ObjectiveThis paper aims to investigate the effects of icariin on spermatogenesis in mice with exercise-induced fatigue and explore the underlying mechanisms. MethodsICR male mice were screened by swimming and randomly divided into normal group， model group， vitamin C group， icariin groups with low， medium， and high doses， and medium-dose icariin+N-nitro-L-arginine methyl ester （L-NAME） group， with 10 mice per group. Except for the normal group， all the other groups underwent weighted swimming training to establish an exercise-induced fatigue model. No gavage was administered during the first two weeks of the weighted training. From week three to four， the icariin groups with low， medium， and high doses received 0.03， 0.06， and 0.12 g·kg^-1 icariin via gavage， respectively. The vitamin C group received 0.2 g·kg^-1 vitamin C. The L-NAME group received 0.06 g·kg^-1 icariin and 0.01 g·kg^-1 L-NAME via intraperitoneal injection. The normal and model groups received equivalent physiological saline. After the experiment， body weight and the last exhaustive swimming time were recorded. Blood urea nitrogen （BUN）， lactate （LA）， lactate dehydrogenase （LDH）， malondialdehyde （MDA）， testicular testosterone （T）， testicular Ca²⁺/Mg²⁺-adenosine triphosphatase （ATPase） （micro-assay）， and the levels of testicular cyclic guanosine monophosphate （cGMP） were measured by using kits. Sperm CD46 levels were detected by flow cytometry. Testicular seminiferous tubules were observed via hematoxylin-eosin （HE） staining， and the testicular morphometric score （TMS） was used to evaluate the spermatogenic function. Protein expression of regucalcin （RGN， SMP30）， cGMP-dependent protein kinase 1 （PKG）， and cGMP-dependent protein kinase anchoring protein （GKAP1） was detected by Western blot. Testicular regucalcin expression was examined by immunofluorescence （IF）. The epididymal sperm quality of mice was observed under a microscope. Fluorescence-stained sections of stimulated by retinoic acid gene 8 （STRA8）， synaptonemal complex protein 3 （SCP3）， and transition protein 1（TNP1） in testicular seminiferous tubules were assessed by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group showed decreased body weight and exhaustive swimming time （P<0.01）， significantly increased fatigue markers （LA， LDH， and BUN） and lipid peroxidation product MDA （P<0.01）， reduced testicular RGN， PKG， GKAP1， testosterone， Ca²⁺/Mg²⁺-ATPase， and cGMP levels （P<0.01）， decreased sperm motility， sperm count， and TMS scores， and downregulated the expression of STRA8， SCP3， and TNP1. Compared with the model group， the icariin group with high dose exhibited increased exhaustive swimming time （P<0.01）， reduced LA， LDH， BUN， and MDA levels （P<0.01）， elevated superoxide dismutase （SOD） （P<0.01）， upregulated testicular RGN， PKG， GKAP1， testosterone， Ca²⁺/Mg²⁺-ATPase， and cGMP levels （P<0.01）， improved sperm motility， sperm count， and TMS scores， and enhanced STRA8， SCP3， and TNP1 expression. Compared with the L-NAME group， the icariin group with medium dose showed increased expression of STRA8， SCP3， and TNP1 in the testicular tissue （P<0.01） and elevated cGMP and GKAP1 levels （P<0.01）. ConclusionExercise-induced fatigue reduces the expression of RGN and cGMP/PKG/GKAP1 in mice， thereby causing abnormal spermatogenesis and impairing reproductive function in mice. Icariin ameliorates spermatogenic dysfunction in exercise-induced fatigue mice by promoting the expression of RGN and cGMP/PKG/GKAP1， thereby mitigating the damage of exercise-induced fatigue to the reproductive system.

