Objective:To evaluate surgical strategies and clinical outcomes in supra-labyrinthine cholesteatoma management, providing evidence-based guidance for therapeutic decision-making. Methods:Seven patients with supra-labyrinthine cholesteatoma in our hospital from 2021 to 2023 were enrolled in this study. The clinical manifestations, imaging findings, and surgical outcomes of patients were retrospectively analyzed. A systematic literature review focused on surgical anatomy correlations and imaging-based approach selection. Results:All seven cases of supra-labyrinthine cholesteatoma were unilateral. Preoperative otoendoscopy, CT, and intraoperative findings confirmed that they were classified as supral-abyrinthine cholesteatoma according to Sanna's classification. Two cases were operated entirely with otoendoscopy, three cases used a postauricular approach with microscopic assistance, and two cases involved a combined approach with endoscopy and microscopy. Hearing reconstruction with ossicular prosthesis was performed in five cases, while two cases did not undergo hearing reconstruction due to preoperative anacusis confirmed by both subjective and objective hearing tests. In all seven cases, various segments of the facial nerve were exposed during surgery, but postoperative facial nerve function remained intact, hearing was preserved, no cerebrospinal fluid leakage occurred, and no recurrences have been observed to date（as of June 2024）. Conclusion:With the advancement of imaging techniques and microsurgical technology, early diagnosis and surgical methods for supral-abyrinthine cholesteatoma have significantly improved. Compared to traditional approaches, the newer methods reduce unnecessary complications and offer advantages such as minimal surgical trauma, superior hearing preservation rates, and shorter recovery times with better postoperative neural function. This study reviews recent literature on petroclival cholesteatomas, combined with our own cases, to analyze the classification of supral-abyrinthine cholesteatoma and surgical approach selection. The findings aim to optimize treatment strategies and guide appropriate surgical methods, ultimately improving patient prognosis and quality of life.
Humans ; Cholesteatoma/surgery* ; Ear, Inner/surgery* ; Retrospective Studies ; Treatment Outcome

Chronic atrophic gastritis(CAG)is a precancerous lesion of gastric cancer,and its pathogenesis is complicated,with recurrent and prolonged symptoms.Starting from the view of stomach collaterals and sweat pores,the paper analyzed the pathogenesis of CAG,i.e.,stagnation and obstruction of sweat pores,and blood stasis obstructing stomach collaterals.Furthermore,this paper explored the efficacy of wind medicines in treating CAG by opening sweat pores and unblocking stomach collaterals.It is believed that wind medicines are pungent with warm nature,and have the actions of relieving exterior syndrome,regulating qi,elevating yang,unblocking collaterals and dissipating masses,which enable their efficacy on opening sweat pores and unblocking stomach collaterals.In the treatment of CAG,wind medicines are able to open the sweat pores,and the opening of sweat pores promotes the recovery of spleen-stomach function in lifting lucid yang and lowering turbid yin;wind medicines have the actions of directing herbs to the affected meridian or site,and assisting the other Chinese medicines to achieve satisfactory efficacies;wind medicines can also be used for drying dampness,and enhance the efficacy of removing dampness with the help of their actions of opening sweat pores.During the treatment of CAG,the combination of wind medicines can enhance the therapeutic effect of Chinese herbal medicine,and the exploration in this paper will provide reference for traditional Chinese medicine treatment of CAG in clinic.

