In recent years, China has been facing the dual challenges of declining fertility rates and births, with male reproductive health issues, especially the decline in semen quality, identified as a pivotal contributor to this phenomenon. Meanwhile, accumulating evidence indicates that air pollutants, an increasingly severe environmental problem, can damage semen quality not only directly through their biological toxicity but also indirectly by disrupting the composition of microbial communities in the gut and semen, thereby dysregulating immune function, endocrine homeostasis, and oxidative stress responses. The gut microbiota and semen microbiota, as important components of the human microecosystem, play crucial roles in maintaining reproductive health. This article comprehensively reviewed the research progress on the potential effects of air pollutants (particulate matter and gaseous pollutants), gut microbiota, and semen microbiota on semen quality. Specifically, it elucidated the mechanisms of interaction between these factors and explored how they affect male fertility.

Cuproptosis, a recently discovered form of regulated cell death involving copper ion metabolism, has emerged as a promising approach for tumor therapy. This pathway not only directly eliminates tumor cells but also promotes immunogenic cell death (ICD), reshaping the tumor microenvironment (TME) and initiating robust anti-tumor immune responses. However, translating cuproptosis-based therapies into clinical applications is hindered by challenges, including complex metabolic regulation, TME heterogeneity, and the precision required for effective drug delivery. To address these limitations, nanoparticles offer transformative solutions by providing precise delivery of cuproptosis-inducing agents, controlled drug release, and enhanced therapeutic efficacy through simultaneous modulation of metabolic pathways and immune responses. This review systematically discusses recent advancements in nanoparticle-based cuproptosis delivery systems, highlighting nanoparticle design principles and their synergistic effects when integrated with other therapeutic modalities such as ICB, PTT, and CDT. Furthermore, we explore the potential of cuproptosis-based nanomedicine for personalized cancer treatment by emphasizing strategies for TME stratification and therapeutic optimization tailored to patient profiles. By integrating current insights from metabolic reprogramming, tumor immunotherapy, and nanotechnology, this review aims to facilitate the clinical translation of cuproptosis nanomedicine and significantly contribute to the advancement of precision oncology.

Objective:To explore the clinical effects of sequential treatment of extensive skin and soft tissue injuries of the lower leg accompanied by large segmental tibial defects by free transplantation of anterolateral thigh perforator flap combined with bone transport.Methods:This study was a retrospective observational study. From April 2020 to January 2024, 8 patients with extensive skin and soft tissue injuries of the lower leg accompanied by large segmental tibial defects who met the inclusion criteria were admitted to Beijing Dawanglu Emergency Rescue Hospital. Among them, there were 6 males and 2 females, aged 17 to 58 years. After debridement, the area was 17 cm×8 cm to 30 cm×12 cm, and the length of tibial defect was 9 to 12 cm. Stage Ⅰ surgery was performed by free transplantation of anterolateral thigh perforator flap to repair the extensive skin and soft tissue injuries of the lower leg and using autologous skin graft from the thigh to repair the remaining wound. Stage Ⅱ surgery was performed after wound healing, the external fixation bracket was removed and replaced with an Orthofix unilateral external fixation lengthening frame (hereinafter referred to as external fixation lengthening frame) to transport the proximal tibial osteotomy for repairing the large segmental bone defects. The intraoperative arteriovenous anastomosis and the blood supply of the flap during stage Ⅰ surgery were documented, along with the survival status of the flap/skin graft in the donor and recipient areas postoperatively, and the wound healing time in the recipient area. The time required for bone transport completion, the duration of external fixation retention, and the occurrence of complications during this period were recorded after stage Ⅱ surgery. During follow-up, the occurrence of adverse events in the recipient area was recorded. At the final follow-up, fracture healing of the affected limb was evaluated according to the Paley score, and limb function was observed.Results:In 2 patients, the descending branch of the lateral circumflex femoral artery and the accompanying vein were end-to-end anastomosed with the proximal anterior tibial or posterior tibial artery and vein for antegrade blood supply and antegrade reflux; in 2 patients, the descending branch of the lateral circumflex femoral artery was end-to-end anastomosed with the distal anterior tibial artery for retrograde blood supply, and the accompanying vein of the descending branch of the lateral circumflex femoral artery was end-to-end anastomosed with the proximal anterior tibial vein for antegrade reflux; in 3 patients, the descending branch of the lateral circumflex femoral artery was end-to-end anastomosed with the distal posterior tibial artery for retrograde blood supply, and the accompanying vein of the descending branch of the lateral circumflex femoral artery was end-to-end anastomosed with the distal posterior tibial vein for retrograde reflux; one patient underwent repair of the injury in the affected lower leg using a free cross-leg vascular pedicle flap from the healthy limb. The flaps/skin grafts in the donor and recipient areas of all 8 patients survived, and the wound healing time in recipient area was 14 to 30 days. The bone transport duration of the patients in this group was 93 to 125 days, and the external fixation lengthening frame was continuously retained for 7 to 14 months after the bone transport was stopped; during the bone transport period, 1 patient had pin tract infection, which was controlled after dressing change and enhanced nursing. During the follow-up, there was no ulceration of the wound surface in recipient area, and no osteomyelitis or fracture developed in the affected limb. At the last follow-up, the bone healing evaluation was all excellent; the walking posture and function of the affected limb were basically normal.Conclusions:The application of free transplantation of anterolateral thigh perforator flap combined with bone transport in the sequential treatment of extensive skin and soft tissue injuries of the lower leg accompanied by large segmental tibial defecst can achieve wound healing and functional reconstruction of bone defects, and has great clinical application value.

