OBJECTIVES: Tiletamine, a veterinary anesthetic, has emerged as a novel psychoactive substance and has been abused in many parts of the world, causing great harm to public health. However, the sensitivity of existing detection methods cannot meet the needs of forensic practice. This study aims to establish an ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of tiletamine and its metabolite desethyltiletamine in human biological samples, and to verify its applicability in forensic practice. METHODS: SKF_525A was used as the internal standard. Biological samples were extracted with acetonitrile containing 1 ng/mL SKF_525A, vortexed for 10 min, ultrasonicated for 20 min, centrifuged at 10 000 r/min for 10 min, and 500 μL of the supernatant was filtered through a 0.22 μm membrane. Analyses were performed using an ACQUITY UPLC H-Class PLUS system and an XEVO TQ-S Micro triple quadrupole mass spectrometer. An ACQUITY UPLC^® BEH C18 (1.7 µm, 2.1 mm×100 mm) column at a flow rate of 0.3 mL/min was used, and four mobile phase systems were tested to optimize separation. Detection used positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode, with quantifier ion transitions of mass to charge 224.043→179.016 for tiletamine and mass to charge 196.08→151.06 for desethyltiletamine. Calibration curves were established over 0.1-200 ng/mL in spiked blood samples. The linear range, limit of detection (LOD), and limit of quantification (LOQ) were determined. Low (5 ng/mL), medium (20 ng/mL), and high (100 ng/mL) concentrations of tiletamine were spiked into blood, liver, and kidney to evaluate precision, accuracy, matrix effect, recovery, and stability. Finally, actual forensic case samples were tested to validate applicability. RESULTS: The established UPLC-MS/MS method achieved simultaneous detection of tiletamine and desethyltiletamine in human biological samples, with retention times of 3.42 min and 2.82 min, respectively. Using mobile phase A (20 mmol/L ammonium acetate and 0.1% formic acid in water) and mobile phase B (acetonitrile) produced the best separation. In blood, tiletamine showed good linearity from 0.1-200 ng/mL (r=0.992, R²=0.983), LOD 0.03 ng/mL, LOQ 0.1 ng/mL, recovery 92%-107%, and matrix effect 71%-99%. In liver and kidney, recoveries were 91%-98% and 93%-104%, and matrix effects were 69%-96% and 72%-100%, respectively. Intra- and inter-day precision [expressed as relative standard deviation (RSD)] and accuracy [expressed as relative error (RE)] were within 15%, and samples were stable at -20 ℃. Tiletamine was detected in actual case samples at 0.37 μg/mL (blood), 0.15 μg/g (liver), 0.11 μg/g (kidney) in case 1, and 8.75 ng/mL (blood) in case 2; desethyltiletamine was also detected in blood. CONCLUSIONS The UPLC-MS/MS method is efficient, accurate, and sensitive, and is suitable for detecting tiletamine and desethyltiletamine in human biological samples.
Tandem Mass Spectrometry/methods* ; Humans ; Chromatography, High Pressure Liquid/methods* ; Substance Abuse Detection/methods* ; Liquid Chromatography-Mass Spectrometry

OBJECTIVE: To observe the clinical efficacy of Qihuang needle therapy for autism spectrum disorder (ASD) children with sleep disorder. METHODS: A total of 60 ASD children with sleep disorder were randomly divided into an observation group and a control group, 30 cases in each group. Both groups were treated with structured education intervention, 60 min each time, once a day, 6 times a week. Qihuang needle therapy was applied at Yintang (GV24⁺), Baihui (GV20) and bilateral Jueyinshu (BL14), Xinshu (BL15) in the observation group, multi-direction needling was delivered and without needle retaining. The treatment was given 2 times a week, each treatment was delivered at interval of 2 days at least. Behavioral intervention was adopted in the control group. Treatment for consecutive 12 weeks was required in both groups. Before and after treatment, the scores of children's sleep habits questionnaire (CSHQ), the autism behavior checklist (ABC), the childhood autism rating scale (CARS), and the childhood autism behavior scale (CABS) were observed in the two groups. RESULTS: After treatment, the scores of CSHQ, ABC, CARS and CABS were decreased compared with those before treatment (P<0.01), and the above scores in the observation group were lower than those in the control group (P<0.05). CONCLUSION Qihuang needle therapy can effectively treat ASD with sleep disorder, improve the core symptoms of ASD and the sleep quality.
Humans ; Autism Spectrum Disorder/physiopathology* ; Male ; Female ; Child ; Sleep Wake Disorders/physiopathology* ; Child, Preschool ; Acupuncture Therapy ; Acupuncture Points ; Treatment Outcome ; Sleep ; Needles