ObjectiveThis paper aims to investigate the effects of icariin on spermatogenesis in mice with exercise-induced fatigue and explore the underlying mechanisms. MethodsICR male mice were screened by swimming and randomly divided into normal group， model group， vitamin C group， icariin groups with low， medium， and high doses， and medium-dose icariin+N-nitro-L-arginine methyl ester （L-NAME） group， with 10 mice per group. Except for the normal group， all the other groups underwent weighted swimming training to establish an exercise-induced fatigue model. No gavage was administered during the first two weeks of the weighted training. From week three to four， the icariin groups with low， medium， and high doses received 0.03， 0.06， and 0.12 g·kg^-1 icariin via gavage， respectively. The vitamin C group received 0.2 g·kg^-1 vitamin C. The L-NAME group received 0.06 g·kg^-1 icariin and 0.01 g·kg^-1 L-NAME via intraperitoneal injection. The normal and model groups received equivalent physiological saline. After the experiment， body weight and the last exhaustive swimming time were recorded. Blood urea nitrogen （BUN）， lactate （LA）， lactate dehydrogenase （LDH）， malondialdehyde （MDA）， testicular testosterone （T）， testicular Ca²⁺/Mg²⁺-adenosine triphosphatase （ATPase） （micro-assay）， and the levels of testicular cyclic guanosine monophosphate （cGMP） were measured by using kits. Sperm CD46 levels were detected by flow cytometry. Testicular seminiferous tubules were observed via hematoxylin-eosin （HE） staining， and the testicular morphometric score （TMS） was used to evaluate the spermatogenic function. Protein expression of regucalcin （RGN， SMP30）， cGMP-dependent protein kinase 1 （PKG）， and cGMP-dependent protein kinase anchoring protein （GKAP1） was detected by Western blot. Testicular regucalcin expression was examined by immunofluorescence （IF）. The epididymal sperm quality of mice was observed under a microscope. Fluorescence-stained sections of stimulated by retinoic acid gene 8 （STRA8）， synaptonemal complex protein 3 （SCP3）， and transition protein 1（TNP1） in testicular seminiferous tubules were assessed by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group showed decreased body weight and exhaustive swimming time （P<0.01）， significantly increased fatigue markers （LA， LDH， and BUN） and lipid peroxidation product MDA （P<0.01）， reduced testicular RGN， PKG， GKAP1， testosterone， Ca²⁺/Mg²⁺-ATPase， and cGMP levels （P<0.01）， decreased sperm motility， sperm count， and TMS scores， and downregulated the expression of STRA8， SCP3， and TNP1. Compared with the model group， the icariin group with high dose exhibited increased exhaustive swimming time （P<0.01）， reduced LA， LDH， BUN， and MDA levels （P<0.01）， elevated superoxide dismutase （SOD） （P<0.01）， upregulated testicular RGN， PKG， GKAP1， testosterone， Ca²⁺/Mg²⁺-ATPase， and cGMP levels （P<0.01）， improved sperm motility， sperm count， and TMS scores， and enhanced STRA8， SCP3， and TNP1 expression. Compared with the L-NAME group， the icariin group with medium dose showed increased expression of STRA8， SCP3， and TNP1 in the testicular tissue （P<0.01） and elevated cGMP and GKAP1 levels （P<0.01）. ConclusionExercise-induced fatigue reduces the expression of RGN and cGMP/PKG/GKAP1 in mice， thereby causing abnormal spermatogenesis and impairing reproductive function in mice. Icariin ameliorates spermatogenic dysfunction in exercise-induced fatigue mice by promoting the expression of RGN and cGMP/PKG/GKAP1， thereby mitigating the damage of exercise-induced fatigue to the reproductive system.

Guided by molecular networking, nine novel curvularin derivatives (1-9) and 16 known analogs (10-25) were isolated from the hydrothermal vent sediment fungus Penicillium sp. HL-50. Notably, compounds 5-7 represented a hybrid of curvularin and purine. The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction, electronic circular dichroism (ECD) calculations, ¹³C NMR calculation, modified Mosher's method, and chemical derivatization. Investigation of anti-inflammatory activities revealed that compounds 7-9, 11, 12, 14, 15, and 18 exhibited significant suppressive effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine macrophage RAW264.7 cells, with IC₅₀ values ranging from 0.44 to 4.40 μmol·L^-1. Furthermore, these bioactive compounds were found to suppress the expression of inflammation-related proteins, including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), NLR family pyrin domain-containing protein 3 (NLRP3), and nuclear factor kappa-B (NF-κB). Additional studies demonstrated that the novel compound 7 possessed potent anti-inflammatory activity by inhibiting the transcription of inflammation-related genes, downregulating the expression of inflammation-related proteins, and inhibiting the release of inflammatory cytokines, indicating its potential application in the treatment of inflammatory diseases.
Penicillium/chemistry* ; Mice ; Animals ; Anti-Inflammatory Agents/isolation & purification* ; RAW 264.7 Cells ; Nitric Oxide/metabolism* ; Hydrothermal Vents/microbiology* ; Macrophages/immunology* ; Molecular Structure ; Nitric Oxide Synthase Type II/immunology* ; Cyclooxygenase 2/immunology* ; Geologic Sediments/microbiology* ; NF-kappa B/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology*