Objective To investigate the anesthesia effects of different concentrations of sevoflurane combined with propofol during primary liver cancer resection surgery,as well as the changes in immune function in patients.Methods Using single-blind method,120 cases of primary hepatocellular carcinoma admitted to the Third Affiliated Hospital of Naval Military Medical University from January 2023 to September 2023 were prospectively selected as the study subjects,and the patients were randomly(using the randomized numerical table method)included in the control group(60 cases)and the observation group(60 cases).During hepatic cancer resection,the control group was given 0.5 alveolar minimum effective concentration(MAC)sevoflurane combined with propofol target-controlled infusion anesthesia,and the observation group was given 1.0 MAC sevoflurane combined with propofol target-controlled infusion anesthesia,and both groups were observed for 3 d postoperatively.The perioperative related indexes,the sedation and quality of awakening in the immediate moment of extubation,15 min after extubation,and 30 min after extubation,the cognitive function before and at 1 and 3 d postoperatively,vital signs before induction of anesthesia,after induction of anesthesia,at the moment of intubation,at the end of surgery,immune function before and 1 d postoperative,and adverse reactions during the observation period were compared between the two groups.Results The time for extubation,recovery of spontaneous respiration,recovery of orientation,and awakening in the observation group were(11.25±1.69)min,(9.76±1.34)min,(69.23±3.35)min,and(10.13±1.43)min,and the control group were(14.57±2.28)min,(13.55±2.76)min,(73.44±4.52)min,(14.26±2.25)min,all of which were shorter in the observation group than in the control group(P＜0.05).The Ramsay sedation score at the immediate moment of extubation was(4.16±0.22)in the observation group,and(3.21±0.10)in the control group;the standardized(Aldrete)score in the awakening room of the observation group at the immediate moment of extubation,and 15 min after extubation were(9.56±0.12)and(9.77±0.20),respectively,and the control group was(9.02±0.13),respectively,(9.05±0.17)points;the scores of the brief mental state examination(MMSE)scale in the observation group were(26.23±1.12)points and(25.17±0.98)points in the control group in the 1 d postoperative period,which were higher than those of the control group(P＜0.05).The heart rate(HR)at the moment of intubation and at the end of operation in the observation group were(73.08±4.10)beats/min,(75.27±6.03)beats/min,and the mean arterial pressure(MAP)was(81.56±4.49)mmHg and(86.07±5.48)mmHg,respectively,and in the control group the HR was(75.47±5.78)beats/min,(77.91±6.79)beats/min,and the MAP was(85.22±5.08)mmHg and(88.25±6.01)mmHg in the observation group,respectively,which were lower than those in the control group(P＜0.05).The whole blood natural killer(NK)cells,CD4+and CD4+/CD8+in the observation group at 1 d postoperatively were(35.62±5.54)％,(50.09±3.32)％,and(1.42±0.25),the control group were(24.12±4.09)％,(43.17±4.20)％,and(1.20±0.19),the observation group was higher than the control group(P＜0.05);whole blood CD8+was(26.55±3.02)％in the observation group and(28.71±4.45)％in the control group,the observation group was lower than the control group(P＜0.05).The total incidence of adverse reactions during the observation period was 16.67％in the observation group and 5.00％in the control group,which was higher than the control group(P＜0.05).Conclusion Compared with 0.5 MAC sevoflurane combined with propofol target-controlled infusion anesthesia,1.0 MAC sevoflurane combined with propofol target-controlled infusion anesthesia had less effect on hemodynamics and immune function in patients undergoing resection for primary hepatocellular carcinoma,and it could improve the quality of patients'awakening,cognitive function,and promote postoperative recovery,and the anesthesia was more effective,but it had more adverse effects.

