Cancer is one of the most lethal and burdensome diseases worldwide. Its progression not only causes irreversible damage to the body, but also imposes a substantial psychological burden on patients due to its complex prognosis. Immune imbalance, a hallmark of the tumor microenvironment (TME), accelerates tumor invasion and metastasis by impairing the function of effector immune cells, promoting the abnormal infiltration of immunosuppressive cells, and disrupting cytokine homeostasis, thereby constituting a major barrier to the efficacy of cancer immunotherapy. Compared with conventional chemotherapy and radiotherapy, aerobic exercise has shown considerable potential in antagonizing tumor progression through relatively mild but effective immunomodulatory mechanisms. On the one hand, regular aerobic exercise enhances the number and activity of key effector immune cells, such as CD8⁺ T cells, thereby strengthening their ability to recognize and eliminate tumor cells and alleviate immune imbalance. On the other hand, aerobic exercise promotes tumor vascular normalization, improves vascular maturity, and stimulates the secretion of irisin and other anti-inflammatory myokines, thereby remodeling the TME and relieving its immunosuppressive state to delay tumor progression. However, psychological stress following a cancer diagnosis can not only act as an independent disruptive factor that exacerbates immune imbalance within the TME, but also amplify the effects of other detrimental factors, such as reduced treatment adherence, thereby further weakening the antagonistic effect of aerobic exercise on tumor growth. Psychological stress, as a chronic stressor, promotes the excessive secretion of emotion-related hormones, including glucocorticoids (GCs) and norepinephrine (NE), which further suppress the activation and effector functions of antitumor immune cells such as CD8⁺ T cells and natural killer (NK) cells, while facilitating the recruitment of protumor immune cells such as regulatory T cells (Tregs). These changes ultimately disrupt immune homeostasis in the TME, promote tumor immune evasion, accelerate tumor invasion and metastasis, and offset the beneficial effects of aerobic exercise on tumor control. In addition, psychological stress induces hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis and abnormal excitation of the sympathetic nervous system (SNS), thereby maintaining elevated levels of GCs, NE, and related stress hormones, suppressing inflammatory chemokine expression and immune cell recruitment, and further disturbing immune homeostasis in the TME, which accelerates tumor progression. More importantly, prolonged psychological stress can also disrupt the homeostasis of central neurotransmitters, such as 5-hydroxytryptamine (5-HT) and glutamate (Glu). This not only directly inhibits the activation and effector functions of antitumor immune cells and promotes the establishment of an immunosuppressive microenvironment, but also impairs cellular energy metabolism and continuously provides energy for tumor cells through metabolic reprogramming, thereby sustaining rapid tumor growth and adaptation to a hostile TME. Ultimately, these alterations contribute to the dysregulation of “neuro-endocrine-immune” axis and weaken the protective effect of aerobic exercise against tumor progression. Therefore, this review focuses on the interaction between psychological stress and the “neuro-endocrine-immune” axis, with particular emphasis on the mechanisms by which psychological stress induces immune imbalance and weakens the antagonistic effect of aerobic exercise on tumor progression. We further highlight the important role of psychological stress in tumor progression and propose that combining psychotropic interventions, aerobic exercise, and clinical antitumor immunotherapy may help restore the tumor-killing capacity of the immune system. Such a multimodal strategy may exert synergistic effects at multiple levels, including psychological stress relief, neuroendocrine regulation, and reconstruction of immune homeostasis, thereby providing new perspectives for identifying therapeutic targets in solid tumors, enhancing the efficacy of cancer immunotherapy, and improving patient prognosis.

Objective:To compare the safety,short-term and long-term efficacy of laparoscopic radical antero-grade modular pancreatic-splenic resection(L-RAMPS)and open radical anterograde modular pancreatic-splenic resec-tion(RAMPS)in the treatment of distal pancreatic cancer,providing clinical evidence for the development of minimally in-vasive surgery for distal pancreatic cancer.Methods:Clinical and follow-up data of patients with distal pancreatic can-cer who underwent surgical treatment at Department of Liver Transplantation and Hepatobiliary Surgery,Shandong Pro-vincial Hospital Affiliated to Shandong First Medical University,between January 2019 and October 2021 were retro-spectively collected.Patients were divided into a L-RAMPS group(n=70)and a RAMPS group(n=36)based on the sur-gical approach.Propensity score matching(PSM)was applied in a 1:1 ratio to compare short-term and long-term out-comes between the two groups.Results:After PSM,L-RAMPS group has the advantage of less estimated blood loss(50 mL vs 180 mL,P=0.002)and a shorter postoperative length of stay(6 d vs 8 d,P<0.001).No statistically significant differences were observed in long-term survival and postoperative complication rates between these two groups(P>0.05).Univariate and multivariate analyses identified preoperative serum CA19-9 levels,peritumoral tissue infiltration,perineural invasion,and lymph node metastasis as independent risk factors for early postoperative tumor recurrence.Conclusion:This study has demonstrated that L-RAMPS for patients with distal pancreatic cancer has the advantage of less estimated blood loss and a shorter postoperative length of stay.The short-term and long-term efficacy of L-RAMPS is comparable to that of RAMPS.L-RAMPS is a safe and effective surgical method for patients with distal pan-creatic cancer.

