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.

Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.

The relationship between androgen and prostate cancer treatment has plagued the field of urologic oncology. To investigate the efficacy and safety of bipolar androgen therapy (BAT) followed by immune checkpoint inhibitor therapy in patients with metastatic castration resistant prostate cancer (mCRPC). In August 2020, Beijing Hospital conducted an investigator-initiated study: Bipolar androgen therapy followed by immune checkpoint inhibitor therapy in metastatic castration resistant prostate cancer. Up to now, the study has included 4 patients who completed the entire cycle of treatment. The mean age of the patients was 74.5 (68 to 82) years old, the mean prostate-specific antigen (PSA) was 20.8 (9.9 to 8.36) μg/L, the mean testosterone was 0.50 (0.00 to 1.81) μg/L, and the Gleason score were 10 and 9, 7, 7 respectively. The pain scale score before treatment was 1.5 (1 to 2). In this study, 4 patients completed the entire cycle of treatment, and the treatment effect of the patients showed great heterogeneity. PSA in case 1 decreased from 24.0 μg/L to 0.47 μg/L, testosterone increased from 0.175 6 μg/L to 2.62 μg/L. PSA in case 2 increased from 9.939 μg/L to 168.536 μg/L, and testosterone increased from 0.0 μg/L increased to 2.85 μg/L. PSA increased from 13.31 μg/L to 39.278 μg/L in case 3, testosterone increased from 0.0 μg/L to 2.54 μg/L. and PSA increased from 36.0 μg/L to 350.2 μg/L in the case 4, testosterone increased from 1.81 μg/L to 3.85 μg/L. Except for one patient who showed significant PSA remission, the PSA levels of the remaining three patients remained high overall. There were no adverse reactions reported in 4 patients. In the follow-up, case 1 continued to use PD-1 monoclonal antibody (median progression free survival time was 10 months). Two patients who had previously been resistant to enzalutamide received enzalutamide again after the whole cycle of treatment, and their PSA decreased again, which indicated that the patient was sensitive to enzalutamide again. BAT had a certain therapeutic effect on mCRPC patients, and the safety was controllable. Its tumor control effect still needed long-term follow-up verification in large-sample clinical trials. BAT has a certain therapeutic effect on mCRPC patient, especially the resensitivity of tumors to enzalutamide can be restored. Immune checkpoint inhibitors may have therapeutic potential in patients with prostate cancer treated with BAT and enzalutamide.
Aged ; Aged, 80 and over ; Androgens/therapeutic use* ; Humans ; Immune Checkpoint Inhibitors ; Male ; Nitriles/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Testosterone/therapeutic use* ; Treatment Outcome

Multidrug resistance (MDR) is the main cause of clinical treatment failure and poor prognosis in cancer. Targeting P-glycoprotein (P-gp) has been regarded as an effective strategy to overcome MDR. In this work, we reported our preclinical studies of the triazolo[1,5-a]pyrimidine-based compound WS-716 as a highly potent, specific, and orally active P-gp inhibitor. Through direct binding to P-gp, WS-716 inhibited efflux function of P-gp and specifically reversed P-gp-mediated MDR to paclitaxel (PTX) in multiple resistant cell lines, without changing its expression or subcellular localization. WS-716 and PTX synergistically inhibited formation of colony and 3D spheroid, induced apoptosis and cell cycle arrest at G2/M phase in resistant SW620/Ad300 cells. In addition, WS-716 displayed minimal effect on the drug-metabolizing enzyme cytochrome P4503A4 (CYP3A4). Importantly, WS-716 increased sensitivity of both pre-clinically and clinically derived MDR tumors to PTX in vivo with the T/C value of 29.7% in patient-derived xenograft (PDX) models. Relative to PTX treatment alone, combination of WS-716 and PTX caused no obvious adverse reactions. Taken together, our preclinical studies revealed therapeutic promise of WS-716 against MDR cancer, the promising data warrant its further development for cancer therapy.

Ischemic heart diseases are one of the major causes of death worldwide. Effective restoration of blood flow can significantly improve patients’ quality of life and reduce mortality. However, reperfusion injury cannot be ignored. Flavonoids possess well-established antioxidant properties; They also have other benefits that may be relevant for ameliorating myocardial ischemia-reperfusion injury (MIRI). In this review, we focus on flavonoids with cardiovascular-protection function and emphasize their pharmacological effects. The main mechanisms of flavonoid pharmacological activities against MIRI involve the following aspects: a) antioxidant, b) anti-inflammatory, c) anti-platelet aggregation, d) anti-apoptosis, and e) myocardial-function regulation activities. We also summarized the effectiveness of flavonoids for MIRI.

OBJECTIVETo investigate the features of methylation in the promoter region of glucose-6-phosphate dehydrogenase (G6PD) gene and the association between gene promoter methylation and G6PD deficiency.

METHODSFluorescent quantitative PCR was used to measure the mRNA expression of G6PD in 130 children with G6PD deficiency. Sixty-five children without G6PD deficiency served as the control group. The methylation-sensitive high-resolution melting curve analysis and bisulfite PCR sequencing were used to analyze gene promoter methylation in 22 children with G6PD deficiency and low G6PD mRNA expression. The G6PD gene promoter methylation was analyzed in 44 girls with normal G6PD mRNA expression (7 from G6PD deficiency group and 37 from control group).

RESULTSTwenty-two (16.9%) children with G6PD deficiency had relatively low mRNA expression of G6PD; among whom, 16 boys showed no methylation, and 6 girls showed partial methylation. Among the 44 girls with normal G6PD mRNA expression, 40 showed partial methylation, and 4 showed no methylation (1 case in the G6PD group and 3 cases in the control group).

