Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

Objective:To analyze the risk factors of in-hospital mortality in patients with femoral neck fracture and establish a prediction model for in-hospital mortality.Methods:From 2014 to 2023, a total of 4,028,102 hospitalized patients from six directly affiliated hospitals and two co-constructed affiliated hospitals of Peking University were retrospectively analyzed. Among them, 4,744 patients were hospitalized with femoral neck fractures, including 1,486 males and 3,258 females, aged 74±13.3 years (range, 19-103 years). Gender, age, length of hospital stay, hospitalization costs, preoperative comorbidities, treatment methods, anesthesia methods, and in-hospital mortality were extracted from the medical records. According to the presence or absence of in-hospital death, the patients were divided into death group and survival group. The differences in general data and clinical indicators between the two groups were compared, and the indicators with statistically significant differences were included in binary logistic regression analysis to screen the risk factors for in-hospital death in patients with femoral neck fracture. The receiver operating characteristic (ROC) curve for predicting in-hospital mortality of femoral neck fracture was drawn, and the area under the curve (AUC) was calculated.Results:There were 30 cases in the death group and 4,714 cases in the survival group, with a mortality rate of 0.63%. Among the dead patients, 20 had undergone hip replacement, and 10 had received non-surgical treatment. In the death group, age ( t=7.524, P<0.001), length of hospital stay ( t=3.802, P<0.001), hospitalisation cost ( t=3.961, P<0.001), rate of non-surgical treatment ( P<0.001), anaesthesia modality ( P=0.002), dementia ( P=0.045), malignant tumour ( P<0.001), renal insufficiency (χ 2=27.901, P<0.001), hypertension (χ 2=4.155, P=0.042), cerebral infarction (χ 2=8.271, P=0.004), urinary infections ( P=0.043), electrolyte disorders (χ 2=16.660, P<0.001), post-cholecystectomy ( P=0.070), abnormal liver function ( P=0.015), schizophrenia ( P=0.062), myocardial infarction (χ 2=19.057, P<0.001), diabetes mellitus with end-organ damage ( P=0.036), congestive heart failure (χ 2=93.122, P<0.001), and chronic obstructive pulmonary disease (χ 2=27.714, P<0.001) were greater than in the survival group, and the differences were statistically significance ( P<0.10). Bicategory logistic regression analysis showed age ( OR=1.08, P=0.008), non-surgical treatment ( OR=2.87, P=0.017), combined malignancy ( OR=9.35, P<0.001), renal insufficiency ( OR=4.07, P=0.004), hypertension ( OR=4.45, P=0.007), cerebral infarction ( OR=2.42, P=0.040), electrolyte disorders ( OR=4.29, P=0.009), schizophrenia ( OR=41.23, P=0.002), chronic obstructive pulmonary disease ( OR=3.84, P=0.002), and congestive heart failure ( OR=7.08, P<0.001) were the independent risk factors for in-hospital mortality of femoral neck fracture. The AUC and its 95% confidence interval (CI) for the predictive model were 0.908(0.84, 0.97), indicating excellent predictive value. Conclusion:Elderly, non-surgical treatment, malignant tumor, renal insufficiency, hypertension, cerebral infarction, electrolyte disturbance, schizophrenia, chronic obstructive pulmonary disease, congestive heart failure are associated with higher in-hospital mortality in patients with femoral neck fracture.

