Prognostic characterization of copper death-related immune checkpoint genes and analysis of immunologic and pharmacologic therapy in bladder cancer

Objective:Copper death-induced tumor cell death and immune checkpoint blockade therapy are highly selective.Combining their advantages and understanding their characteristics in bladder cancer is very important for the development of new targeted therapy.The identification of bladder cancer by screening the characteristic genes of copper death-related immune checkpoints provide a theoretical basis for the selection of adjuvant treatment options and the application of new targets.Methods:The expression samples of normal bladder tissue and bladder cancer were obtained from TCGA and GEO databases,and 13 cop-per death genes and 79 immune checkpoint genes were extracted from previous studies.The mRNA expression of prognostic genes was verified by qPCR.The copper death-related immune checkpoint genes were screened by correlation analysis to construct a prognostic model,and the differences in the efficacy of immunotherapy and chemotherapy between the high-risk group and the low-risk group were evaluated.Results:A prognostic model consisting of BTNL9,CD160,TNFRSF14 and TNFRSF18 was constructed.Its reliable predictive ability was proved in both databases,and qPCR showed that the expression levels of the four genes were significantly different between the normal group and the cancer cell group.The effect of immunotherapy in the lowrisk group was better than that in the high-risk group.Patients in the high-risk group had better chemotherapy efficacy.Conclusion:The copper death-related immune checkpoint gene model can accurately predict the prognosis of patients.Drug and immune analysis provide a basis for clinical treatment,and the discovery of potential targets provides a new solution for clinical decision-making.

Differential expression and clinical characteristics of Pim1 protein in different lesions of breast

Objective:To investigate the differential expression and clinical features of Pim1 protein in breast tissue of healthy people, mastitis and breast cancer patients.Methods:From September 2017 to September 2018, there were a blank group (39 normal residents), a mastitis group (39 mastitis patients), and a paracancerous tissue group (39 paracancerous tissues of breast cancer patients). Four groups of subjects in the adenocarcinoma group (39 breast cancer patients with breast cancer) were studied. To detect the difference of Pim1 protein expression levels in breast tissue of four groups of subjects, and analyze the effect of clinical condition on the expression of Pim1 protein in breast cancer patients.Results:Compared with the blank group, the difference of Pim1 protein expression between the mastitis group, the adenocarcinoma group and the paracancerous group was statistically significant. There was a statistically significant difference in Pim1 protein expression between the paracancerous tissue group and the adenocarcinoma tissue group. Pim1 protein expression is associated with lymph node metastasis, TNM stage, and ER expression in breast cancer patients, regardless of age, histological grade, PR, and Her-2. Pim1 protein expression was evaluated as a dependent variable in breast cancer patients. Lymph node metastasis, TNM staging, and ER were independent variables. The main factors affecting Pim1 protein expression in breast cancer patients were: ER expression (OR=4.759), lymph node metastasis (OR= 3.127), TNM staging (OR = 2.664).Conclusions: Pim1 protein is closely related to the occurrence and development of mastitis and breast cancer. The detection of this index can assess the status of breast inflammation and the risk of cancer in a certain degree, and it has certain reference value for early diagnosis of breast cancer.

High expression of the circadian clock gene NPAS2 is associated with progression and poor prognosis of gastric cancer:A singlecenter study

