Flap transplantation is a critical surgical strategy for the reconstruction of tissue defects caused by trauma, tumor resection, and congenital malformations, and its survival rate directly determines surgical efficacy and patient prognosis. Following transplantation, flaps inevitably undergo ischemia-reperfusion (I/R) injury, during which oxidative stress, inflammatory responses, and metabolic disturbances are intricately intertwined, ultimately leading to cellular injury and tissue necrosis. Recent studies have demonstrated that multiple forms of programmed cell death—including apoptosis, pyroptosis, ferroptosis, necroptosis, and PANoptosis—play central roles in flap I/R injury. The extensive crosstalk and molecular interactions among these pathways form a highly complex cell death network. Specifically, apoptosis is mediated by the imbalance of Bcl-2 family proteins and the activation of cysteine-dependent aspartate-specific protease (caspase) cascades; pyroptosis is driven by the NLRP3-caspase-1-GSDMD axis, resulting in membrane pore formation and the release of pro-inflammatory cytokines; ferroptosis is characterized by iron-dependent lipid peroxidation and dysfunction of glutathione peroxidase 4 (GPX4); necroptosis is triggered by the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-RIPK3-MLKL signaling complex, leading to membrane rupture; and PANoptosis represents an integrated form of inflammatory cell death that coordinates multiple death pathways. Importantly, these forms of programmed cell death are not independent but are interconnected through extensive signaling crosstalk. Key regulatory molecules, including caspase-8, reactive oxygen species (ROS), nuclear factor-κB (NF-κB), and nuclear factor erythroid 2-related factor 2 (Nrf2), collectively modulate the dynamic balance among these pathways. Therefore, the multidimensional interplay and spatiotemporal dynamics of programmed cell death constitute a fundamental pathological basis of flap I/R injury. This review systematically summarizes the latest advances in the mechanisms and interactions of various programmed cell death pathways in flap I/R injury, aiming to elucidate the underlying regulatory network. These insights may provide novel theoretical foundations for optimizing flap protection strategies, improving flap survival, and promoting tissue repair.

Bladder cancer has the characteristics of multiple and easy recurrence after surgery.At present,the main treatment methods include surgery,chemotherapy,radiotherapy,and so on.However,the recurrence rate and metastasis rate are still very high,seriously threatening human health.Oncolytic viruses have become an important part of a comprehensive cancer treatment strategy.Compared with surgery,radiotherapy and chemotherapy,oncolytic virus therapy is more precise and less toxic,which is expected to significantly improve patients' quality of life.However,the therapeutic effects of oncolytic viruses alone are satisfactory.Currently,oncolytic viruses are combined with immunotherapy,chemotherapy or radiotherapy to improve the overall anti-tumor effects.The combination of oncolytic viruses and immunotherapy has a relatively broader prospect.This article reviews the research progress of the clinical application of adenovirus vectors,lentiviral vectors,adeno-associated virus vectors,and oncolytic viruses combined with immunotherapy,chemotherapy,and radiotherapy for bladder cancer.

Objective To investigate the correlation between skeletal muscle fat content and diabetic peripheral neuropathy(DPN)in patients with type 2 diabetes mellitus(T2DM).Methods 290 patients with T2DM admitted to our hospital were enrolled in this study from January 2023 to February 2024 and divided into two groups according to whether they were complicated with DPN:simple T2DM group(T2DM,n=98)and T2DM with DPN group(DPN,n=192).The general data,biochemical indexes and fat distribution indexes measured based on quantitative CT were compared between the two groups.Spearman correlation was used to analyze the relationship between fat distribution indexes and DPN,logistic regression analysis of influencing factors of T2DM complicated with DPN.Results Age,DM duration,WHR,FIns,insulin resistance index(HOMA-IR)and FF were higher in DPN group than in T2DM group(P<0.05).Ca,subcutaneous abdominal fat area(SFA)and liver fat content were lower in DPN group than in T2DM group(P<0.05).Spearman correlation analysis showed that DPN was negatively correlated with SFA and liver fat content(r=-0.127,-0.123,P<0.05),and positively correlated with FF(r=0.117,P<0.05).Logistic regression analysis showed that without adjusting for confounding factors and adjusting for DM duration,WHR,HOMA-IR,Ca,SFA and liver fat content,FF was an influential factor for DPN in T2DM patients.Conclusions Skeletal muscle FF was associated with DPN in patients with T2DM.

