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.

To evaluate long-term survival and clinical outcomes of patients with knee osteo-arthritis undergoing total knee arthroplasty (TKA) through long-term follow-up.

Abstract On September 26, 2024, a municipal hospital in Jiaxing City reported a maternal case of Listeria monocytogenes infection. In order to clarify the source of infection, the Jiaxing Center for Disease Control and Prevention immediately conducted the epidemiological investigation, laboratory testing and related disposal work. The case presented with fever (37.9 ℃), gradually intensifying paroxysmal abdominal pain without obvious cause, and went to hospital on the day of onset. Due to fetal intrauterine distress, a male infant was delivered by cesarean section on the same day. The epidemiological investigation identified that the case usually consumed fruits, often store fruits such as watermelon and grapes in the refrigerator alongside raw meat, and the refrigerator had never been cleaned or disinfected, posing a risk of cross contamination. Laboratory tests on amniotic fluid sample from the pregnant woman, infant blood sample showed positive results for Listeria monocytogenes infection. One strain of Listeria monocytogenes was detected in a smear sample from the inner wall of the refrigerator, and all the strains were ST2 type. Consuming fruits contaminated with Listeria monocytogenes may be the main source of infection. Food safety education for pregnant women and their family members should be strengthened to reduce the risk of infection.

OBJECTIVE To optimize the simmering technology of Rheum palmatum from Menghe Medical School and compare the difference of chemical components before and after processing. METHODS Using appearance score， the contents of gallic acid， 5-hydroxymethylfurfural （5-HMF）， sennoside A+sennoside B， combined anthraquinone and free anthraquinone as indexes， analytic hierarchy process （AHP）-entropy weight method was used to calculate the comprehensive score of evaluation indicators； the orthogonal experiment was designed to optimize the processing technology of simmering R. palmatum with fire temperature， simmering time， paper layer number and paper wrapping time as factors； validation test was conducted. The changes in the contents of five anthraquinones （aloe-emodin， rhein， emodin， chrysophanol， physcion）， five anthraquinone glycosides （barbaloin， rheinoside， rhubarb glycoside， emodin glycoside， and emodin methyl ether glycoside）， two sennosides （sennoside A， sennoside B）， gallic acid and 5-HMF were compared between simmered R. palmatum prepared by optimized technology and R. palmatum. RESULTS The optimal processing conditions of R. palmatum was as follows: each 80 g R. palmatum was wrapped with a layer of wet paper for 0.5 h， simmered on high heat for 20 min and then simmered at 140 ℃， the total simmering time was 2.5 h. The average comprehensive score of 3 validation tests was 94.10 （RSD＜1.0%）. After simmering， the contents of five anthraquinones and two sennosides were decreased significantly， while those of 5 free anthraquinones and gallic acid were increased to different extents； a new component 5-HMF was formed. CONCLUSIONS This study successfully optimizes the simmering technology of R. palmatum. There is a significant difference in the chemical components before and after processing， which can explain that simmering technology slows down the relase of R. palmatum and beneficiate it.