Objective To elucidate how the overexpression of cystathionine-β-synthase(CBS)plays an antihypertensive role by affecting peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α)expression.Methods The adeno-associated viruses(AAVs),ones that overexpressed CBS,and another knocked down PGC-1α,were injected into the hypothalamic paraventricular nucleus(PVN)of spontaneously hypertensive rats(SHRs).The rats'blood pressure was monitored,and the level of norepinephrine(NE)was examined by ELISA;PVN inflammatory response,oxidative stress and tyrosine hydroxylase(TH)expression were detected with RT-qPCR and immunofluorescence.Results PVN overexpression of CBS could increase the transcription level of CBS(by 3.8 times,P＜0.05)and PGC-1α(by 1.6 times,P＜0.05)in PVN of SHR.PVN overexpression of CBS could reduce blood pressure in SHR(from 177.81 mmHg to 128.77 mmHg,P＜0.001),but PVN knockdown of PGC-1αweakened such effect(from 128.77 mmHg to 152.79 mmHg,P＜0.05).PVN overexpression of CBS could alleviate PVN inflammatory response and oxidative stress,but this effect was weakened or even eliminated when knocking down PGC-1α was performed at the same time.Conclusion PVN overexpression of CBS can reduce blood pressure in SHR,and this effect may be achieved by increasing the transcriptional level of PGC-1α,alleviating PVN inflammatory response,oxidative stress,and improving sympathetic nerve excitation.

Objective To investigate the anesthesia effects of different concentrations of sevoflurane combined with propofol during primary liver cancer resection surgery,as well as the changes in immune function in patients.Methods Using single-blind method,120 cases of primary hepatocellular carcinoma admitted to the Third Affiliated Hospital of Naval Military Medical University from January 2023 to September 2023 were prospectively selected as the study subjects,and the patients were randomly(using the randomized numerical table method)included in the control group(60 cases)and the observation group(60 cases).During hepatic cancer resection,the control group was given 0.5 alveolar minimum effective concentration(MAC)sevoflurane combined with propofol target-controlled infusion anesthesia,and the observation group was given 1.0 MAC sevoflurane combined with propofol target-controlled infusion anesthesia,and both groups were observed for 3 d postoperatively.The perioperative related indexes,the sedation and quality of awakening in the immediate moment of extubation,15 min after extubation,and 30 min after extubation,the cognitive function before and at 1 and 3 d postoperatively,vital signs before induction of anesthesia,after induction of anesthesia,at the moment of intubation,at the end of surgery,immune function before and 1 d postoperative,and adverse reactions during the observation period were compared between the two groups.Results The time for extubation,recovery of spontaneous respiration,recovery of orientation,and awakening in the observation group were(11.25±1.69)min,(9.76±1.34)min,(69.23±3.35)min,and(10.13±1.43)min,and the control group were(14.57±2.28)min,(13.55±2.76)min,(73.44±4.52)min,(14.26±2.25)min,all of which were shorter in the observation group than in the control group(P＜0.05).The Ramsay sedation score at the immediate moment of extubation was(4.16±0.22)in the observation group,and(3.21±0.10)in the control group;the standardized(Aldrete)score in the awakening room of the observation group at the immediate moment of extubation,and 15 min after extubation were(9.56±0.12)and(9.77±0.20),respectively,and the control group was(9.02±0.13),respectively,(9.05±0.17)points;the scores of the brief mental state examination(MMSE)scale in the observation group were(26.23±1.12)points and(25.17±0.98)points in the control group in the 1 d postoperative period,which were higher than those of the control group(P＜0.05).The heart rate(HR)at the moment of intubation and at the end of operation in the observation group were(73.08±4.10)beats/min,(75.27±6.03)beats/min,and the mean arterial pressure(MAP)was(81.56±4.49)mmHg and(86.07±5.48)mmHg,respectively,and in the control group the HR was(75.47±5.78)beats/min,(77.91±6.79)beats/min,and the MAP was(85.22±5.08)mmHg and(88.25±6.01)mmHg in the observation group,respectively,which were lower than those in the control group(P＜0.05).The whole blood natural killer(NK)cells,CD4+and CD4+/CD8+in the observation group at 1 d postoperatively were(35.62±5.54)％,(50.09±3.32)％,and(1.42±0.25),the control group were(24.12±4.09)％,(43.17±4.20)％,and(1.20±0.19),the observation group was higher than the control group(P＜0.05);whole blood CD8+was(26.55±3.02)％in the observation group and(28.71±4.45)％in the control group,the observation group was lower than the control group(P＜0.05).The total incidence of adverse reactions during the observation period was 16.67％in the observation group and 5.00％in the control group,which was higher than the control group(P＜0.05).Conclusion Compared with 0.5 MAC sevoflurane combined with propofol target-controlled infusion anesthesia,1.0 MAC sevoflurane combined with propofol target-controlled infusion anesthesia had less effect on hemodynamics and immune function in patients undergoing resection for primary hepatocellular carcinoma,and it could improve the quality of patients'awakening,cognitive function,and promote postoperative recovery,and the anesthesia was more effective,but it had more adverse effects.

