Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

ObjectiveTo explore the effects of Jingui Shenqiwan （JSW） and Liuwei Dihuangwan （LDW） on the reproductive ability and brain function of normal mice and compare the actions of the two medications. MethodsSeven groups of female and male mice were divided at a ratio of 2∶1. Except for the control group， the other six groups were as follows： a group of both males and females receiving JSW （3.0 g·kg^-1）， a group of both males and females receiving LDW （4.5 g·kg^-1）， a group of males receiving water and females receiving JSW， a group of males receiving water while females receiving LDW， a group of females receiving water while males receiving JSW， and a group of females receiving water while males receiving LDW. Each group was administered the drug for 14 days and then caged together at a 2∶1 （female∶male） ratio to detect the number of pregnant mice and calculate the pregnancy rate. Pregnant mice continued receiving the drug until they naturally gave birth， which was followed by the observation of newborn mice， calculation of their average number， and the measurement of the offspring's preference for sugar water and neonatal recognition index. At the end of the experiment， the weights of the thymus and spleen were measured to calculate the organ coefficients， and mRNA or protein expression was analyzed in the brain and testes or ovaries. A 1% sucrose solution was used to examine the euphoria of their brain reward systems， while novel object recognition test （NOR） was applied to assess their memory capabilities. mRNA expression was detected using real-time quantitative polymerase chain reaction （Real-time PCR） assay， and protein expression was analyzed with Western blot. ResultsCompared with the control group， oral administration of JSW to both male and female mice for 14 days significantly increased the pregnancy rate of female mice on day 2 after being caged together （P<0.05）， while LDW showed a trend but no statistical significance. Additionally， compared with the control group， JSW could upregulate the gene expression of gonadotropin-releasing hormone （GnRH） in the thalamus， as well as reproductive stem cell factor （SCF） and tyrosine kinase receptor （c-Kit） in the testes and reproductive stem cell marker mouse vasa homologue （MVH） in the ovaries， upregulate the expression of proteins influencing neuronal functional activity， such as brain-derived neurotrophic factor （BDNF）， in hippocampal neurons （P<0.05）， and enhance sucrose preference in male mice （P<0.05）. Compared with the control group， JSW significantly increased sucrose preference and novel object recognition index in offspring mice （P<0.05）， which was related to the upregulation of hippocampal dopamine D1 receptor （D1R） and N-methyl-D-aspartate receptor （Nmdar） gene expression. Compared with the control group， both JSW and LDW could upregulate the protein expression of glucocorticoid receptor （GR）， BDNF， and tyrosine kinase receptor B （TrkB） in the hippocampus of offspring mice （P<0.05）. ConclusionJSW significantly enhances the reproductive ability of normal mice， which is not only related to the release of gonadotropin but also associated with its regulation of brain function. Additionally， JSW has a certain regulatory effect on the brain function of the offspring mice.

