BACKGROUND:Human periodontal stem cells have a certain inhibitory effect on the pro-inflammatory function of M1-type macrophages,and it is not clear whether icariin,which has anti-inflammatory and other pharmacological activities,can enhance the inhibitory effect of human periodontal stem cells on M1-type macrophages. OBJECTIVE:To investigate the effect of icariin on M1 macrophages after pretreatment of human periodontal stem cells. METHODS:Primary human periodontal stem cells were isolated,cultured and characterized.THP-1 was induced and M1-type macrophages were identified by immunofluorescence staining and PCR.Human periodontal stem cells were cultured with α-MEM complete medium containing concentrations of 10-7,10-6,10-5,and 10-4 mol/L icariin,and the cytotoxicity of Icariin on human periodontal stem cells was detected by the CCK-8 assay at 1,3,5,and 7 days,respectively.α-MEM complete medium,untreated α-MEM conditioned medium for human periodontal stem cells and α-MEM conditioned medium for human periodontal stem cells pretreated with icariin for 24 hours were conditioned with RPMI-1640 complete medium in a 1:1 ratio for M1-type macrophages in the control,untreated,and pretreated groups,and 24 hours later,the mRNA expression of inflammatory factors in M1 macrophages was detected by RT-PCR.The protein expression of inflammatory factors in M1 macrophages was detected by ELISA.The expression of surface markers and nuclear factor-κB pathway-related proteins in M1/M2 macrophages was detected by western blot assay. RESULTS AND CONCLUSION:(1)CCK-8 assay results showed that 10-7,10-6,10-5,10-4 mol/L icariin was not cytotoxic to the human periodontal stem cells,and from day 5 onwards,all the concentrations increased the cell viability,and promoted the cell proliferation.10-4 mol/L icariin was selected for follow-up experiment.(2)RT-PCR and ELISA results showed that compared with the control group,the untreated group and the pretreated group both decreased the expression and secretion of interleukin-1β,interleukin-6,and tumor necrosis factor-α of M1-type macrophages(P<0.05),and the pretreated group was lower than the untreated group(P<0.05).(3)Western blot assay results showed that compared with the untreated group,the expression of CD86 was significantly lower in the pretreated group(P<0.05);compared with the control group,the expression of CD206,a surface marker of M2-type macrophages,was elevated in both the untreated and pretreated groups(P<0.01),and it was significantly higher in the pretreated group than in the untreated group(P<0.01).In M1-type macrophages after 24 hours of conditioned culture,compared with the control group,the expression of nuclear factor-κB/P65 was decreased in the untreated group and the pretreated group(P<0.01),and the expression of p-IκBα was decreased only in the pretreated group(P<0.01);the expression of both nuclear factor-κB/P65 and p-IκBα was significantly reduced in the pretreated group compared with the untreated group(P<0.05),while the difference of IκBα in the three groups was not statistically significant.(4)These results indicated that icariin enhanced the inhibitory effect of human periodontal stem cells on M1-type macrophages,and this effect may be related to the inhibition of the nuclear factor-κB signaling pathway of macrophages.

