Conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation (TET) family proteins leads to the accumulation of 5hmC in the central nervous system; however, the role of 5hmC in the postnatal brain and how its levels and target genes are regulated by TETs remain elusive. We have generated mice that lack all three Tet genes specifically in postnatal excitatory neurons. These mice exhibit significantly reduced 5hmC levels, altered dendritic spine morphology within brain regions crucial for cognition, and substantially impaired spatial and associative memories. Transcriptome profiling combined with epigenetic mapping reveals that a subset of genes, which display changes in both 5hmC/5mC levels and expression patterns, are involved in synapse-related functions. Our findings provide insight into the role of postnatally accumulated 5hmC in the mouse brain and underscore the impact of 5hmC modification on the expression of genes essential for synapse development and function.
Animals ; Brain/growth & development* ; 5-Methylcytosine/metabolism* ; Mice ; Synapses/genetics* ; Proto-Oncogene Proteins/metabolism* ; DNA-Binding Proteins/metabolism* ; Dioxygenases/metabolism* ; Cognition/physiology* ; Gene Expression ; Mixed Function Oxygenases/metabolism* ; Epigenesis, Genetic ; Mice, Knockout ; Mice, Inbred C57BL

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.
Humans ; Anti-Bacterial Agents/therapeutic use* ; China ; Drug Monitoring/methods* ; Polymyxin B ; Practice Guidelines as Topic

Objective:To investigate the clinical effect of surgical treatment of concealed penis based on the idea of flap transfer in the treatment of hypospadias.Methods:Retrospectively analyzed the clinical data of children with concealed penis admitted to the Urology Department of Chengdu Second People’s Hospital and Department of Pediatric Surgery at Children’s Medical Center of Sichuan Provincial People’s Hospital, from July 2017 to July 2021. The control group used the traditional surgical method and the experimental group used a modified surgical approach based on the idea of flap transfer in the treatment of hypospadias. Short-term complications such as flap ischemia, edema, and skin dehiscence were statistically analyzed in the two groups, as well as the Boemers rating of penile appearance (good, general, poor), Vancouver scar scale (VSS) (mild, moderate, severe), overall penis shape (tower, cylindrical, inverted tower) at 6 months after surgery. Count data were analyzed using the Chi-square test.Results:298 children, aged 2.5 to 13.7 years, with a mean age of 6.4 years, were enrolled in the study. 103 children were in the control group, and 195 children were in the experimental group. All enrolled patients were operated successfully in the first stage and were discharged 3-4 days after the operation, with an average recovery time of 3-4 weeks. After a follow-up of more than 6 months, in the control group, 2 cases (1.9%) of flap ischemia and 3 cases (2.9%) of skin dehiscence occurred after surgery. Two children (1.0%) in the experimental group had skin dehiscence after surgery, and the difference in the recent complication rate between the two groups was not significant [4.9%(5/103) vs. 1.0%(2/195), P>0.05]. The proportion of Boemers rated"good"in the experimental group was higher than that in the control group [93.3% (182/195) vs. 71.8% (74/103), P<0.01]. The proportion of moderate to severe scarring assessed by VSS was lower in the experimental group than in the control group [6.2% (12/195) vs. 26.2% (27/103), P<0.01]. The proportion of the overall penis shape of the penis close to the cylindrical shape of the normal penis in the experimental group was significantly higher than that in the control group [81.5% (159/195) vs. 60.2% (62/103), P<0.01]. Conclusion:Compared with the traditional surgical method, the modified surgical approach based on the idea of flap transfer in the treatment of hypospadias attaches more importance to the overall planning of the flap and the tension distribution of the fascial layer, which can be more effective to solve the problem of insufficient coverage of the concealed penile skin and reduce postoperative scar formation. Moreover, the appearance of the external genitalia is natural and closer to normal, the surgical effect is exact, and the long-term postoperative complications are lower.

Objective:To investigate the clinical effect of surgical treatment of concealed penis based on the idea of flap transfer in the treatment of hypospadias.Methods:Retrospectively analyzed the clinical data of children with concealed penis admitted to the Urology Department of Chengdu Second People’s Hospital and Department of Pediatric Surgery at Children’s Medical Center of Sichuan Provincial People’s Hospital, from July 2017 to July 2021. The control group used the traditional surgical method and the experimental group used a modified surgical approach based on the idea of flap transfer in the treatment of hypospadias. Short-term complications such as flap ischemia, edema, and skin dehiscence were statistically analyzed in the two groups, as well as the Boemers rating of penile appearance (good, general, poor), Vancouver scar scale (VSS) (mild, moderate, severe), overall penis shape (tower, cylindrical, inverted tower) at 6 months after surgery. Count data were analyzed using the Chi-square test.Results:298 children, aged 2.5 to 13.7 years, with a mean age of 6.4 years, were enrolled in the study. 103 children were in the control group, and 195 children were in the experimental group. All enrolled patients were operated successfully in the first stage and were discharged 3-4 days after the operation, with an average recovery time of 3-4 weeks. After a follow-up of more than 6 months, in the control group, 2 cases (1.9%) of flap ischemia and 3 cases (2.9%) of skin dehiscence occurred after surgery. Two children (1.0%) in the experimental group had skin dehiscence after surgery, and the difference in the recent complication rate between the two groups was not significant [4.9%(5/103) vs. 1.0%(2/195), P>0.05]. The proportion of Boemers rated"good"in the experimental group was higher than that in the control group [93.3% (182/195) vs. 71.8% (74/103), P<0.01]. The proportion of moderate to severe scarring assessed by VSS was lower in the experimental group than in the control group [6.2% (12/195) vs. 26.2% (27/103), P<0.01]. The proportion of the overall penis shape of the penis close to the cylindrical shape of the normal penis in the experimental group was significantly higher than that in the control group [81.5% (159/195) vs. 60.2% (62/103), P<0.01]. Conclusion:Compared with the traditional surgical method, the modified surgical approach based on the idea of flap transfer in the treatment of hypospadias attaches more importance to the overall planning of the flap and the tension distribution of the fascial layer, which can be more effective to solve the problem of insufficient coverage of the concealed penile skin and reduce postoperative scar formation. Moreover, the appearance of the external genitalia is natural and closer to normal, the surgical effect is exact, and the long-term postoperative complications are lower.