Objective To investigate the therapeutic effect and underlying mechanism of piceatannol against hepatic ischemia-reperfusion injury (HIRI) in fatty liver. Methods A mouse model of fatty liver combined with HIRI was established, and experimental animals were assigned into four groups: sham operation group, fatty liver HIRI group, fatty liver HIRI + piceatannol group, and fatty liver HIRI + piceatannol + ML385 group (n=5). Serum levels of alanine transaminase (ALT), aspartate transaminase (AST) and lactate dehydrogenase (LDH) were detected in each group. Hepatic tissue injury was evaluated by hematoxylin-eosin staining. Biochemical assays were performed to measure the contents of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD). Reactive oxygen species (ROS) were quantified using the DHE fluorescent probe method, while the expression of 4-hydroxynonenal (4-HNE) was determined via immunohistochemical staining. Western blot was adopted to detect the protein expression of glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4), heme oxygenase-1 (HO-1) and nuclear factor E2-related factor 2 (Nrf2). Primary mouse hepatocytes were isolated and cultured in vitro. After treatment with palmitic acid, an hypoxia/reoxygenation (H/R) model was established. Cellular experiments were divided into control group, steatosis H/R group, steatosis H/R + piceatannol group, and steatosis H/R + piceatannol + ML385 group. Calcein-AM/PI dual staining was used to observe cell viability, C11 BODIPY staining was used to determin lipid peroxidation levels, and DCFH-DA fluorescent probe was utilized to test intracellular ROS levels. Western blot was used to detect the protein abundances of GPX4, ACSL4, HO-1 and Nrf2, and real-time fluorescence quantitative polymerase chain reaction was applied to quantify their corresponding messenger RNA (mRNA) expression levels. Results Compared with the sham operation group, the levels of ALT, AST and LDH, liver injury score, DHE positive rate, MDA level and 4-HNE level increased, the levels of GSH and SOD decreased, the relative expression level of ACSL4 protein increased, and the relative expression levels of GPX4, Nrf2 and HO-1 proteins decreased in the fatty liver HIRI group; compared with the fatty liver HIRI group, the levels of ALT, AST and LDH, liver injury score, DHE positive rate, MDA level and 4-HNE level decreased, the levels of GSH and SOD increased, the relative expression level of ACSL4 protein decreased, and the relative expression levels of GPX4, Nrf2 and HO-1 proteins increased in the fatty liver HIRI + piceatannol group; compared with the fatty liver HIRI + piceatannol group, the levels of ALT, AST and LDH, liver injury score, DHE positive rate, MDA level and 4-HNE level increased, the levels of GSH and SOD decreased, the relative expression level of ACSL4 protein increased, and the relative expression levels of Nrf2 and HO-1 proteins decreased in the fatty liver HIRI + piceatannol + ML385 group (all P<0.05). Compared with the control group, the mean fluorescence intensity of DCFH-DA and MDA level increased, the levels of GSH and SOD decreased, the proportion of oxidized lipids increased, the protein and mRNA expression levels of ACSL4 increased, and the protein and mRNA expression levels of GPX4, HO-1 and Nrf2 decreased in the steatosis H/R group; compared with the steatosis H/R group, the mean fluorescence intensity of DCFH-DA and MDA level decreased, the levels of GSH and SOD increased, the proportion of oxidized lipids decreased, the relative protein and mRNA expression levels of ACSL4 decreased, and the relative protein and mRNA expression levels of GPX4, HO-1 and Nrf2 increased in the steatosis H/R + piceatannol group; compared with the steatosis H/R + piceatannol group, the mean fluorescence intensity of DCFH-DA and MDA level increased, the levels of GSH and SOD decreased, the proportion of oxidized lipids increased, the relative protein and mRNA expression levels of ACSL4 increased, and the relative protein and mRNA expression levels of GPX4, HO-1 and Nrf2 decreased in the steatosis H/R + piceatannol + ML385 group (all P<0.05). Conclusions Piceatannol relieves HIRI in fatty liver by activating the Nrf2/HO-1 signaling pathway to suppress ferroptosis in hepatocytes.

