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.

Objective: To investigate the timing of pericardial drainage catheter removal and restart of the anticoagulation in patients with atrial fibrillation (AF) suffered from perioperative pericardial tamponade during atrial fibrillation catheter ablation and uninterrupted dabigatran. Methods: A total of 20 patients with pericardial tamponade, who underwent AF catheter ablation with uninterrupted dabigatran in Beijing Anzhen Hospital from January 2019 to August 2021, were included in this retrospective analysis. The clinical characteristics of enrolled patients, information of catheter ablation procedures, pericardial tamponade management, perioperative complications, the timing of pericardial drainage catheter removal and restart of anticoagulation were analyzed. Results: All patients underwent pericardiocentesis and pericardial effusion drainage was successful in all patients. The average drainage volume was (427.8±527.4) ml. Seven cases were treated with idarucizumab, of which 1 patient received surgical repair. The average timing of pericardial drainage catheter removal and restart of anticoagulation in 19 patients without surgical repair was (1.4±0.7) and (0.8±0.4) days, respectively. No new bleeding, embolism and death were reported during hospitalization and within 30 days following hospital discharge. Time of removal of pericardial drainage catheter, restart of anticoagulation and hospital stay were similar between patients treated with idarucizumab or not. Conclusion: It is safe and reasonable to remove pericardial drainage catheter and restart anticoagulation as soon as possible during catheter ablation of atrial fibrillation with uninterrupted dabigatran independent of the idarucizumab use or not in case of confirmed hemostasis.
Humans ; Atrial Fibrillation/drug therapy* ; Dabigatran/therapeutic use* ; Cardiac Tamponade/complications* ; Anticoagulants/therapeutic use* ; Retrospective Studies ; Treatment Outcome ; Drainage/adverse effects* ; Catheter Ablation ; Catheters/adverse effects*

The aim of this paper was to investigate the effect of total saponins from Panax japonicus( SPJ) on cognitive decline of natural aging rats and its mechanism. Thirty male SD rats of eighteen month old were randomly divided into three groups: aged group,10 mg·kg~(-1) SPJ-treated group and 30 mg·kg~(-1) SPJ-treated group. The SPJ-treated groups were given SPJ at the dosages of 10 mg·kg~(-1) and 30 mg·kg~(-1),respectively,from the age of 18 to 24 months. Aged group were lavaged the same amount of saline,10 six-month-old rats were used as control group,with 10 rats in each group. The open field test,novel object recognition and Morris water maze were performed to detect the changes of cognitive function in each group. The changes of synaptic transmission of long-term potentiation( LTP) in hippocampal CA1 region were detected by field potential recording. Western blot was used to detect the protein levels of NLRP3,ASC,caspase-1 and the changes of Glu A1,Glu A2,CAMKⅡ,CREB and phosphorylation of CAMKⅡ,CREB in each group.The results showed that SPJ could improve the decline of cognitive function in aging rats,reduce the damage of LTP in the hippocampal CA1 region of aged rats,and decrease the expression of NLRP3,ASC,caspase-1 in aging rats. At the same time,SPJ could enhance the membrane expression of AMPA receptor( Glu A1 and Glu A2),and increase the expression of p-CAMKⅡand p-CREB in aging rats.SPJ could improve cognitive decline of natural aging rats,and its mechanism may be related to regulating NLRP3 inflammasome,thus regulating the membrane expression of AMPA receptor,and enhancing the expression phosphorylation of CAMKⅡ and CREB.
Aging ; Animals ; CA1 Region, Hippocampal ; physiology ; Cognition ; drug effects ; Inflammasomes ; metabolism ; Long-Term Potentiation ; Male ; NLR Family, Pyrin Domain-Containing 3 Protein ; metabolism ; Panax ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Saponins ; pharmacology