Objective To elucidate how the overexpression of cystathionine-β-synthase(CBS)plays an antihypertensive role by affecting peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α)expression.Methods The adeno-associated viruses(AAVs),ones that overexpressed CBS,and another knocked down PGC-1α,were injected into the hypothalamic paraventricular nucleus(PVN)of spontaneously hypertensive rats(SHRs).The rats'blood pressure was monitored,and the level of norepinephrine(NE)was examined by ELISA;PVN inflammatory response,oxidative stress and tyrosine hydroxylase(TH)expression were detected with RT-qPCR and immunofluorescence.Results PVN overexpression of CBS could increase the transcription level of CBS(by 3.8 times,P＜0.05)and PGC-1α(by 1.6 times,P＜0.05)in PVN of SHR.PVN overexpression of CBS could reduce blood pressure in SHR(from 177.81 mmHg to 128.77 mmHg,P＜0.001),but PVN knockdown of PGC-1αweakened such effect(from 128.77 mmHg to 152.79 mmHg,P＜0.05).PVN overexpression of CBS could alleviate PVN inflammatory response and oxidative stress,but this effect was weakened or even eliminated when knocking down PGC-1α was performed at the same time.Conclusion PVN overexpression of CBS can reduce blood pressure in SHR,and this effect may be achieved by increasing the transcriptional level of PGC-1α,alleviating PVN inflammatory response,oxidative stress,and improving sympathetic nerve excitation.

Objective:To explore the clinical effects of sequential treatment of extensive skin and soft tissue injuries of the lower leg accompanied by large segmental tibial defects by free transplantation of anterolateral thigh perforator flap combined with bone transport.Methods:This study was a retrospective observational study. From April 2020 to January 2024, 8 patients with extensive skin and soft tissue injuries of the lower leg accompanied by large segmental tibial defects who met the inclusion criteria were admitted to Beijing Dawanglu Emergency Rescue Hospital. Among them, there were 6 males and 2 females, aged 17 to 58 years. After debridement, the area was 17 cm×8 cm to 30 cm×12 cm, and the length of tibial defect was 9 to 12 cm. Stage Ⅰ surgery was performed by free transplantation of anterolateral thigh perforator flap to repair the extensive skin and soft tissue injuries of the lower leg and using autologous skin graft from the thigh to repair the remaining wound. Stage Ⅱ surgery was performed after wound healing, the external fixation bracket was removed and replaced with an Orthofix unilateral external fixation lengthening frame (hereinafter referred to as external fixation lengthening frame) to transport the proximal tibial osteotomy for repairing the large segmental bone defects. The intraoperative arteriovenous anastomosis and the blood supply of the flap during stage Ⅰ surgery were documented, along with the survival status of the flap/skin graft in the donor and recipient areas postoperatively, and the wound healing time in the recipient area. The time required for bone transport completion, the duration of external fixation retention, and the occurrence of complications during this period were recorded after stage Ⅱ surgery. During follow-up, the occurrence of adverse events in the recipient area was recorded. At the final follow-up, fracture healing of the affected limb was evaluated according to the Paley score, and limb function was observed.Results:In 2 patients, the descending branch of the lateral circumflex femoral artery and the accompanying vein were end-to-end anastomosed with the proximal anterior tibial or posterior tibial artery and vein for antegrade blood supply and antegrade reflux; in 2 patients, the descending branch of the lateral circumflex femoral artery was end-to-end anastomosed with the distal anterior tibial artery for retrograde blood supply, and the accompanying vein of the descending branch of the lateral circumflex femoral artery was end-to-end anastomosed with the proximal anterior tibial vein for antegrade reflux; in 3 patients, the descending branch of the lateral circumflex femoral artery was end-to-end anastomosed with the distal posterior tibial artery for retrograde blood supply, and the accompanying vein of the descending branch of the lateral circumflex femoral artery was end-to-end anastomosed with the distal posterior tibial vein for retrograde reflux; one patient underwent repair of the injury in the affected lower leg using a free cross-leg vascular pedicle flap from the healthy limb. The flaps/skin grafts in the donor and recipient areas of all 8 patients survived, and the wound healing time in recipient area was 14 to 30 days. The bone transport duration of the patients in this group was 93 to 125 days, and the external fixation lengthening frame was continuously retained for 7 to 14 months after the bone transport was stopped; during the bone transport period, 1 patient had pin tract infection, which was controlled after dressing change and enhanced nursing. During the follow-up, there was no ulceration of the wound surface in recipient area, and no osteomyelitis or fracture developed in the affected limb. At the last follow-up, the bone healing evaluation was all excellent; the walking posture and function of the affected limb were basically normal.Conclusions:The application of free transplantation of anterolateral thigh perforator flap combined with bone transport in the sequential treatment of extensive skin and soft tissue injuries of the lower leg accompanied by large segmental tibial defecst can achieve wound healing and functional reconstruction of bone defects, and has great clinical application value.