Objective To investigate the effect of ubiquitin-specific peptidase(USP)44 and nuclear receptor co-inhibitor 1(NCOR1)expression on prognosis in non-small cell lung cancer.Methods A total of 98 pa-tients with non-small cell lung cancer admitted to a hospital from May 2019 to May 2021 were selected as the study objects,and non-small cell lung cancer tissues and adjacent tissues were collected to detect the expres-sion levels of USP44 and NCOR1 in these tissues by immunohistochemical staining.The relationship between USP44 and NCOR1 expression and pathological features of non-small cell lung cancer patients was analyzed,and the prognostic factors of non-small cell lung cancer patients were analyzed by multivariate Cox regression.Results The positive expression rates of USP44 and NCOR1 in non-small cell lung cancer tissues were higher than those in adjacent tissues,the difference was statistically significant(P<0.05).The positive expression rates of USP44 and NCOR1 in patients with medium-low differentiation,lymph node metastasis,clinical stageⅢ to Ⅳ,and pleural metastasis were higher than those in patients with highly differentiated,no lymph node metastasis,clinical stage Ⅰ to Ⅱ,and no pleural metastasis,and the difference was statistically significant(P<0.05).The 3-year overall survival rate of USP44 and NCOR1 negative non-small cell lung cancer patients was higher than that of USP44 and NCOR1 positive non-small cell lung cancer patients,and the difference was statistically significant(all P<0.05).Multivariate Cox regression analysis showed that pleural metastasis,USP44 positive and NCOR1 positive were prognostic factors in non-small cell lung cancer patients(P<0.05).Conclusion The expression of USP44 and NCOR1 in patients with non-small cell lung cancer can be used as biomarkers for prognosis assessment,and provide evidence for progression assessment and clinical de-cision making of non-small cell lung cancer.

Objective To evaluate the effect of preoperative metabolic syndrome on early function of renal allografts in allogeneic kidney transplant recipients.Methods Clinical data of 117 kidney transplant recipients were retrospectively analyzed.According to the renal allograft function,they were divided into the delayed graft function(DGF)group(n=29)and non-DGF group(n=88).Relevant risk factors of DGF in recipients undergoing allogeneic kidney transplantation were assessed by univariate and multivariate regression analyses.The effect of preoperative metabolic syndrome on early function of renal allografts was analyzed.Results Among 117 kidney transplant recipients,47 cases were complicated with preoperative metabolic syndrome,and 29 cases developed postoperative DGF.In the DGF group,83％of the recipients were complicated with preoperative metabolic syndrome,higher than 74％in the non-DGF group(P＜0.05).Univariate analysis showed that the body mass index(BMI)and terminal serum creatinine(Scr)level of the donors,and BMI,blood glucose level,triglyceride level and the proportion of preoperative metabolic syndrome of the recipients in the DGF group were higher than those in the non-DGF group(all P＜0.05).Multivariate logistic regression analysis revealed that high Scr levels of the donors,high hemoglobin levels of the recipients and preoperative metabolic syndrome of the recipients were the independent risk factors for DGF after kidney transplantation(all P＜0.05).Conclusions Preoperative metabolic syndrome is an independent risk factor for DGF in allogeneic kidney transplant recipients.Corresponding measures should be taken to lower the incidence of DGF and other metabolic complications.

