Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disease caused by abnormal expression of glycosylphosphatidylinositol (GPI) on the cell membrane due to mutations in the phosphatidylinositol glycan class A(PIGA) gene. It is commonly characterized by intravascular hemolysis, repeated thrombosis, and bone marrow failure, as well as multiple systemic involvement symptoms such as renal dysfunction, pulmonary hypertension, swallowing difficulties, chest pain, abdominal pain, and erectile dysfunction. Due to the rarity of PNH and its strong heterogeneity in clinical manifestations, multidisciplinary collaboration is often required for diagnosis and treatment. Peking Union Medical College Hospital, relying on the rare disease diagnosis and treatment platform, has invited multidisciplinary clinical experts to form a unified opinion on the diagnosis and treatment of PNH, and formulated the Expert Consensus of Multidisciplinary Diagnosis and Treatment for Paroxysmal Nocturnal Hemoglobinuria (2024), with the hope of promoting the standardization of PNH diagnosis and treatment.

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 safety and efficacy of the TRIANGLE operation after neoadjuvant chemotherapy in locally advanced pancreatic cancer(LAPC).Methods:This study is a retrospective case series analysis. Between January 2020 and December 2022, a total of 103 patients were diagnosed as LAPC who underwent neoadjuvant chemotherapy at the Pancreas Center, the First Affiliated Hospital of Nanjing Medical University. Among them, 26 patients (25.2%) underwent the TRIANGLE operation. There were 15 males and 11 females,with a age of (59±7) years (range: 49 to 74 years). The pre-treatment serum CA19-9( M(IQR)) was 248.8(391.6)U/ml (range: 0 to 1 428 U/ml),and the serum carcinoembryonic antigen was 4.1(3.8)μg/L(range: 1.4 to 13.4 μg/L). The neoadjuvant chemotherapy regimens included: mFOLFIRINOX regimen in 6 cases(23.1%), GnP regimen in 14 cases(53.8%), and mFOLFIRINOX+GnP regimen in 6 cases(23.1%). The follow-up duration extended until June 2023 or until the occurrence of the patient′s death or loss to follow-up. The Kaplan-Meier method was employed to estimate the 1-year and 3-year overall survival rates. Results:After neoadjuvant chemotherapy,CA19-9 levels decreased by 92.3(40.1)%(range:2.1% to 97.7%). Evaluation of the response to treatment revealed 13 cases(50.0%) of stable disease,11 cases(42.3%) of partial response,and 2 cases(7.7%) of complete response. The surgical operation consisted of 12 cases(46.2%) of pancreaticoduodenectomy,12 cases(46.2%) of distal pancreatectomy,and 2 cases(7.7%) of total pancreatectomy. Margin determination was based on the “standardised pathology protocol” and the “1 mm” principle. No R2 and R1(direct) resections were observed,while the R0 resection rate was 61.5%(16/26), and the R1(1 mm) resection rate was 38.5%(10/26).The R1(1 mm) resection rates for the anterior margin,posterior margin,transected margin,portal vein groove margin,and uncinate margin were 23.1%(6/26),19.2%(5/26),12.5%(3/24),2/14, and 1/12, respectively. The overall postoperative complication rate was 57.8%(15/26),with major complications including grade B/C pancreatic fistula 25.0%(6/24,excluding 2 cases of total pancreatectomy),delayed gastric emptying in 23.1%(6/26),wound complications 11.5%(3/26),postoperative hemorrhage 7.7%(2/26), chylous fistula 7.7%(2/26) and bile fistula 3.8%(1/26). No reoperation was performed during the perioperative period(<90 days). One patient died on the 32 nd day postoperatively due to a ruptured pseudoaneurysm. A total of 25 patients were followed up,with a follow-up time of 21(24)months(range: 8 to 42 months). During the follow-up period,8 cases(32.0%) died due to tumor recurrence and metastasis,while 17 patients(68.0%) remained alive,including 11 cases of disease-free survival,5 cases of distant metastasis,and 1 case of local recurrence. The overall survival rates at 1- and 3-year after the initiation of neoadjuvant chemotherapy were 95.8% and 58.9%, respectively. The overall survival rates at 1- and 3-year after surgery were 77.7% and 57.8%, respectively. Conclusion:Performing pancreatoduodenectomy according to the Heidelberg triangle protocol in LAPC patients after neoadjuvant chemotherapy might increase the R0 resection rate without increasing perioperative mortality or the incidence of major postoperative complications.