ObjectiveTo explore the effect of Shenge Bushen Capsules （SBC） on sexual development in normal 3-week-old mice. MethodsThe experiment consisted of two parts. In the first part， mice were divided into four groups： The control group and the low， medium， and high-dose SBC groups （234.7， 469.4， 938.7 mg·kg^-1， respectively）. In the second part， mice were divided into four groups： Control group， Pseudostellariae Radix polysaccharide （PRP） group， total flavonoids group， and SBC group， all receiving a dose of 469.4 mg·kg^-1. After 7 days of administration， the vaginal opening of female mice and the descent of testes and scrotum in male mice， as well as the ovarian and testicular organ indices， were observed. After 4 weeks of administration， female and male mice were housed together for 2 days， and the pregnancy rate of females was monitored. After delivery， the pregnant female mice continued receiving the treatment for 4 weeks， and the sexual development of their offspring， including vaginal opening， testicular descent， and organ indices of ovaries and testes， was observed. Serum sex hormones were measured by enzyme-linked immunosorbent assay （ELISA）， and the expression of gonadotropin-releasing hormone （GnRH） and growth hormone （GH） proteins in the hypothalamus was assessed by Western blot. ResultsCompared with the control group， there was no significant effect on the vaginal opening of female mice or the descent of testes in male mice after 7 days of SBC administration. After 4 weeks of administration， the pregnancy rate in the low-dose group was significantly reduced （P<0.05）， but no significant effects were observed in the other groups. The three doses of SBC did not significantly affect the ovarian or testicular organ indices， and there was no significant upregulation in the expression of GnRH or GH in the hypothalamus. The primary component of SBC， Pseudostellariae Radix polysaccharide， significantly reduced the vaginal opening in female mice after 7 days of administration （P<0.05）. After 4 weeks， the serum estradiol levels of non-pregnant female mice were decreased （P<0.05）， but there was no significant effect on the expression of GnRH or GH proteins in the hypothalamus of either male or female mice. Additionally， there were no significant effects on precocious puberty indicators， such as vaginal opening and testicular descent， in the offspring mice. ConclusionSBC does not significantly promote precocious puberty in young mice， and it does not have any noticeable effects on the pregnancy rate of adult mice or the sexual development of their offspring.

With the rapid development of artificial intelligence （AI） technology， the ethical governance of AI has gained increasing attention. The Recommendation on the Ethics of Artificial Intelligence was issued by the United Nations Educational， Scientific and Cultural Organization in 2021， which clarified several principles for the ethical governance of AI. In the field of rehabilitation medicine， the research and application of AI technology have significantly improved patients’ quality of life and survival. However， due to the specificity of the service population in rehabilitation medicine， which is mostly for the sick， injured， disabled， and elderly， a series of complex ethical issues have also arisen. This paper analyzed in detail the ethical issues and challenges encountered in the research and application of AI technology in the field of rehabilitation medicine from various aspects， such as informed consent， security of privacy and data， patients’ physical and mental rehabilitation， compliance regulation， protection of specific groups， and promotion of equity. According to the principles of the Recommendation on the Ethics of Artificial Intelligence and others， response strategies were proposed， including multi-party collaboration and interdisciplinary cooperation， improving and refining relevant laws and regulations， strengthening ethical education across society， establishing accountability mechanisms， increasing investment， promoting equity， and other measures， to promote the healthy development of research and application of AI technology in the field of rehabilitation， as well as benefit humanity.

Objective Based on the phosphatidylinositol kinase(PI3K)/protein kinase B(AKT)pathway and M2 polarization of macrophages,the effects of polydatin on malignant phenotype of osteosarcoma cells were investigated.Methods The macrophages were divided into M0 group,M2 group,polydatin group,and polydatin+PI3K pathway agonist 740Y-P group.The expression of arginase-1(Arg-1)and CD206 mRNAs and proteins in macrophages were detected by RT-qPCR and Western blot.Western blot was used to detect p-PI3K/PI3K and p-AKT/AKT protein expression in macrophages.The osteosarcoma cells MG-63 were divided into control group,control group(RPMI-1640 medium culture),CM-M0 group(M0 group M0 macrophage supernatant is collected for osteosarcoma cells),CM-M2 group(M2 group M2 macrophage supernatant is collected for osteosarcoma cells),CM-polydatin group(M2 macrophage supernatant in the polydatin group was collected on osteosarcoma cells),and CM-polydatin+740Y-P group(M2 macrophage supernatant was collected on osteosarcoma cells in the CM-polydatin+740Y-P group).Edu staining assay was used to detect the proliferation of MG-63 cells.Scratches and Transwell assays were used to detect the migration and invasion of MG-63 cells.Results Compared with the M0 group,the Arg-1,CD206,IL-10,p-PI3K/PI3K,p-AKT/AKT increased in the M2 group significantly(P<0.05).Compared with the M2 group,the Arg-1,CD206,IL-10,p-PI3K/PI3K,p-AKT/AKT decreased in the polydatin group significantly(P<0.05).Compared with the polydatin group,the Arg-1,CD206,IL-10,p-PI3K/PI3K,p-AKT/AKT increased in the polydatin+740Y-P group significantly(P<0.05).Compared with the CM-M0 group,the proportion of Edu-positive cells in the CM-M2 group increased significantly(P<0.05),and MG-63 cell migration and invasion rates increased significantly(P<0.05).Compared with the CM-M2 group,the proportion of Edu-positive cells in the CM-polydatin group decreased significantly(P<0.05),and MG-63 cell migration and invasion rates decreased significantly(P<0.05).Compared with the CM-polydatin group,the proportion of Edu-positive cells in the CM-polydatin+740Y-P group increased significantly(P<0.05),and MG-63 cell migration and invasion rates increased significantly(P<0.05).Conclusion Polygonum cuspidatum can inhibit the proliferation,migration and invasion of osteosarcoma cells by inhibiting the M2 polarization of macrophages,and its mechanism may be related to the inhibition of PI3K/AKT signaling pathway.