BACKGROUND The prognostic assessment of patients after surgical resection of gastric cancer(GC)patients is critical.However,the role of the circadian clock gene NPAS2 expression in GC remains unknown.AIM To explore the relationship between NPAS2 and the survival prognosis of GC patients and clarify its role in evaluating GC prognosis.METHODS The tumor tissues and clinical data of 101 patients with GC were collected retrospectively.Immunohistochemical staining(IHC)was used to detect the expression of NPAS2 protein in GC and adjacent tissues.Univariate and multivariate Cox regression analysis was used to determine the independent prognostic factors of GC,and a nomogram prediction model was established.The receiver operating characteristic(ROC)curve,the ROC area under the curve,the calibration curve,and C-index were used to evaluate the predictive effectiveness of the model.Kaplan Meier analysis was used to compare the risk stratification of subgroups according to the median score in the nomogram model of each patient.RESULTS Microarray IHC analysis showed that the positive rate of NPAS2 protein expression in GC tissues was 65.35%,which was significantly higher than 30.69%in adjacent tissues.The high expression of NPAS2 was correlated with tumor-node-metastasis(TNM)stage(P<0.05),pN stage(P<0.05),metastasis(P<0.05),venous invasion(P<0.05),lymphatic invasion(P<0.05),and lymph node positive(P<0.05)of GC.Kaplan Meier survival analysis showed that the 3-year overall survival(OS)of patients with high NPAS2 expression was significantly shortened(P<0.0001).Univariate and multivariate COX regression analysis showed that TNM stage(P=0.009),metastasis(P=0.009),and NPAS2 expression(P=0.020)were independent prognostic factors of OS in GC patients for 3 years.The nomogram prediction model based on independent prognostic factors has a C-Index of 0.740(95%CI:0.713-0.767).Furthermore,subgroup analysis showed that the 3-year OS time of the high-risk group was significantly lower than that of the low-risk group(P<0.0001).CONCLUSION NPAS2 is highly expressed in GC tissues and is closely related to worse OS in patients.Therefore,the evaluation of NPAS2 expression may be a potential marker for GC prognosis evaluation.Notably,the nomogram model based on NPAS2 can improve the accuracy of GC prognosis prediction and assist clinicians in postoperative patient management and decision-making.

Identification of CD13,CD107a,and CD164 as novel basophil-activation markers and dissection of two response patterns in time kinetics of IgE-de-pendent upregulation

Using two-colour flow cytometry>200 antibodies submitted to the 8^(th) International Workshop of Human Leukocyte Differentiation Antigens(HLDA8)have been analyzed for their reactivity with resting and activated CD203c^(+)basophils.Four antibodies either non-reactive or weakly reactive with resting basophils exhibited an increased reactivity with basophils activated by anti-IgE-mediated cross-linking of the high affinity IgE receptor(FcεRI).These include antibod-ies against CD164(WS-80160,clone N6B6 and WS-80162,clone 67D2),as well as two reagents with previously unknown specificities that were identified as CD13(WS-80274,clone A8)and CD107a(WS-80280,clone E63-880).The activation patterns followed either the“CD203c-like”or“CD63-like”activation profile.The CD203c profile is characterized by a rapid and significant upregulation(of CD13,CD164,and CD203c),reaching maximum levels after 5-15 min of stimulation.The phosphoinositide-3-kinase(PI3K)-specific inhibitor wortmannin inhibited the upregulation of these markers whereas 12-O-tetradecanoyl-phorbol-13-acetate(TPA)induced a rapid and FcεRI-independent upregulation within 1-2 min.In the CD63 profile,maximum upregulation(of CD63 and CD107a)was detected only after 20-40 min,and upregulation by TPA reached maximum levels after 60 min.In summary,our data identify CD13,CD107a,and CD164 as novel basophil-activation antigens.Based on time kinetics of upregulation,we hypothesize that molecules of the“CD203c group”and the“CD63 group”are linked to two different mechanisms of basophil activation.

Rosmarinic acid ameliorates hypoxia/ischemia induced cognitive deficits and promotes remyelination