Objective:To analyze the risk factors of in-hospital mortality in patients with femoral neck fracture and establish a prediction model for in-hospital mortality.Methods:From 2014 to 2023, a total of 4,028,102 hospitalized patients from six directly affiliated hospitals and two co-constructed affiliated hospitals of Peking University were retrospectively analyzed. Among them, 4,744 patients were hospitalized with femoral neck fractures, including 1,486 males and 3,258 females, aged 74±13.3 years (range, 19-103 years). Gender, age, length of hospital stay, hospitalization costs, preoperative comorbidities, treatment methods, anesthesia methods, and in-hospital mortality were extracted from the medical records. According to the presence or absence of in-hospital death, the patients were divided into death group and survival group. The differences in general data and clinical indicators between the two groups were compared, and the indicators with statistically significant differences were included in binary logistic regression analysis to screen the risk factors for in-hospital death in patients with femoral neck fracture. The receiver operating characteristic (ROC) curve for predicting in-hospital mortality of femoral neck fracture was drawn, and the area under the curve (AUC) was calculated.Results:There were 30 cases in the death group and 4,714 cases in the survival group, with a mortality rate of 0.63%. Among the dead patients, 20 had undergone hip replacement, and 10 had received non-surgical treatment. In the death group, age ( t=7.524, P<0.001), length of hospital stay ( t=3.802, P<0.001), hospitalisation cost ( t=3.961, P<0.001), rate of non-surgical treatment ( P<0.001), anaesthesia modality ( P=0.002), dementia ( P=0.045), malignant tumour ( P<0.001), renal insufficiency (χ 2=27.901, P<0.001), hypertension (χ 2=4.155, P=0.042), cerebral infarction (χ 2=8.271, P=0.004), urinary infections ( P=0.043), electrolyte disorders (χ 2=16.660, P<0.001), post-cholecystectomy ( P=0.070), abnormal liver function ( P=0.015), schizophrenia ( P=0.062), myocardial infarction (χ 2=19.057, P<0.001), diabetes mellitus with end-organ damage ( P=0.036), congestive heart failure (χ 2=93.122, P<0.001), and chronic obstructive pulmonary disease (χ 2=27.714, P<0.001) were greater than in the survival group, and the differences were statistically significance ( P<0.10). Bicategory logistic regression analysis showed age ( OR=1.08, P=0.008), non-surgical treatment ( OR=2.87, P=0.017), combined malignancy ( OR=9.35, P<0.001), renal insufficiency ( OR=4.07, P=0.004), hypertension ( OR=4.45, P=0.007), cerebral infarction ( OR=2.42, P=0.040), electrolyte disorders ( OR=4.29, P=0.009), schizophrenia ( OR=41.23, P=0.002), chronic obstructive pulmonary disease ( OR=3.84, P=0.002), and congestive heart failure ( OR=7.08, P<0.001) were the independent risk factors for in-hospital mortality of femoral neck fracture. The AUC and its 95% confidence interval (CI) for the predictive model were 0.908(0.84, 0.97), indicating excellent predictive value. Conclusion:Elderly, non-surgical treatment, malignant tumor, renal insufficiency, hypertension, cerebral infarction, electrolyte disturbance, schizophrenia, chronic obstructive pulmonary disease, congestive heart failure are associated with higher in-hospital mortality in patients with femoral neck fracture.

The feasibility and safety of intracardiac echocardiography (ICE)-guided catheter ablation for atrial fibrillation (AF) using a minimal/zero-fluoroscopy approach have recently been reported. This approach helps to reduce ionizing radiation exposure and orthopedic complications resulting from using lead aprons. The objectives of this planned prospective, multicenter randomized controlled trial (RCT) (paroxysmal AF (PAF)-ICE trial; ChiCTR2000033624) are to evaluate the efficacy and safety of ICE-guided minimal-fluoroscopy ablation in patients with PAF and the impact on occupational hazards among lab staff.Patients will be randomized in a 1:1 ratio to 2 groups: minimal fluoroscopy group ( n = 216) and traditional approach group ( n = 216). In the minimal fluoroscopy group, an ICE catheter will be used for geometry/anatomic construction, transseptal puncture, catheter tracking, and effusion monitoring. Pulmonary vein isolation (PVI) will be performed using an open-irrigated radiofrequency SmartTouch Surround Flow or SmartTouch catheter (Biosense Webster, Diamond Bar, California, USA), and confirmed by a multipolar Lasso or PentaRay catheter (Biosense Webster). In the traditional approach group, an ICE catheter will not be used. Transseptal puncture will be performed under fluoroscopic guidance, with all geometries constructed by mapping the catheters. The primary efficacy endpoint is freedom from AF recurrence (without antiarrhythmic medications) at 12 months after ablation. Other endpoints include duration of lead apron use, measures of intra-procedural efficiency, and peri-procedural complications. This RCT will evaluate the efficacy and safety of ICE-guided minimal-fluoroscopy ablation in patients with PAF, also evaluate the benefits to lab staff (regarding reducing occupational hazards) related to this "minimal/zero-fluoroscopy" and "leadless" mode.

