Obesity usually exacerbates the immunosuppressive tumor microenvironment (ITME), hindering CD8⁺ T cell infiltration and function, which further represents a significant barrier to the efficacy of immunotherapy. Herein, a multifunctional liposomal system (CR-Lip) for encapsulating celastrol (CEL) was utilized to remodel obesity-related ITME and improve cancer immunotherapy, wherein Ginsenoside Rg3 (Rg3) was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome. CR-Lip had a relatively uniform size (116.5 nm), facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells. Upon reaching the tumor region, CR-Lip was found to induce the immunogenic cell death (ICD) of HFD tumor cells. Notably, the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources. In vivo, experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues, DC maturation, CD8⁺ T-cell infiltration, and synergistic anticancer therapeutic potency with aPD-1 (tumor inhibition rate = 82.1%) towards obesity-related melanoma. Consequently, this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication, inducing ICD, and reprogramming metabolism. Furthermore, it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.

Objective To analyze the detrimental effects of exposure to environmental noise alone and combined with carbon monoxide(CO)on spermatogenesis in male rats,investigate the underlying mechanisms involved in such damage,and evaluate the protective role of pterostilbene(PTE)against these adverse effects.Methods Sixty male SD rats(6～8 weeks old,weighing 200±10 g)were randomly divided normal control group(standard housing),sham-exposure control group(restraint stress only),noise exposure(85 dB),CO exposure(460 mg/m3),combined exposure(simultaneous exposure),and PTE intervention(80 mg/kg pretreatment),with 10 animals in each group.The rats were exposed daily for 2 h via a nose-only inhalation exposure system within a multifactorial environmental simulation chamber for 60 consecutive days.Sperm count and viability were measured after exposure.Histopathological changes of testicular tissues were observed with HE staining.qRT-PCR was used to measure stage-specific mRNA levels in germ cells.Serum sex hormone levels and adenosine triphosphate(ATP)concentrations in testes and sperm were detected.Transmission electron microscopy(TEM)was applied to observe the ultrastructural damage in the spermatocytes.Additionally,transcriptome sequencing was performed on testicular tissue,followed by bioinformatics analysis.Results Compared with the negative control group,the combined exposure group exhibited significant reductions in sperm viability and count(P<0.05),and developmental arrest of immature germ cells in the testicular tissue,with obviously less spermatogonia,spermatocytes,and round/elongated spermatids(P<0.01).Additionally,significantly reduced levels of reproductive-related hormones,such as gonadotropin-releasing hormone,follicle-stimulating hormone,luteinizing hormone and testosterone,and ATP levels in testes and sperm were observed in the mice after combined exposure(P<0.01),accompanied by mitochondrial rupture and cristae disruption in spermatocytes.Conversely,the PTE intervention group showed marked alleviation of these impairments,with parameters recovering almost to normal levels.Transcriptome sequencing identified biological processes related to reproductive development and ATP-dependent pathways as potential contributors to testicular injury induced by noise and CO exposure,with key genes including Nppa,Adm,Gnrh1,Ptafr,Atp13a5,Atp8b1,and LOC102555469.Conclusion Noise and CO exposure induce spermatogenic damage in rats,which may be related with energy metabolism and hormonal regulation,while PTE demonstrates significant protective effects against such reproductive impairments.