Objective To investigate associations of herpes simplex virus(HSV)infection with elevated high-sensitivity C-reactive protein(hsCRP)level and the development of atrial fibrillation(AF) in elderly individuals.Methods Through screening a total of 2,603 individuals,49 patients aged 60 years or over with AF and without structural heart diseases and known risk factors for AF were selected for data collection.Fifty-five elderly healthy control subjects were selected from a population based Chinese Arrhythmia Registry.Baseline characteristics,plasma antibody levels against HSV-1 and-2,and level of hsCRP were analyzed.Results Level of antibodies against HSV-1 was significantly higher in AF patients[(314.5±63.6)mg/L than in control subjects(216.0±50.7) mg/L,P＜0.01].Level of antibodies against HSV-2 was significantly higher in AF patients[(400.1±50.7) mg/L than in control subjects (306.3 ± 64.5) mg/L,P ＜ 0.01].Linear regression analysis demonstrated a positive correlation of plasma levels of hsCRP with both anti-HSV-1 and anti-HSV-2 IgG antibodies (r =0.291,0.188,all P ＜ 0.01).In multiple logistic regression analysis,HSV-1 and HSV-2 antibody levels were significantly associated with AF occurrence(OR =1.035 and 1.034,all P ＜0.01).The optimal cut-off point for predicting AF occurrence was 284.96 mg/L for anti-HSV-1 with sensitivity of 67.3％ and a specificity of 92.7％,and was 366.26 mg/L for anti-HSV-2 with a sensitivity of 67.3％ and a specificity of 85.5％,respectively.Conclusions The increased plasma levels of anti-HSV-1 and anti-HSV-2 antibodies are significantly associated with AF occurrence in elderly adults.

Objective: To analyze the interpretation results on the pathogenic classification of KCNH2 variants and SCN5A variants of long QT syndrome (LQTS) based on American College of Medical Genetics and Genomics (ACMG) guidelines by 4 clinical gene screening agencies from Beijing. Methods: Pathogenic classification of 16 variants in KCNH2 and SCN5A was made by 4 clinical gene screening agencies from Beijing based on ACMG guideline. Krippendorff's alpha was used to assess the inter-agency variation consistency. Results: All 4 agencies made pathogenic assessment on all the variants and provided the interpretation results for the classification. For the eight variants from the patients with LQTS, the consistency of classification was only 1/8 and the alpha test value was - 0.01. For the eight variables from incidental findings, the consistency of classification was 4/8 and the alpha test value was 0.407. Evidence analysis of the 4 variants with large differences in classification among agencies showed that the main reasons for the discrepancies originated from the comprehensiveness of the literature search and the inconsistency of the subjective determination of the evidence grade. Conclusion The consistency of the pathogenic classification of LQTS gene variants based on ACMG guidelines among clinical gene screening agencies from Beijing is poor, which will result in great impact on the clinical treatment strategies of the patients with LQTS. The standardization of pathogenic evaluation of variants in clinical gene screening agencies needs to be improved urgently.

BACKGROUND: The majority of children with β-thalassemia major have iron overload, and iron overload may have negative effects on hematopoietic stem cell transplantation. OBJECTIVE: To assess the effects of liver and cardiac iron overload detected by magnetic resonance imaging (MRI) T2* on HLA-identical allogeneic hematopoietic stem cell transplantation in children with β-thalassemia major. METHODS: Eighty-one children with β-thalassemia major who were over 3 years of age and could cooperate with MRI detection were subjected to liver and heart MRI T2* tests before or after HLA-identical allogeneic hematopoietic stem cell transplantation. According to the test results, we calculated the liver and cardiac iron content, defined as an indicator of liver and heart iron overload. Then, there was a correlation analysis between the liver and cardiac iron content and serum ferritin, time of hematopoietic reconstitution, mortality rate, implantation rate and the morbidity of transplantation related complications, such as graft-versus-host disease, infections, autoimmune hemolysis, pancytopenia, hepatic veno-occlusive disease, septicemia. RESULTS AND CONCLUSION: The liver iron content was positively correlated with the time of hemoglobin implantation (r=0.229, P=0.043), and the cardiac iron content were positively correlated with the mortality rate (r=0.266, P=0.017); the serum ferritin level was negatively correlated with the implantation rate (r=-0.289, P=0.009), and positively correlated with the morbidity of septicemia (r=0.251, P=0.024) and pancytopenia (r=0.276, P=0.013). Therefore, iron overload exerts negative effects on HLA-identical allogeneic hematopoietic stem cell transplantation in β-thalassemia major children, and it is necessary to detect serum ferritin level and assess liver and cardiac iron overload before cell transplantation.

