Objective:To introduce a new design of super-micro flap for endoscopic ear surgery, and to evaluate the application effect of super-micro flap in endoscopic tympanoplasty. Methods:Between January, 2023 and March, 2024, 58 patients（64 ears） with tympanosclerosis underwent tympanoplasty with super-micro flap. Continuous irrigating mode endoscopic ear surgery（CIM-EES） was used to complete type Ⅱ or Ⅲ tympanoplasty with the tragus cartilage with followed up for 12 to 24 months. The operation time, postoperative efficacy and complications were statistically analyzed. Results:Of the 64 ears, 63 ears had primary healing of the tympanic membrane, and 1 ear had cartilage necrosis due to multi-drug resistant bacteria infection. The second operation was performed one year later, and the success rate of operation was 98.40%. The average operation time was （48.40±8.86） minutes. The average hearing threshold of 0.5 kHz to 4.0 kHz before operation was （59.63±10.62） dB HL, and the average air conduction threshold of 0.5 kHz to 4.0 kHz one year after operation was（38.79±10.91） dB HL, which was significantly improved compared with that before operation（P<0.01）. Bone conduction threshold also improved significantly （24.49±8.55） dB HL vs（21.88±7.58） dB HL（P<0.01）. No outer tympanic membrane healing and ear canal scar stenosis occurred. Conclusion:The design of super-micro flap can effectively solve the interference of flap floating during continuous irrigating mode in endoscopic ear surgery, relieve the difficulty of flap reposition, simplify the operation process, help to shorten the operation time, and reduce the possibility of circular scar stenosis of conventional free flap, which provides a new flap design option for endoscopic ear surgery.
Humans ; Tympanoplasty/methods* ; Endoscopy/methods* ; Surgical Flaps ; Male ; Female ; Adult ; Myringosclerosis/surgery* ; Middle Aged ; Treatment Outcome ; Tympanic Membrane/surgery* ; Adolescent ; Young Adult

Ischemic stroke is the leading cause of disability and mortality worldwide. The blood‒brain barrier (BBB) is the first line of defense after ischemic stroke. Disruption of the BBB induced by brain microvascular endothelial cells (BMECs) dysfunction is a key event that triggers secondary damage to the central nervous system, where blood-borne fluids and immune cells penetrate the brain parenchyma, causing cerebral edema and inflammatory response and further aggravating brain damage. Here, we develop a novel artificial mesenchymal stem cell (MSC) extracellular vesicles by integrating MSC membrane proteins into liposomal bilayers, which encapsulated miR-132-3p with protective effects on BMECs. The artificial extracellular vesicles (MSCo/miR-132-3p) had low immunogenicity to reduce non-specific clearance by the mononuclear phagocytosis system (MPS) and could target ischemia-injured BMECs. After internalization into the damaged BMECs, MSCo/miR-132-3p escaped the lysosomes via the H_II phase transition of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and decreased cellular reactive oxygen species (ROS) and apoptosis levels by regulating the RASA1/RAS/PI3K/AKT signaling pathway. In the transient middle cerebral artery occlusion (tMCAO) models, MSCo/miR-132-3p targeted impaired brain regions (approximately 9 times the accumulation of plain liposomes at 12 h), reduced cerebral vascular disruption, protected BBB integrity, and decreased infarct volume (from 44.95% to 6.99%).

Objective To rationally allocate pharmaceutical and healthcare human resources,and to explore the feasibility of implementing the system of licensed assistant pharmacists in retail pharmacies.Methods Through literature review,questionnaire surveys,and statistical analysis of exam scores,the training status of pharmacy technicians with secondary vocational education,the employment situation in retail pharmacies,and the results of the licensed pharmacist qualification examination were deeply understood.Results Every year,a certain number of graduates with a secondary vocational education in pharmacy entered society,and retail pharmacies were willing to recruit pharmacy technicians with this educational background,their professional competence were recognized.Pharmacy technicians with secondary vocational education can obtain the professional qualification of practicing pharmacists through hard work,and demonstrated the basic competency for working as licensed assistant pharmacists.Conclusion The implementation of the licensed assistant pharmacist system among pharmacy technicians with secondary vocational education in retail pharmacies is feasible.This system can fully leverage the role of pharmacy technicians with secondary vocational education,make up for the shortage of professional personnel in certain regions,promote the construction of the pharmaceutical care system in retail pharmacies,and ensure drug quality and medication safety.