Objective:Flotillin-2(FLOT2)is a prototypical oncogenic and a potential target for cancer therapy.However,strategies for targeting FLOT2 remain undefined.Post-translational modifications are crucial for regulating protein stability,function,and localization.Understanding the mechanisms and roles of post-translational modifications is key to developing targeted therapies.This study aims to investigate the regulation and function of lysine acetylation of FLOT2 in nasopharyngeal carcinoma,providing new insights for targeting FLOT2 in cancer intervention. Methods:The PhosphoSitePlus database was used to analyze the lysine acetylation sites of FLOT2,and a lysine acetylation site mutation of FLOT2[FLOT2(K211R)]was constructed.Nasopharyngeal carcinoma cells were treated with histone deacetylase(HDAC)inhibitor trichostatin A(TSA)and Sirt family deacetylase inhibitor nicotinamide(NAM).TSA-treated human embryonic kidney(HEK)-293T were transfected with FLOT2 mutant plasmids.Co-immunoprecipitation(Co-IP)was used to detect total acetylation levels of FLOT2 and the effects of specific lysine(K)site mutations on FLOT2 acetylation.Western blotting was used to detect FLOT2/FLAG-FLOT2 protein expression in TSA-treated nasopharyngeal carcinoma cells transfected with FLOT mutant plasmids,and real-time reverse transcription PCR(real-time RT-PCR)was used to detect FLOT2 mRNA expression.Nasopharyngeal carcinoma cells were treated with TSA combined with MG132 or chloroquine(CQ)to analyze FLOT2 protein expression.Cycloheximide(CHX)was used to treat HEK-293T cells transfected with FLAG-FLOT2(WT)or FLAG-FLOT2(K211R)plasmids to assess protein degradation rates.The BioGrid database was used to identify potential interactions between FLOT2 and HDAC6,which were validated by Co-IP.HEK-293T cells were co-transfected with FLAG-FLOT2(WT)/FLAG-FLOT2(K211R)and Vector/HDAC6 plasmids,and grouped into FLAG-FLOT2(WT)+Vector,FLAG-FLOT2(WT)+HDAC6,FLAG-FLOT2(K211R)+Vector,and FLAG-FLOT2(K211R)+HDAC6 to analyze the impact of K211R mutation on total lysine acetylation levels.In 6-0B cells,overexpression of FLOT2(WT)and FLOT2(K211R)was performed,and the biological functions of FLOT2 acetylation site mutants were assessed using cell counting kit-8(CCK-8),colony formation,and Transwell invasion assays. Results:The PhosphoSitePlus database indicated that FLOT2 has an acetylation modification at the K211 site.Co-IP confirmed significant acetylation of FLOT2,with TSA significantly increasing overall FLOT2 acetylation levels,while NAM had no effect.Mutation at the K211 site significantly reduced overall FLOT2 acetylation,unaffected by TSA.TSA decreased FLOT2 protein expression in nasopharyngeal carcinoma cells without affecting FLOT2 mRNA levels or FLOT2(K211R)protein expression in transfected cells.The degradation rate of FLOT2(K211R)protein was significantly slower than that of FLOT2(WT).The proteasome inhibitor MG132 prevented TSA-induced FLOT2 degradation,while the lysosome inhibitor CQ did not.BioGrid data suggested a potential interaction between FLOT2 and HDAC6,confirmed by Co-IP.Knockdown of HDAC6 in nasopharyngeal carcinoma cells significantly increased FLOT2 acetylation;co-transfection of HDAC6 and FLAG-FLOT2(WT)significantly decreased total lysine acetylation levels,whereas co-transfection of HDAC6 and FLAG-FLOT2(K211R)had no effect.Knockdown of HDAC6 significantly reduced FLOT2 protein levels without affecting mRNA levels.MG132 prevented HDAC6-knockdown-induced FLOT2 degradation.Knockdown of HDAC6 significantly accelerated FLOT2 degradation.Nasopharyngeal carcinoma cells transfected with FLOT2(K211R)showed significantly higher proliferation and invasion than those transfected with FLOT2(WT). Conclusion:The K211 site of FLOT2 undergoes acetylation modification,and HDAC6 mediates deacetylation at this site,inhibiting proteasomal degradation of FLOT2 and maintaining its stability and tumor-promoting function in nasopharyngeal carcinoma.

Objective:To summarize the clinical features associated with respiratory syncytial virus (RSV) infection in patients following the hematopoietic stem cell transplant (HSCT) and exploring the risk factors for death.Methods:Patients who had RSV infection after undergoing HSCT from October 2023 to January 2024 in the hematology department of Peking University People’s Hospital were enrolled in the study. The clinical characteristics of the participating patients were summarized. The clinical characteristics of the surviving and the dying patients were compared, and the risk factors of death were analyzed by binary logistic regression.Results:Among the 43 RSV-positive HSCT patients, 20 (46.5%) were hypoxemic, six (14.0%) were admitted to the ICU for further treatment, four (9.3%) required tracheal intubation assisted ventilation, and seven patients (16.3%) died. A comparison of the clinical features of the surviving patients and the deceased patients demonstrated that the deceased patients had a lower PLT when infected with RSV [74.5 (8.0-348.0) ×10 9/L vs 15.0 (10.0-62.0) ×10 9/L, P=0.003], a higher incidence of simultaneous bacterial infections (85.7% vs 41.7%, P=0.046), and a higher rate of hematological recurrence (71.4% vs 13.9%, P=0.004). Hematological recurrence ( OR=15.500, 95% CI 2.336-102.848, P=0.005), influenza A viral infection ( OR=14.000, 95% CI 1.064-184.182, P=0.045), and low PLT at the time of RSV infection ( OR=0.945, 95% CI 0.894-0.999, P=0.048) were the factors associated with death following HSCT. Conclusion:Patients infected with RSV after undergoing HSCT have a poor prognosis, and active prevention and treatment of RSV in the autumn and winter requires urgent attention.