Objective:To explore the neuroprotective effect of α7 nicotinic acetylcholine receptor (α7nAChR) on rat models of Parkinson's disease (PD) and its underlying mechanism.Methods:Forty-eight 8-week-old SPF-grade SD rats were randomly divided into a normal control group, a PD model group, an α7nAChR empty vector group and an α7nAChR overexpression group, with 12 rats in each group. PD models in the latter 3 groups of rats were established by 6-hydroxydopamine (6-OHDA). Four weeks after modeling, rats in the latter 2 groups were injected with 2 μL α7nAChR overexpression lentivirus or empty vector lentivirus through stereotactic intracerebral injection, while rats in the normal control group did not receive any treatment. Two weeks after injection, the behavioral changes of these rats were detected by apomorphine-induced rotation test; the right substantia nigra pars compacta (SNc) was prepared and performed the following experiments: hematoxylin-eosin (HE) staining and Nissl staining were used to detect the neuron morphological changes, TUNEL was used to detect the neuron apoptosis, fluorescent double labeling was used to detect the expressions of tyrosine hydroxylase (TH) and α-synuclein (α-Syn), ELISA was used to detect the expressions of 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA), and Western blotting was used to detect the expressions of ferroptosis-related proteins (ferritin heavy chain 1 [FTH1], Sigma receptor 1 [S1R], glutathione peroxidase 4 [GPX4], long chain acyl-coa synthetase 4 [ACSL4], solute carrier family 7 member11 [SLC7A11]), and the expressions of proteins related to CAMKII/ERK pathway (phosphorylated calmodulin kinase Ⅱ [p-CAMK Ⅱ], phosphorylated extracellular signal regulated kinase [p-ERK], and phosphorylated Kirsten rat sarcoma viral oncogene homolog [p-KRAS]).Results:(1) Compared with the normal control group, the PD model group, α7nAChR empty vector group and α7nAChR overexpression group had significantly larger number of rotations ( P<0.05); compared with the PD model group, the α7nAChR overexpression group had significantly smaller number of rotations ( P<0.05). (2) HE staining and Nissl staining showed that the PD model group had decreased number of dopaminergic neurons and Nissl bodies, accompanied by neuronal distribution disorder, nuclear condensation or swelling; the α7nAChR-overexpression group had obviously improved appearance of dopaminergic neurons, with normal morphology and less cell degeneration. (3) TUNEL results showed that compared with the normal control group, the PD model group, α7nAChR empty vector group, and α7nAChR overexpression group had significantly higher apoptosis rate ( P<0.05); compared with the PD model group, the α7nAChR overexpression group had statistically lower apoptosis rate ( P<0.05). (4) Double immunofluorescent staining results showed that compared with the normal control group (303.61±48.40, 13 985.80±1 956.06), the PD model group, α7nAChR empty vector group and α7nAChR overexpression group had significantly increased α-Syn expression (4 310.40±518.43, 3 846.60±524.47 and 1 033.55±59.98) and statistically decreased TH expression (760.97±57.26, 842.55±113.41 and 8 101.82±1 171.85) in the right SNc ( P<0.05); compared with the PD model group, the α7nAChR overexpression group had significantly decreased α-Syn expression and increased TH expression in the right SNc ( P<0.05). (5) ELISA results showed that the 4-HNE and MDA expressions in the right SNc of the PD model group, α7nAChR empty vector group and α7nAChR overexpression group were significantly higher than those in the normal control group ( P<0.05); the 4-HNE and MDA expressions in the α7nAChR overexpression group were significantly lower than those in the PD model group ( P<0.05). (6) Western blotting results showed that compared with the normal control group, the PD model group, α7nAChR empty vector group and α7nAChR overexpression group had significantly decreased FTH1, S1R, GPX4, and SLC7A11 protein expressions, and statistically increased ACSL4 protein expression in the right SNc ( P<0.05); compared with the PD model group, the α7nAChR overexpression group had significantly increased FTH1, S1R, GPX4, and SLC7A11 protein expressions and decreased ACSL4 protein expression in the right SNc ( P<0.05). Compared with the normal control group, the PD model group, α7nAChR empty vector group and α7nAChR overexpression group had significantly increased p-KRAS, p-CAMKII, and p-ERK protein expressions in the right SNc ( P<0.05); compared with the PD model group, the α7nAChR overexpression group had significantly decreased p-KRAS, p-CAMKII, and p-ERK protein expressions in the right SNc ( P<0.05). Conclusion:The α7nAChR may exert neuroprotective effect on PD rat models by regulating the CAMKII/ERK pathway and ferroptosis-related proteins.