BACKGROUND:Poisoned patients often suffer damage to multiple systems,and those experiencing central nervous system disorders present more severe conditions,prolonged hospital stays,and increased mortality rates.We aimed to assess the efficacy of rehabilitation interventions for patients with toxic encephalopathy. METHODS:This retrospective,observational,comparative cohort study was performed at the teaching hospital affiliated of Nanjing Medical University,from October 2020 to December 2022.Patients who met the diagnostic criteria for toxic encephalopathy and exclusion criteria were included,and patients were divided into three subgroups according to Glasgow Coma Scale(GCS).Demographic and clinical characteristics were collected.The effect of the rehabilitation intervention on patients were assessed in the improvement of consciousness status(Glasgow Coma Scale[GCS]score),muscle strength and movement and swallowing function(Fugl-Meyer Assessment[FMA]scale,Water Swallow Test[WST],and Standardized Swallowing Assessment[SSA]).Subgroup analysis was based on different toxic species. RESULTS:Out of the 464 patients with toxic encephalopathy,184 cases received rehabilitation treatments.For the severe toxic encephalopathy patients,patients without rehabilitation intervention have a 2.21 times higher risk of death compared to patients with rehabilitation intervention(Hazard ratio[HR]=2.21).Subgroup analysis revealed that rehabilitation intervention significantly increased the survival rate of patients with pesticide poisoning(P=0.02),while no significant improvement was observed in patients with drug/biological agent poisoning(P=0.44).After rehabilitation intervention,significant improvement in GCS and FMA were observed in severe patients with toxic encephalopathy(P<0.01). CONCLUSION:Active rehabilitation intervention for patients exposed to poisons that can potentially cause toxic encephalopathy may improve the prognosis and reduce the mortality rate in clinical practice.

In vertebrate embryonic development, the segmentation clock controls the cyclic formation of somites through presomitic mesoderm (PSM) cells. Somites are paired segmented structures along the anterior-posterior axis that eventually develop into vertebrae and ribs. Disruptions in the segmentation clock leads to defects in somitogenesis, resulting in congenital spinal diseases. The major patterning modules that are involved in segmentation clock is the clock and wavefront, which primarily relies on signaling gradients and cyclic oscillation. Mesodermal differentiation is regulated by combinatorial gradient system that involves the activity of the fibroblast growth factor (FGF), the Wnt/β-catenin, and the retinoic acid (RA) signaling pathways. The antagonistic gradients of these signals set a position of the determination front. In the tail bud and posterior mesoderm, FGF and Wnt signaling prevent cell maturation and the molecular oscillators start to express. The molecular oscillators rely on negative feedback loops to maintain their oscillatory expression patterns. As the cells move anteriorly, FGF signaling gradually decays and RA signaling began to strengthen. Meanwhile, the molecular oscillators propagate anteriorly with wave pattern. At the determination front, low levels of FGF signaling and high levels of RA signaling eliminate differentiation inhibition and initiate molecular oscillators to activate cyclic genes, such as Mesp2, leading to the formation of repetitive structures in somites. Advancements in live reporter and 2D culture systems have revealed that coupling delays in cell communication can maintain the synchronous segmentation clock between adjacent cells. Studies have shown that these coupling delays are controlled by Lfng gene, it can adjust coupling delays to fit in-phase oscillations by increasing the time required for intercellular DLL1-Notch signaling. To sum up, the dual homeostasis of opposing signaling gradients determines the segment boundaries, the distance traveled by a molecular oscillator in one oscillation cycle determines the somite size, and the delayed coupling in intercellular signaling regulates the synchronization of clock oscillations. These three factors interact with each other to form a segmentation clock network coordinating somitogenesis. Recent studies have revealed that the intercellular coupling delay mechanism is a major factor influencing the maintenance of oscillation synchronization. Intercellular coupling delay errors, such as increased or decreased delay time, can desynchronizing intercellular oscillations and resulting in somite fusion. However, the mechanisms governing how intercellular communication becomes involved in oscillation synchronization remains unclear. Congenital scoliosis (CS) is a result of anomalous development of the vertebrate which associate with somitogenesis malformation. We observed that deficiency or overdose of vitamin A intake in gestation may lead to CS. While the deep mechanism of how RA signaling regulates oscillation synchronization still need to be detected. With the rapid development of 3D culture systems, researchers have successfully recapitulated the formation of somite-like structures with antero-posterior identity and indicated that the rate of metabolism is directly proportional to that of development. In summary, deconstructing the segmentation clock in vitro facilitates the dissection of regulation networks of the segmentation clock and offers an excellent proxy for studying the metabolic regulation of somitogenesis speed across species and the mechanisms underlying the formation of bilateral symmetry. It also creates a platform for exploring dysregulation mechanisms involved in the development of pathological somite defects.

