Objective:To investigate the relationship between mutated genes and clinical features in patients with essential thrombocythemia(ET).Methods:The clinical data of 69 patients with ET from October 2018 to March 2022 were retrospectively analyzed.According to driver mutation type,patients were divided into JAK2 group,CALR group and triple-negative group.The sex,age,cardiovascular risk factors,thrombosis,splenomegaly,routine blood test and coagulation status of patients in three groups were analyzed.Results:Among 69 ET patients,46 cases were associated with JAK2 mutation,14 cases with CALR mutation,8 cases with triple-negative mutation,and one with MPL gene mutation.There were no significant differences in age and sex among the three groups(P＞0.05).The highest thrombotic rate was 26.09％(12/46)in JAK2 group,then 12.5％(1/8)in triple-negative group,while no thrombotic events occurred in CALR group.The incidence of splenomegaly was the highest in JAK2 group(34.78％),while no splenomegaly occurred in triple-negative group.The white blood cell(WBC)count in JAK2 group was(9.00±4.86)× 109/L,which was significantly higher than(6.03±2.32)× 109/L in CALR group(P＜0.05).The hemoglobin(Hb)and hematocrit(HCT)in JAK2 group were(148.42±18.79)g/L and(0.44±0.06)％,respectively,which were both significantly higher than(131.00±15.17)g/L and(0.39±0.05)％in triple-negative group(P＜0.05).The platelet(PLT)in JAK2 group was(584.17±175.77)× 109/L,which was significantly lower than(703.07±225.60)× 109/L in CALR group(P＜0.05).The fibrinogen(Fg)in JAK2 and triple-negative group were(2.64±0.69)g/L and(3.05±0.77)g/L,respectively,which were both significantly higher than(2.24±0.47)g/L in CALR group(P＜0.05,P＜0.01).The activated partial thromboplastin time(APTT)in triple-negative group was(28.61±1.99)s,which was significantly decreased compared with(31.45±3.35)s in CALR group(P＜0.05).Conclusions:There are differences in blood cell count and coagulation status among ET patients with different driver gene mutations.Among ET patients,JAK2 mutation is most common.Compared with CALR group,the thrombotic rate,WBC and Fg significantly increase in JAK2 group,while PLT decrease.Compared with triple-negative group,the incidence of splenomegaly and HCT significantly increase.Compared with CALR group,Fg significantly increases but APTT decreases in triple-negative group.