At present,more and more scientific experiments are used in the research of traditional Chinese medicine(TCM),which promotes the elucidation of the effects of TCM.However,the real significance of scientific experiment lies in the discussion of the original theory,and in the guidance role in the original theory based on the discovery.Therefore,it will lose its real significance and value to only position scientific experiments as"explain"the mechanism of TCM effects rather than guiding the clarification and development of the principles of TCM.This paper analyzes the theoretical paradigms of modern science and TCM from the perspective of historical development,and theoretically discusses the due position and importance of scientific experiments in the theoretical research and development of TCM on their similarities and differences and their possible intersections.It holds that although scientific experiment and TCM belong to different theoretical paradigms,their objective materiality from clinical practice determines the interconnectedness between scientific experiment and TCM,that is,linking scientific experiment and TCM with the pathophysiological changes;In order to ensure the correctness of the connection between this scientific experiment and TCM,we should pay attention to the implementation of the scientific concept in scientific experiments to ensure the specificity of the research results,and finally making due contributions to the development of TCM theory.

Aim To explore the effects of exercise during pregnancy on renal structure,function and angiotensin Ⅱ(Ang Ⅱ)/transforming growth factor-β1(TGF-β1)/connective tissue growth factor(CTGF)signaling pathway in 3-month-old offspring of spontaneously hypertensive rats(SHR),the aim of this study was to provide experimental basis for early intervention of hypertension and protection of key target organs.Methods After mating SHR and WKY rats,pregnant rats were randomly divided into sedentary group(p-WKY-SED,p-SHR-SED)and exercise group(p-WKY-EX,p-SHR-EX).Blood pressure,serum urea nitrogen and creatinine were measured by caudal artery non-invasive blood pressure system and colorimetry in 3-month-old offspring rats.HE staining,Masson staining,ELISA and Western blot were used to detect the renal structure,collagen volume fraction,Ang Ⅱ concentration,renin-angiotension-aldosterone sys-tem(RAAS)and protein expression related to fibrogenic signal pathway in 3-month-old rats.Results(1)The sys-tolic blood pressure(SBP),diastolic blood pressure(DBP)and mean arterial pressure(MAP)of offspring rats in p-SHR-SED group were significantly higher than those in p-WKY-SED group.The SBP,DBP and MAP of SHR male off-spring rats were significantly decreased by exercise during pregnancy(P＜0.05),but had no effect on the female offspring rats(P＞0.05).(2)There was no significant difference in serum urea nitrogen and creatinine among the groups(P＞0.05).(3)The glomerular volume and the collagen volume fraction in p-SHR-SED group were significantly higher than those in p-WKY-SED group(P＜0.05),and the glomerular volume and the collagen volume fraction in p-SHR-EX group were significantly lower than those in p-SHR-SED group(P＜0.05).(4)Renal Ang Ⅱ level of offspring rats in p-SHR-SED group was significantly higher than that in p-WKY-SED group,and renal Ang Ⅱ level of offspring rats in p-SHR-EX group was significantly lower than that in p-SHR-SED group(P＜0.05).(5)The expression levels of angiotensin Ⅱ type 1 receptor(AT1R),TGF-β1 and CTGF protein in p-SHR-SED group were significantly higher than those in p-WKY-SED group(P＜0.05),while the expression levels of angiotensin converting enzyme 2(ACE2),angiotensin Ⅱ type 2 receptor(AT2R)and MasR protein in p-SHR-SED group were significantly lower than those in p-WKY-SED group(P＜0.05).Conclusion(1)Exercise during pregnancy can significantly decrease the blood pressure of 3-month-old male offspring rats of hypertensive rats,but has no significant effect on that of 3-month-old female offspring.(2)Exercise during preg-nancy may reduce renal fibrosis in 3-month-old female/male offspring of hypertensive rats by regulating RAAS balance and inhibiting Ang Ⅱ/TGF-β1/CTGF signaling pathway.