Rosmarinic acid,a common ester extracted from Rosemary,Perilla frutescens,and Salvia miltiorrhiza Bunge,has been shown to have protective effects against various diseases.This is an investigation into whether rosmarinic acid can also affect the changes of white matter fibers and cognitive deficits caused by hypoxic injury.The right common carotid artery of 3-day-old rats was ligated for 2 hours.The rats were then prewarmed in a plastic container with holes in the lid,which was placed in 37°C water bath for 30 minutes.Afterwards,the rats were exposed to an atmosphere with 8% O2 and 92% N2 for 30 minutes to establish the perinatal hypoxia/ischemia injury models.The rat models were intraperitoneally injected with rosmarinic acid 20 mg/kg for 5 consecutive days.At 22 days after birth,rosmarinic acid was found to improve motor,anxiety,learning and spatial memory impairments induced by hypoxia/ischemia injury.Furthermore,rosmarinic acid promoted the proliferation of oligodendrocyte progenitor cells in the subventricular zone.After hypoxia/ischemia injury,rosmarinic acid reversed to some extent the downregulation of myelin basic protein and the loss of myelin sheath in the corpus callosum of white matter structure.Rosmarinic acid partially slowed down the expression of oligodendrocyte marker Olig2 and myelin basic protein and the increase of oligodendrocyte apoptosis marker inhibitors of DNA binding 2.These data indicate that rosmarinic acid ameliorated the cognitive dysfunction after perinatal hypoxia/ischemia injury by improving remyelination in corpus callosum.This study was approved by the Animal Experimental Ethics Committee of Xuzhou Medical University,China (approval No.20161636721) on September 16,2017.

Comparison of immersion ultrasound and low coherence reflectometry for ocular biometry in cataract patients

AIM： To compare the results of axial length （AL） biometry in cataract eyes by three methods： immersion B-ultrasound （IB） biometry, immersion A-ultrasound （IA） biometry and optical low coherence reflectometry. METHODS： In this prospective observational study of eyes with cataract AL measurements were performed using immersion ultrasound and optical low coherence reflectometry device. The results were evaluated using Bland-Altman analyses. The differences between both methods were assessed using the paired t-test, and its correlation was evaluated by Pearson coefficient. RESULTS： Eighty eyes of 80 patients （39 men and 41 women） for cataract surgery were included in the study. The values of AL could be got from all 80 eyes by IB and IA, the difference of AL measurements between IA and IB was of no statistical significance （P=0.97）; the mean difference in AL measurements was -0.031 mm （P=0.26; 95%CI, -0.09 to 0.02）; linear regression showed an excellent correlation （r=0.98, P〈0.0001）. Forty-five of eighty eyes with results of AL measurements, which can be obtained by three methods; the difference of AL measurements was of no statistical significance （IA vs IB, P=0.18; IA vs Lenstar, P=0.51; IB vs Lenstar, P=0.07）; linear regression showed an excellent correlation （IA vs IB, r=0.99; IA vs Lenstar, r=0.96; IB vs Lenstar, r=0.96）; Bland-Altman analysis also showed good agreement between the two methods [IA vs IB, 95% limits of agreement （LoA）, -0.36 to 0.28 mm; IA vs Lenstar, 95% LoA, -0.65 to 0.69 mm; IB vs Lenstar, 95% LoA, -0.55 to 0.68 mm]. CONCLUSION： Measurements with the optical low coherence reflectometry correlated well with IB and IA. In the eyes with serious refractive medium opacity, the measurements of AL could not be achieved or existed deviations when using optical low coherence reflectometry device. Under such circumstances, we should choose IA or IB as the optimization method to obtain measurements, in order to get much more accurate results.

Effect of bilateral supraclavicular postoperative radiotherapy in middle and lower thoracic esophageal carcinoma

AIM: To evaluate whether postoperative radiotherapy is an alternative to neck lymph node surgery and if it provides a survival benefit for those receiving two-field, chest and abdomen, lymphadenectomy.

