Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

OBJECTIVE: To study bioactive compounds from the endophytic fungus Penicillium sp. HJT-A-6 isolated from stem of Rhodiola tibetica, and evaluate its allelopathic activity. METHODS: The chemical constituents were isolated and purified by silica gel, Sephadex LH-20 column chromatography and semi-preparative HPLC. Their structures were elucidated by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. In addition, the allelopathic activity of compound 1 was evaluated by measuring the seed germination rate of R. tibetica. RESULTS: Two new polyketides 4-hydroxy-3,6-dimethyl-2H-pyran-2-one (1) and penilactone E (2), together with six known compounds walterolactone A (3), 5-hydroxyhexan-4-olide (4), 3-methyl-2-penten-5-olide (5), chaetoquadrin F (6), (Z)-6-acetyl-3-(1,2-dihydroxypropylidene)-5-hydroxy-8-methylchroman-2-one (7) and 4-hydroxy-3-(4-hydroxyhexanoyl)-5-methylfuran-2(5H)-one (8) were isolated from Penicillium sp. HJT-A-6. Compound 1 showed moderate seed-germination-promoting activity at a concentration of 0.001 mg/mL while inhibiting the seed germination at concentrations of 0.1 and 0.01 mg/mL. Compared with the positive drug 6-benzyladenine (6-BA), compound 1 could extend the seed-germination period of R. tibetica (up to 11 d). CONCLUSION Two new compounds were isolated from R. tibetica endophytic fungus Penicillium sp. HJT-A-6. Compound 1 displayed plant hormone-like activity, which inhibited the seed germination of the host plant at high concentrations and promoted the seed germination of the host plant at low concentrations. The results not only enrich the chemical constituents of the endophytic fungi isolated from Rhodiola tibetica, but also provide a theoretical basis for understanding the interaction mechanism between Rhodiola tibetica endophytic fungi and the host plant.

Percutaneous dilatational tracheostomy (PDT) is a surgical method for quickly establishing an artificial airway, which has been favored by clinicians because of its simple operation, small trauma and bedside operation. However, for patients with tracheal intubation in intensive care unit (ICU), the tip and balloon of the existing endotracheal tube will not only hinder percutaneous puncture, but also hinder insertion of guidewire and tracheotomy tube, and consequently affect the process of PDT. On the contrary, blind withdrawal of the existing endotracheal tube may cause the tracheal tube tipleave the glottis, leading to an emergency airway situation that endangers the patient's life. Therefore, the medical staff from intensive care medicine department of the First People's Hospital of Chenzhou designed a laryngeal mask and its monitoring device, which is convenient for withdrawal of endotracheal tube, and obtained the national utility model patent of China (patent number: ZL 2020 2 2795887.1). The device is composed of a laryngeal mask and a monitoring device. The laryngeal mask mainly includes a laryngeal mask body, a vent tube, a guidance tube and other components. The laryngeal mask body is mainly used to seal the throat and provide the air supply channel for the patient together with the ventilation tube. The main function of the guidance tube is to accommodate the tracheal tube and facilitate the withdrawal of the inserted tracheal tube. During percutaneous dilatation tracheotomy, this device can monitor the withdrawal of tracheal catheter in real time, and immediately ensure the airway patency of patients without re-intubation when the cuff of tracheal catheter exits the glottis. The utility model has the advantages of real-time monitoring, simple operation, safety and convenience, and is worthy of transformation and promotion.