Objective To observe the pharmacokinetic effect of amoxicillin and clavulanate potassium tablets on amoxicillin in Chinese healthy subjects under fasting and high fat and high calorie diet.Methods 71 healthy subjects were given a single dose of amoxicillin potassium clavulanate tablets(0.375 g)on fasting or high fat diet,and venous blood samples were collected at different time points.The concentrations of amoxicillin in human plasma were determined by HPLC-MS/MS method,and the pharmacokinetic parameters were calculated by non-atrioventricular model using PhoenixWinNonlin 8.0 software.Results The main pharmacokinetic parameters of amoxicillin potassium clavulanate tablets after fasting and high fat diet were(5 105.00±1 444.00),(4 593.00±1 327.00)ng·mL-1,and postprandial-fasting ratio 89.40％,90％confidence interval(79.55％-100.19％);t1/2 were(1.52±0.16),(1.39±0.22)h;AUC0-t were(12 969.00±1 841.00),(11 577.00±1 663.00)ng·mL-1·h,and postdietary/fasting ratio 89.20％,90％confidence interval(83.92％-94.28％);AUC0-∞ were(13 024.00±1 846.00),(11 532.00±1 545.00)ng·mL-1·h,and postprandial-fasting ratio 88.60％,90％confidence interval(83.48％-93.50％).The median Tmax(range)were 1.63(0.75,3.00)and 2.50(0.75,6.00)h,respectively,and the Tmax of postprandial medication was delayed(P＜0.01).Conclusion Compared with fasting condition,amoxicillin Tmax was significantly delayed after high fat diet,while Cmax,AUC0-t and AUC0-∞ were not significantly changed,indicating that food could delay the absorption of amoxicillin,but did not affect the degree of absorption.

Objective:To explore the surgical intervention strategy for metastatic cervical lymph nodes surrounding the carotid artery in head and neck squamous cell carcinoma.Methods:A total of 62 patients with advanced head and neck tumors and carotid wrap by disease treated in Department of Otorhinolaryngology and Head and Neck Surgery, the Affiliated BenQ Hospital of Nanjing Medical University between June 2019 and December 2023 were reviewed, of whom 9 patients presented with metastatic squamous cell carcinoma in cervical lymph nodes of unknown primary or with no recurrence of primary lesion and all the 9 patients were males, aged from 48 to 79 years old, with≤level 2 of Eastern Cooperative Oncology Group-Performance Status (ECOG-PS). Radiographically common carotid artery (CCA) and/or internal carotid artery (ICA) were surrounded by≥270° with tumor. All the 9 patients received implantation of covered stent in carotid artery and radical resection of metastatic cervical lymph nodes. The success rate, complications, surgery-related complications, local recurrence rate, quality of life (QOL) and overall survival (OS) were analyzed. The QOL of patients was compared by paired rank sum test, and P<0.05 indicated statistically significant difference. The OS was analyzed by Kaplan-Meier. Results:The success rate of stent implantation was 100%, with no implantation-related complications. R0 resection was performed in 8 cases and R1 resection in 1 case. The QOL of patients after surgery was improved, and the improvements in "pain", "mood" and "anxiety" were statistically significant( Z values were -2.236, -2.460 and -2.200, respectively, and all P values were<0.05). Follow-up was 1-18 months, with a median of 7 months, and 1 case was lost to follow-up. Local recurrence occurred in 3 patients with an incidence of 37.5% (3/8). OS was 59.9% at 12 months after surgery. Conclusion:Implantation of covered stent in carotid artery combined with radical resection is an effective method for the treatment of cervical lymph node metastasis.