CYLD deletion triggers nuclear factor-κB-signaling and increases cell death resistance in murine hepatocytes

AIM:To analyze the role of CYLD for receptor-mediated cell death of murine hepatocytes in acute liver injury models.METHODS:Hepatocyte cell death in CYLD knockout mice(CYLD-/-)was analyzed by application of liver injury models for CD95-(Jo2)and tumor necrosis factor(TNF)-α-[D-Gal N/lipopolysaccharide(LPS)]induced apoptosis.Liver injury was assessed by measurement of serum transaminases and histological analysis.Apoptosis induction was quantified by cleaved PARP staining and Western blotting of activated caspases.Nuclear factor(NF)-κB,ERK,Akt and jun amino-terminal kinases signaling were assessed.Primary Hepatocytes were isolated by two step-collagenase perfusion and treated with recombinant TNF-αand with the CD95-ligand Jo2.Cell viability was analyzed by MTT-assay.RESULTS:Livers of CYLD-/-mice showed increased anti-apoptotic NF-κB signaling.In both applied liver injury models CYLD-/-mice showed a significantly reduced apoptosis sensitivity.After D-Gal N/LPS treatment CYLD-/-mice exhibited significantly lower levels of alanine aminotransferase(ALT)(295 U/L vs 859 U/L,P<0.05)and aspartate aminotransferase(AST)(560 U/L vs 1025 U/L,P<0.01).After Jo injection CYLD-/-mice showed 2-fold lower ALT(50 U/L vs 110 U/L,P<0.01)and lower AST(250 U/L vs 435 U/L,P<0.01)serumlevels compared to WT mice.In addition,isolated CYLD-/-primary murine hepatocytes(PMH)were less sensitive towards death receptor-mediated apoptosis and showed increased levels of Bcl-2,XIAP,c IAP1/2,survivin and c-FLIP expression upon TNF-and CD95-receptor triggering,respectively.Inhibition of NF-κB activation by the inhibitor of NF-κB phosphorylation inhibitor BAY 11-7085 inhibited the expression of antiapoptotic proteins and re-sensitized CYLD-/-PMH towards TNF-and CD95-receptor mediated cell death.CONCLUSION:CYLD is a central regulator of apoptotic cell death in murine hepatocytes by controlling NF-κB dependent anti-apoptotic signaling.

Adverse outcomes in type 1 diabetic pregnant women with proliferative diabetic retinopathy

AIM: To report maternal and fetal adverse outcomes, in spite of appropriate treatment and regular follow up, in diabetic pregnant women with proliferative diabetic retinopathy. METHODS: Case series of four young pregnant diabetics aged between 20 and 25 years with type 1 diabetes mellitus and proliferative diabetic retrinopathy. RESULTS: The maternal adverse outcomes were abortion in one patient, pre-eclampsia and preterm delivery in one patient, and renal failure requiring dialysis in one patient. The fetal adverse outcomes were neonatal death in one case and premature baby in another case. CONCLUSION: These cases highlight the fact that diabetic pregnant women should be closely followed up by the obstetricians and physicians when they have proliferative retinopathy. The proliferative diabetic retinopathy should be considered as a part of the assessment when counseling a diabetic woman in antenatal check up and also in the follow up visits during pregnancy.

Etiopathogenesis of primary biliary cirrhosis

Primary biliary cirrhosis(PBC) is an autoimmune disease of the liver characterized by progressive bile duct destruction eventually leading to cirrhosis and liver failure.The serological hallmark of the disease is the presence of circulating antimitochondrial antibodies(AMA).These reflect the presence of autoreactive T and B cells to the culprit antigens,the E2 subunits of mitochondrial 2-oxo-acid dehydrogenase enzymes,chiefly pyruvate dehydrogenase(PDC-E2).The disease results from a combination of genetic and environmental risk factors.Genetic predisposition is indicated by the higher familial incidence of the disease particularly among siblings and the high concordance rate among monozygotic twins.Environmental triggering events appear crucial to disrupt a pre-existing unstable immune tolerance of genetic origin allowing,after a long latency,the emergence of clinical disease.Initiating mimetopes of the vulnerable epitope of the PDC-E2 autoantigen can be derived from microbes that utilize the PDC enzyme or,alternatively,environmental xenobiotics/chemical compounds that modify the structure of native proteins to make them immunogenic.A further alternative as a source of antigen is PDC-E2 derived from apoptotic cells.In the effector phase the biliary ductular cell,by reason of itsproclivity to express the antigen PDC-E2 in the course of apoptosis,undergoes a multilineage immune attack comprised of CD4+ and CD8+ T cells and antibody.In this article,we critically review the available evidence on etiopathogenesis of PBC and present interpretations of complex data,new developments and theories,and nominate directions for future research.