On the basis of establishing the prescription of Xinjianqu and clarifying the increase of the lipid-lowering active ingredients of Xinjianqu by fermentation, this paper further compared the differences in the lipid-lowering effects of Xinjianqu before and after fermentation, and studied the mechanism of Xinjianqu in the treatment of hyperlipidemia. Seventy SD rats were randomly divided into seven groups, including normal group, model group, positive drug simvastatin group(0.02 g·kg~(-1)), and low-dose and high-dose Xinjianqu groups before and after fermentation(1.6 g·kg~(-1) and 8 g·kg~(-1)), with ten rats in each group. Rats in each group were given high-fat diet continuously for six weeks to establish the model of hyperlipidemia(HLP). After successful modeling, the rats were given high-fat diet and gavaged by the corresponding drugs for six weeks, once a day, to compare the effects of Xinjianqu on the body mass, liver coefficient, and small intestine propulsion rate of rats with HLP before and after fermentation. The effects of Xinjianqu before and after fermentation on total cholesterol(TC), triacylglyceride(TG), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), alanine aminotransferase(ALT), aspartate aminotransferase(AST), blood urea nitrogen(BUN), creatinine(Cr), motilin(MTL), gastrin(GAS), and the Na~+-K~+-ATPase levels were determined by enzyme-linked immunosorbent assay(ELISA). The effects of Xinjianqu on liver morphology of rats with HLP were investigated by hematoxylin-eosin(HE) staining and oil red O fat staining. The effects of Xinjianqu on the protein expression of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphorylated AMPK(p-AMPK), liver kinase B1(LKB1), and 3-hydroxy-3-methylglutarate monoacyl coenzyme A reductase(HMGCR) in liver tissues were investigated by immunohistochemistry. The effects of Xinjianqu on the regulation of intestinal flora structure of rats with HLP were studied based on 16S rDNA high-throughput sequencing technology. The results showed that compared with those in the normal group, rats in the model group had significantly higher body mass and liver coefficient(P<0.01), significantly lower small intestine propulsion rate(P<0.01), significantly higher serum levels of TC, TG, LDL-C, ALT, AST, BUN, Cr, and AQP2(P<0.01), and significantly lower serum levels of HDL-C, MTL, GAS, Na~+-K~+-ATP levels(P<0.01). The protein expression of AMPK, p-AMPK, and LKB1 in the livers of rats in the model group was significantly decreased(P<0.01), and that of HMGCR was significantly increased(P<0.01). In addition, the observed＿otus, Shannon, and Chao1 indices were significantly decreased(P<0.05 or P<0.01) in rat fecal flora in the model group. Besides, in the model group, the relative abundance of Firmicutes was reduced, while that of Verrucomicrobia and Proteobacteria was increased, and the relative abundance of beneficial genera such as Ligilactobacillus and Lachnospiraceae＿NK4A136＿group was reduced. Compared with the model group, all Xinjianqu groups regulated the body mass, liver coefficient, and small intestine index of rats with HLP(P<0.05 or P<0.01), reduced the serum levels of TC, TG, LDL-C, ALT, AST, BUN, Cr, and AQP2, increased the serum levels of HDL-C, MTL, GAS, and Na~+-K~+-ATP, improved the liver morphology, and increased the protein expression gray value of AMPK, p-AMPK, and LKB1 in the liver of rats with HLP and decreased that of LKB1. Xinjianqu groups could regulate the intestinal flora structure of rats with HLP, increased observed＿otus, Shannon, Chao1 indices, and increased the relative abundance of Firmicutes, Ligilactobacillus(genus), Lachnospiraceae＿NK4A136＿group(genus). Besides, the high-dose Xinjianqu-fermented group had significant effects on body mass, liver coefficient, small intestine propulsion rate, and serum index levels of rats with HLP(P<0.01), and the effects were better than those of Xinjianqu groups before fermentation. The above results show that Xinjianqu can improve the blood lipid level, liver and kidney function, and gastrointestinal motility of rats with HLP, and the improvement effect of Xinjianqu on hyperlipidemia is significantly enhanced by fermentation. The mechanism may be related to AMPK, p-AMPK, LKB1, and HMGCR protein in the LKB1-AMPK pathway and the regulation of intestinal flora structure.
Rats ; Animals ; AMP-Activated Protein Kinases/metabolism* ; Rats, Sprague-Dawley ; Cholesterol, LDL ; Fermentation ; Aquaporin 2/metabolism* ; Lipid Metabolism ; Liver ; Lipids ; Hyperlipidemias/genetics* ; Adenosine Triphosphate/pharmacology* ; Diet, High-Fat/adverse effects*

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.
Humans ; Polymyxin B/adverse effects* ; Retrospective Studies ; Gram-Negative Bacterial Infections/complications* ; Fever/drug therapy* ; Sepsis/drug therapy* ; Anti-Bacterial Agents/therapeutic use* ; Bacteremia/complications*

Objective To study whether bergapten (BG) protects PC12 cells from oxygen-glucose deprivation (OGD) induced cell injury by regulating long non-coding RNA (lncRNA) opioid receptor gene (Oprm1) expression. Methods PC12 cells were divided into control (Con) group, OGD group, OGD+ low concentration BG (BG-L) group, OGD+medium concentration BG (BG-M) group, OGD + high concentration BG (BG-H) group, OGD + pcDNA group, OGD+pcDNA-Oprm1 group, OGD+BG+si-NC group, OGD+BG+si-Oprm1 group. The malondialdehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were measured by the kits. Cell apoptosis rate was analysed by flow cytometry. The expression level of Oprm1 was analysed by Real-time PCR. Results Compared with the Con group, the apoptosis rate and MDA content of PC12 cells in OGD group increased significantly, whereas Oprm1 expression, SOD and GSH-Px activity decreased significantly (P < 0. 05). Compared with the OGD group, the apoptosis rate and MDA content of PC12 cells in the OGD + BG-L group, OGD + BG-M group, OGD + BG-H group were significantly reduced, whereas the Oprm1 expression, SOD and GSH-Px activities increased significantly (P < 0. 05). Compared with the OGD+pcDNA group, the apoptosis rate and MDA content of the PC12 cells in the OGD+pcDNA-Oprm1 group reduced significantly, whereas the SOD and GSH-Px activities increased significantly (P<0. 05). Compared with the OGD+BG+si-NC group, the apoptosis rate and MDA content of PC12 cells in the OGD+BG+si-Oprm1 group increased significantly, whereas the SOD and GSH-Px activities decreased significantly (P < 0. 05). Conclusion Bergapten may alleviate OGD-induced PC12 cell injury, which is correlated to the up-regulation of lncRNA Oprm1 expression.