Objective:To compare the clinical efficacy between microscopic varicocelectomy and laparoscopic varicocelectomy in the treatment of varicocele(VC)with male infertility.Methods:A total of 307 patients who were diagnosed with VC complicated with male infertility and admitted to the Affiliated Hospital of Qingdao University from October 2018 to October 2022 were recruited for retrospective analysis.The patients were divided into the microscopic group(180 cases)and laparoscopic group(127 cases)according to the surgery method.The pre-and postoperative clinical data of these two groups were analyzed,including the degree of dilatation and reflux time of internal spermatic vein,hemodynamic parameters of testicular capsular artery,proportion of progressive motility spermato-zoa(PR),concentration of spermatozoa,proportion of normal morphology sperm,the pregnancy outcome of spouses and the incidence of complications related with surgery within 2 years postoperatively.Results:All the surgeries for the 307 patients in this study were successful.There was no significant difference in operation time,hospitalization time and management expenses between the microscop-ic group and the laparoscopic group(P＞0.05).Compared to the patients in laparoscopic group,the patients in the microscopic group received a better improvement in venous diameter,reflux time of spermatic veins and hemodynamic parameters of testicular capsular ar-tery(P＜0.05).Moreover,the semen analysis showed that the PR,spermatozoa concentration and proportion of normal morphology sperm in the microscopic group were also obviously increased than those in the laparoscopic group(P＜0.05).During the 2-year fol-low-up period,the conception rate of spouses in the microscopic group was 67.2％,while only 47.2％in the laparoscopic group,in which the difference was statistically significant(P＜0.05).Besides,the time-to-pregnancy(TTP)within 2 years postoperatively in the microscopic group was significantly shorter than that in the laparoscopic group(P＜0.05).Meanwhile,the incidence of adverse pregnancy outcomes in the microscopic group was also significantly lower than that in the laparoscopic group(P＜0.05).It is worth mentioned that the spontaneous conception rate of spouses with successful pregnancy in the microscopic group was also significantly higher than that in the laparoscopic group(P＜0.05).Severe complication such as testicular atrophy,bleeding and infection did not appear in both of two groups.However,the incidences of testicular hydrocele and recurrence of VC postoperatively in the laparoscopic group were significantly higher than those in the microscopic group(P＜0.05).Conclusion:Both microscopic varicocelectomy and laparoscopic varicocelectomy can be applied to the management of VC combined with male infertility.But microscopic varicocelectomy showed better clinical efficacy in improving the testicular hemodynamic parameters,semen quality,pregnancy outcome and postopera-tive complications,which is worthy of further clinical applications.