OBJECTIVE To evaluate the short-term efficacy of single-session microwave ablation for benign thyroid nodule.METHODS Patients with benign thyroid nodules treated by microwave ablation between June 2019 and December 2022 at the Department of Otolaryngology Head and Neck Surgery,the First Affiliated Hospital of Xi'an Jiaotong University,were included for analysis.Thyroid function was tested 1 month after treatment,and ultrasound and thyroid function were performed 3 months,6 months and 1 year after treatment.Volume reduction rates(VRR)of nodules were calculated.Data of the last follow-up within 1 year were included for analysis.Variables including gender,age,whether Hashimoto's thyroiditis was present,longitudinal diameter of nodules,solid volume of nodules were included for univariate and multivariate analysis.RESULTS A total of 151 patients with 163 nodules were included.The perioperative complication rate was 1.99%(3/151).The VRR at half year after treatment was(79.58±17.70)%,and the success rate at half year after treatment was 93.43%(128/137).The VRR of at 1year after treatment was(81.24±24.29)%.The 1-year treatment success rate was 92.77%(77/83).Univariate and multivariate analysis showed that nodular solid volume and age were independent factors affecting VRR after ablation.Regression coefficient of age and solid volume was 0.34(P<0.05)and-0.47(P<0.05),respectively.For every 1 cm3 increase in solid volume,1-year VRR(%)decreased by 0.47.Regression equation:1-year VRR=68.92+0.34×age-0.47×solid volume.Serum FT4 gradually decreased and the thyroid stimulating hormone(TSH)gradually increased within 6 months after ablation,and the differences were statistically significant(P<0.05).After 6 months,serum FT4 gradually recovered to the normal level and TSH gradually recovered.However,TSH still did not reach the preoperative level one year after ablation.FT3 decreased gradually after treatment,but there was no significant difference between the values at each time point(P=0.40).After the ablation of thyroid nodule,the mean value of thyroid function index fluctuated,but all of them were within the normal reference range.CONCLUSION Microwave ablation is a safe and effective treatment method for benign thyroid nodules,with an overall success rate of over 90%.Solid nodule volume and age are independent factors affecting the microwave ablation effect of benign thyroid nodules.

Objective:To explore the practical application and clinical significance of modified grading system for Gastrointestinal Symptom Rating Scale (GSRS) scores in evaluating long-term postoperative gastrointestinal dysfunction (PGID) in patients after colon cancer surgery.Methods:A retrospective analysis was conducted on the case data of 122 patients who underwent right hemicolectomy for colorectal cancer at Beijing Friendship Hospital, Capital Medical University from September 2021 to September 2022. Among these patients, 69 were males (56.6%), and 53 were females (43.4%). The median age was 66.5 years, and the body mass index was (24.4±3.3) kg/m 2. The main observe indiator was GSRS scores of patients. The measurement data of normal distribution were represented as mean±standard deviation( ± s), and intergroup comparisons were conducted using ANOVA. The measurement data of non-normal distribution were expressed as the median (interquartile distance) [ M( Q1, Q3)], the Kruskal-Wallis H test was employed. Unordered count data comparisons were performed using the χ2 test, while comparisons for ordered count data between groups were conducted using the Kruskal-Wallis H test. GSRS scores were represented using density plots, and the scores were categorized into five symptom groups, presented using radar charts to illustrate the distribution of each symptom group. Results:Among the 122 patients, the most common long-term PGID syndromes was dyspepsia, followed by abdominal pain, diarrhea, and constipation. GSRS score data in the study population exhibited a nearly trimodal trend. Based on the overall data trend, the GSRS scale was refined, with cut-off values of 20 and 30, categorizing patients with right-sided colon cancer into low-risk, moderate-risk, and high-risk groups for quantifying the severity of long-term PGID. In terms of gender distribution, the differences among the three groups was statistically significant ( P=0.031), suggesting that males may be more susceptible to long-term PGID. However, there were no significant differences among the three groups concerning age, tumor location, surgical approach, anastomotic technique, lymph node dissection, pathological staging, adjuvant chemotherapy, and other factors. Conclusions:The modified grading system for GSRS scores aligns with the distribution characteristics of postoperative gastrointestinal function in colorectal cancer patients. It can quantify the risk of long-term PGID, allowing for a graded management approach to improve the postoperative quality of life for patients.

Objective:To explore the relevance of a new comprehensive respiratory mechanics parameter, elastic power, to the 28-day prognosis of ARDS patients.Methods:Patients with ARDS hospitalized for at least 48 h with invasive mechanical ventilation in five intensive care units in three local hospitals in Lianyungang City from June 2018 to June 2022 were included in the study. Their baseline data and respiratory mechanics parameters were collected. Elastic power, mechanical power, driving pressure and lung compliance are calculated according to the corresponding formulae. The prognostic risk factors of ARDS patients were analysed using COX multi-factor regression, and the predictive value of EP/Cst on the 28-day prognosis of ARDS patients was evaluated based on ROC curve analysis and Kaplan-Meier survival curve.Results:There was no significantly difference in tidal volume and PEEP settings between the patients in the ARDS survivor and death groups ( P> 0.05). However, the differences in respiratory rate, plateau pressure, driving pressure, lung compliance, mechanical work, elastic work, EP/cst and MP/cst between the two groups were significantly different (all P< 0.01). Multifactorial COX regression analysis showed that EP/cst ( HR=1.211, 95% CI:1.091-1.323) and RR ( HR=1.209, 95% CI:1.046-1.339) were strongly associated with a more severe degree of illness and a worse prognosis in ARDS. And the cumulative survival rate at 28 d was significantly lower in the high Cst-EP group than in the low Cst-EP group (50.00% vs. 82.40%, P < 0.01). Conclusions:The new respiratory mechanics parameters EP and EP/Cst can assess the severity of ARDS with a good predictive effect on patient prognosis at 28 days.

