database construction to September 30,2022. The guidelines were independently assessed by 4 researchers, and the remaining literature was independently evaluated by 2 researchers. The literature that met the criteria was extracted. Finally, the expert meeting integrated the evidence and summarized the evidence topics.Results:A total of 17 articles were included, including 6 clinical decision-making, 3 guidelines, 2 practice advisories,5 systematic reviews, and 1 expert consensus. A total of 32 pieces of best evidence and 5 evidence topics were formed: personnel placement, perioperative evaluation, points of surgical position, key points in special surgery or situation, other general principles.Conclusion:This study summarized the best evidence for the prevention and management of surgical position related nerve injuries, and provides a scientific theoretical reference for postural management of adult patients undergoing operation with general anesthesia, to reduce the incidence of nerve injuries related position.

The clinical data, laboratory testing, genetic testing results, diagnosis and treatment process of a child with PERCHING syndrome diagnosed and treated in the Department of Neonatology, the Third Affiliated Hospital of Zhengzhou University in June 2022 were retrospectively analyzed, and the relevant literatures were reviewed.The proband mainly presented with dyspnea and feeding difficulties after delivery, facial nevus flammeus, protrusion of eyes, small fissure of eyes, wide nasal root, limited opening of mouth, slightly high palatal arch, special posture, cryptorchid, hypospadias, and high muscle tone of limbs.Magnetic resonance imaging of the brain suggested possible agenesis of corpus callosum.Genetic testing showed complex heterozygous variations in the KLHL7 gene, and the two mutation sites have not been previously reported.A case of PERCHING syndrome caused by the KLHL7 gene mutation in China was reported for the first time, which provided new ideas for the diagnosis and treatment of children with PERCHING syndrome and reliable genetic evidence for family reproduction.

Radionuclide-contaminated wounds are common in medical response to nuclear emergencies, which have different manifestations in different types of accidents. Medical treatment is the key part of the response. Based on the drill experience gained from medical response to nuclear emergencies, the authors summarize the research advances in radionuclide-contaminated wounds in recent years, mainly involving the biokinetic characteristics, medical response, surgical debridement, and prevention and treatment of internal contamination of radionuclide-contaminated wounds; the authors summarize the key points of technical operations and provide suggestions on improvements in the drills. The authors believe that medical treatment of radionuclide-contaminated wounds requires highly compatible integration of the practical skills from clinical medicine and radiological knowledge; emergency response, surgical debridement, and prevention and treatment of internal contamination all together constitute an integrated rescue and treatment strategy with internal logic correlations. However, targeted improvements are needed to achieve desired effects in the drills.

Due to the rapid proliferation and growth of tumor cells, hypoxic microenvironment exists in many solid tumors, and hypoxia inducible factors (HIF) are critical for sensing oxygen tension within tumors and subsequently mediating the activation of hypoxia responses. Hepatocellular carcinoma (HCC) is one of the most hypoxic tumors. This article summarizes the mechanism of action of HIF in promoting the development and progression of HCC by promoting glycolysis, angiogenesis, invasion and metastasis, immune escape, and cancer stem cell formation. At present, the development of targeted drugs for HIF inhibitors has broad prospects in the treatment of HCC, and the detection of HIF also has a potential value in prognostic evaluation HCC.

Objective: To assess left atrial(LA)function by evaluating changes of LA wall movement and volume detected by real-time three-dimensional speckle tracking imaging(RT3D-STI)in elderly patients with ischemic mitral regurgitation(IMR). Methods: Eighty-six elderly patients with coronary heart disease(CHD)were enrolled in this study.According to whether or not to have IMR, the patients were divided into the pure CHD group(n=32)and the CHD-induced ischemic mitral regurgitation(IMR)group(n=54, including 20 cases of mild IMR, 18 cases of moderate IMR and 16 cases of severe IMR). Thirty-two healthy elderly volunteers were considered as control group.RT3D-STI was used to evaluate the global atrial longitudinal strain(GLS), global circumferential strain(GCS), global radial strain(GRS)and LA maximal, minimal and pre-systolic volumes(LAVmax, LAVmin, and LAVp). LA ejection fraction(LAEF), LA passive ejection fraction(LApEF)and LA active ejection fraction(LAaEF)were calculated.The relationship of LA volume changes and myocardial strain with LA function was analyzed. Results: The left ventricular ejection fraction(LVEF)and LAEF were reduced in CHD group and IMR group as compared with the control group, and were lower in IMR group than in CHD group(P<0.05). Compared with the control group, the LAVmin was increased, and the LAaEF was decreased in the IMR group(P<0.05). Compared with the control group, the GLS, GCS, GRS were declined in the CHD and IMR groups, and were lower in IMR group than in control group(P<0.05). Along with the increased severity of regurgitation, GLS, GCS, and GRS were decreased in varying degrees.The standard deviations of time to peak longitudinal strains(TLS-SD), of time to peak circumferential strains(TCS-SD), and of time to peak radial strain(TRS-SD)rose in the IMR group as compared with the control group(P<0.05). The myocardial motion indicators(GLS, GCS, GRS)had a quite strong correlation with LAEF in the CHD and IMR groups(CHD group: r=-0.745, -0.718 and 0.627, P=0.006, 0.007 and 0.009; IMR group: r=-0.785, -0.781, 0.643, P=0.006, 0.007 and 0.008). The receiver operating characteristic(ROC)curves analysis showed that the sensitivity and specificity of TLS-SD, TCS-SD and TRS-SD were 89.7% and 81.8%, 78.6% and 84.8%, 85.7% and 72.1%, respectively in the evaluation of LA function changes. Conclusions RT3D-STI can precisely and objectively assess the LA function changes by measuring the volume changes and tracing the myocardial motion in elderly IMR patients.