Objective:To explore the prospective associations between physical activity and incident ischemic stroke in adults.Methods:Data of China Kadoorie Biobank study in Tongxiang of Zhejiang were used. After excluding participants with cancers, strokes, heart diseases and diabetes at baseline study, a total of 53 916 participants aged 30-79 years were included in the final analysis. The participants were divided into 5 groups according to the quintiles of their physical activity level. Cox proportional hazard regression models was used to calculate the hazard ratios ( HR) for the analysis on the association between baseline physical activity level and risk for ischemic stroke. Results:The total physical activity level in the participants was (30.63±15.25) metabolic equivalent (MET)-h/d, and it was higher in men [(31.04±15.48) MET-h/d] than that in women [(30.33±15.07) MET-h/d] ( P<0.001). In 595 526 person-years of the follow-up (average 11.4 years), a total of 1 138 men and 1 082 women were newly diagnosed with ischemic stroke. Compared to participants with the lowest physical activity level (<16.17 MET-h/d), after adjusting for socio-demographic factors, lifestyle, BMI, waist circumference, and SBP, the HRs for the risk for ischemic stroke in those with moderate low physical activity level (16.17-24.94 MET-h/d), moderate physical activity level (24.95-35.63 MET-h/d), moderate high physical activity level (35.64-43.86 MET-h/d) and the highest physical activity level (≥43.87 MET-h/d) were 0.93 (95% CI: 0.83-1.04), 0.87 (95% CI: 0.76-0.98), 0.82 (95% CI: 0.71-0.95) and 0.76 (95% CI: 0.64-0.89), respectively. Conclusion:Improving physical activity level has an effect on reducing the risk for ischemic stroke.

Objective:To investigate the prospective association of sleep duration with the development of chronic obstructive pulmonary disease (COPD) in adults in Suzhou.Methods:The study used the data of 53 269 participants aged 30-79 years recruited in the baseline survey from 2004 to 2008 and the follow-up until December 31, 2017 of China Kadoorie Biobank (CKB) conducted in Wuzhong District, Suzhou. After excluding participants with airflow limitation, self-reported chronic bronchitis/emphysema/coronary heart disease history at the baseline survey and abnormal or incomplete data, a total of 45 336 participants were included in the final analysis. The association between daily sleep duration and the risk for developing COPD was analyzed by using a Cox proportional hazard regression model, and the hazard ratio ( HR) values and their 95% CI were calculated. The analysis was stratified by age, gender and lifestyle factors, and cross-analysis was conducted according to smoking status and daily sleep duration. Results:The median follow-up time was 11.12 years, with a total of 515 COPD diagnoses in the follow-up. After adjusting for potential confounders, multifactorial Cox proportional hazard regression analysis showed that daily sleep duration ≥10 hours was associated with higher risk for developing COPD ( HR=1.42, 95% CI: 1.03-1.97). The cross analysis showed that excessive daily sleep duration increased the risk for COPD in smokers ( HR=2.49, 95% CI: 1.35-4.59, interaction P<0.001). Conclusion:Longer daily sleep duration (≥10 hours) might increase the risk for COPD in adults in Suzhou, especially in smokers.