Cryptococcus infection with asymptomatic diffuse pulmonary disease in an immunocompetent patient:A case report

BACKGROUND Cryptococcus presenting as an opportunistic pathogen mainly affects immunocompromised patients,but the disseminated form of infection is rare among immunocompetent populations.The partial radiographic characteristics of pulmonary cryptococcosis mimic lung carcinoma,leading to unnecessary open chest exploratory surgery,and the lack of a gold-standard noninvasive diagnostic increases the risk of misdiagnosis.Positron emission tomography/computed tomography(PET/CT),a sensitive method for distinguishing malignant tumors,coupled with cryptococcal latex agglutination test showing a high positive rate may overcome these issues.CASE A 36-year-old man presented for general examination,without health complaints.Routine CT showed multiple pulmonary nodules and a mass with high maximum standardized uptake value.Initially,we suspected primary malignancy with hematogenous metastasis.Although his routine fungal analysis had been negative,subsequent CT-guided percutaneous core needle biopsy and histopathology examination indicated a diagnosis of pulmonary cryptococcosis.Fluconazole(200 mg/d)antifungal drug treatment was initiated,and 1 mo later the pulmonary mass had reduced in size markedly(on chest CT scan)without any complications.CONCLUSION Serologic and PET/CT examinations may not rule out cryptococcosis,and percutaneous lung puncture is critical under all circumstances.

R. sinicus should be reservoir of SL-CoV but not SARSCoV: critical comments on Ge et al.'s paper in Nature

The study of the origin of SARS coronavirus(SARS CoV)and SARS-like coronavirus(SL-CoV)is very important for the prevention of novel human infections with these viruses.Recently,Ge et al.suggest that Chinese horseshoe bats are natural reservoirs of SARSCoV[1].But this conclusion is incorrect.It should be"Chinese horseshoe bats are natural reservoirs of SLCoV"[2-7].The paper also has several methodological problems,leading to errors in the conclusions.

A case of bowel schitosomiasis not adhering to endoscopic findings

Schistosomiasis is a chronic worm infection caused by a species of trematodes, the Schistosomes. We may distinguish a urinary form from Schistosomes haematobium and an intestinal-hepatosplenic form mainly from Schistosomes mansonicharacterized by nausea, meteorism, abdominal pain, bloody diarrhea,rectal tenesmus, and hepatosplenomegaly. These infections represent a major health issue in Africa,Asia, and South America, but recently S mansoni has increased its prevalence in other countries, such as Europe countries and USA, due to international travelers and immigrants, with several diagnostic and prevention problems. We report a case of a 24-yearold patient without HIV infection, originated from Ghana, admitted for an afebrile dysenteric syndrome.All microbiologic studies were negative and colonoscopy revealed macroscopic lesions suggestive of a bowel inflammatory chronic disease. Since symptoms became worse, a therapy with mesalazine (2 g/d) was started,depending on the results of a bowel biopsy, but without any resolution. The therapy was stopped after 2 wk when the following result was available: a diagnosis of"intestinal schistosomiasis" was done (two Schistosoma eggs were detected in the colonic mucosa) and this was confirmed by the detection of Schistosoma eggs in the feces. Therapy was therefore changed to praziquantel(40 mg/kg, single dose), a specific anti-parasitic agent,with complete recovery. Schistosomiasis shows some peculiar difficulties in terms of differential diagnosis from the bowel inflammatory chronic disease, as the two disorders may show similar colonoscopic patterns.Since this infection has recently increased its prevalence worldwide, it was considered in the differential diagnosis of our patient with gastrointestinal symptoms.

