BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

Objective:To investigate the application value of combined open and laparos-copic incisional hernia repair (hereinafter referred to as hybrid technique) in the treatment of recurrent incisional hernia.Methods:The retrospective and descriptive study was conducted. The clinical data of 36 patients with recurrent incisional hernia who were admitted to the Affiliated Beijing Chaoyang Hospital of Capital Medical University from January 2015 to December 2021 were collected. There were 10 males and 26 females, aged 62(range, 25-83)years. All patients underwent incisional hernia repair using the hybrid technique. Observation indicators: (1) intraoperative situa-tions; (2) postoperative situations; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Intraoperative situations. All 36 patients did not undergo component separation and successfully closed the hernia defect before completing the surgery. The operation time, defect area and area of mesh of the 36 patients were (102±41)minutes, (73±39)cm 2 and 300(range, 150-600)cm 2. Of the 36 patients, 9 cases required complete removal of the previous mesh, 2 cases had partial removal of the previous mesh and 25 cases did not require mesh removal. Two of the 36 patients had intestinal serosal tears, which needed suture repair during the operation. (2) Postoperative situations. Eight of the 36 patients had post-operative complications, including 6 cases of seroma, 1 case of subcutaneous hematoma and 1 case of undetected iatrogenic intestinal injury during the operation. The duration of the postoperative hospital stay of the 36 patients was 14(range, 7-57)days. (3) Follow-up. All 36 patients were followed up for 64 (range, 13-96)months. During the follow-up period, 2 cases had hernia recurrence and 1 case had intestinal obstruction. Conclusion:The hybrid technique in the treatment of recurrent incisional hernia is safe and feasible.

Nasal tip hypertrophy is one of the common nasal tip morphological abnormalities in clinical practice. A comprehensive treatment regimen is possible only when one can correctly understand the mechanism of nasal tip hypertrophy. In this paper, the mechanism and treatment of nasal tip hypertrophy were analyzed and summarized in order to provide some reference for rhinoplastic surgeons.

Nasal tip hypertrophy is one of the common nasal tip morphological abnormalities in clinical practice. A comprehensive treatment regimen is possible only when one can correctly understand the mechanism of nasal tip hypertrophy. In this paper, the mechanism and treatment of nasal tip hypertrophy were analyzed and summarized in order to provide some reference for rhinoplastic surgeons.

Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1^KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1^KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABA_A receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1^KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.
Animals ; Disease Models, Animal ; Fragile X Mental Retardation Protein/metabolism* ; Fragile X Syndrome/metabolism* ; Humans ; Mice ; Mice, Knockout ; Neurons/metabolism*

Nasal tip hypertrophy is one of the common nasal tip morphological abnormalities in clinical practice. We make a reasonable and comprehensive treatment plan only when correctly understanding the mechanism of nasal tip hypertrophy. In this paper, the mechanism and treatment of nasal tip hypertrophywere analyzed and summarized in order to provide some guidance for rhinoplastic surgeons.

Nasal tip hypertrophy is one of the common nasal tip morphological abnormalities in clinical practice. We make a reasonable and comprehensive treatment plan only when correctly understanding the mechanism of nasal tip hypertrophy. In this paper, the mechanism and treatment of nasal tip hypertrophywere analyzed and summarized in order to provide some guidance for rhinoplastic surgeons.