Objective To investigate the effect of α/β hydrolase folded protein 5(ABHD5)and cellular immunity markers on the response to tirellizumab targeted therapy in patients with advanced non-small cell lung cancer(NSCLC).Methods A total of 123 patients with advanced NSCLC who received tiralizumab in Kailuan General Hospital from October 2020 to December 2023 were selected.The efficacy of the target lesions was evaluated 4 weeks after treatment,and the patients were divided into response group and non-response group according to the treatment effect.Quantitative real time polymerase chain reaction(RT-qPCR)was used to detect the relative expression of ABHD5 in lesion tissues.The expression level of ABHD5,immune indexes[CD4+T,CD8+T,CD4+T/CD8+T,regulatory T cell(Treg),T helper cell 17(Th17),Treg/Th17]and other clinical indexes were compared between the two groups.Multivariate logistic regression analysis of independent factors influencing response to tirelizumab targeted therapy.The predictive value of ABHD5,CD4+T and CD8+T in non-response to treatment of advanced NSCLC was analyzed by receiver operating characteristic(ROC).ABHD5 expression was correlated with CD4+T and CD8+T cells by Pearson correlation analysis.Results Among the 123 patients enrolled,90 responded to treatment and 33 did not respond.The expression of ABHD5(1.16±0.18)and the levels of CD4+T(31.52%±4.26%)and CD8+T(24.39%±1.87%)cells in the non-response group were lower than those in the response group(1.47±0.21,36.43%±4.08%,29.13%±2.15%),and the levels of Treg(7.24%±0.89%)and Th17(6.23%±1.10%)cells were higher than those in the response group(6.37%±0.91%,5.42%±0.66%),and the differences were statistically significant(t=4.725～11.200,all P<0.05).There were significant differences in tumor size,number of metastases and levels of carcinoembryonic antigen(CEA),albumin(ALB)and total bilirubin(TBIL)between the two groups,and the differences were statistically significant(t=2.969～6.523,all P<0.05).ABHD5 expression and CD4+T,CD8+T cell levels were independent protective factors affecting the response to tirelizumab targeted therapy in advanced NSCLC(Wald χ2=15.803,7.954,8.631,all P<0.05).ABHD5 predicted that the AUC of non-response to treatment of advanced NSCLC was 0.897,which was higher than that of 0.860 and 0.835 predicted by CD4+T and CD8+T cells,and the prediction sensitivity and specificity were 72.73%and 94.45%,respectively.ABHD5 expression was positively correlated with the levels of CD4+T and CD8+T cells(r=0.367,0.355,all P<0.05).Conclusion The response to tirelizumab targeted therapy in advanced NSCLC is significantly correlated with the expression of ABHD5 and the levels of CD4+T and CD8+T cells,and ABHD5 has high predictive value in the treatment of advanced NSCLC.

Bladder cancer has the characteristics of multiple and easy recurrence after surgery.At present,the main treatment methods include surgery,chemotherapy,radiotherapy,and so on.However,the recurrence rate and metastasis rate are still very high,seriously threatening human health.Oncolytic viruses have become an important part of a comprehensive cancer treatment strategy.Compared with surgery,radiotherapy and chemotherapy,oncolytic virus therapy is more precise and less toxic,which is expected to significantly improve patients' quality of life.However,the therapeutic effects of oncolytic viruses alone are satisfactory.Currently,oncolytic viruses are combined with immunotherapy,chemotherapy or radiotherapy to improve the overall anti-tumor effects.The combination of oncolytic viruses and immunotherapy has a relatively broader prospect.This article reviews the research progress of the clinical application of adenovirus vectors,lentiviral vectors,adeno-associated virus vectors,and oncolytic viruses combined with immunotherapy,chemotherapy,and radiotherapy for bladder cancer.

ObjectiveTo explore the changes in volatile components， total polysaccharides， enzyme activity， and chromaticity value of Myristicae Semen Koji（MSK） during the fermentation process， and conduct correlation analysis. MethodsBased on gas chromatography-mass spectrometry（GC-MS）， the changes of volatile components in MSK at different fermentation times were identified. The phenol sulfuric acid method， dinitrosalicylic acid method（DNS）， and carboxymethyl cellulose sodium salt method（CMC-Na） were used to investigate the total polysaccharide content， amylase activity， and cellulase activity during the fermentation process. Visual analysis technology was used to explore the changes in chromaticity values， revealing the fermentation process of MSK and the dynamic changes of various measurement indicators， partial least squares-discriminant analysis（PLS-DA） was used to explore the differential compounds of MSK at different fermentation degrees， and Pearson correlation analysis was used to explore the correlation between volatile components of MSK and total polysaccharides， enzyme activity， and chromaticity values. ResultsA total of 60 volatile compounds were identified from MSK， the relative contents of components such as （+）-α-pinene， β-phellandrene， β-pinene， （+）-limonene， and p-cymene obviously increased， while the relative contents of components such as safrole， methyl isoeugenol， methyleugenol， myristicin， and elemicin significantly decreased. During the fermentation process， the total polysaccharide content showed an upward trend， while the activities of amylase and cellulase showed an initial increase followed by a decrease， and reached their maximum value at 40 h. the overall brightness（L^*） and total color difference（ΔE^*） gradually increased， while the changes in red-green value（a^*） and yellow-blue value（b^*） were not obvious. PLS-DA results showed that MSK could be clearly distinguished at different fermentation times， and 13 differential biomarkers were screened out. Pearson correlation analysis results showed that the contents of α-terpinene， β-phellandrene， methyleugenol， β-cubebene and myristic acid had an obvious correlation with chromaticity values. ConclusionAfter fermentation， the volatile components， total polysaccharides， amylase activity， and cellulase activity of MSK undergo significant changes， and there is a clear correlation between them and chromaticity values， which reveals the dynamic changes in the fermentation process and related indicators of MSK， laying a foundation for the quality control.