Objective:To look into the security of a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) using rabbit anti-human thymocyte immunoglobulin (rATG) .Methods:Twenty-seven patients who used rATG in the first and second allo-HSCT at the Institute of Hematology, Peking University were enrolled in the study. Experienced toxicities associated with the conditioning protocol within 10 days (-5 d to +3 d) following the beginning of the rATG application, including fever, diarrhea, arrhythmia, reduced blood pressure, liver damage, seizures, and other problems.Results:The overall incidence of conditioning regimen early adverse reactions during the first transplantation and the second allo-HSCT conditioning regimen was 96.3% and 77.8% ( P=0.043) . Fever rates were 81.5% and 63.0% ( P=0.129) , diarrhea rates were 59.3% and 25.9% ( P=0.013) , liver damage rates were 22.2% and 25.9% ( P=0.75) , and the rates of other events (cardiac arrhythmia, low blood pressure, and epilepsy) were 3.7% and 18.5% ( P=0.083) . Adverse reactions that occurred during both the first and second course of rATG applications have been improved with symptomatic treatment, and no treatment interruptions occurred. Conclusion:Reusing rATG in a second transplant was risk-free and did not result in higher early toxicities.

Relapse is the main problem after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The outcome of a second allo-HSCT (HSCT2) for relapse post-HSCT has shown promising results in some previous studies. However, little is known about the efficacy of HSCT2 in patients with relapsed/refractory acute leukemia (AL) post-chemotherapy plus modified donor lymphocyte infusion (post-Chemo + m-DLI) after the first allo-HSCT (HSCT1). Therefore, we retrospectively analyzed the efficacy of HSCT2 in 28 patients with relapsed/refractory AL post-Chemo + m-DLI in our center. With a median follow-up of 918 (457-1732) days, 26 patients (92.9%) achieved complete remission, and 2 patients exhibited persistent disease. The probabilities of overall survival (OS) and disease-free survival (DFS) 1 year after HSCT2 were 25.0% and 21.4%, respectively. The cumulative incidences of nonrelapse mortality on day 100 and at 1 year post-HSCT2 were 7.1% ± 4.9% and 25.0% ± 8.4%. The cumulative incidences of relapse were 50.0% ± 9.8% and 53.5% ± 9.9% at 1 and 2 years post-HSCT2, respectively. Risk stratification prior to HSCT1 and percentage of blasts before HSCT2 were independent risk factors for OS post-HSCT2, and relapse within 6 months post-HSCT1 was an independent risk factor for DFS and relapse post-HSCT2. Our findings suggest that HSCT2 could be a salvage option for patients with relapsed AL post-Chemo + m-DLI.
Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute/therapy* ; Lymphocytes ; Recurrence ; Retrospective Studies ; Transplantation, Homologous

Objective To study the diagnostic value of heart fat acid binding protein (h‐FABP) in myocardial damage of children with hand‐foot‐mouth disease (HFMD) .Methods From February 2012 to December 2014 ,100 children with HFMD were chosen as study objects .All children study were divided into 2 sub‐groups according to the severity of disease:71 in ordinary HFMD sub‐group ,29 in severe HFMD sub‐group .At the same time ,100 healthy children were chosen as control group .The routine blood test , rate of abnormal electrocardiography ,rate of abnormal cTnI and rate of abnormal h‐FABP were compared among all children .The cTnI and h‐FABP at different time were compared between ordinary HFMD sub‐group and severe HFMD sub‐group .Results The WBC ,RBC and L had significant difference among different groups/sub‐groups(P<0 .05) ,the difference of PLT had no statistical significance(P>0 .05) .In ordinary HFMD sub‐group ,rate of abnormal electrocardiography was 19 .72% (14/71) ,rate of abnormal cTnI was 4 .23% (3/71)and rate of abnormal h‐FABP was16 .39% (10/71);in severe HFMD group ,rate of abnormal electrocardio‐graphy was 72 .41% (21/29) ,rate of abnormal cTnI was 82 .76% (23/29) and rate of abnormal h‐FABP was 82 .96% (23/29);in control group ,rate of abnormal electrocardiography was 1 .00% (1/100) ,rate of abnormal cTnI was 2 .00% (2/100)and rate of ab‐normal h‐FABP was 0 .00% (0/100) ,the difference had statistical significance(P<0 .05) .The cTnI and h‐FABP at different time had significant difference between ordinary HFMD sub‐group and severe HFMD sub‐group(P<0 .05) .Conclusion Heart fat acid binding protein (h‐FABP) can reflect the early myocardial damage in children with hand‐foot‐mouth disease .

AIM: To observe the local expression of nuclear factor-?B(NF-?B) in spontaneously hypertensive rat(SHR) kidney and effects of AT1 receptor contagonist valsartan.METHODS: 16 SHRs were randomly divided into two groups: SHR control group and valsartan group.Another 8 WKY rats act as normal control group.Systolic blood pressure(SBP) of SHR was measured at the beginning and the end of 2,4,6 and 8 weeks of intervention treatment.Radioimmunoassay was used to determine the activities of rennin and angiotensin II(AngII).The renal tissue NF-?B protein expression was detected by immunobiochemistry.RESULTS: SBP of SHR was remarkably decreased after valsartan intervention.However,the rennin activities and AngII level in plasma increased in valsartan group.In the renal tissue of SHR,there was remarkably increased in expression of NF-?B protein.Valsartan could significantly reduced NF-?B expression.CONCLUSION: Valsartan can depress NF-?B renal expression in protein level and might benefit hypotension renal function.