Objective: To summarize the application of temporalis muscle flap in the salvage nasopharyngectomy for advanced recurrent nasopharyngeal carcinoma (rNPC), and to provide guidance for the repair of extensive skull base defects in salvage rNPC. Methods: A total of 54 patients with the application of temporalis muscle flap in the salvage nasopharyngectomy for advanced rNPC were retrospectively analyzed, including 42 males and 12 females, aging from 29 to 71 years. There were 36 patients with rT3 and 18 patients with rT4. The surgical methods of temporalis muscle flap repair were summarized. The general situation, survival time and postoperative complications of patients were recorded, and the advantages and disadvantages of temporalis muscle flap were discussed. Results: The temporal muscle flap could completely cover the defect area of nasopharynx and skull base, without the need for other autologous repair materials. The follow-up period was 2 to 28 months. The survival rate of temporalis flap was 98.1% (53/54). The 1-year overall survival rate was 84.5% while 1-year progression-free survival rate was 49.0%. None of the patients had facial nerve injury. Three patients (5.6%) had necrosis of the cranial membrane required surgical intervention and four patients (7.4%) required a chonoplasty due to severe chonostril stenosis or chonostril atresia. Eleven cases (20.4%) had mouth opening restriction, chewing weakness, dysphagia and other eating difficulties. Conclusions: Temporalis muscle flap is an alternative flap for the salvage nasopharyngectomy for advanced rNPC. Temporal muscle flap shows high survival rate and wide coverage, but the surgeon should apprehend the possible complications and reduce the occurrence of them.
Humans ; Male ; Female ; Nasopharyngeal Carcinoma ; Retrospective Studies ; Surgical Flaps ; Nasopharyngeal Neoplasms/pathology* ; Muscles/pathology*

Objective: To evaluate the efficiency of internal carotid artery (ICA) embolization technology in endoscopic salvage surgery for recurrent nasopharyngeal carcinoma (rNPC) invading the ICA. Methods: From January 2016 to March 2021, 83 patients with rNPC who invaded the ICA and underwent endoscopic extended nasopharyngectomy were retrospectively collected from the Eye & ENT Hospital in Fudan University, including 60 males and 23 females. The age of the patients ranged from 27 to 77 years. The standard of ICA invasion was that the distance from the lesion to the ICA on enhanced MRI was ≤ 1.8 mm. The clinical characteristics, ICA management strategy and survival prognosis of patients were analyzed, and the effectiveness of ICA embolization was evaluated. Kaplan-Meier method was used to calculate the survival rate and Log-rank test was used to compare the difference. Results: In 83 patients with rNPC, there were 13 patients with rT2, 38 patients with rT3, 32 patients with rT4, and 16 patients had lymph node metastasis. A total of 37 patients (44.6%) underwent ICA coil embolization before surgery, of which 2 cases underwent external carotid-middle cerebral artery artery bypass grafting and ICA embolization due to positive balloon occlusion test (BOT). Patients with positive surgical margin accounted for 24.1% (20/83). Among them, patients with rT4 and patients without ICA embolization had a higher positive rate of surgical margin (P value was 0.001, 0.043, respectively). The 3-year overall survival (OS) and progression free survival (PFS) rate of all patients was 46.5% and 26.7%, respectively. In addition, the 3-year OS and PFS of patients with ICA embolization was significantly higher than those without ICA embolization, respectively (69.1% vs 27.8%, P=0.003; 33.9% vs 18.9%, P=0.018). Only 2 patients (2/37, 5.4%) had cerebral infarction complications after coil embolization of the affected ICA due to negative BOT. Conclusion: Preoperative ICA embolization can be used to treat patients with rNPC invading the ICA, improve the total removal rate and survival rate of patients, which is an effective salvage treatment.
Humans ; Male ; Female ; Adult ; Middle Aged ; Aged ; Nasopharyngeal Carcinoma ; Salvage Therapy ; Retrospective Studies ; Carotid Artery, Internal ; Neoplasm Recurrence, Local/surgery* ; Nasopharyngeal Neoplasms/pathology*

Calreticulin/genetics* ; DNA Methylation ; Female ; Humans ; Janus Kinase 2/genetics* ; Mutation ; Myeloproliferative Disorders/genetics* ; Polycythemia Vera/genetics*