CONCLUSIONSGene promoter methylation is not associated with G6PD deficiency in boys. Girls have partial methylation or no methylation in the G6PD gene, suggesting that the methylation may be related to G6PD deficiency in girls.

Adolescent ; Child ; Child, Preschool ; DNA Methylation ; Female ; Glucosephosphate Dehydrogenase ; genetics ; Glucosephosphate Dehydrogenase Deficiency ; genetics ; Humans ; Infant ; Male ; Promoter Regions, Genetic ; RNA, Messenger ; analysis ; Sex Characteristics

REVERSIBLE posterior leukoencephalopathy syndrome (RPLS) is a rare neurological syndrome characterized by headache, altered mental status, seizures, and visual disturbance, associated with reversible white matter changes.1 It has been commonly reported in patients with severe hypertension and pre-eclampsia. Here we report a case with nephrotic syndrome complicated by RPLS.
Brain ; diagnostic imaging ; drug effects ; pathology ; Child ; Female ; Humans ; Magnetic Resonance Imaging ; Nephrotic Syndrome ; complications ; diagnosis ; drug therapy ; Posterior Leukoencephalopathy Syndrome ; complications ; diagnosis ; drug therapy ; Tomography, X-Ray Computed ; Treatment Outcome

Objective To evaluate the pharmacokinetics of multiple doses of ampiroxicam tablets in Chinese healthy subjects .Methods A randomized, open study was conducted.Twelve subjects were orally administrated with 27 mg ampiroxicam tablets, once a day for 11 days. The blood samples were collected on the 8th , 9th , and 10th day before ad-ministration.On the 11 th day, the blood and urine samples were collected at different time points after administration , and the concentrations of am-piroxicam in serum and urine were determinated by HPLC method . Results One subject exited on the 7th day.The main pharmacokinetics parameters of 11 subjects after oral doses for 11 days were as follows:Cmax were(8.14 ±2.81) mg? L-1; t1 /2β was (50.10 ±18.10 ) h; tmax was (5.60 ±4.10) h; AUC0 -∞ was (837.05 ±441.47 ) mg? h? L respectively.Urinary recovery rate was (0.55 ±0.51 )% from zero to 192 hours, respectively.Conclusion After multiple dosing, there was a very high trough concentration before dosing because of a very long half -life of ampiroxicam.Blood concentration and pharmacokinetic parameters are individually different, and little drug is excreted by kidney.

Objective To explore the expression of glutathione hormone (GSH) and γ-glutamyl cysteine synthetase (γ-GCS) in premature newborn rats exposed to hyperoxia,and to study antioxidant role of GSH and γ-GCS in hyperoxia-induced lung injury.Methods One-day old preterm SD rats were divided randomly into 2 groups:hyperoxia group and air group.Newborn rats in hyperoxia group were continuously exposed to oxygen(oxygen ＞ 850 mL/L),and newborn rats in air group were exposed in room air.After 1,7,14 days of exposure,the preterm SD rats of 2 groups were killed,and whole lung of these rats were isolated.GSH and γ-GCS of pulmonary tissue homogenate were detected by double antibody sandwich enzyme linked immunosorbent assay (ELISA).Bicinchoninic acid (BCA) was used to detect GSH protein in lung tissue homogenate.Total lung RNA was extracted and γ-GCS mRNA was detected by reverse transcription polymerase chain reaction.Results 1.The results were detected by ELISA method and BCA method,compaired with air group,the expression of GSH protein in lung tissue induced by hyperoxia was significantly increased after 1,7 days of exposure(all P ＜ 0.05),but the expression of GSH became significantly weak after 14 days of exposure (P ＜0.05).2.The expression of γ-GCS mRNA and protein level were significantly increased in 1,7 days (all P ＜0.05),but the general tendency decreased after 14 days of exposure,the expression of γ-GCS mRNA became stronger than its expression after 14 days of air group,both were no significantly different(P ＞0.05).Conclusions The changes of GSH and γ-GCS in the lung of premature SD rats induced by oxidation outbreak participate in the development of hyperoxia-induced lung injury,the activity of γ-GCS may be increased by hyperoxia,and alleviate hyperoxia lung injury in premature rats through antioxidation of GSH.

Objective To study the prevalence rates of knowledge,attitudes and use of the nutrition labeling and related influential factors in Hangzhou supermarket consumers.Methods Using a self-developed survey questionnaire,randomly selected customers were conducted a face-toface interview program in a large supermarket of Hangzhou city.Results 586 people were interviewed,including 202 males and 384 females,with the mean age as 41.6±17.23 years.The Facts Labels'were as follows:dietary fiber(71.84%),fat(70.99%),calcium(60.75%),salt (58.36%),energy(50.85%)and sugar(39.42%).The support rates of the three attitudes indicators were"support marking the Nutrition Facts Label"(90.44%)."support marking the nutrition claims"(87.03%)and"want to know more relative knowledge"(77.13%).There were 58.36% and 80.03%first-time buyers who would read the Nutrition Facts Food Labels and the Nutrition Claims.Through logistic model analysis,male,youth,low-educated people were found to be the risk factors related to the nutrition label reading behavior.Conclusion The capacity of the reading,understanding and correct application of nutrition labeling among consumers was not satisfactory.Improvement on the readability and the authority of nutrition labeling and the development of the national nutrition knowledge and health education programs were in urgent needs.