Pharmaceutical care of a patient with antibiotic-associated encephalopathy

Objective:To provide reference of pharmaceutical care for the clinical treatment of a severe patient with antibiotic-associated encephalopathy.Methods:Clinical pharmacists participated in the clinical treatment of the patient with antibiotic-associated encephalopathy,provided pharmaceutical care for clinicians,including the evaluation of adverse drug events and the prevention of adverse drug interaction and development of anti-infection programs by using Pharmacokinetics/pharmacodynamics theory and therapeutic drug monitoring technique.Results:Through active clinical treatment and pharmaceutical care,the symptoms of patients with encephalopathy were relieved,and the infection was effectively controlled.Conclusion:Clinical pharmacists play a positive role in the treatment for the case with antibiotic associated encephalopathy.

Analysis of the Association between Intestinal Microflora and Long-lived Elderly People

The intestinal microbiota is the cornerstone of the human intestinal microecosystem and plays an unnegligible role in the growth and health maintenance of the human body.In recent years,many studies have been committed to exploring the potential connection of gut flora and the elderly population.The changes of gut flora are affected by various factors such as age increase,disease,medication,living habits,nutritional structure,and the intestinal flora is expected to be applied to the comprehensive evaluation of elderly health and longevity in the future.Based on this,the research progress of the general elderly and its related influencing factors.

Whole breast ultrafractionation radiotherapy after breast-conserving surgery in early breast cancer: A single-center, prospective, observational study from China

Objective:This single-center,prospective,observational study was designed to investigate the toxicities,patient-reported outcome(PRO),and dosimetric analysis of whole breast ultrafractionation radiotherapy(RT)after breast-conserving surgery(BCS)in early breast cancer(BC).Patients and methods:Patients diagnosed with BC stage I,II and treated with BCS were enrolled.A dose of 26 Gray(Gy)in five fractions was prescribed to the whole breast and tumor bed.Clinical endpoints included toxicities,PRO,and dosimetric analysis.PRO was measured by the European Organization for Research and Treatment of Cancer general quality of life questionnaire(EORTC QLQ-C30)and the BC-specific questionnaire(EORTC QLQ-BR23)questionnaires.Results:Between January 2022 and June 2023,62 female patients were enrolled.The median age was 45 years.Most patients(83.9%)were diagnosed with pathological stage I disease.The median planning target volume(PTV)was 456.4 mL.The minimum,maximum,and mean doses,and D95(dose of PTV irradiated volume more than 95%)to PTV were 20.2,28.8,27.2,and 26.3 Gy,respectively.The median mean lung dose and percentage lung volume receiving 8 Gy(V8)were 3.6 Gy and 13.4%,respectively.The median mean heart dose,V1.5(percentage of organ volume irradiated with 1.5 Gy or higher),and V7(percentage of organ volume irradiated with 7 Gy or higher)were 0.6 Gy,6.8%,and 0.4%,respectively.Cosmetic effects before RT showed no obvious differences compared to that post RT.No toxicities of grade 3 or higher occurred.Five patients had asymptomatic radiation pneumonia(grade 1),and 12 patients had radiation dermatitis(grade 1).No factor was significantly related to radiation dermatitis or radiation pneumonia.For the EORTC QLQ-C30 and QLQ-BR23 questionnaires,all function and symptom scores before RT had no significant differences compared with that after RT,1−2 months after RT,and 3−4 months after RT.Ultrafractionation RT did not worsen PRO.The 1-year crude local control was 100%.Conclusion:Whole breast ultrafractionation RT after BCS in early BC has no severe toxicities and does not affect PRO.These results need to be further validated with a longer follow-up and a larger sample size.