Objective:To analyze the correlation between oral health behaviors and the incidence of dental caries two years later in infants and toddlers.Methods:It was a retrospective cohort study. Based on the Beijing Stomatological Public Project Network data system, 1 663 children were recruited to participate in 0-3 years project in 2021 and 3-6 years fluoridated foam project in 2023. In 2021, the children were 2 years old, the parents answered 11 questions related to dental caries in the children. The children with four or more caries-inducing factors were classified as having a "high risk" of developing dental caries, otherwise, they were classified as "low risk". In 2023, the children were 4 years old, and their caries status was checked by the dentists. The correlation between different caries risk levels at the age of 2 and caries status at the age of 4 in the children was compared.Results:Infants who often fell asleep with milk, drank night milk at night, and rarely gargle or drink water after eating had a relatively high caries rate and caries after 2 years, and the difference was statistically significant (all, P<0.05). Infants whose parents did not brush their teeth every day, did not floss, and ate sweets or snacks twice or more a day had a relatively high caries rate and caries after 2 years, and the difference was statistically significant (all, P<0.001). The caries risk of 1 174 (70.6%) 2-year-old children was rated as "dangerous", and that of 489 (29.6%) 2-year-old children was rated as "safe". After 2 years, the incidence of dental caries in "dangerous" group was higher than that in the "safe" group (52.7% vs 41.5%, χ2=17.36, P<0.001), and the DMFT index in "dangerous" group was also higher than that in the "safe" group (1(0, 4)比0(0, 2), H=-4.789, P<0.001). Conclusions:Oral health behavior is closely related to the incidence of dental caries caries 2 years later in infants and toddlers, and questionnaire-based caries risk assessment is feasible.

Objective:To investigate the application value of the maximum standardized uptake value (SUVmax) of 18F prostate-specific membrane antigen (PSMA) PET/CT combined with the minimum apparent diffusion coefficient (ADCmin) of biparametric magnetic resonance imaging (bpMRI) in predicting pathological upgrading after radical prostatectomy (RP) for prostate cancer. Methods:The data of 89 patients with localized prostate cancer treated at Beijing Hospital from April 2019 to October 2023 were retrospectively analysed. The average age of patients was (68.4±7.0) years old, with prostate-specific antigen (PSA) level of 7.7 (5.4, 12.9) ng/ml, prostate volume of 34.6 (26.9, 47.1) ml, tumor diameter of 1.3 (1.0, 1.8) cm, prostate imaging reporting and data system(PI-RADS) score of 5 in 29 cases (32.6%), clinical stage ≥T 3 in 13 cases (14.6%). There were 31 cases (34.8%) in group 1 of targeted biopsy International Society of Urological Pathology (ISUP)grading groups, 36 cases (40.4%) in group 2, 11 cases (12.4%) in group 3, and 11 cases (12.4%) in group 4. All patients underwent 18F-PSMA PET/CT and bpMRI examinations before RP. The index lesion, identified as the highest Gleason score in pathological whole-mount sections, were outlined. SUVmax and ADCmin values were calculated from the images' region of interest. Pathological upgrading was defined as the post-RP grade group higher than the targeted-biopsy grade group. Clinical data of patients with and without pathological upgrading were compared. Spearman correlation coefficient analysis was used to assess the correlation between SUVmax and ADCmin. Multivariate logistic regression analysis was conducted to evaluate the factors influencing pathological upgrading. Receiver operating characteristic (ROC) curve analysis was employed to assess the predictive value of each indicator for pathological upgrading. Results:Among the 89 cases, 31 cases (34.8%) experienced pathological upgrading. Compared with the patients without pathological upgrading, the SUVmax [11.3 (8.1, 16.4) vs. 6.7 (4.6, 9.2)], SUVmax/ADCmin ratio [3.1 (2.0, 4.6) vs. 1.4 (0.9, 2.1)], PSA [9.8 (6.3, 15.6) ng/ml vs. 7.1 (5.1, 10.5) ng/ml], PSA density [0.3 (0.2, 0.5) ng/ml 2 vs. 0.2 (0.1, 0.3) ng/ml 2], and post-RP ISUP grade group [≥3 group 17 cases (54.8%) vs. 13 cases(22.4%) ]were higher in patients with pathological upgrading, while ADCmin [3.8 (3.0, 5.3) ×10 -4 mm 2/s vs. 5.2 (3.6, 6.1)×10 -4 mm 2/s] and targeted biopsy ISUP grade group [≤2 group 27 cases(87.1%) vs. 40 cases(69.0%) ] were lower (all P<0.05). Spearman analysis showed a negative correlation between SUVmax and ADCmin ( R = -0.227, P = 0.032). Multivariate logistic regression analysis revealed that SUVmax ( OR = 1.108, 95% CI 1.020-1.238), ADCmin ( OR=0.607, 95% CI 0.390-0.874), and SUVmax/ADCmin ratio ( OR = 1.815, 95% CI 1.282-2.949) independently predicted pathological upgrading. The AUC of the SUVmax/ADCmin ratio for predicting pathological upgrading (AUC = 0.817) was higher than that of SUVmax (AUC = 0.774) and ADCmin (AUC=0.686), indicating a higher predictive efficiency. Conclusions:SUVmax, ADCmin, and SUVmax/ADCmin ratio can independently predict pathological upgrading in targeted biopsy of prostate cancer. The SUVmax/ADCmin ratio has a stronger predictive value for pathological upgrading.