【Objective】 To explore the role of ZFP36 in cardiomyocyte injury and autophagy induced by hypoxia/reoxygenation (H/R) so as to clarify its molecular regulatory mechanism. 【Methods】 H9C2 rat cardiomyocytes were infected with ZFP36 overexpressing lentivirus (OE-ZFP36) or its negative control lentivirus (OE-ZFP36 NC) to construct stable cell lines, respectively. Transfection of ATG4D overexpression plasmid (OE-ATG4D) improved the expression of ATG4D. Hypoxia/reoxygenation (H/R) induced myocardial cell injury. H9C2 cells were mainly divided into control group, H/R group, OE-ZFP36 NC+H/R group, OE-ZFP36+H/R group, OE-ATG4D NC+H/R group, OE-ATG4D+H/R group, OE-ZFP36+OE-ATG4D NC+H/R group, and OE-ZFP36+OE-ATG4D+H/R group. The protein expressions of ATG4D, Beclin1, LC3 and ZFP36 in H9C2 cells were detected by Western blotting. The mRNA levels of ZFP36 and ATG4D in H9C2 cells were detected by Real-time fluorescence quantitative PCR (qPCR). The viability of H9C2 cells was detected by CCK-8 assay. The levels of interleukin (IL-6) and tumor necrosis factor (TNF-α) in H9C2 cells were detected by enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) in H9C2 cells were detected by DCFH-DA method. SOD detection kit was used to detect the SOD level in H9C2 cells. The apoptosis of H9C2 cells was detected by flow cytometry. LC3 autophagosomes in H9C2 cells were detected by cellular immunofluorescence. Dual-luciferase reporter gene assay was used to detect the binding of ZFP36 and ATG4D mRNA in H9C2 cells. 【Results】 Compared with control group, H/R group showed decreased cell viability, increased IL-6 and TNF-α levels, increased ROS levels and decreased SOD levels, increased cell apoptosis. Up-regulated ATG4D and Beclin1 protein expression, increased LC3Ⅱ/LC3Ⅰ ratio, as well as upregulated ZFP36 expression were found in H/R group (all P<0.05). Compared with OE-ZFP36 NC+H/R group, elevated cell viability, decreased IL-6 and TNF-α levels, decreased ROS levels and increased SOD levels, reduced cell apoptosis (P<0.05), and downregulated ATG4D and Beclin1 protein expression, decreased LC3Ⅱ/LC3Ⅰ ratio were shown in OE-ZFP36+H/R group (all P<0.05). Compared with infection with OE-ZFP36 NC lentivirus, infection with OE-ZFP36 lentivirus decreased the luciferase activity of ATG4D 3′-UTR reporter gene, decreased the stability of ATG4D mRNA, and downregulated the H/R-induced ATG4D mRNA expression (all P<0.05). Compared with OE-ATG4D NC+H/R group, OE-ATG4D+H/R group had upregulated ATG4D mRNA and protein expression, decreased cell viability, increased IL-6 and TNF-α levels, increased ROS levels, decreased SOD levels and elevated cell apoptosis (all P<0.05). Compared with OE-ZFP36+OE-ATG4D NC+H/R group, OE-ZFP36+OE-ATG4D+H/R group had decreased cell viability, increased IL-6 and TNF-α levels, increased ROS levels, decreased SOD levels and elevated cell apoptosis (all P<0.05). 【Conclusion】 The expression of ZFP36 is upregulated in H/R-induced cardiomyocyte injury. The overexpression of ZFP36 inhibits H/R-induced cardiomyocyte injury and autophagy by regulating ATG4D, thus resisting cardiomyocyte H/R injury. It proves that ZFP36 is an important regulatory molecule against MI/RI.

Objective:To investigate the current situation of pregnancy distress and related factors in the third trimester of pregnancy,and explore its association with self-compassion and emotional inhibition.Methods:A total of 214 women in the third trimester of pregnancy were selected and measured the pregnancy pain,self-compassion and emotional depression levels of pregnant women in the third trimester with the Tilburg Pregnancy Pain Scale(TPDS),Self-Compassion Scale(SCS),and Emotional Suppression Scale(EIS).Results:The average score of pregnancy distress of 214 pregnant women in the third trimester was(26.7±4.9),with a medium level of pregnan-cy distress.Multiple linear regression analysis showed that the total scores of pregnancy distress in the third trimes-ter of pregnancy were negatively associated with the accompanying situation of the lover(β=-0.15,P＜0.05),the number of accompanying prenatal examinations(β=-0.24,P＜0.05)and the total scores of self-compassion(β=-0.12,P＜0.05),while positively correlated with gestational age(β=0.14,P＜0.05),complications(β=0.15,P＜0.05),and the total score of emotional suppression(β=0.17,P＜0.05).Conclusion:Pregnancy distress is common in pregnant women in the third trimester,which may be related to gestational age and complications,companionship of loved ones,number of accompanying prenatal examinations,self-compassion level and emotional inhibition.