Objective:To investigate the efficacy of plasma exchange (PE) in treatment of patients with acute respiratory distress syndrome (ARDS).Methods:Forty-two patients who met the inclusion criteria in the intensive care unit of Chenzhou First People′s Hospital were randomly divided into control group and plasma exchange (PE) group with 21 cases in each group. The control group received conventional treatment; while the PE group received conventional treatment plus PE. The mechanical ventilation time (MVT), length of ICU stay (ICU LOS), 28-day mortality and 90-day mortality of patients were analyzed. The oxygenation index, SOFA score, norepinephrine (NE) dose, C-reactive protein (CRP), procalcitonin (PCT) and IL-6 levels were evaluated before and after treatment.Results:In the control group the oxygenation index, IL-6, PCT and CRP were significantly improved after treatment ( t=-4.50, 2.46, Z=-3.53, t=5.55, all P<0.05), but the SOFA score and NE dose were not significantly changed ( t=1.98, Z=-0.47,all P>0.05). In the PE group, the oxygenation index, SOFA score, IL-6, PCT, CRP were significantly improved and the NE dose was reduced after treatment ( t=2.18, 9.23, 5.26, Z=-3.77, t=7.27 and Z=-2.54,all P<0.05). The oxygenation index, SOFA score, IL-6, CRP were significantly better after treatment and NE dose was lower in PE group than those in the control group ( t=2.18, -2.21, -2.12, -2.61 and Z=-2.11, all P<0.05). Compared with the control group, the MVT(14.0±5.2d vs. 18.4±6.3d), ICU LOS(19.3±4.9d vs. 23.2±7.3d) and 28-day mortality (14.3%(3/21) vs. 42.8%(10/21)) in the PE group were significantly decreased ( t=-2.48, -2.04 and χ2=4.20,all P<0.05). There was no significant difference in the 90-d mortality between the two groups (28.6%(6/21) vs. 52.4%(11/21), χ2=2.47, P=0.208). Conclusion:Therapeutic plasma exchange can significantly reduce the inflammatory response, improve the organ function and reduce the short-term mortality of ARDS patients.

Objective:To evaluate the role of brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling pathway in 17β estradiol-induced reduction of long-term cognitive impairment induced by multiple propofol anesthesia in developing rats.Methods:Eighty 7-day-old clean-grade healthy newborn Sprague-Dawley rats of both sexes, weighing 11-17 g, were divided into 4 groups ( n=20 each) using a random number table method: control group (group C), propofol group (group P), 17β estradiol plus propofol group (EP group) and 17β estradiol plus propofol plus BDNF/TrkB signaling pathway blocker K252a group (K group). Propofol 80 mg/kg was intraperitoneally injected every day for 5 days in P, EP and K groups.The equal volume of fat emulsion was given instead in group C. In EP and K groups, 17β estradiol 600 μg/kg was subcutaneously injected at 30 min before propofol injection.BDNF/TrkB signaling pathway blocker K252a 100 μg/kg was intraperitoneally injected in group K. Morris water maze test was performed on days 30-34 after birth to assess the cognitive function.The rats were sacrificed after the end of Morris water maze test, and the hippocampal tissues were removed for determination of the apoptosis rate of hippocampal neurons (by flow cytometry), expression of BDNF, p-Trkb and cleaved caspase-3 (by Western blot and immunofluorescence), and expression of Bcl-2 and Bax mRNA (by real-time polymerase chain reaction) and for microscopic examination of the pathological changes in hippocampal CA1 region (with a light microscope). Bax mRNA/Bcl-2 mRNA ratio was calculated. Results:Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of BDNF and p-TrkB was down-regulated, the expression of cleaved caspase-3 was up-regulated, the apoptosis rate of hippocampal neurons and Bax mRNA/Bcl-2 mRNA ratio were increased ( P<0.05), and the pathological changes in hippocampal CA1 region were accentuated in group P. Compared with group P, the escape latency was significantly shortened, the number of crossing the original platform was increased, the expression of BDNF and p-TrkB was up-regulated, the expression of cleaved caspase-3 was down-regulated, the apoptosis rate of hippocampal neurons and Bax mRNA/Bcl-2 mRNA ratio were decreased( P<0.05), and the pathological changes in hippocampal CA1 region were attenuated in group EP.Compared with group EP, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of BDNF and p-TrkB was down-regulated, the expression of cleaved caspase-3 was up-regulated, the apoptosis rate of hippocampal neurons and Bax mRNA/Bcl-2 mRNA ratio were increased( P<0.05), and the pathological changes in hippocampal CA1 region were accentuated in group K. Conclusions:BDNF/TrkB signaling pathway is involved in 17β estradiol-induced reduction of long-term cognitive impairment induced by multiple propofol anesthesia in developing rats.