Objective To explore the predictive value of cardiopulmonary exercise test (CPET) combined with clinical indexes in the postoperative complications. Methods The clinical data and CPET data (including lung function) of patients undergoing radical esophagectomy in Xuzhou Central Hospital from January 2018 to March 2022 were collected. Univariate analysis and multivariate logistic regression analysis were used to analyze the meaningful evaluation index for the occurrence of postoperative complications. Results A total of 77 patients with esophageal cancer were included, including 59 (76.6%) males and 18 (23.4%) females aged 47-80 years. There were 42 (54.5%) patients in the non-complication group and 35 (45.5%) patients in the complication group. Univariate analysis results showed that the occurrence of postoperative complications was significantly correlated with age, body mass index (BMI), smoking index, tumor stage, the length of postoperative hospital stay, peak work rate (WRpeak), peak kilogram oxygen uptake (VO2peak/kg), the ventilatory equivalent for carbon dioxide slope (VE/VCO2 slope), forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) and maximum expiratory flow rate (MMEF) (P<0.05). The results of multivariate logistic regression analysis showed that BMI [OR=1.35, 95%CI (1.03, 1.77), P=0.031], peakVO2/kg [OR=0.64, 95%CI (0.45, 0.93), P=0.018], oxygen uptake-anaerobic threshold (ATVO2) [OR=0.66, 95%CI (0.44, 0.98), P=0.044] and VE/VCO2 slope [OR=1.49, 95%CI (1.10, 2.02), P=0.011] were the related indexes of complications after radical resection of esophageal cancer. The sensitivity of BMI, VO2peak/kg, ATVO2/kg and VE/VCO2 slope in predicting postoperative complications was 82.10%, and the specificity was 87.44%, 95%CI (0.744, 0.955). Conclusion BMI, VO2peak/kg, ATVO2/kg and VE/VCO2 slope can be used as predictors for postoperative complications of esophageal cancer.