BACKGROUND:Acupuncture is an effective method for lumbar pain in lumbar disc herniation,but its mechanism has not yet been clarified.Factors related to the JAK2/STAT3 signaling pathway regulate the body's inflammatory response and are involved in the process of neuropathic pain. OBJECTIVE:To study the mechanism of acupuncture on lumbar disc herniation in a rat model based on the JAK2/STAT3 signaling pathway. METHODS:Forty Sprague-Dawley rats were randomly divided into four groups:sham operation group,model group,acupuncture group,and acupuncture+agonist group,with 10 rats in each group.Animal models of L5 lumbar disc herniation was constructed through autologous disc cell transplantation in the model group,acupuncture group,and acupuncture+agonist group.Rats in the acupuncture group and the acupuncture+agonist group received acupuncture treatment(Yanglingquan,Shenshu,Huantiao,and Dachangshu acupoints)at 3 days after modeling,and acupuncture treatment was given once a day,20 minutes each,for 15 consecutive days.Rats in the acupuncture+agonist group were injected intrathecally with coumermycin A1,a JAK2 agonist,into the L4/L5 intervertebral space,once a day,20 minutes each,prior to the acupuncture at 6,12,and 18 days after modeling.Paw withdrawal mechanical threshold was detected before and 3,6,9,12,15,and 18 days after modeling.At 18 days after modeling,serum inflammatory factor levels were detected,hematoxylin-eosin staining was performed to observe the morphology of L5-L6 tissues,RT-PCR was performed to detect the expression of JAK2 and STAT3 mRNAs in L5-L6 tissues,and western blot was performed to detect the expression of JAK2,p-JAK2 and p-STAT3 proteins in L5-L6 tissues. RESULTS AND CONCLUSION:The paw withdrawal mechanical thresholds of rats in the model group at different time points after modeling were lower than those in the sham operation group(P<0.05),the paw withdrawal mechanical thresholds of rats in the acupuncture group were higher than those in the model group at 9,12,15,and 18 days after modeling(P<0.05),and the paw withdrawal mechanical thresholds of rats in the acupuncture+agonist group were lower than those in the acupuncture group at 9,12,15,and 18 days after modeling(P<0.05).The levels of interleukin 6,tumor necrosis factor α,neurotransmitter substance P,and brain neuropeptide Y were elevated in the model group compared with the sham operation group(P<0.05);the levels of all four inflammatory factors were reduced in the acupuncture group compared with the model group(P<0.05);and the levels of all four inflammatory factors were elevated in the acupuncture+agonist group compared with the acupuncture group(P<0.05).Hematoxylin-eosin staining showed that lumbar degeneration was obvious in the model group but reduced in the acupuncture group and the acupuncture+agonist group.Moreover,the reduction was more obvious in the acupuncture group compared with the acupuncture+agonist group.The JAK2 and STAT3 mRNA expression as well as the p-JAK2 and p-STAT3 protein expression were elevated in the model group compared with the sham operation group(P<0.05),were decreased in the acupuncture group compared with the model group(P<0.05),and were increased in the acupuncture+agonist group compared with the acupuncture group(P<0.05).To conclude,acupuncture can alleviate inflammation to exert analgesic effects in the rat model of lumbar disc herniation,and its mechanism of action may be related to the inhibition of the JAK2/STAT3 signaling pathway.

OBJECTIVE To investigate the effects and mechanism of Wenpi tongluo kaiqiao formula （WPTL） against neuronal necroptosis in Alzheimer’s disease （AD） mice based on the Z-DNA binding protein 1 （ZBP1）/mixed lineage kinase domain-like protein （MLKL） signaling pathway. METHODS Forty APP/PS1 transgenic AD mice were randomly divided into model group， WPTL low-dose （WPTL-L） group （10.4 g/kg， calculated by the raw medicine）， WPTL high-dose （WPTL-H） group （20.8 g/kg， calculated by the raw medicine） and donepezil hydrochloride group （3 mg/kg）， with 10 mice in each group； another 10 C57BL/6J mice were selected as normal control group. Intragastric administration， once a day， for 30 consecutive days. Twenty-four hours after the last administration， Morris water maze test was performed to evaluate learning and memory abilities； the pathological morphology of hippocampal tissues was observed； the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） were determined； the expressions of amyloid precursor protein （APP）， Tau protein， and ZBP1/MLKL signaling pathway-related proteins in hippocampal tissues were detected； the positive expression of phosphorylated receptor-interacting protein kinase 3 （p-RIPK3） in the neurons of hippocampal tissues and mRNA expression of ZBP1 were measured in hippocampal tissues. RESULTS Compared with normal control group， the escape latency of mice in model group was prolonged significantly on day 3 to 5 （P＜0.05）， the times of crossing platform reduced significantly （P＜0.05）， and obvious pathological changes were observed in the hippocampal tissue. The level of TNF- α， the expressions of APP， p-Tau and ZBP1， the phosphorylation levels of RIPK1， RIPK3 and MLKL， the fluorescence intensity of p-RIPK3 as well as the mRNA expression of ZBP1 were significantly increased （P＜0.05）， while the serum level of IL-4 was decreased significantly （P＜0.05）. Compared with model group， above indexes were reversed significantly in administration groups （P＜0.05）， and pathological damage of hippocampal tissue was alleviated. CONCLUSIONS WPTL can inhibit the ZBP1/MLKL signaling pathway， reduce neuronal necroptosis in AD mice， and inhibit inflammatory responses， thereby improving learning and spatial memory abilities in AD mice.

Background: The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies. Methods: MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function. Results: Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores. Conclusion Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Background: The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies. Methods: MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function. Results: Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores. Conclusion Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Background: The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies. Methods: MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function. Results: Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores. Conclusion Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Background: The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies. Methods: MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function. Results: Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores. Conclusion Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.