Objective To investigate the population pharmacokinetic characteristics of milnacipran in Chinese healthy volunteers and factors co-variables that might impact its clearance.Methods The clinical data and blood samples were collected from a pharmacokinetics (PK) study (n =24) which was designed as a randomized,three-way cross-over,single dose (25,50 or 100 mg) and in multiple doses for 8 d (up to 100 mg · d-1 administered as 50 mg twice daily) in Chinese healthy volunteers.Both the single and multiple-dose studies included 12 volunteers (six males and six females).The concentration of milnacipran in plasma was analyzed by HPLC-MS/MS.Non-linear mixed-effects model (NONMEM) was used to assess the influence of demographic characte-ristics on PK characters of milnacipran.The final model was diagnosed by goodness-of-fit plots and evaluated by bootstrap methods.Results A one-compartment model was developed to capture the milnacipran pharmacokinetics.Typical value of clearance (CL),the volume of distribution (V),and maximum absorption rate (Ka) were 37.53-44.16 (40.84 ± 1.69) L h-1,382.89-433.37 (408.13 ± 12.86) L and 0.81-1.31 (1.06 ± 0.13) /h,respectively,and age or sex had no influence on CL of milnacipran.No obvious bias was found by bootstrap method.Conclusions The developed model can capture milnacipran pharmacokinetics well in healthy volunteers.Age and genderhad no influenceon minacipran PK profiles in healthy subjects.

OBJECTIVETo compare the differences in the clinical function and lumbar and abdominal myodynamia in patiants of lumbar disc herniation treated with moxibustion at Dazhui (GV 14) and Guanyuan (CV 4) and acupuncture.

METHODSForty cases were randomized into a moxibustion group and an acupuncture group, 20 cases in each group. In the moxibustion group, the warm moxibustion was applied alternatively at Dazhui (GV 14) and Guanyuan (CV 4) once every other day, 1 h each time, once every day. In the acupuncture group, acupuncture was applied to the corresponding acupoints based on the affected lumbar vertebras, such as Jiaji (EX-B 2), Shens-hu (BL 23), Dachangshu (BL 25) and Huantiao (GB 30), etc. , once evey day 30 min each time. The treatment for 3 weeks was taken as one session in each group. Totally, one session treatment was required. Surface electromyography (SEMG) of bilateral paraspinal muscle and rectus muscle, and JOA score of low back pain were observed in the two groups.

RESULTS(1) JOA score: the score of subjective symptoms, score of activity of daily living (ADL) and total score were improved obviously as compared with those before treatment in the two groups (P<0.01, P<0.05). The results of subjective symptoms score, score of ADL and total score in the acupuncture group were superior to those in the moxibustion group after treatment (6.95+/-0.94 vs 5.50 +/-0.89,10. 90+/-1.86 vs 8.90+/- 1. 92,22.50 +/- 2.82 vs 19.35 +/- 2. 70, all P<0. 05). (2) SEMG comparison: root-mean-square value (RMS) was all reduced in SEMG of the anteflexion, rear protraction, orthostatism, bilateral bending and neck and leg rear flexion for strengthening lumbar muscle as compared with those before treatment in the two groups (P< 0.05, P<0. 01). RMS of the anteflexion and bilateral bending in the acupunture group were reduced much obviously as compared with the moxibustion group. In terms of sitting position anteflexion, rear protraction, orthostatism, bilateral bending and neck and leg rear flexion for strengthening lumbar muscle, median frequency (MF) after treatment was all improved as compared with that before treatment in the two groups (P<0. 05, P<0. 01). In terms of anteflexion, the electrode MF after treatment was improved much obviously in the acupuncture group(P<0. 05).

CONCLUSIONMoxibustion at Dazhui (GV 14) and Guanyuan (CV 4) and conventional acupuncture all improve muscle function, relieve muscle fatigue, increase the ability of anti-muscle fatigue, strengthen lumbar vertebral stability, release subjective symptoms and improve ADL. But, the effects of moxibustion are slightly lower than those of acupuncture.

Acupuncture Therapy ; Adult ; Aged ; Electromyography ; Female ; Humans ; Intervertebral Disc Displacement ; physiopathology ; therapy ; Lumbar Vertebrae ; physiopathology ; Male ; Middle Aged ; Moxibustion ; Young Adult

BACKGROUNDPodocyte apoptosis is recently indicated as an early phenomenon of diabetic nephropathy. Pancreatic β-cells exposed to saturated free fatty acid palmitate undergo irreversible endoplasmic reticulum (ER) stress and consequent apoptosis, contributing to the onset of diabetes. We hypothesized that palmitate could induce podocyte apoptosis via ER stress, which initiates or aggravates proteinuria in diabetic nephropathy.