This study aims to understand the epidemic distribution characteristics,antimicrobial resistance,virulence genes,and biofilm adhesion ability of Enterococcus in yaks on the Tibetan plateau.Three hundred and forty-six fresh yak fecal samples and 311 milk samples were collected from four provinces on the Tibetan plateau(Xizang,Sichuan,Gansu,Qinghai),totaling 657 sam-ples.Bacterial isolation and identification were conducted,followed by 16S rDNA gene detection and the construction of a systematic evolutionary tree.The isolated strains were tested for antimi-crobial resistance and virulence genes using PCR,and sensitivity tests were performed using 18 types of antibiotics.The biofilm adhesion ability of the isolated bacteria was determined using an improved semi-quantitative crystal violet staining method.The results showed that the total isola-tion rate of Enterococcus was 32.27％,with Sichuan having the highest at 60.23％,followed by Gansu,Qinghai,and Tibet autonomous region at 42.70％,23.47％,and 18.31％respectively.In terms of sample types,the isolation rate in fecal samples was 36.71％,and in milk samples,it was 27.33％.Through PCR amplification,bands of approximately 1 400 bp were obtained,and 5 strains were selected for evolutionary analysis,forming a separate cluster.Among the 212 isolated strains,a high resistance to clindamycin,quinupristin-dalfopristin,linezolid,levofloxacin,and erythromycin was observed,with various resistance phenomena,accounting for 60.85％.Only 5 out of 12 resist-ant genes were detected,namely erm(B),tet(L),tet(O),tet(M),and ant(6)-Ia.All 13 virulence genes were detected in Enterococcus,with detection rates in the range of 5.19％to 95.76％,where cpd was 95.75％,gelE was 91.98％,efaA was 86.79％,asal was 86.32％,and the rest ranged from 5.19％to 55.66％.The fsr virulence gene was not detected in Enterococcus from milk sources.Among the isolated strains,3.30％showed medium adhesive ability,48.58％showed weak adhesive ability,and 48.11％showed no adhesive ability.The above research revealed the preva-lence of yak derived Enterococcus,the carrying status of resistance and virulence genes,and the correlation between biofilm phenotypes,laying the foundation for mastering research data on yak-derived Enterococcus in the Tibetan plateau.

This study analyzed the burden and trends in enteric infections in China from 1990 to 2021 from a One Health perspec-tive.Data on mortality associated with enteric infections were extracted from the 2021 Global Burden of Disease(GBD)database.The analysis focused on assessing the mortality rates of enteric infectious diseases attributed to various etiologies and risk factors,along with the age and sex distribution,from 1990 to 2021.Average annual percentage change(AAPC)was used to assess the total changes in disease burden.The age-standardized mortality rate of intestinal infections in China decreased from 9.642/100 000 in 1990 to 0.439/100 000 in 2021,with an AAPC of-57.103%(95%CI:-57.118%to-57.088%).In 2021,Rotavirus,Norovirus,and Crypto-sporidium were the top three etiologies contributing to disease burden,with mortality rates of 1.020/100 000,0.040/100 000 and 0.079/100 000,respectively.A significant variation in etiology distribution was observed across age groups:Rotavirus,Shigella,and Crypto-sporidium dominated among children under 5 years of age,whereas Cryptosporidium,Norovirus,and Clostridioides difficile were more prevalent in older populations.Risk factor analysis indicated that unsafe water sources and poor sanitation accounted for 73.394%of all enteric disease-related deaths.In conclusion,the burden of enteric infections in China markedly declined from 1990 to 2021,and sig-nificant variations in the etiological spectrum and disease burden were observed across age groups.The persistent effects of unsafe wa-ter sources and poor sanitation underscore the need for targeted interventions to further decrease the burden of these diseases.Our find-ings highlight the success of public health interventions in decreasing the burden of enteric infections in China,while emphasizing the need for targeted measures to address disparities in high-risk populations and improve environmental sanitation.

G protein-coupled receptors(GPCRs)are the largest family of membrane proteins in eukaryotes,with nearly 800 genes coding for these proteins.They are involved in many physiological processes,such as light perception,taste and smell,neurotransmitter,metabolism,endocrine and exocrine,cell growth and migration.Importantly,GPCRs and their ligands are the targets of approximately one third of all mar-keted drugs.GPCRs are traditionally known for their role in transmitting signals from the extracellular environment to the cell's interior via the plasma membrane.However,emerging evidence suggests that GPCRs are also localized on mitochondria,where they play critical roles in modulating mitochondrial functions.These mitochondrial GPCRs(mGPCRs)can influence processes such as mitochondrial respi-ration,apoptosis,and reactive oxygen species(ROS)production.By interacting with mitochondrial signaling pathways,mGPCRs contribute to the regulation of energy metabolism and cell survival.Their presence on mitochondria adds a new layer of complexity to the understanding of cellular signaling,highlighting the organelle's role as not just an energy powerhouse but also a crucial hub for signal transduction.This expanding understanding of mGPCR function on mitochondria opens new avenues for research,particularly in the context of diseases where mitochondrial dysfunction plays a key role.Ab-normalities in the phase conductance pathway of GPCRs located on mitochondria are closely associated with the development of systemic diseases such as cardiovascular disease,diabetes,obesity and Alz-heimer's disease.In this review,we examined the various types of GPCRs identified on mitochondrial membranes and analyzed the complex relationships between mGPCRs and the pathogenesis of various diseases.We aim to provide a clearer understanding of the emerging significance of mGPCRs in health and disease,and to underscore their potential as therapeutic targets in the treatment of these conditions.