Objective:To evaluate the efficacy and safety of intensity modulated radiotherapy (IMRT) and programmed death-1 (PD-1) immunotherapy combined with single-agent chemotherapy for patients with local failure of esophageal cancer after initial radical chemoradiotherapy.Methods:Clinical data of 80 patients with local failure of esophageal cancer after initial radical chemoradiotherapy treated with IMRT or PD-1 immunotherapy combined with single-agent chemotherapy in People's Hospital of Xinghua between June 2014 and June 2023 were retrospectively analyzed. IMRT was delivered at 1.8-2.0 Gy per fraction, 5 fractions per week, with a total dose of 45.0-60.0 Gy in 40 patients (IMRT group). The other 40 patients received PD-1 immunotherapy combined with single-agent chemotherapy (PD-1 immunotherapy combined with single-agent chemotherapy group). Kaplan-Meier method was used for univariate analysis and the cumulative survival probability. Log-rank test was used for survival significance test. Cox proportional hazards model was used for multivariate analysis of related factors affecting overall survival (OS), progression-free survival (PFS) and local control (LC).Results:By December 2023, the follow-up rate was 100%. The 1- and 2-year OS rates in the IMRT group were 66.1% and 18.9%, with a median OS time of 10.1 months. In the PD-1 immunotherapy combined with single-agent chemotherapy group, the 1- and 2-year OS rates were 72.3% and 36.9%, with a median OS time of 12.4 months. There was a significant difference in OS rates between two groups ( χ2=3.89, P=0.049). The 1- and 2-year PFS rates in the IMRT group were 47.4% and 31.6%, with a median PFS time of 8.5 months. In the PD-1 immunotherapy combined with single-agent chemotherapy group, the 1- and 2-year PFS rates were 70.0% and 64.2%, with a median PFS time of 11.9 months. There was no significant difference in the PFS rates between two groups ( χ2=2.66, P=0.103). The 1- and 2-year LC rates in the IMRT group were 68.6% and 62.3%, with a median LC time of 8.9 months. In the PD-1 immunotherapy combined with single-agent chemotherapy group, the 1- and 2-year LC rates were 72.8% and 66.7%, with a median LC time of 12.0 months. There was no significant difference in LC rates between two groups ( χ2=0.18, P=0.672). Grade 2 radiation esophagitis and radiation pneumonitis developed in 82.5% (33/40) and 32.5% (13/40) in the IMRT group, respectively. The incidence of grade 1-2 peripheral blood leukopenia was 40.0% (16/40), 50.0% (20/40) for grade 1-2 peripheral blood thrombocytopenia, 27.5% (11/40) for moderate to severe anemia, and 20.0% (8/40) for grade 1-2 thyroid dysfunction in the PD-1 immunotherapy combined with single-agent chemotherapy, respectively. Single- and multi-factor analysis showed that the failure site ( χ2=9.01, P=0.011) and short-term efficacy ( χ2=7.78, P=0.005) were the independent prognostic factors affecting OS. The short-term efficacy was the independent prognostic factor for PFS ( χ2=31.63, P<0.001). The short-term efficacy was the independent prognostic factors affecting LCS ( χ2=17.64, P=0.001) too. Conclusion:For the patients with local failure of esophageal cancer after initial radical chemoradiotherapy, the combination of PD-1 immunotherapy with single-agent chemotherapy yields better survival prognosis than re-irradiation alone, but it is still necessary to pay attention to the related drug toxicities.

Due to the limitations of current anti-HBV therapies, the HBV core (HBc or HBcAg) protein assembly modulators (CpAMs) are believed to be potential anti-HBV agents. Therefore, discovering safe and efficient CpAMs is of great value. In this study, we established a HiBiT-based high-throughput screening system targeting HBc and screened novel CpAMs from an in-house marine chemicals library. A novel lead compound 8a, a derivative of the marine natural product naamidine J, has been successfully screened for potential anti-HBV activity. Bioactivity-driven synthesis was then conducted, and the structure‒activity relationship was analyzed, resulting in the discovery of the most effective compound 11a (IC₅₀ = 0.24 μmol/L). Furthermore, 11a was found to significantly inhibit HBV replication in multiple cell models and exhibit a synergistic effect with tenofovir disoproxil fumarate (TDF) and IFNa2 in vitro for anti-HBV activity. Treatment with 11a in a hydrodynamic-injection mouse model demonstrated significant anti-HBV activity without apparent hepatotoxicity. These findings suggest that the naamidine J derivative 11a could be used as the HBV core protein assembly modulator to develop safe and effective anti-HBV therapies.