Objective:To analyze the differences between trans-radial access (TRA) and trans-femoral access (TFA) in hepatic arterial perfusion chemotherapy (HAIC) in terms of patient experience, postoperative complications, and patient preferences; explore whether TRA in HAIC is associated with better patient experience and compliance; and determine whether it is safer than TFA.Methods:The study was a retrospective cohort study of patients with advanced hepatocellular carcinoma and liver metastases from colorectal cancer treated with HAIC. We enrolled a total of 91 patients with advanced liver malignancies treated with HAIC from November 2022 to May 2023 in the Department of Interventional Therapy and Hepatobiliary Medicine at Tianjin Medical University Cancer Hospital. The patients were divided into three groups: group TRA ( n=20, receiving TRA HAIC only), group TFA ( n=33, receiving TFA HAIC only), and crossover group [ n=19, receiving TFA HAIC (Cross-TFA group) first, followed by TRA HAIC (Cross-TRA group)]. Meanwhile, to facilitate the expression of partial results, all patients receiving TRA HAIC were defined as the TRA-HAIC group ( n=39, TRA+Cross-TRA group), and all patients receiving TFA HAIC were defined as the TFA-HAIC group ( n=52, TFA+Cross-TFA group). The primary research index was the Quality of Life (QOL) visualization scale score. The secondary research index included approach-related and catheter-related adverse events, duration of surgery, and mean length of patient stay. We used various statistical methods such as Mann-Whitney U test, t-test, Chi-square test, Fisher′s exact test, univariate logistic regression analysis, and multi-factor analysis. Results:TRA patients had significantly lower QOL scores than TFA patients (all P<0.001). The QOL scores of the Cross-TRA group were significantly lower than those of the Cross-TFA group (pain at the puncture site Z=-3.24, P=0.001, others P<0.001). The QOL scores of the Cross-TRA group were compared with those of the TRA group, which showed that the scores of the Cross-TRA group in overall discomfort ( Z=-3.07, P=0.002), postoperative toilet difficulty ( Z=-2.12, P=0.034), and walking difficulty ( Z=-2.58, P=0.010) were significantly lower than those of the TRA group. Satisfaction scores were significantly higher in the Cross-TRA group than in the Cross-TFA group ( Z=-3.78, P<0.001), and patients were more likely to receive TRA HAIC as the next procedure ( χ2=30.42, P<0.001). In terms of mean length of stay, patients receiving TRA HAIC had a significantly lower mean length of stay than those receiving TFA HAIC (50.1±3.2 h vs. 58.4±6.4 h, t=7.98, P<0.001). The incidence of radial artery occlusion (RAO) as an approach-related adverse event was 15.4% (6/39) in the TRA-HAIC group, which was significantly higher than that in the TFA-HAIC group (15.4% vs. 0, χ2=8.56, P=0.005). Notably, multifactorial analysis of RAO-related factors showed that intraoperative enoxaparin use and patency of radial artery flow during pressure were significantly associated with a reduced risk of postoperative RAO ( P=0.037 for enoxaparin use and P=0.049 for pressure). Conclusions:With respect to procedure approach, TRA was significantly better than TFA in terms of patient satisfaction and mean length of stay. Through further process optimization and prevention of adverse reactions, the incidence of adverse reactions can be maintained at a relatively low level, so that patients can benefit from TRA in future operations in terms of cost-effectiveness and medical efficiency.

【Objective】 To investigate the association between genetic variations in the glucagon-like peptide-1 receptor (GLP-1R) gene and BP responses to sodium and potassium intake. 【Methods】 A total of 514 subjects from 124 families were recruited in Meixian County, Shaanxi Province, in 2004, resulting in the establishment of a "salt-sensitive hypertension study cohort" . The subjects followed a dietary regimen which involved a normal diet for 3 days, a low-salt diet for 7 days, a high-salt diet for 7 days, and a high-salt potassium-supplemented diet for 7 days. BP measurement was conducted at different intervention periods, and peripheral blood samples were collected. Additionally, eight single nucleotide polymorphisms (SNPs) of the GLP-1R gene were genotyped using the MassARRAY detection platform. 【Results】 The GLP-1R gene SNP rs9462472 exhibited a significant association with systolic BP, diastolic BP, and mean arterial pressure response to high-salt intervention. Similarly, SNP rs2268637 showed a significant association with systolic BP response to high-salt intervention. Furthermore, SNP rs2268637 was significantly associated with systolic BP and mean arterial pressure responses to high-salt plus potassium supplementation intervention. 【Conclusion】 Our findings indicate a significant association of genetic variations in the GLP-1R gene with BP responses to sodium and potassium intake. This suggests that the GLP-1R gene plays a role in the regulation of BP salt sensitivity and potassium sensitivity.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.