Objective: To evaluate the feasibility of the endoscopic transnasal approach (ETA) and to analyze the outcomes and factors of this surgical technique in the management of the tumor invading the anterior skull base. Methods: A retrospective analysis was performed on 42 patients (31 males and 11 females, with mean age of 49 years) with sinonasal tumor invading the anterior skull base, who underwent ETA from June 2015 to April 2019 in Eye, Ear, Nose and Throat Hospital of Fudan University. Pathologically, there were 15 cases of squamous carcinoma (14 patients with T4bN0M0 and 1 patient with T4bN1M0) and 27 of olfactory neuroblastomas with Kadish stage C. Anterior skull base reconstruction was performed using the vascular pedicled nasoseptal mucoperiosteal flap and fascia lata. Brain non-contrast-enhanced CT was performed on the first postoperative day to exclude massive pneumocephalus, relevant brain edema and subarachnoid hemorrhage. Sinonasal contrast-enhanced MR was performed to assess the extent of the tumor removal. Kaplan-Meier analysis was used to calculate the overall survival (OS) and Cox multivariate regression analysis was used to determine the prognostic factors. Results: The mean duration of the surgery was 452 minutes. Total resection was performed in 36 patients (85.7%), subtotal resection in 2 patients (4.8%) with orbital involvement, partial resection in one patient (2.4%) with injury of the internal carotid artery. One patient (2.4%) underwent the second resection because of the tumor residual, two patients (4.8%) with unsure tumor residual. Mean follow-up was 20 months, with 17 months of median follow-up. One-, two-and three-year overall survival was 86.5%, 76.9% and 64.5%, respectively. For squamous carcinoma, one-, two-and three-year overall survival was 86.2%, 86.2% and 57.4%, respectively. For olfactory neuroblastomas, One-, two-and three-year overall survival was 86.9%, 75.3% and 67.8%, respectively. Multivariate analysis showed that tumor residual (P=0.001) and recurrence (P<0.01) were independent prognostic factors for survival. Conclusions: The ETA is safe and feasible in selected patients with sinonasal tumor invading the anterior skull base. Tumor residual and recurrence are independent prognostic factors for survival.
Female ; Humans ; Male ; Middle Aged ; Nasal Cavity ; Neoplasm Recurrence, Local ; Nose Neoplasms/surgery* ; Retrospective Studies ; Skull Base/surgery* ; Skull Base Neoplasms/surgery*

OBJECTIVE: To study the expression of multiple negative costimulatory molecules on peripheral blood T cells in patients with acute myeloid leukemia (AML) and its affection on prognosis. METHODS: The peripheral blood samples from patients with newly diagnosed AML, complete remission (CR), and no-remission (NR) were collected, the expression levels PD-1、VISTA and TIM-3 in CD4 and CD8 T cells were detected by flow cytometry , and the clinical data of patients were analyzed. RESULTS: The expression levels of PD-1、VISTA and TIM-3 of CD4 and CD8 T cells in the newly diagnosed AML patients were significantly higher than those in control group (P＜0.05). The expression levels of PD-1、TIM-3 and VISTA of CD4 and CD8 T cells in the CR group were significantly lower than those in newly diagnosed and the NR group (P＜0.05). The TIM-3 expression level positively correlated with VISTA expression level of CD4 and CD8 T cells in newly diagnosed AML patients (r=0.85 and 0.73). The VISTA and PD-1 expression level of CD4 T cells in newly diagnosed AML, NR after first induction chemotherapy and high risk patients significantly increased (P＜0.05), the TIM-3 expression level of CD8 T cells in high risk group significantly increased (P＜0.05), and the VISTA expression level of CD8 T cells in CBFβ-MYH11 mutation-positive group significantly decreased (P＜0.05). CONCLUSION The expression of PD-1、TIM-3 and VISTA in AML peripheral blood T cells may be involved in the immune escape of AML and can be the targets of treatment for acute myeloid leukemia patients.
B7 Antigens ; CD8-Positive T-Lymphocytes ; Flow Cytometry ; Hepatitis A Virus Cellular Receptor 2 ; Humans ; Leukemia, Myeloid, Acute ; Programmed Cell Death 1 Receptor

Analgesia ; methods ; Betacoronavirus ; Conscious Sedation ; methods ; Consensus ; Coronavirus Infections ; complications ; Humans ; Pandemics ; Pneumonia, Viral ; complications