ObjectiveTo study the effects of Epimedii Folium polysaccharides on mice with exercise-induced fatigue and explore its possible mechanism of action. MethodICR male mice screened by swimming training were randomly divided into a control group， model group， vitamin C group， and low， medium， and high dose groups of Epimedii Folium polysaccharides， with eight mice in each group. The exercise-induced fatigue model was established by weight-bearing swimming training in each group except for the control group. After two weeks of weight-bearing swimming， the Epimedii Folium polysaccharide groups were given 100， 200， 400 mg∙kg^-1 of Epimedii Folium polysaccharides by gavage， and the vitamin C group was given 200 mg∙kg^-1 of vitamin C by gavage. The control group and the model group were given equal amounts of saline for 14 d. At the end of the experimental period， the body mass of the mice in each group and the time of last swimming due to exhaustion were recorded. Serum urea nitrogen （BUN）， lactic acid （LA）， lactate dehydrogenase （LDH）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione peroxidation （GSH-Px）， myoglycogen （MG） in skeletal muscle， hepatic glycogen （HG） in the liver were detected by kits. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in muscle tissue. Western blot was used to detect the protein expression of p38 mitogen-activated protein kinase （p38 MAPK）， phosphorylation （p）-p38 MAPK， extracellular signal-regulated kinase1/2 （ERK1/2）， nuclear factor-κB （NF-κB）， p-NF-κB， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in muscle tissue. The immunofluorescence （IF） method was used to detect the expression of tumor necrosis factor-α （TNF-α） in skeletal muscle tissue of mice in each group. ResultCompared with the control group， the body mass of mice in the model group decreased， and the time of last swimming due to exhaustion decreased （P<0.01）. In addition， there were significantly higher serum levels of the fatigue metabolites LA， LDH， BUN， and lipid peroxidation product MDA （P<0.01） and decreased levels of MG， HG， SOD， and GSH-Px （P<0.01）. The protein expressions of p-p38 MAPK， ERK1/2， p-NF-κB， IL-1β， IL-6， and TNF-α in skeletal muscle tissue were significantly higher than those of the control group （P<0.01）. Compared with the model group， the body mass and time of last swimming due to exhaustion of the mice in the low， medium， and high dose groups of Epimedii Folium polysaccharides and the vitamin C group were increased （P<0.05， P<0.01）， and the contents of LA， LDH， BUN， and MDA were significantly decreased （P<0.05， P<0.01）. The levels of MG， HG， SOD， and GSH-Px increased （P<0.05， P<0.01）， and the protein expression levels of p-p38 MAPK， ERK， p-NF-κB， IL-1β， IL-6， and TNF-α in skeletal muscle tissue decreased （P<0.05， P<0.01）. ConclusionEpimedii Folium polysaccharides can play a role in alleviating exercise-induced fatigue by inhibiting the p38 MARK/NF-κB signaling pathway， thereby reducing the accumulation of metabolites， improving the activity of antioxidant enzymes， increasing the glycogen content of the body， and reducing inflammation in skeletal muscle.

Objective:To study the feasibility and efficacy of pericranial flaps for the repairs of large anterior skull base defects.Methods:The average length of the pericranial flaps needed for skull base repair was determined with computed tomography measurements in 20 adults and anatomical dissections in 5 cadaver specimen. A series of patients who underwent endoscopic skull base surgeries and subsequent reconstructions with pericranial flaps at the Department of Otolaryngology Head and Neck Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People′s Hospital from 2016 to 2022 were retrospectively reviewed. There were 19 males and 6 females, aged from 11 to 59 years, including 13 cases of cerebrospinal fluid (CSF) rhinorrhea (12 traumatic) and 12 cases of sinonasal skull base tumors. Descriptive statistical methods were used.Results:The mean areas of anterior skull base, sellar, and clival defects were 16.13, 14.03 and 13.12 cm 2, respectively, and the mean pericranial flap lengths were (18.77±3.44)mm, (133.99±5.08)mm, (181.76±6.31)mm, respectively. Among sinonasal skull base neoplasms, the pathologies included olfactory neuroblastoma ( n=6), squamous cell carcinoma ( n=3), chondrosarcoma ( n=1), osteosarcoma ( n=1), and invasive schwannoma ( n=1), in whom 8 patients underwent adjuvant radiotherapy after surgery. One patient (7.7%) had acoustic neuroma-related CSF leak before radiotherapy. All 25 patients successfully underwent skull base reconstruction without complications such as CSF leak, intracranial infection, forehead wrinkles disappearance, or scalp necrosis. All flaps survived well with no CSF leaks within the follow-up period of 2-4 years. Conclusion:Pericranial flap is a safe choice for large anterior skull base defects following resection of sinonasal skull base neoplasms and complex traumatic CSF leaks when endonasal flaps are not available.