Objective:To investigate the impact of peripheral blood prolymphocyte percentage on the prognosis of patients with chronic lymphocytic leukemia (CLL) .Methods:This study included 300 patients diagnosed with CLL at the Department of Hematology of Jiangsu Provincial People’s Hospital from October 2011 to December 2020. The association between prolymphocyte percentage and other parameters was analyzed, and the optimal cutoff prolymphocyte percentage was determined by X-tile analysis. Further survival analysis and prognostic model construction were used to validate the predictive value of prolymphocyte percentage.Results:Of the 300 eligible patients with CLL who were enrolled, 50 received Bruton tyrosine kinase inhibitors (BTKi) as first-line treatment. The group with higher prolymphocyte percentage comprised more patients in the advanced stages ( P=0.010) and had higher β 2-microglobulin ( P<0.001), unmutated immunoglobulin heavy-chain variable region gene ( P<0.001), and TP53 aberration ( P=0.004). The optimal cutoff percentage of prolymphocytes was 1%. Patients with a prolymphocyte percentage >1% had significantly shorter treatment-free survival (TFS) ( P<0.001) and overall survival time ( P=0.007) than patients with a prolymphocyte percentage ≤1%. On multivariate analysis, prolymphocyte percentage >1% tended to have an independent prognostic value for TFS [ HR=1.405 (95% CI 0.971~2.032), P=0.071]. Compared with the nomogram of CLL international prognostic index (CLL-IPI) alone, the nomogram of CLL-IPI combined with prolymphocyte percentage showed better discrimination (area under the curve: 0.778 vs. 0.637; P=0.006). In addition, patients with a prolymphocyte percentage >1% were more likely to progress after BTKi treatment ( P=0.038) . Conclusion:Peripheral blood prolymphocyte percentage was associated with various clinical and biological parameters and prognosis among patients with treatment-naive CLL.

Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe₃O₄ loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4⁺/CD8⁺ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.

This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

Objective:To establish a quantitative diagnostic standard for Crohn's disease with dampness syndrome based on clinical data using a disease syndrome combination model and conduct bidirectional validation.Methods:256 patients with Crohn's disease from the Department of Spleen and Stomach Diseases at Guangdong Provincial Hospital of Chinese Medicine, the Department of Gastroenterology at the Sixth Affiliated Hospital of Sun Yat-sen University, and the Outpatient Department of Guangdong Provincial Hospital of Chinese Medicine from October 2021 to January 2022 were selected as the observation objects. They were divided into an operation group of 205 patients and a verification group of 51 patients in an 8:2 ratio using a random number table method. The frequency advantage method, χ2 test, and binary logistic regression analysis were used to screen for relevant standard factors. The conditional probability method was used to assign scores to relevant items, and the maximum likelihood method was used to determine the quantitative diagnostic threshold. A quantitative diagnostic standard for Crohn's disease with dampness syndrome based on disease syndrome combination was established, and it was retrospectively analyzed and prospectively verified. Results:On the basis of the 20 candidate quantitative diagnostic criteria items for Crohn's disease dampness syndrome, binary logistic regression analysis was performed to calculate the OR values between each item. The quantitative diagnostic criteria for Crohn's disease with dampness syndrome included tongue coating greasiness (7 points), body heaviness (13 points), waist and knee soreness (8 points), head weight (9 points), bland mouth (6 points), anal heaviness (8 points), uncomfortable bowel movements (8 points), and sticky stools (7 points), with a quantitative diagnostic threshold of 11. Conclusion:The scoring of relevant items in the quantitative diagnostic criteria for Crohn's disease with dampness syndrome is reasonable and has good diagnostic value, which can provide reference for further quantitative research on Crohn's disease syndromes.

Addressing the challenge of traditional physical/semi physical simulation methods being difficult to achieve full process and full element simulation of extravehicular activities,virtual reality technology is utilized to break through the limitations of physical environments and establish a virtual reality simulation system for extravehicular activities.Based on the application characteristics of space station extravehicular activity engineering,with the goal of improving system practicality and usability,integrating the visual immersion of virtual images,the ontology of real operation,and the consistency of virtual and real space perception,a three-dimensional scene simulation,multi-mode joystick interaction paradigm,continuous operation actions simulation of extravehicular operations,and interactive operation virtual/real space consistency method that were proposed and designed for the realistic visual perception and extravehicular operation.The system has been successfully applied to astronaut training,program validation,joint exercise,and flight control support for sixteen extravehicular activities from SZ-12 to SZ-18.The results showed that the complete reproduction of the static/dynamic realistic comprehensive scene was achieved on the ground for the human-machine operation in the entire process of extravehicular activity,and the system is an essential and important means of ground simulation for extravehicular activity.