Objective:To investigate the association between magnesium sulfate exposure within 24 h before birth and short-term outcomes in preterm infants under 34 weeks' gestation.Methods:This retrospective cohort study analyzed data from preterm infants under 34 weeks admitted to the neonatal intensive care unit of the Affiliated Hospital of Qingdao University between June 1, 2020, and December 31, 2024. Infants were categorized into the exposure and the control groups based on magnesium sulfate administration within 24 hours before delivery. Maternal characteristics, birth parameters, and neonatal outcomes were compared using independent t-tests or Chi square tests (Fisher's exact test), with logistic regression assessing magnesium sulfate's effect on non-cerebral palsy outcomes. Results:The cohort comprised 384 preterm infants (24-33 +6 weeks), with 290 (75.5%) in the exposure group and 94 (24.5%) in the control group. (1) Baseline characteristics showed no significant differences in maternal hypertensive disorders, antenatal corticosteroids administration, premature rupture of membranes, delivery mode, or male infant proportion (all P>0.05). The exposure group had lower birth weight [(1 583±451) vs. (1 744±473) g; t=2.97] and gestational age [(31.3±2.1) vs.(31.8±2.4) weeks; t=2.20; both P<0.05)]. (2) The exposure group demonstrated reduced incidence of in-hospital mortality [0.3% (1/290) vs. 6.4% (6/94); Fisher's exact test], grade Ⅲ-Ⅳ intracranial hemorrhage [1.7% (5/290) vs. 9.6% (9/94); χ2=12.86], and white matter injury [2.1% (6/290) vs. 9.1% (8/94); χ2=9.08] (all P<0.01). (3) Univariate logistic regression identified antenatal magnesium sulfate as protective against grade Ⅲ-Ⅳ intracranial hemorrhage ( OR=0.20, 95% CI: 0.04-0.96), white matter injury ( OR=0.11, 95% CI: 0.01-0.91), and in-hospital mortality ( OR=0.93, 95% CI: 0.88-0.99). (4) Multivariate analysis confirmed the independent protective effect of antenatal exposure of magnesium sulfate against intracranial hemorrhage in preterm infants under 34 weeks ( OR=0.19, 95% CI: 0.04-0.95), particularly pronounced in infants <32 weeks ( OR=0.11, 95% CI: 0.01-0.96). (5) No significant differences emerged in secondary outcomes including 5-minute Apgar scores, respiratory distress syndrome, surfactant administration, mechanical ventilation, bronchopulmonary dysplasia, hemodynamically significant patent ductus arteriosus, necrotizing enterocolitis, early-onset sepsis, retinopathy of prematurity, metabolic bone disease, or hospitalization duration (all P>0.05). Conclusions:Magnesium sulfate exposure within 24 hours before delivery reduces grade Ⅲ-Ⅳ intracranial hemorrhage risk in preterm infants under 34 weeks, with enhanced protection in those <32 weeks, without increasing adverse effects in other organ systems.

Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.