Objective:To explore the effect of UMedic-Harvey simulation system in teaching cardiac auscultation.Methods:A total of 161 undergraduate students (Grade 3) who majored in clinical medicine and were enrolled in 2018 at The Second Clinical College of Wuhan University were selected as research subjects. The students were divided into reformed-teaching group ( n=40) and routine-teaching group ( n=121) to receive training in the skills presented in the "Cardiac Auscultation" chapter of the textbook Diagnostics. Before class, teachers prepared the preview resource package according to the teaching contents and objectives as well as the standardized cases in the UMedic series courses, and published the pre-class preview task through the specific learning platform. Students completed the pre-class test online. In the class, UMedic-Harvey simulation system was adopted to carry out situational simulation teaching in the reformed-teaching group, while traditional teaching mode was adopted in the routine-teaching group. After class, we conducted a post-class assessment and questionnaire survey through the learning platform and WeChat group, and collected the final examination scores of cardiac auscultation skills and electrocardiogram interpretation in the same batch of students who participated in the course of diagnostics. SPSS 25.0 was used for the t-test and chi-square test. Results:There was no significant difference in the baseline scores of cardiac auscultation skills between the two groups ( t=0.83, P=0.410). The post-class scores of cardiac auscultation skills were significantly higher for students in the reformed-teaching group than those in the routine-teaching group [(76.87±6.11) vs. (61.85±11.37), t=7.98, P<0.001]. Moreover, the final examination scores of cardiac auscultation skills were significantly higher for students in the reformed-teaching group than those in the routine-teaching group [(74.17±6.20) vs. (62.33±10.16), t=6.95, P<0.001). In addition, the final examination scores of electrocardiogram interpretation were higher for students in the reformed-teaching group than those in the routine-teaching group, but the difference was not statistically significant ( t=1.92, P=0.060). Conclusions:The application of UMedic-Harvey simulation system improves the effectiveness and quality of teaching cardiac auscultation skills.

Objective To investigate the impact of whole body vibration training combined with intermittent blood flow restriction on the motor function and community activity in elderly stroke patients with hemiplegia.Methods A total of 80 convalescent hemiplegic patients after stroke who were hospitalized in the Rehabilitation Medicine Department of Yichang Central People's Hospital(Xiling Campus)from October 2021 to December 2023 were included and randomly divided into control group(n=25),vibration group(n=28)and combination group(n=27)using the random number table method.All patients received conventional rehabilitation training,on the basis;the vabration group received whole body vibration training,while the combination group received whole body vibration training combined with intermittent blood flow restriction.Before and after 6 weeks of training,the balance function was evaluated with Berg balance scale(BBS),while the gait function was tested with 6-minute walking test(6MWT)and the Community Balance and Mobility scale(CB&M)was used to assess the community activity ability.The community balance and mobility(CB&M)were evaluated in the first and third month after discharge.Results There was no significant difference in BBS,CB&M scores and 6MWT walking distance between the three groups before training(P>0.05).After 6 weeks of training,the three groups showed significant increases in the BBS,CB&Mscores and the walk distance of 6MWT(P<0.001).Furthermore,compared with the control group,the combination group and the vibration group were significantly beter(P<0.05),and there was no signifi-cant difference between the combination group and the vibration group(P>0.05).At the first and third month of follw-up after discharge,the CB&M scores of the three groups were significantly higher than those of the control group(P<0.05),while there was no significant difference between the CB&M scores of the combination group and the vibration group at the first month of follow-up(P>0.05).But the CB&M scores of the combination group was higher than those of the vibration group at the third month of follow-up,and the difference was statistically signifi-cant(P<0.05).Conclusion On the basis of conventional rehabilitation,whole body vibration training combined with intermittent blood flow restriction can significantly enhance balance function,balance confidence,walking ability and mobility in early stage of community life for elderly stroke patients with hemiplegia,potentially facilitat-ing their return to community life.

In recent years,the prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKP)infection has become a global public health issue.Ceftazidime/avibactam(CAZ/AVI)has been approved as a novel antimicrobial agent for the treatment of healthcare-associated pneumonia/ventilator-associated pneumonia,bloodstream infection,infection after kidney transplantation,and severe infection combined with liver cirrhosis.However,the use of CAZ/AVI has also led to the emergence of drug-resistant strains.The major mechanisms of drug-resistance include over-expression of blaKPC gene,mutation of β-lactamase and amino acids at key sites,changes in cell permeability caused by loss of membrane porin,and over-expression of efflux pump.This article reviews the research progress of CAZ/AVI in the treatment of CRKP infection,providing reference for clinical diagnosis and treatment.

Perihilar cholangiocarcinoma(PHC)is a common malignancy of biliary tract,for which surgery is the most effective treatment.However,its prognosis is not satisfactory even after surgical resection.In recent years,there have been some new advances in the surgical treatment of PHC.In this paper,we reviewed the existing literatures,demonstrated the current situation of preoperative biliary drainage,liver hyperplasia,hepatic resection,liver transplantation and minimally invasive surgery in the treatment of PHC,and prospected the future research direction.