OBJECTIVE To predict the development trends of licensed pharmacist staffing in retail pharmacies within the western China and provide reference for the formulation of policies related to licensed pharmacists. METHODS Based on the data of retail pharmacies and licensed pharmacists in the western China from 2016 to 2022， a grey model was constructed to analyze and predict the number development trends of retail pharmacies and licensed pharmacists in the western China from 2023 to 2026. RESULTS Currently， the 1∶1 staffing requirement for licensed pharmacists and retail pharmacies had been met in Shaanxi， Guangxi and Gansu. Based on current trends， Inner Mongolia， Chongqing， Yunnan， and Qinghai were expected to meet the 1∶1 staffing requirement for licensed pharmacists and retail pharmacies between 2023 and 2026. Sichuan and Xinjiang were also expected to meet this requirement in the future. However， there was still a significant gap in Guizhou， Xizang， and Ningxia towards achieving the above goals. CONCLUSIONS There is still a discrepancy between the deployment of licensed pharmacists and the national requirements in certain western provinces. Local authorities should formulate relevant policies according to local circumstances. Regions that have already met or will soon achieve the staffing requirement for licensed pharmacists should continue to enhance the quantity and quality of their licensed pharmacist workforce. In areas where meet this criterion in the short term is not feasible， it is necessary to strengthen the development of the licensed pharmacist workforce， and control the number of new retail pharmacies.

OBJECTIVE: To investigate the effect of inhibitor of growth protein-2 (Ing2) silencing on angiotensin Ⅱ (AngⅡ)-induced cardiac remodeling in mice and explore the underlying mechanism. METHODS: An adenoviral vector carrying Ing2 shRNA or empty adenoviral vector was injected into the tail vein of mice, followed 48 h later by infusion of 1000 ng · kg^-1 · min^-1 Ang Ⅱ or saline using a mini-osmotic pump for 42 consecutive days. Transthoracic echocardiography was used to assess cardiac geometry and function and the level of cardiac hypertrophy in the mice. Masson and WGA staining were used to detect myocardial fibrosis and cross-sectional area of cardiomyocytes, and myocardial cell apoptosis was detected with TUNEL assay. Western blotting was performed to detect myocardial expressions of cleaved caspase 3, ING2, collagen Ⅰ, Ac-p53(Lys382) and p-p53 (Ser15); Ing2 mRNA expression was detected using real-time PCR. Mitochondrial biogenesis, as measured by mitochondrial ROS content, ATP content, citrate synthase activity and calcium storage, was determined using commercial assay kits. RESULTS: The expression levels of Ing2 mRNA and protein were significantly higher in the mice with chronic Ang Ⅱ infusion than in saline-infused mice. Chronic infusion of AngⅡ significantly increased the left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) and reduced left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in the mice. Ing2 silencing obviously alleviated AngⅡ-induced cardiac function decline, as shown by decreased LVEDD and LVESD and increased LVEF and LVFS, improved myocardial mitochondrial damage and myocardial hypertrophy and fibrosis, and inhibited cardiomyocyte apoptosis. Chronic AngⅡ infusion significantly increased myocardial expression levels of Ac-p53(Lys382) and p-p53(Ser15) in the mice, and Ing2 silencing prior to AngⅡ infusion lessened AngⅡ- induced increase of Ac-p53(Lys382) without affecting p53 (ser15) expression. CONCLUSION Ing2 silencing can inhibit AngⅡ-induced cardiac remodeling and dysfunction in mice by reducing p53 acetylation.
Animals ; Mice ; Angiotensin II ; Tumor Suppressor Protein p53 ; Acetylation ; Stroke Volume ; Ventricular Remodeling ; Ventricular Function, Left ; Myocytes, Cardiac