Objective:To understand the security status of newborn fathers and analyze its related factors.Methods:A total of 256 fathers(aged 22-49 years old)of newborns born within 1 week were select-ed.They were assessed with the self-designed general information questionnaire,Parents'Postnatal Sense of Securi-ty(father version),Emotional Inhibition Scale,and Marriage Satisfaction Subscale of Enrich Marital Inventory.Results:The average score of security was(36.0±4.4).Multiple linear regression analysis showed that the security scores were positively correlated with residence area(β=0.35),education level(β=0.25),preterm birth(β=0.11)and the marital satisfaction scores(β=0.25);and were negatively associated with daily crying time(β=-0.28)and the EIS scores(β=-0.18).Conclusion:The sense of security of postpartum fathers is moderate,and it is associated with residence area,education level,preterm birth,marital satisfaction,daily crying time and emotional inhibition.

Objective:To understand the status and related factors of emotional inhibition among women re-ceiving in vitro fertilization-embryo transfer(IVF-ET).Methods:A total of 791 women receiving IVF-ET from a specialized hospital in Changsha were selected,and surveyed with the General Questionnaire,Emotional Inhibition Scale(EIS),Locke-Wollance Marital Adjustment Questionnaire,Self-Compassion Scale and Medical Coping Mode Questionnaire.Results:The average score of EIS in women receiving IVF-ET was(28.0±6.4).Multiple linear re-gression analysis showed that the EIS scores in women receiving IVF-ET were negatively associated with infertility factors(β=-9.23,-4.56,-2.86),personality type(β=-1.11),and marital adjustment,confrontation and self-compassion scores(β=-0.03,-0.13,-0.05),and positively associated with residence and surrender di-mension scores(β=0.82,0.20).Conclusion:It suggests that women receiving IVF-ET have a certain degree of e-motional inhibition,which is related to infertility factors,residence,personality type,self-compassion,marital adjust-ment,confrontation,and surrender.

Objective To explore the clinical application value of emergency bedside echocardiography(EB-Echo)in the diagnosis and treatment of reverse-Takotsubo syndrome(r-TTS).Methods A retrospective study method was conducted,the EB-Echo imaging and clinical data of 10 patients already diagnosed with r-TTS and admitted to the department of critical care medicine of Zhengzhou People's Hospital from January 2014 to December 2021 were selected.The r-TTS group,while data from 33 concurrently admitted patients with classic Takotsubo syndrome(TTS)were selected as the classic TTS group.Comparisons were made in terms of EB-Echo detection rates,diagnosis times,cardiac function indicators[left ventricular ejection fraction(LVEF),left ventricular stroke volume(LVSV)],blood volume indicators[inferior vena cava diameter(IVCD),collapse degree of inferior vena cava(cIVC)],complications[acute left ventricular outflow tract obstruction(ALVOTO),acute mitral regurgitation(AMR),and pulmonary hypertension(PH)],and prognosis between the two groups.Results The detection rate of EB-Echo in the r-TTS group was significantly higher than that in the classic TTS group[100.0%(10/10)vs.66.7%(22/33),P<0.05],and the diagnosis time was significantly shorter(minutes:26.80±3.77 vs.41.18±6.61,P<0.05).In terms of cardiac function indicators,both LVEF and LVSV were significantly lower in the r-TTS group compared to the classic TTS group[LVEF:0.36±0.05 vs.0.41±0.04,LVSV(mL):36.43±4.30 vs.40.65±5.09,both P<0.05].However,there were no significant differences in blood volume indicators(IVCD and cIVC)between the r-TTS group and the classic TTS group[IVCD(mm):15.02±1.88 vs.14.94±1.75,cIVC:(0.43±0.06)%vs.(0.44±0.07)%,both P>0.05].Concerning complications,the incidence of ALVOTO was slightly lower in the r-TTS group compared to the classic TTS group[0%(0/10)vs.21.2%(7/33),P>0.05],while the incidences of AMR and PH were similar between the two groups[AMR incidence:40.0%(4/10)vs.24.2%(8/33),PH incidence:30.0%(3/10)vs.18.2%(6/33),both P>0.05].After a follow-up ranging from 6 months to 3 years,no deaths were reported in the r-TTS group,whereas there was one fatality in the classic TTS group.Nevertheless,the mortality difference between the groups was not statistically significant.Conclusion EB-Echo demonstrates significant clinical value in the early diagnosis,guiding therapy,and enhancing prognosis of r-TTS.