Objective To investigate the protective effect of sappanone A(SA)against high-fat diet-induced myocardial lipotoxicity through ferroptosis in rats.Methods Sixteen healthy male rats were equally divided into the normal diet(NCD)and model groups(n=8).Another 40 healthy male rats were equally divided into the high-fat diet(HFD),high-fat diet+normal saline(HFD+saline),high-fat diet+low-dose SA(HFD+10 mg/kg SA),high-fat diet+medium-dose SA(HFD+20 mg/kg SA),and high-fat diet+high-dose SA(HFD+40 mg/kg SA)groups(n=8).Ultrasonography detected the changes in cardiac systolic function in the rats.Changes of myocardial hypertrophy,myocardial fibrosis,and myocardial cell apoptosis were evaluated by HE,Masson,Sirius red,and TUNEL staining.Differen-tially expressed genes in the myocardium of the HFD+20 mg/kg SA and HFD groups were analyzed by transcriptome sequencing.The SA signaling pathway was analyzed using the Kyoto Encyclopedia of Genes and Genomes.Results Compared with the NCD group,the model group had significantly increased left ventricular wall thickness,cross-sectional area of the myocardium,percentage of myocardial fibrosis,myocardial collagen deposition,and apoptosis,and significantly reduced short-axis shortening rate(all P＜0.05).Compared with the HFD group,the SA treatment groups has significantly reduced left ventricular wall thickness,cross-sectional area of the myocardium,percentage of myocardial fibrosis,myocardial collagen deposition,and apoptosis,and significantly increased short-axis shortening rate(all P＜0.05).Transcriptome sequencing revealed that ferroptosis was the most abundant pathway.Conclusion High-fat diet can induce myocardial lipotoxicity,and SA has a protective effect against myocardial lipotoxicity through ferroptosis.

Background::Copper and zinc are involved in the development of multiple malignancies; yet, epidemiological evidence on hepatocellular carcinoma (HCC) is limited. This study aimed to investigate the association between dietary intake and serum levels of copper and zinc with the risk of HCC.Methods::A total of 434 case-control pairs matched for sex and age (±1 year) were included in this study. Cases with newly diagnosed HCC were from the Guangdong Liver Cancer Cohort (GLCC) study, and healthy controls were from the Guangzhou Nutrition and Health Study (GNHS). A semi-quantitative 79-item food frequency questionnaire (FFQ) was used to assess habitual dietary intakes of copper and zinc. Serum levels of copper and zinc were measured by using inductively coupled plasma mass spectrometry. The copper (Cu)/ zinc (Zn) ratio was computed by dividing copper levels by zinc levels. Conditional logistic regression models were performed to calculate the odds ratio (OR) and 95% confidence intervals (CI) for per 1 standard deviation increase (per-SD increase) in copper and zinc levels.Results::Higher dietary intake (OR per-SD increase = 0.65, 95% CI: 0.44, 0.96, Ptrend = 0.029) and serum levels of zinc (OR per-SD increase = 0.11, 95% CI: 0.04, 0.30, Ptrend <0.001) were both associated with a lower risk of HCC. Subgroup analyses showed that the inverse association was only pronounced in men but not in women ( Pinteraction = 0.041 for dietary zinc intake and 0.010 for serum zinc levels). Serum copper levels (OR per-SD increase = 2.05, 95% CI: 1.39, 3.03, Ptrend = 0.020) and serum Cu/Zn ratio (OR per-SD increase = 6.53, 95% CI: 2.52, 16.92, Ptrend <0.001) were positively associated with HCC risk, while dietary copper intake and dietary Cu/Zn ratio were not associated with HCC risk. Conclusion::Zinc may be a protective factor for HCC, especially among men, but the effects of copper on HCC risk are not clear.