OBJECTIVE: To explore the diagnosis, treatment and genetic analysis of an infant with Schaaf-Yang syndrome (SYS). METHODS: An infant suspected for SYS at the Hunan Provincial Children's Hospital on June 10, 2022 was subjected to trio-whole exome sequencing, and Sanger sequencing was used to verify the candidate variant. Structure of the wild-type and mutant proteins was constructed to analyze the potential hazard. RESULTS: The infant was found to harbor a heterozygous frameshifting variant of c.1908delG (p.R637Gfs*65) of the MAGEL2 gene, which was found in neither of his parents. The variant has not been recorded by the public databases, and no relevant literature was retrieved. As the result of the variant, the MAGEL2 protein only retained part of its proline domain, which may lead to destruction and/or down-regulation of its function. CONCLUSION The c.1908delG (p.R637Gfs*65) variant of the MAGEL2 gene probably underlay the pathogenesis in this child. Combined with his clinical characteristics, the child was diagnosed with SYS. Above finding has also enriched the mutational spectrum of the MAGEL2 gene.
Humans ; Infant ; Down-Regulation ; Heterozygote ; Mutation ; Parents ; Proteins

Objective:To summarize the experience and the clinical data of patients with primary hyperparathyroidism undergoing endoscopic parathyroidectomy.Methods:A total of 24 patients who underwent endoscopic parathyroidectomy for primary hyperparathyroidism in Peking Union Medical College Hospital during Feb. 2021 to May. 2022 were concluded in this study (20 cases of parathyroidectomy via axillary approach and 4 cases of parathyroidectomy via thoracic and breast approach) . The operation time, postoperative drainage, length of stay, level of parathyroid hormone and serum calcium of those patients were collected. Postoperative complications and recurrence of hyperparathyroidism were also observed.Results:The postoperative levels of serum parathyroid hormone and serum calcium were significantly reduced (over 50%) compared with preoperative level ( P<0.05) . The average operation time was (96±22) min (64-157 min) . The mean postoperative drainage volume was (47±16) ml on day 1, (46±11) ml on day 2, and (30±9) ml on day 3, respectively. The average length of postoperative hospital stay was (2.8±1.1) days (2-6 days) . In one case of parathyroidectomy via axillary approach, the operation was converted to open surgery because of the low position of lesion. Other cases completed endoscopic surgery and obtained satisfactory cosmetic results. There were no postoperative complications such as bleeding, permanent hoarseness, coughing while drinking water, or surgical site infection. The mean follow-up time was (7.4±4.2) months (1-16 months) . There was no obvious discomfort and no recurrence during follow-up. Conclusion:Endoscopic parathyroidectomy is safe and effective in the treatment of primary hyperparathyroidism, which can be used as a surgical option for patients with cosmetic requirements.

Objective:To explore the clinical features and treatment strategy of rare tumor in the internal auditory canal(IAC).Methods:A retrospective study was carried out in 213 patients with lesion of ICA form January 2010 to December 2020. According to imaging features, surgical findings, and pathological diagnosis, there were 7 cases of non-sporadic acoustic neuroma, including 2 cases of cavernous hemangioma, 2 cases of aneurysm, 1 case of intralabyrinthical schwannoma, 1 case of meningioma, and 1 case of unilateral neurofibromatosis type 2 (NF2). The clinical manifestations, imaging data and intraoperative conditions as well as the formulation of individualized treatment strategies and prognosis were comprehensively analyzed.Results:In addition to hearing loss, cavernous hemangioma early appeared damage of facial nerve. CT showed expansion and calcification of IAC. Patients with aneurysm appeared tinnitus and vertigo early. CT showed enlargement of ampulla shape of IAC. DSA or MRA can help confirm the diagnosis. Patients with intralabyrinthine schwannoma early appeared refractory vertigo. High resolution MRI was helpful for diagnosis. “Dural tail sign” can be seen on enhanced MRI of meningeoma. Neurofibromatosis type 2 usually presented as bilateral vestibular schwannomas,but a few patients presented only with unilateral vestibular schwannomas.. All patients underwent labyrinth approach resection except one patient with NF2 for followed-up. Their postoperative symptoms were relieved. No tumor recurrence was observed during 6-3 years of follow-up.Conclusions:The clinical and imaging manifestations of rare tumors of the internal auditory canal are different. The principle of treatment is also different. It is helpful to avoid the serious consequences caused by blind operation to confirm diagnosis before operation.