The feasibility and safety of intracardiac echocardiography (ICE)-guided catheter ablation for atrial fibrillation (AF) using a minimal/zero-fluoroscopy approach have recently been reported. This approach helps to reduce ionizing radiation exposure and orthopedic complications resulting from using lead aprons. The objectives of this planned prospective, multicenter randomized controlled trial (RCT) (paroxysmal AF (PAF)-ICE trial; ChiCTR2000033624) are to evaluate the efficacy and safety of ICE-guided minimal-fluoroscopy ablation in patients with PAF and the impact on occupational hazards among lab staff.Patients will be randomized in a 1:1 ratio to 2 groups: minimal fluoroscopy group ( n = 216) and traditional approach group ( n = 216). In the minimal fluoroscopy group, an ICE catheter will be used for geometry/anatomic construction, transseptal puncture, catheter tracking, and effusion monitoring. Pulmonary vein isolation (PVI) will be performed using an open-irrigated radiofrequency SmartTouch Surround Flow or SmartTouch catheter (Biosense Webster, Diamond Bar, California, USA), and confirmed by a multipolar Lasso or PentaRay catheter (Biosense Webster). In the traditional approach group, an ICE catheter will not be used. Transseptal puncture will be performed under fluoroscopic guidance, with all geometries constructed by mapping the catheters. The primary efficacy endpoint is freedom from AF recurrence (without antiarrhythmic medications) at 12 months after ablation. Other endpoints include duration of lead apron use, measures of intra-procedural efficiency, and peri-procedural complications. This RCT will evaluate the efficacy and safety of ICE-guided minimal-fluoroscopy ablation in patients with PAF, also evaluate the benefits to lab staff (regarding reducing occupational hazards) related to this "minimal/zero-fluoroscopy" and "leadless" mode.

Objective:To investigate the influence of frailty on post-treatment outcomes in elderly heart failure patients with reduced ejection fraction treated with Sacubitril/Valsartan.Methods:The 231 heart failure patients aged 60 years or over with reduced ejection fraction were enrolled from October 2017 to October 2018 in Department of Geriatric Medicine, Henan Provincial People's Hospital.Patients were divided into the frailty group(n=116)and the control group(n=115). Frailty diagnosis was made by five indexes suggested by LP Fried.Both groups were treated with sacubitril/valsartan(49/51 mg)for 1 year.The left ventricular ejection(LVEF), estimated glomerular filtration rate(eGFR), N-terminal pro B-type natriuretic peptide(NT-proBNP)and other clinical and laboratory indexes were detected before and after treatment and compared between the frailty group and the control group.Results:16 subjects in the frailty group and 11 subjects in the control group dropped out of the study.The frailty group versus the control group showed a higher mortality rate of cardiovascular causes(13.0% or 13/100 vs.6.7% or 7/104, χ2=6.437, P=0.027), a higher first re-hospitalization rate(18.0% or 18/100 vs.11.5% or 12/104, χ2=4.458, P=0.043)and a higher all-cause mortality(16.0% or 16/100 vs.8.6% or 9/104, χ2=3.875, P=0.039). In the frailty group, levels of serum NT-proBNP and creatinine were higher and eGFR was lower after treatment than before treatment[(2 253±144) ng/L vs.(2 094±136) ng/L, (137±24) μmol/L vs.(125±23) μmol/L, (49.2±5.9) ml·min -1·1.73 m -2vs.(56.7±6.3) ml·min -1·1.73 m -2, t=3.674, 2.893 and 2.068, P=0.017, 0.026 and 0.029]. In the control group, serum NT-proBNP levels were lower after treatment than before treatment[(1 828±123) ng/L vs.(1 945±128) ng/L, t=1.896, P=0.043], while serum creatinine levels[(120±22) μmol/L vs.(117±19) μmol/L, t=2.099, P=0.650]and eGFR[(59.8±6.5) ml·min -1·1.73 m -2vs.(61.6±6.8) ml·min -1·1.73 m -2, t=2.444, P=0.173]had no significant difference between post-treatment and pre-treatment. Conclusions:Frailty has adverse affects on the mortality, re-hospitalization rate and renal function in elderly heart failure patients with reduced ejection fraction treated with Sacubitril/Valsartan.