OBJECTIVE To eval uate the cost-util ity of regimen containing bortezomib in the treatment of newly diagnosed multiple myeloma in China. METHODS From the perspective of China ’s health system ，Markov model was constructed based on SWOG S 0777 clinical trial. The simulation time limit was 10 years，and the cycle was set with reference to the treatment cycle. Taking quality adjusted life years （QALYs）as the utility index ，the utility and cost were discounted at a discount rate of 5％；the willingness to pay （WTP）threshold was set to be 3 times of China ’s per capita gross domestic product （GDP）in 2021（242 928 yuan/QALY）. The incremental cost-utility ratio （ICER）of dexamethasone combined with bortezomib and lenalidomide （VRD） versus dexamethasone combined with lenalidomide （RD）were compared with cost-utility analysis. The sensitivity analysis was performed for the uncertainty of the model. RESULTS Results of baseline analysis showed that VRD regimen could obtain 0.65 more QALYs than RD scheme ，but its treatment cost was 135 782.77 yuan more than RD regimen ，ICER was 206 623.35 yuan/ QALY，which was lower than the WTP threshold set in this study ，VRD regimen was cost-effective. Single factor sensitivity analysis showed that the health utility value in progressive free survival had the greatest impact on the results ，the decrease of utility value would make the ICER higher than the WTP threshold ，and VRD regimen would no longer have advantages. Under the WTP threshold of 3 times of China ’s per capita GDP in 2021，the probability of VRD regimen being cost-effective was 86.5％； with the increase of WTP threshold ，the possibility of VRD regimen becoming more cost-effective than RD regimen would increase. CONCLUSIONS Under the WTP threshold of 3 times of China ’s per capita GDP in 2021，compared with RD regimen，VRD regimen is cost-effective in the treatment of newly diagnosed multiple myelo ma in China.

Objective: To evaluate the effectiveness and safety of the endoscope combined with microscope for the microvascular decompression in hemifacial spasm. Methods: A total of 26 patients underwent endoscope combined with microscopic facial nerve microvascular decompression through retrolabyrinthine approach from January 2013 to December 2016 were retrospectively reviewed in Ear Institute, Shanghai Jiaotong University School of Medicine. Among them, 9 were male and 17 were female, with a mean age of (51.9±11.4) years;15 cases of left side and 11 of right side patients were followed up for 1-3 years. The pre-and post-operative Cohen Classification was used for hemifacial spasm, House-Brackmann Grade for facial nerve function, hearing level and complication rates were reviewed. SPSS 19.0 software was used to analyze the data. Results: All 26 patients were operated successfully. No recurrence was seen during 1-3 year follow-up. Post-operative Cohen Grade were as follows: 25 cases with Cohen Grade I and 1 case with Cohen Grade II. The difference in Cohen grade between pre-and post-operative was statistically significant (Z=-4.87, P<0.01). Post-operative facial nerve function was satisfactory in all patients (House-Brackmann Grade I-II in all patients). No hearing loss was observed. No facial paralysis and other lower cranial nerve dysfunction were observed. No postoperative complications such as cerebrospinal fluid leakage occurred. Conclusions Using an angled endoscope combined with microscope in microvascular decompression in hemifacial spasmis is safe and effective.

Objective To investigate the diagnostic value of endotoscopy,tympanometry,pure tone audiometry (PTA) and high resolution temporal bone CT in children with secretory otitis media (SOM).Methods The study comprised 414 ears in 207 children with adenoid hypertrophy.Endotoscopy,tympanometry,PTA and high resolution temporal bone CT were conducted to evaluate the function of middle ear.Based on the imaging findings of tympanic cavity fluid by high resolution temporal bone CT,the diagnostic accordance rate of endotoscopy,tympanograms and PTA for SOM were studied.Results The diagnostic accordance rate of endotoscopy,tympanometry and PTA for SOM were 98.79％(409/414),98.07％ (406/414) and 88.41％ (366/414),respectively.The sensitivity of the three examinations were 99.20％(124/125),100％ (125/125),63.20％ (79/125),respectively.The specificity of the three examinations were 98.62％ (285/289),97.23％ (281/289),99.31％ (287/289),respectively.The diagnostic accordance rate of endotoscopy combined with tympanometry for SOM was significantly higher than any single examination or any combined examinations.Conclusion Endotoscopy combined with tympanometry shows a great value in diagnosing SOM,which is accurate and safe.