BACKGROUND:The imbalance between bone resorption and bone formation in microgravity environments leads to significant bone loss in astronauts.Current research indicates that bone loss under microgravity conditions is the result of the combined effects of various cells,tissues,and systems. OBJECTIVE:To review different biological effects of microgravity on various cells,tissues,or systems,and summarize the mechanisms by which microgravity leads to the development of osteoporosis. METHODS:Databases such as PubMed,Web of Science,and the Cochrane Database were searched for relevant literature from 2000 to 2023.The inclusion criteria were all articles related to tissue engineering studies and basic research on osteoporosis caused by microgravity.Ultimately,85 articles were included for review. RESULTS AND CONCLUSION:(1)In microgravity environment,bone marrow mesenchymal stem cells tend to differentiate more into adipocytes rather than osteoblasts,and hematopoietic stem cells in this environment are more inclined to differentiate into osteoclasts,reducing differentiation into the erythroid lineage.At the same time,microgravity inhibits the proliferation and differentiation of osteoblasts,promotes apoptosis of osteoblasts,alters cell morphology,and reduces the mineralization capacity of osteoblasts.Microgravity significantly increases the number and activity of osteoclasts.Microgravity also hinders the differentiation of osteoblasts into osteocytes and promotes the apoptosis of osteocytes.(2)In a microgravity environment,the body experiences changes such as skeletal muscle atrophy,microvascular remodeling,bone microcirculation disorders,and endocrine disruption.These changes lead to mechanical unloading in the bone microenvironment,insufficient blood perfusion,and calcium cycle disorders,which significantly impact the development of osteoporosis.(3)At present,the mechanism by which microgravity causes osteoporosis is relatively complex.A deeper study of these physiological mechanisms is crucial to ensuring the health of astronauts during long-term space missions,and provides a theoretical basis for the prevention and treatment of osteoporosis.

Objective: Miniscrews are commonly utilized as temporary anchorage devices (TADs) in cases of maxillary protrusion and premolar extraction. This study aimed to investigate the effects and potential side effects of two conventional miniscrew configurations on the maxillary incisors. Methods: Eighty-two adult patients with maxillary dentoalveolar protrusion who had undergone bilateral first premolar extraction were retrospectively divided into three groups: non-TAD, two posterior miniscrews only (P-TADs), and two anterior and two posterior miniscrews combined (AP-TADs). Cone-beam computed tomography was used to evaluate the maxillary central incisors (U1). Results: The APTADs group had significantly greater U1 intrusion (1.99 ± 2.37 mm, n = 50) and less retroclination (1.70° ± 8.80°) compared to the P-TADs (–0.07 ± 1.65 mm and 9.45° ± 10.68°, n = 60) and non-TAD group (0.30 ± 1.61 mm and 1.91° ± 9.39°, n = 54).However, the AP-TADs group suffered from significantly greater apical root resorption (ARR) of U1 (2.69 ± 1.38 mm) than the P-TADs (1.63 ± 1.46 mm) and non-TAD group (0.89 ± 0.97 mm). Notably, the incidence of grade IV ARR was 16.6% in the AP-TADs group, significantly higher than the rates observed in the P-TADs (6.7%) and non-TAD (1.9%) groups. Multiple regression analysis revealed that after excluding tooth movement factors, the AP-TADs configuration resulted in an additional 0.5 mm of ARR compared with the P-TADs group. Conclusions In cases of maxillary protrusion and premolar extraction, the use of combined anterior and posterior miniscrews enhances incisor intrusion and minimizes torque loss of the maxillary incisors. However, this approach results in more severe ARR, likely due to the increased apical movement and composite force exerted.