Objective To evaluate the effects of age factors on sedation induced by dexmedetomidine.Methods One hundred and thirty-nine patients,aged 18-103 yr,with body mass index ≤ 30 kg/m2,scheduled for elective surgeries on lower abdomen or lower extremities,were divided into4 groups according to the age:group Ⅰ (18 yr≤age≤44 yr,n=40);group Ⅱ (45 yr≤age≤59 yr,n=38);group Ⅲ (60 yr≤age≤89 yr,n=39);group Ⅳ (≥90 yr,n=22).A catheter was placed in the subarachnoid space at L3,4 interspace,and ropivacaine 10-20 mg was injected via the catheter.At 20 min after ropivacaine injection,dexmedetomidine 1 μg/kg was infused via a pump over 10 min.The onset time and duration of sedation were recorded,and the occurrence of adverse effects such as hypoxemia,bradycardia and hypotension was observed.Results There was no significant difference in the onset time of sedation and incidence of bradycardia among the 4 groups (P＞0.05).Compared with group Ⅰ,the duration of sedation was significantly prolonged in Ⅱ-Ⅳ groups (P＜0.05).Compared with Ⅱ and Ⅲ groups,the duration of sedation was significantly prolonged in group Ⅳ (P ＜ 0.05).The incidence of hypoxemia and hypotension was significantly higher in group Ⅳ than in Ⅰ-Ⅲ groups (P＜0.05).Conclusion Dexmedetomidine-induced sedation is influenced by age factors,the duration of sedation induced by dexmedetomidine is prolonged,and the occurrence of adverse effects is increased,especially if the patients ≥ 90 yr of age.

Objective To evaluate the surgical strategy for giant pituitary adenomas apoplexy complicated with obstructive hydrocephalus.Methods Twenty-three patients with giant apoplectic pituitary adenomas associated with obstructive hydrocephalus,admitted to our hospital from January 2010 to March 2015,were chosen;their clinical and surgery data were retrospectively summarized.Results Transsphenoidal microsurgery was conducted in 22 patients and craniotomy in one.All tumors showed cystic degeneration and soft texture.Seven patients had faint yellow or hyaline cyst fluid and 16 had soybean sauce or dark red cyst fluid.Near-total tumor resection was achieved in 2 patients (8.7％),subtotal resection in 16 (69.6％),and partial resection in 5 (21.7％).Twenty-three patients were followed up for 4-38 months,one patient accepted repeated operation for residual rumors,5 had postoperative adjuvant radiation therapy,and no other patients showed re-growth or recurrence.Postoperatively,there was no long-term cerebrospinal fluid leakage and diabetes insipidus,with hydrocephalus disappeared in 100％,visual improved in 60.9％,and headache relieved in 81.8％.Conclusions Pituitary adenoma presented with apoplexy and concurrent obstructive hydrocephalus is often soft.Transsphenoidal microsurgery is the preferred safe and effective method which can relieve hydrocephalus and achieve improved clinical symptoms.