OBJECTIVE To explore the significance of intraoperative auditory monitoring(IAMA) in surgery of acoustic neuroma and to compare the value of auditory brainstem response(ABR) and cochlear nerve action potential(CNAP) in auditory monitoring.METHODS Retrospective analysis of 12 cases of acoustic neuroma from January 2016 to December 2016 was performed.All patients have a practical hearing(AAO-HNS,grade class a,b),the ABR waveform can be elicited,wave v differentiation,All tumors were removed via posterior sigmoid sinus approach.RESULTS ABR waveform of all patients were prolonged with different degrees of change(0.68±0.41) ms compared with the preoperative data.Amplitude of CNAP diverse in different individuals,with an average prolong compared to the data before operation(0.25±0.16) ms.In all 12 cases,8 (66.7％) patients remained usable hearing after the operation,4 cases(33.3％) failed to have a usable hearing.Among these 4 patients,3 showed disappearance of wave v,1 patient showed wave v latency prolong in the ABR,meanwhile,2 patients showed P1 dissapear,2 patients showed P1 latency prolong in CNAP.The intraoperative auditory monitoring could play a role in preventing the hearing damage in the procedure.Drilling,noise,surgical nerve stretch or thermal injury may cause the hearing damage.A 5 minutes pause could get some degree of regain,with the amplitude rise again.CONCLUSION A combination use of the ABR and CNAP monitoring has a certain significance in surgery of acoustic neuroma.ABR waveform is stable and reliable,but costs longer time;CNAP stack quickly and improve monitoring sensitivity,but waveform varies.Vibration and noise caused by drilling,nerve stretch during operation and heat damage can be monitored timely.Combined use of ABR and CNAP monitoring can enhance the auditory preservation rate during acoustic neuroma surgery.

OBJECTIVE To evaluate the application ofretrolabyrinthine approach in cerebellopontine angel(CPA) region surgeries.METHODS A total of 42 patients underwent microscopic-endoscopic cooperative surgeries for CPA lesions via retrolabytinthine approach were reviewed.They were hospitalized from January 1st 2011 to January 1st 2016 in our institution.The microscopic-endoscopic technique was applied in all surgeries.RESULTS Complete removal was obtained in all tumor resections and satisfactory symptom-relief was achieved in all microvascular decompressions and neurectomies.In cases with acoustic neuroma and cholesteatoma,useful hearing (AAO-HNS classes A,B and C) was obtained in 66.7％(6/9) patients.No facial paralysis and postoperative complications such as cerebrospinal fluid leakage occurred during follow-up.In cranial nerve rhizopathies cases,complete relief was achieved in all patients.No facial paralysis and other lower cranial nerve dysfunction occurred.CONCLUSION With the preservation of labyrinthine structures,the microscopic-endoscopic cooperative surgeries for CPA lesions via retrolabytinthine approach could increase the hearing preservation level without facial nerve injury.Retrolabyrinthine approach is a good option for cranial nerve rhizopathies and tumors smaller than 15 mm in diameter without involvement of the fundus of internal auditory canal in the CPA region.

OBJECTIVE To analyse the diagnosis of non-acoustic lesions in internal auditory canal(IAC) and cerebellopontine angle(CPA),and discuss the effects of imaging examinationon differential diagnosis.METHODS A retrospective study was carried out in 185 patients with non-acoustic lesions of IAC and CPA from January 2001 to December 2016,in which lower cranial schwannoma,facial nerve tumor,meningioma,cholesteatoma,malignant tumor,trigeminal schwannoma,cavernous hemangioma,arachnoid cyst,lipoma were diagnosed in 65,55,25,9,9,8,6,5 and 3 patients,respectively.All patients were performed surgeries,and preoperative diagnosis and surgical approach were decided according to clinical manifestation,CT and MRI findings.Postoperative diagnosis were confirmed by pathological examination.RESULTS Total removal of lesion was achieved in 185 patients [96 men and 89 women,11-77 years old,mean age (46.4±25.6) years] and mean follow-up time was (5.1 ±3.2) years.Postoperative complication was leakage of cerebrospinal (4 patients,2.2％).4 patients with malignancy were dead and 1 patient with cholesteatoma was found recurrent during the follow-up.All kinds of non-acoustic lesions in IAC and CPA had its characteristic imaging findings.Preoperative diagnostic accuracy rate was 93.5％(173/185).CONCLUSION Accurate preoperative diagnosis has great significance in developing treatment strategy for IAC and CPA lesions;Preoperative diagnosis should be achieved according to clinical manifestation,CT and MRI findings,which can significantly improve the accuracy rate of diagnosis.