OBJECTIVE: To investigate the efficacy of minimally invasive osteotomy with preservation of blood supply to the transversely transported bone segment in the treatment of chronic ischemic lower limb diseases using tibial transverse bone transport. METHODS: A retrospective analysis was conducted on the clinical data of 12 patients with chronic ischemic lower limb diseases who met the selection criteria and were treated between June 2016 and December 2023. The cohort included 7 males and 5 females, aged 26-87 years (mean, 61.2 years). Among them, 7 patients had diabetic foot (DF), including 2 cases complicated by arteriosclerosis obliterans (ASO), with a DF duration ranging from 1.7 to 23.0 months (mean, 9.6 months) and ulcer sizes ranging from 3.2 cm×2.4 cm to 10.0 cm×6.6 cm. Three patients had ASO with a disease duration of 1.7-23.0 months (mean, 10.4 months) and ulcer or post-amputation wound sizes ranging from 2.2 cm×2.1 cm to 12.0 cm×7.7 cm. Additionally, 2 patients with thromboangiitis obliterans (TAO) had a disease duration of 7 and 12 months, respectively. Preoperatively, the mean foot skin temperature was (27.63±0.34)℃, and the visual analogue scale (VAS) score was 8.5±0.7. All patients underwent tibial transverse bone transport using minimally invasive osteotomy while preserving the blood supply to the transported bone segment. Postoperative complications and foot ulcer healing were observed. The effectiveness of tibial transverse bone transport was evaluated by comparing preoperative and postoperative foot skin temperature, VAS scores, as well as through CT angiography (CTA). RESULTS: One DF patient with ASO was lost to follow-up, while the remaining 11 patients were followed up 10-29 months (mean, 20.5 months). One DF patient had a displaced fracture at the site of tibial transport due to trauma, which healed after plaster immobilization; 1 DF patient had a small amount of pigmentation in the skin of the donor site, but the blood circulation was good; no complication such as pin tract infection, skin necrosis, or osteomyelitis occurred in the donor site of all patients. At 2-3 weeks postoperatively, the foot skin temperature was (34.21±0.65)℃, and the VAS score was 0.3±0.1, both significantly improved compared to preoperative ones ( t=-31.578, P<0.001; t=49.000, P<0.001). Two TAO patients experienced recurrent, persistent, intolerable pain at 7-10 days postoperatively, with no reduction in ulcer size or necrotic areas; 1 underwent toe amputation, and the other required a mid-leg amputation. The remaining patients achieved complete ulcer healing, with healing time ranging from 5.1 to 9.2 weeks (mean, 6.8 weeks). CTA showed no new vascular occlusions or embolisms. X-ray films at 4 months postoperatively demonstrated proper repositioning and good healing of the transported tibial bone segment. CONCLUSION The application of minimally invasive osteotomy with preserved blood supply to the transversely transported bone segment in tibial transverse bone transport for the treatment of chronic ischemic lower limb diseases effectively minimizes extensive soft tissue dissection, reduces surgical soft tissue damage, and better maintains local blood supply. This approach lowers the risk of postoperative infection and skin necrosis while accelerating postoperative recovery.
Humans ; Osteotomy/methods* ; Middle Aged ; Male ; Female ; Aged ; Tibia/surgery* ; Minimally Invasive Surgical Procedures/methods* ; Retrospective Studies ; Adult ; Bone Transplantation/methods* ; Aged, 80 and over ; Diabetic Foot/surgery* ; Treatment Outcome ; Arteriosclerosis Obliterans/surgery* ; Ischemia/surgery* ; Lower Extremity/blood supply*

Objective: Miniscrews are commonly utilized as temporary anchorage devices (TADs) in cases of maxillary protrusion and premolar extraction. This study aimed to investigate the effects and potential side effects of two conventional miniscrew configurations on the maxillary incisors. Methods: Eighty-two adult patients with maxillary dentoalveolar protrusion who had undergone bilateral first premolar extraction were retrospectively divided into three groups: non-TAD, two posterior miniscrews only (P-TADs), and two anterior and two posterior miniscrews combined (AP-TADs). Cone-beam computed tomography was used to evaluate the maxillary central incisors (U1). Results: The APTADs group had significantly greater U1 intrusion (1.99 ± 2.37 mm, n = 50) and less retroclination (1.70° ± 8.80°) compared to the P-TADs (–0.07 ± 1.65 mm and 9.45° ± 10.68°, n = 60) and non-TAD group (0.30 ± 1.61 mm and 1.91° ± 9.39°, n = 54).However, the AP-TADs group suffered from significantly greater apical root resorption (ARR) of U1 (2.69 ± 1.38 mm) than the P-TADs (1.63 ± 1.46 mm) and non-TAD group (0.89 ± 0.97 mm). Notably, the incidence of grade IV ARR was 16.6% in the AP-TADs group, significantly higher than the rates observed in the P-TADs (6.7%) and non-TAD (1.9%) groups. Multiple regression analysis revealed that after excluding tooth movement factors, the AP-TADs configuration resulted in an additional 0.5 mm of ARR compared with the P-TADs group. Conclusions In cases of maxillary protrusion and premolar extraction, the use of combined anterior and posterior miniscrews enhances incisor intrusion and minimizes torque loss of the maxillary incisors. However, this approach results in more severe ARR, likely due to the increased apical movement and composite force exerted.