Objective To establish a rapid,sensitive,and specific multiplex PCR detection method for the simultaneous detection of Cryptosporidium,Eimeria,and bovine parvovirus.Methods Specific primers targeting the SSU rRNA genes of Cryptosporidium and Eimeria,as well as the VP2 gene of bovine parvovirus were designed and the corresponding recombinant plasmid standards were constructed.To establish the multiplex PCR method,the reaction conditions were optimized using temperature gradient PCR and single-variable control methods.The sensitivity,specificity,reproducibility,and clinical application of the protocol were evaluated.Results The optimal annealing temperature was found to be 60.5℃,and the forward and reverse primer concentrations were determined to be 0.2 μmol/L for Eimeria,and 0.4 μmol/L for Cryptosporidium and bovine parvovirus.The assay demonstrated high sensitivity,with detection limits of 243,260,and 3 110 copies for the recombinant plasmid standards of Cryptosporidium,Eimeria,and bovine parvovirus,respectively.Specificity testing showed no cross-reactivity with ten common bovine pathogens,including Salmonella,bovine viral diarrhea virus,and bovine rotavirus.Consistent intra-and inter-batch results confirmed the strong reproducibility of the method.Clinical application to 81 diarrhea samples from various regions in the Ganzi Prefecture,Sichuan,revealed positivity rates of 18.52%(15/81)for Cryptosporidium,34.57%(28/81)for Eimeria,and 18.52%(15/81)forbovineparvovirus,withamixedinfectionrateof3.7%(3/81).Conclusions Themultiplex PCR method established in this study offers a reliable tool for differential diagnosis and epidemiological investigation of the three common diarrheal pathogens in yaks.

Objective To explore the clinical value of high-frequency ultrasound-guided labial gland biopsy in patients with suspected Sj?gren's syndrome(SS).Methods Totally 126 patients with clinically suspected SS and salivary gland involvement who underwent labial gland biopsy in Department of Ultrasound and Department of Rheumatology and Immunology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from Sep.2022 to Dec.2024 were enrolled.The patients who underwent traditional excision labial gland biopsy from Sep.2022 to Feb.2023 were selected as control group(n=53),and the patients who received high-frequency ultrasound-guided labial gland biopsy from Mar.2023 to Dec.2024 were selected as ultrasound-guided group(n=73).The success rate of sampling,the number of salivary lobes,wound healing time,and adverse reaction incidence were analyzed in the 2 groups.Results The success rate of sampling in the ultrasound-guided group(100.00％,73/73)was significantly higher than that in the control group(92.45％,49/53),the number of salivary lobes(6[6,7])was significantly greater than that in the control group(6[5,6]),and the wound healing time was significantly shorter than that in the control group(4[4,5]d vs 5[5,6]d)(all P＜0.05).One(1.37％)patient of the ultrasound-guided group had postoperative adverse reactions,and 5(9.43％)patients of the control group had adverse reactions,with no significant difference(P＞0.05).Conclusion High-frequency ultrasound can clearly locate labial gland,improve the success rate of sampling and shorten the wound healing time,and it is worthy of clinical promotion and application.

BACKGROUND: Early control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the progress of cardiovascular disease. However, its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive. Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China. METHODS: The retrospective cohort study of 1546 men aged 69.74 ± 11.30 years conducted in Beijing, China from 2015 to 2022. And the incidence of primary osteoporosis was annually recorded. LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C. The association of baseline LDL-C for osteoporosis was estimated using hazard ratio (HR) with 95% CI in Cox proportional hazard model, while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio (OR) with 95% CI in logistic regression model. RESULTS: During the median 6.2-year follow-up period, 70 men developed primary osteoporosis. The higher level of baseline LDL-C (HR = 1.539, 95% CI: 1.012-2.342) and mean LDL-C (OR = 2.190, 95% CI: 1.443-3.324) were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates. Compared with those in the LDL-C trajectory of low-stable decrease, participants with medium-fluctuant trajectory, whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease, were negatively associated with osteoporosis risk (OR = 2.451, 95% CI: 1.152-5.216). And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk (OR = 0.718, 95% CI: 0.212-2.437). CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men. Early controlling a stable level of LDL-C is also essential for bone health.