Objective To observe the effect of Xiaoxianxiong Decoction combined with metformin on glucose and lipid metabolism of phlegm-heat type 2 diabetic patients (T2DM). Methods Totally 104 phlegm-heat T2DM patients were randomly divided into two groups (each contains 52 cases), and given the diabetes lifestyle intervention. Control group additionally took 0.5 g metformin twice daily. And treatment group, besides taking 0.5 g metformin, was given Xiaoxianxiong Decoction, one dose and three times per day warmly. After 12 weeks, FBG, HbA1C, TC, TG, HDL-C, LDL-C, 2 hPG of the two groups were determined, and the therapeutic effect was evaluated. Results The total effective rate in the treatment group was 92.31%, and 76.92%in control group (P<0.01). The difference in symptom score, FBG, 2 hPG, TC, TG, HDL-C and LDL-C between the two group were significant, so as that between before and after treatment of both groups (P<0.05). Conclusion Xiaoxianxiong Decoction combined with metformin can effectively lower the levels of blood glucose and blood lipid in phlegm-heat T2DM patients, enhance the therapeutic effect and improve the metabolism of glucose and lipid.

Objective To explore the effects of lactoferrin on T cells ( the levels of CD4 + T and CD8 +T lymphocytes) and the development of intestinal mucous membrane (villus heights, crypt depths, villus circumferences, and villus areas) in neonatal SD rats. Methods Totally 96 neonatal (one week old) SD rats were equally and randomly divided into twelve groups, in which animals were fed with lactoferrin at a dose of 1.0 g/( kg · d) (dose Ⅰ group), 3.0 g/(kg · d) (dose Ⅱ group), or 5.0 g/(kg · d) (dose Ⅲ group) for 2, 3, or4 weeks,with corresponding blank control groups. Rats in the dosage groups were killed at the set time points and the levels of venous blood CD4 + and CD8 + T lymphocytes were detected using immunofluorescence method. Jejunum ( 1 cm)and ileum (1 cm) specimens were obtained for pathological sectioning, and the villus height, crypt depth, villus circumferences, and villus areas were measured through image analysis system. Results The CD4 + T lymphocyte levels at two weeks were significantly different among dose I group, dose Ⅱ group, and control groups ( all P ＜0. 05).The CD8 + T lymphocyte levels at two weeks were significantly different among dose Ⅱ group, dose Ⅲ group,and control groups ( all P ＜ 0. 05 ). The villus heights, crypt depths, villus circumferences, and villus areas of jejunum at two weeks between feeding groups and control groups were not significantly different ( all P ＞ 0. 05 ), while the condition in ileum was on the contrary. The CD4 + T lymphocyte levels at three weeks were significantly different between feeding groups and control groups ( P ＜ 0. 05 ). The CD8 + T lymphocyte levels at three weeks between dose Ⅲ group and control groups were significantly different ( P ＜ 0. 05 ). The villus heights, crypt depths, villus circumferences, and villus areas of jejunum and ileum at three weeks were significantly different between feeding groups and control groups ( all P ＜ 0. 05 ). The CD4 + T lymphocyte levels at four weeks between feeding groups and control groups were significantly different (P ＜0. 05). The CD8 + T lymphocyte levels at four weeks were significantly different among dose Ⅱ group, dose Ⅲ group, and control groups ( all P ＜ 0. 05 ). Except villus areas of ileum, the villus heights, crypt depths, villus circumferences of jejunum and ileum, and villus areas of jejunum at four weeks were significantly different between feeding groups and control groups ( all P ＜ 0.05 ). Conclusions Lactoferrin can promote the levels of CD4 + and CD8 + T lymphocytes in venous blood and facilitate the development of the mucous membranes of jejunum and ileum. However, such effects are affected by the dose and timing of lactoferrin feeding.