METHODSPodocyte apoptosis was detected by 4',6-diamidio-2-phenylindole (DAPI) stained apoptotic cell count and Annexin V-PI stain. The expressions of ER molecule chaperone glucose-regulated protein 78 (GRP78), indicators of ER-associated apoptosis C/EBP homologous protein (CHOP), and Bcl-2 were assayed by Western blotting and real-time PCR. GRP78 and synaptopodin were co-localized by immunofluorescence stain.

RESULTSPalmitate significantly increased the percentage of cultured apoptotic murine podocytes time-dependently when loading 0.75 mmol/L (10 hours, 13 hours, and 15 hours compared with 0 hour, P < 0.001) and dose-dependently when loading palmitate ranging from 0.25 to 1.00 mmol/L for 15 hours (compared to control, P < 0.001). Palmitate time-dependently and dose-dependently increased the protein expression of GRP78 and CHOP, and decreased that of Bcl-2. Palmitate loading ranging from 0.5 to 1.0 mmol/L for 12 hours significantly increased mRNA of GRP78 and CHOP, and decreased that of Bcl-2 compared to control (P < 0.001), with the maximum concentration being 0.75 mmol/L. Palmitate 0.5 mmol/L loading for 3 hours, 8 hours, and 12 hours significantly increased mRNA of GRP78 and CHOP, and decreased that of Bcl-2 compared to 0 hour (P < 0.001), with the maximum effect at 3 hours. Confocal microscopy demonstrated that GRP78 expression was significantly increased when exposed to 0.5 mmol/L of palmitate for 8 hours compared to control.

CONCLUSIONPalmitate could induce podocyte apoptosis via ER stress, suggesting podocyte apoptosis and consequent proteinuria caused by lipotoxic free fatty acid could be ameliorated by relief of ER stress.

Apoptosis ; drug effects ; Cells, Cultured ; Endoplasmic Reticulum Stress ; physiology ; Heat-Shock Proteins ; analysis ; physiology ; Humans ; Insulin Resistance ; Palmitic Acid ; pharmacology ; Podocytes ; drug effects ; pathology

OBJECTIVETo explore the clinical characteristics and risk factors of refracture in patients suffering from osteoporosis-related fractures as well as effective interventions.

METHODSFrom January 2006 to January 2008, both out-patients and in-patients in our hospital who were over 50 years old and suffered from osteoporosis-related fractures were selected for this research. They were divided into fracture group and refracture group. The refracture rate was followed up for 2 years, during which 11 patients developed refracture, thus were included in the refracture group. Therefore, 273 patients, 225 first-fracture cases, aged (67.7+/-8.5) years, and 48 refracture cases, aged (72.7+/-9.5) years, were included in this study. General data including age and sex, fracture types, femoral neck bone mineral density (BMD) T-scores tested by dual-energy X-rays absorptiometry (DEXA), Charlson index, time-frame between two fractures as well as mobility skill assessment were collected and analyzed by single-factor and multivariate statistical methods.

RESULTSFemales accounted for 70.2% of the fracture group and 77.1% of the refracture group. The most common refracture type was vertebral fracture for the first time and femoral neck fracture for the second time during the follow-up. The second fracture happened 3.7 years after the first one on average. The refracture rate was 2.12% within one year, and 4.66% within two years. Risk factors for a second fracture in osteoporotic fracture patients included age (larger than 75 years, HR equal to 1.23, 95%CI 1.18-1.29; larger than 85 years, HR equal to 1.68, 95% CI 1.60-1.76), female sex (HR equal to 1.36, 95%CI 1.32-1.40), prior vertebral fractures (HR equal to 1.62, 95%CI 1.01-2.07), prior hip fractures (HR equal to 1.27, 95%CI 0.89-2.42), BMD T-score less than -3.5 (HR equal to 1.38, 95%CI 1.17-1.72) and weakened motor skills (HR equal to 1.27, 95%CI 1.09-1.40).

CONCLUSIONSThe risks of second fracture among patients with initial brittle fracture are substantial. There is adequate time between the first and second fractures for interventions to reduce the risks of refracture, especially for the old women with a vertebral or hip fracture. Medication, motor functional rehabilitation and fall-down prevention training are helpful.

Age Factors ; Aged ; Aged, 80 and over ; Bone Density ; Female ; Humans ; Male ; Middle Aged ; Motor Skills ; Multivariate Analysis ; Osteoporotic Fractures ; etiology ; Risk Factors