Objective To explore the mediating effect of coping styles of newly graduated nurses between personality traits and transitional shock,aiming to provide references for managers to help new nurses reduce the level of transitional shock and smoothly go through the role transition period.Methods By convenience sampling,580 new nurses from 13 tertiary A hospitals in Guangzhou,Changsha,and Zhuzhou were surveyed from May to October 2023.A general information questionnaire,Eysenck Personality Questionnaire short form,Transition Shock of Newly Graduated Nurses Scale,and Brief Coping Style Scale were used for the survey.Structural equation modeling was employed to examine the mediating effect of newly graduated nurses'coping styles between personality traits and transitional shock.Results A total of 537 new nurses participated in the survey.Psychoticism and neuroticism were positively correlated with transformational shock and negative coping styles(P＜0.01),but negatively correlated with positive coping styles(P＜0.01).Extroversion was negatively correlated with transformational shock and negative coping style(P＜0.0 1),but positively correlated with positive coping style(P＜0.01).The results of the mediation effect analysis show that coping styles play a partial mediating role between personality traits and transformational shock.The mediating effects of coping styles on psychoticism,extraversion,and neuroticism are 0.095,-0.051,and 0.134,respectively,accounting for 43.18％,30.36％,and 32.29％of the total effect.Conclusion Coping styles of newly graduated nurses act as mediating variables between personality traits and transitional shock.Nursing managers should pay attention to cultivating good individual personality traits and establishing a supportive work environment to enhance new nurses'positive coping and reduce the level of transitional impact.

Objective:To explore the short-term efficacy on 3D printing assisted reconstruction of traumatic digit joint defects using rib and costo-osteochondral autograft.Methods:From August 2022 to July 2023, 7 patients with open digit joint defects had undergone emergency primary debridement and fracture fixation in the Department of Orthopaedics, 988th Hospital of the Joint Logistics Support Force of PLA. Patients with more phalangeal defects that could not be aligned were treated with antibiotic bone cement filling in the emergency surgery. In the second stage surgery, bone cement was removed and transfer of rib cartilage graft was performed to reconstruct the digit joint defect. According to a 1∶1 3D printed hand templates, rib cartilage grafts were crafted to the shape of digit joints, and then spliced together the digit joints and bone defects for fixation. Follow-up X-ray examinations were taken and assessment of the healing status of rib and fractures of phalangeal and metacarpophalangeal bones were carried out according to the Paley fracture healing score. At the outpatient follow-up, assessment of transferred joint movement and evaluation of upper limb function were conducted according to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association. Visual Analogue Scale (VAS) pain scores were evaluated from the affected digits and donor sites.Results:After reconstructive surgery, all 7 patients had primary healing of the wounds of hand. One patient had fat liquefaction at the donor site, and the rest had primary donor site healing. One patient received further surgery for extensor tendon repair after rib cartilage grafting due to the digital extensor tendon injury. All 7 patients were included in postoperative follow-up for 6-11 months, with an average of 9 months. All patients had excellent fracture healing according to the Paley fracture healing score. At the final follow-up, the extension and flexion of the digit joints were found at 40°-80° (average 56.2°) for proximal interphalangeal joints (4 patients), and 10° in extension and 85° in flexion for metacarpophalangeal joint (1 patient). The range of motion of the thumb interphalangeal joint (2 patients) was 20°-35° (average 27.5°). Hand function was assessed according to Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association and it was found that 3 patients were in excellent, 3 in good and 1 in fair.Conclusion:This study focused on the treatment of traumatic digit joint defects by transfer of individually crafted rib cartilages in reconstruction of the defected digit joint. It significantly improves the appearance and function of the defected digit joints, especially suitable for the irregular defects of phalangeal bones.

Liver cancer is one of the common malignant tumors, and most patients are in the middle and advanced stages when they seek medical attention. Ablation therapy is the main treatment for patients with early or unresectable liver cancer. Changes in the tumor microenvironment may affect the efficacy and prognosis of patients after ablation of liver cancer. In recent years, more and more studies have explored the potential synergistic effect between ablation therapy for liver cancer and the tumor microenvironment to improve the efficacy of ablation therapy and improve survival rate. Exploring the key components of the tumor microenvironment and the immunomodulatory role of the tumor microenvironment in the ablation treatment of liver cancer can provide a new strategy for the treatment of liver cancer.