This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Nav1.7,Nay1.8,and Nay1.9 and Kv7 channels,a crucial regulator in controlling NP symptoms.The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP.Through an experimental design involving both in vitro and in vivo methods,E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury(CCI)mouse model.The results demonstrated that E0199 significantly inhibited Nav1.7,Nav1.8,and Nav1.9 channels with a particularly low half maximal inhibitory concentration(ICs0)for Nay1.9 by promoting sodium channel inactivation,and also effectively increased Kv7.2/73,Kv7.2,and Kv7.5 channels,excluding Kv7.1 by promoting potassium channel acti-vation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alle-viated pain hypersensitivity in mice at low doses,indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically.The safety of E0199 was supported by neurobehavioral evaluations.Conclusively,E0199 represents a ground-breaking approach in NP treatment,showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe thera-peutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.

Objective To study the influence of stent and balloon shape on hemodynamics in tapered vessels with multiple stenosis.Methods The hemodynamic model was established after the implantation of vascular stent in tapered vessel with multiple stenosis.The numerical simulation method was used to study the effect of the combination of different shaped stents and balloons on postoperative hemodynamics.Results When the cylindrical stent was expanded using the cylindrical balloon and tapered balloon respectively,compared with cylindrical balloon expansion,the proportion of low-speed blood flow area generated by tapered balloon expansion was reduced by 0.58％,and the proportion of low time-averaged wall shear stress(TAWSS)area was reduced by 3.22％.The use of tapered balloon for expansion could produce less low-speed blood flow and low TAWSS area.When tapered balloon was used to expand the cylindrical stent and tapered stent respectively,compared with expanding tapered stent,the proportion of low-speed blood flow area generated by expanding cylindrical stent decreased by 1.35％,and the proportion of low TAWSS area decreased by 9.73％.Conclusions The hemodynamic environment of tapered vessel with multiple stenosis was influenced by the shape of stent and balloon.The use of tapered balloon to expand the cylindrical stent in tapered vessels with multiple stenosis can achieve favorable hemodynamic environment and reduce the risk of ISR occurence.This study can provide a scientific basis for the rational formulation of clinical intervention scheme.

Objective:To explore the application value of part-cut jejunal transection in digestive tract reconstruction of totally laparoscopic total gastrectomy.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 112 patients with gastric cancer who underwent totally laparoscopic total gastrectomy in The Second Affiliated Hospital of Anhui Medical University from June 2018 to September 2022 were collected. There were 81 males and 31 females, aged (70±8)years. Among the 112 patients, 60 patients undergoing diges-tive tract reconstruction by Roux-en-Y anastomosis with part-cut jejunum were set as the part-cut group, and 52 patients undergoing digestive tract reconstruction by traditional Roux-en-Y anasto-mosis were set as the traditional group. Observation indicators: (1) propensity score matching status and comparison of clinical data of patients between the two groups after matching; (2) intraopera-tive and postoperative conditions; (3) follow-up. Comparison of measurement data with normal dis-tribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Com-parison of ordinal data was conducted using the nonparametic rank sum test. Propensity score matching was performed using the 1∶1 nearest neighbor matching method, with the caliper value of 0.02. Results:(1) Propensity score matching status and comparison of clinical data of patients between the two groups after matching. Of the 112 patients, 90 patients were successfully matched, with 45 cases in each of the part-cut group and the traditional group. After propensity score matching, the elimination of body mass index, clinical TNM staging confounding bias ensured comparability. (2) Intraoperative and postoperative conditions. After propensity score matching, the total operation time and digestive tract reconstruction time of patients in the part-cut group were (217.0±15.1)minutes and (34.7±1.8)minutes, versus (252.6±21.9)minutes and (52.6±7.4)minutes in the traditional group, respectively, showing significant differences in the above indicators between the two groups ( t=?8.97, ?15.66, P<0.05). (3) Follow-up. After propensity score matching, 90 patients were followed up postoperatively for (47±15)months. During the follow-up, no patient in either group received secondary surgery, and there was no death. There were 3 cases and 10 cases of Roux stasis syndrome in the part-cut group and the traditional group, respectively, showing a significant difference between the two groups ( χ2=4.41, P<0.05). Conclusion:Compared with traditional Roux-en-Y anastomosis, the Roux-en-Y anastomosis with part-cut jejunum in totally laparoscopic total gastrectomy can signifi-cantly shorten the time for digestive tract reconstruction and reduce the incidence of postoperative Roux stasis syndrome.