Objective To explore the clinical efficacy of Delta endoscopic lumbar decompression fusion for the treatment of giant lumbar disc herniation(GILDH).Method A retrospective analysis was performed on 36 cases of GILDH from April 2020 to May 2022,including 18 cases in the Delta group and 18 cases in the open group.There was no statistically significant difference in gender,age,and responsible section between the two groups of patients.Compare the surgical time,perioperative indicators,and clinical efficacy between the two groups.Results The intraoperative bleeding and drainage volume in the Delta group were lower than those in the open group,the incision length and hospital stay were shorter than those in the open group,the degree of paraspinal muscle injury was lighter than that in the open group,and the surgical time was longer than that in the open group,with statistical significance(P＜0.05);The lumbago visual analogue scale(VAS)of the two groups of patients at each postoperative period was significantly reduced compared to preoperative,and the lumbar spine function score of the Japanese Orthopaedic Association(JOA)was significantly increased compared to preoperative,with statistical significance(P＜0.05);The lumbago VAS of the Delta group was significantly lower than that of the open group at all postoperative stages,and the lumbar spine function JOA score was significantly higher than that of the open group,with statistical significance(P＜0.05);There was no statistically significant difference in the modified MacNab score between the two groups of patients at the last follow-up after surgery(P＞0.05).Conclusion Delta endoscopic lumbar decompression fusion for GILDH has significant therapeutic effects,with advantages such as less bleeding,small surgical incision,and fast postoperative recovery;After crossing the Delta endoscopic learning curve and optimizing the surgical process,this technology can become an alternative to conventional open surgery.

Objective:To explore the clinical efficacy of DELTA endoscopic lumbar interbody fusion for the treatment of mild to moderate, single segment lumbar spondylolisthesis.Methods:A retrospective analysis was conducted on the clinical data of 48 surgical cases of grade Ⅰ to Ⅱ lumbar spondylolisthesis admitted to the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from February 2020 to March 2022. Among them, 24 cases treated with DELTA endoscopic lumbar interbody fusion surgery were classified as the DELTA group, and 24 cases treated with traditional minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) surgery were classified as the MIS-TLIF group. Two groups of patients were compared in terms of perioperative indicators (surgical time, postoperative drainage volume, incision length, hospital stay), clinical efficacy [Visual Analogue Scale (VAS) score for low back and leg pain, lumbar Japanese Orthopaedic Association Scores (JOA), improved MacNab standard excellence rate], and lumbar fusion rate (Bridwell intervertebral fusion grade).Results:The DELTA group had longer surgical time than the MIS-TLIF group, and the postoperative drainage volume, incision length, and hospital stay were all lower than the MIS-TLIF group, with statistically significant differences (all P<0.05). The VAS score of lower back and leg pain and lumbar JOA score of the two groups of patients at 1 week, 3 months, and the last follow-up were significantly improved compared to those before surgery (all P<0.01), and the DELTA group had better VAS score of lower back and leg pain and lumbar JOA score at all time points after surgery than the MIS-TLIF group, with statistically significant differences (all P<0.05). The improved MacNab standard was used to evaluate the efficacy of the two groups of patients at the last follow-up after surgery, and there was no statistically significant difference in the excellent and good rates ( P>0.05); There was no statistically significant difference ( P>0.05) in the fusion rate between the two groups. Conclusions:DELTA endoscopic lumbar interbody fusion has a significant therapeutic effect on lumbar spondylolisthesis, with the advantages of small surgical incision and fast recovery; After crossing the DELTA endoscopic learning curve and optimizing surgical procedures, this technology can become an alternative to MIS-TLIF technology.

Fibroblast activating protein (FAP) is an important biomarker of cancer associated fibroblasts and activated fibroblasts, which is highly expressed in activated fibroblasts of many tumor and fibrotic tissues, but not in normal tissues and non malignant lesions. Therefore, FAP has become an excellent target for diagnosis and treatment of tumors and other diseases. PET imaging and internal radiotherapy based on FAP inhibitor (FAPI) have been used in the diagnosis and treatment of many diseases, such as cancer and fibrosis. We first introduce the mechanism of disease occurrence and progression mediated by FAP and its clinical significance as a therapeutic target.Then,we systematically summarize the FAP probes labeled with 125I, 68Ga, 64Cu and other radionuclides, including their structural evolution, imaging, biodistribution and pharmacokinetic properties.After that, the reported strategies to improve the pharmacokinetic properties and target affinity of probes are summarized, including the use of squaramide linkers,modification with albumin binding agent,the development of dual-targeting probes.Finally, some suggestions for the future development of novel radioactive probes targeting FAP and the clinical application of classical probes are proposed.