Objective     To verify the feasibility and accuracy of the "lung surface intersegmental constant proportion landmarks", developed by our center, in identifying intersegmental planes during pulmonary segmentectomy. Methods    We prospectively enrolled the patients who planned to receive thoracoscopic segmentectomy in West China Hospital of Sichuan University and The Third People's Hospital of Chengdu from September 2021 to October 2021. We took a relatively objective and feasible method, intravenous injection of indocyanine green, in identifying intersegmental planes as standard control. We intraoperatively judged the consistency between "lung surface intersegmental constant proportion landmarks" and intravenous injection of indocyanine green in identifying intersegmental planes. We discerned main landmarks of intersegmental plane by the constant proportion segment module, which was built based on the "lung surface intersegmental constant proportion landmarks", as well as distinguished the planes with discrepant fluorescence by peripheral intravenous indocyanine green injection. When the distance between the landmarks determined by the "ung surface intersegmental constant proportion landmarks" and the segmental boundaries displayed by indocyanine green  fluorescence staining was ≤1 cm, the landmarks were judged to be consistent with the planes with discrepant fluorescence. As long as one of the landmarks was judged to be consistent, the method was considered to be feasible and accurate. Results 聽 聽 A total of 21 patients who underwent thoracoscopic segmentectomy were enrolled, with 5 male and 16 female patients. The median age was 55 years, ranging from 34 to 76 years. A total of 11 patients received left-side surgery, while 10 patients received right-side surgery. In the operations of 21 pulmonary segmentectomies, at least one intersegmental landmark determined by the "lung surface intersegmental constant proportion landmarks" was consistent with the intersegmental plane determined by indocyanine green fluorescence staining in each patient. Conclusion 聽 聽The intersegmental landmarks determined by the "lung surface intersegmental constant proportion landmarks" are consistent with that determined by indocyanine green fluorescence staining. The method of "lung surface intersegmental constant proportion landmarks" is feasible and accurate in identifying intersegmental planes during pulmonary segmentectomy.

Histone acetylation is a well-characterized epigenetic modification controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). Imbalanced histone acetylation has been observed in many primary cancers. Therefore, efforts have been made to find drugs or small molecules such as HDAC inhibitors that can revert acetylation levels to normal in cancer cells. We observed dose-dependent reduction in the endogenous and exogenous protein expression levels of KAT8 (also known as human MOF), a member of the MYST family of HATs, and its corresponding histone acetylation at H4K5, H4K8, and H4K16 in chemotherapy drug gemcitabine (GEM)-exposed T24 bladder cancer (BLCA) cells. Interestingly, the reduction in MOF and histone H4 acetylation was inversely proportional to GEM-induced γH2AX, an indicator of chemotherapy drug effectiveness. Furthermore, pGL4-MOF-Luc reporter activities were significantly inhibited by GEM, thereby suggesting that GEM utilizes an MOF-mediated anti-BLCA mechanism of action. In the CCK-8, wound healing assays and Transwell ® experiments, the additive effects on cell proliferation and migration were observed in the presence of exogenous MOF and GEM. In addition, the promoted cell sensitivity to GEM by exogenous MOF in BLCA cells was confirmed using an Annexin V-FITC/PI assay. Taken together, our results provide the theoretical basis for elucidating the anti-BLCA mechanism of GEM.

BACKGROUND: Tendon is a fibrous tissue that connects bone and muscle. The main function is to conduct stress from the muscles to the bone during exercise. Tendinopathy is a commonly seen disease, characterized by tendon inflammation, degeneration and injury. Autophagy is widely involved in the development of many degenerative diseases. The research method based on autophagy provides a new idea for tendon repair. OBJECTIVE: To review the process and regulation mechanism of autophagy, and to analyze the pathological mechanism of autophagy involved in the tendinopathy so as to provide a reference for the prevention and treatment of tendinopathy. METHODS: The articles concerning autophagy and tendinopathy were retrieved by computer in CNKI, WanFang and PubMed databases. The keywords were "autophagy, tendon, fibroblast, tendinopathy" in English and Chinese, respectively. Finally, 54 articles were obtained through systematic induction and analysis after excluding the irrelevant and repetitive articles. RESULTS AND CONCLUSION: Autophagy can alleviate the damage to human tendon stem cells induced by oxidative stress. With the increase of the degree of extracellular matrix degradation in the tendon tissue, autophagic cell death occurs in the tendon cells due to excessive autophagy. Prostaglandin E2 significantly induces fibroblast death and autophagy in a dose-dependent manner. The muscle atrophy after the rotator cuff injury is regulated by autophagy. Rapamycin prevents peritendinous fibrosis through activation of autophagy. In conclusion, autophagy plays an important role in tendinopathy. Autophagy will become a new hotspot in tendinopathy. Further understanding of autophagy and its role in tendinopathy will contribute to finding a targeted autophagy pathway and provide new theoretical and methodological support for the intervention and treatment of tendinopathy.