Objective:To explore the application of compound Huangbai solution sitz bath in patients after surgery for perianal abscess.Methods:A convenient sampling method was used to select 100 patients with perianal abscess who received surgical treatment in Huai'an First Hospital Affiliated to Nanjing Medical University Nanjing Medical University from January 2020 to December 2021. Patients admitted from January to December 2020 and January to December 2021 were included in the control group (50 cases) and the observation group (50 cases), respectively. The control group was given warm water sitz bath, while the observation group was given compound Huangbai solution sitz bath. The clinical curative effects, wound edema, granulation growth, wound pain, exudation, recovery of anal function and inflammatory reaction were compared between the two groups.Results:After 7 days of intervention, the total effective rate of the observation group was higher than that of the control group, and the difference was statistically significant ( P<0.05). The CRP levels of wound edema and granulation growth, wound pain, exudate and Wexner scores, and CRP levels were lower than those before and 3 days after intervention, and the observation group was lower than that of the control group after 7 days of intervention, and the differences were statistically significant ( P<0.05) . Conclusions:Compound Huangbai solution sitz bath can effectively promote wound healing and anal function improvement of patients after perianal abscess operation, reduce the inflammatory response of patients, and then improve the therapeutic effect.

ObjectiveTo investigate the risk factors for failure in emergency endoscopic injection sclerotherapy (EIS) combined with sequential histoacryl injection (HI) for esophagogastric variceal bleeding (EGVB) with portal vein embolus (PVE). MethodsA total of 109 EGVB patients with PVE who underwent emergency gastroscopy in Beijing Shijitan Hospital, Capital Medical University, and The Fifth Medical Center of Chinese PLA General Hospital from January 2018 to December 2019 were enrolled, and according to the outcome of hemostatic treatment under emergency gastroscopy, the patients were divided into hemostatic failure group with 28 patients and hemostatic success group with 81 patients. The two groups were compared in terms of general information, varices and bleeding manifestations under gastroscopy, blood biochemical parameters, Child-Pugh class, and Model for End-Stage Liver Disease (MELD) score, and the risk factors for hemostatic failure were analyzed. The t-test or the Mann-Whitney U test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups; a logistic regression analysis was used for multivariate analysis. ResultsCompared with the hemostatic success group, the hemostatic failure group had significantly higher peripheral white blood cell count (WBC), total bilirubin (TBil), Child-Pugh class, and MELD score (Z=3.794, Z=4.751, χ2=40.104, Z=6.412, all P＜0001) and significantly lower prothrombin time activity (PTA), albumin (Alb), and cholinesterase (CHE) (t=9.653, Z=3.093, Z=4.092, P＜0.001, P=0.002, and P＜0.001). WBC (odds ratio ［OR］=28.543, 95% confidence interval ［CI］: 1.285-634.113, P＜0.05), PTA(OR=0.194, 95%CI: 0.045-0.835, P＜0.05), TBil (OR=2.197, 95%CI: 1.004-4.810, P＜0.05), Alb (OR=0448, 95%CI: 0.209-0.961, P＜0.05), and Child-Pugh class (OR=5.164, 95%CI: 1.307-20.406, P＜0.05) were independent risk factors for hemostatic failure. ConclusionWBC, PTA, TBil, Alb, and Child-Pugh class are independent risk factors for failure in emergency EIS combined with sequential HI in the treatment of EGVB with PVE, and adequate preoperative evaluation and correction may help to improve the success rate of hemostasis.