The Chinese Society of Clinical Oncology(CSCO)clinical guidelines for the diagnosis and treatment of nasopharyngeal carcinoma

Nasopharyngeal carcinoma(NPC)is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa.To develop these comprehensive guidelines for the diagnosis and management of NPC,the Chinese Society of Clinical Oncology(CSCO)arranged a multi-disciplinary team comprising of experts from all sub-specialties of NPC to write,discuss,and revise the guidelines.Based on the findings of evidencebased medicine in China and abroad,domestic experts have iteratively developed these guidelines to provide proper management of NPC.Overall,the guidelines describe the screening,clinical and pathological diagnosis,staging and risk assessment,therapies,and follow-up of NPC,which aim to improve the management of NPC.

Lipid scrambling in immunology:why it is important

Asymmetric lipid distribution in the plasma membrane(PM)is one of the fundamental features of living cells.Lipids not only serve as structural components of the biophysical structure of the PM that preserves cell integrity but also participate directly in signaling.Acidic phospholipids(PLs),such as phosphatidylserine(PS),phosphatidylethanolamine(PE),and phosphoinositol(PI),are preferentially located in the inner layer of the PM,creating electrostatic charges for the docking of membrane-associated and cytoplasmic proteins carrying polybasic stretches of amino acids.However,there is emerging evidence that reversible changes in the distribution of these lipids take place in the PM and that these changes are critical for normal cell signaling,functions and homeostasis[1–3].They can also be implicated in the genesis of pathologies.

Predictors of surgical complications in boys with hypospadias:data from an international registry

Background Complications are frequently reported after hypospadias repair and there is a need to understand the factors that influence their occurrence.Methods Data from boys with hypospadias born between 2000 and 2020 were obtained from the International Disorders of Sex Development(l-DSD)Registry.Logistic regressions,fisher's exact tests and spearman's correlation tests were performed on the data to assess associations between clinical factors and complication rates.Results Of the 551 eligible boys,data were available on 160(29%).Within the cohort,the median(range)External Masculinization Score(EMS)was 6(2,9).All presented with one or more additional genital malformation and 61(38%)presented with additional extragenital malformations.Disorders of androgen action,androgen synthesis and gonadal development were diagnosed in 28(18%),22(14%)and 9(6%)boys,respectively.The remaining 101(62%)patients were diagnosedas having non-specific 46,XY Disorders of Sex Development.Eighty(50%)boys had evidence of abnormal biochemistry,and gene variants were identified in 42(26%).Median age at first hypospadias surgery was 2 years(0,9),and median length of follow-up was 5 years(0,17).Postsurgical complications were noted in 102(64%)boys.There were no significant associations with postsurgical complications.Conclusions Boys with proximal hypospadias in the I-DSD Registry have high rates of additional comorbidities and a high risk of postoperative complications.No clinical factors were significantly associated with complication rates.High complication rates with no observable cause suggest the involvement of other factors which need investigation.

CACA guidelines for holistic integrative management of nasopharyngeal carcinoma

Purpose Nasopharyngeal carcinoma(NPC)is a malignant epithelial tumor originating in the nasopharynx and is particularly prevalent in southern China.Unfortunately,international guidelines,such as NCCN or ESMO,fail to adequately coincide with clinical practice in China,making it difficult to achieve precision personalized therapy in China.The aim of this guideline is to better promote a"Multidisciplinary Team to Holistic Integrative Medicine"(MDT to HIM)system for the prevention,screening,diagnosis,treatment,and rehabilitation of NPC.Methods The China Anti-Cancer Association(CACA)invited domestic multi-disciplinary experts,involving radiologists,oncologists,surgeons,pathologists,herbalists,physiatrists,and psychologists,to write,discuss,and revise the guidelines.Based on the integration of research evidence,clinical experience,and patient needs,the domestic experts have iteratively developed these guidelines to provide proper and feasible management of NPC.Results and conclusion The CACA Guidelines for Holistic Integrative Management of Nasopharyngeal Carcinoma are more suitable for China’s clinical practice,highlight Chinese characteristics,and have important clinical significance.