BackgroundObsessive-compulsive disorder （OCD） is a common neuropsychiatric illness and is listed as one of the top ten disabling conditions causing loss of income and reduced quality of life. Psychological distress is an important cause of anhedonia in OCD patients， and is closely related to psychosomatic symptoms. Therefore， exploring the role of anhedonia in the relationship between psychological distress and psychosomatic symptoms is of great significance for optimizing clinical psychological treatment protocols for OCD patients. ObjectiveTo explore the role of anhedonia in the relationship between psychological distress and psychosomatic symptoms in OCD patients， with the aim of providing references for managing psychosomatic symptoms in patients. MethodsA total of 90 patients who met the diagnostic criteria for OCD according to the International Classification of Diseases， tenth edition （ICD-10）， and who visited the Mental Health Center outpatient clinic of General Hospital of Ningxia Medical University from September 2023 to November 2024 were selected as the study objects. The instruments and techniques used for the evaluation were： Dimensional Anhedonia Rating Scale （DARS）， 10-item Kessler Psychological Distress Scale （K10） and Psychosomatic Symptom Scale （PSSS）. Model 4 of the Process for SPSS 26.0 was used to test the mediating role of anhedonia in the relationship between psychological distress and psychosomatic symptoms， with Bootstrapping used to assess the significance of mediating effect. ResultsA total of 84 patients （93.33%） completed the valid questionnaire. K10 score was positively correlated with PSSS total score， psychological symptom score and physical symptom score （r=0.559， 0.460， 0.551， P<0.01）. K10 score was negatively correlated with DARS total score （r=-0.527， P<0.01）. The total score of DARS was negatively correlated with PSSS total score （r=-0.497， P<0.01）. Anhedonia mediated the relationship between psychological distress and psychosomatic symptoms， with an indirect effect value was 0.148 （95% CI： 0.042~0.278）， accounting for 26.48% of the total effect. ConclusionPsychological distress can affect the psychosomatic symptoms in OCD patients both directly and indirectly via anhedonia.

OBJECTIVE: To screen the optimal regimen of acupuncture and moxibustion for obstructive sleep apnea hypopnea syndrome (OSAHS), so as to provide the evidences for clinical decision-making. METHODS: From 7 databases in Chinese and English i.e. the Full-Text Database of China Journal Network (CNKI), Wanfang Data Knowledge Service Platform (Wanfang), VIP Information Chinese Journal Service Platform (VIP), Chinese Biomedical Literature Database (SinoMed), PubMed, Web of Science (WOS) and Cochrane Library, randomized controlled trial (RCT) articals of OSAHS treated with acupuncture and moxibustion were searched. The quality of evidence was evaluated with the modified Jadad scale, the evaluation index was established and the optimal regimen of acupuncture and moxibustion for OSAHS was screened by multi-index decision analysis. RESULTS: A total of 10 RCTs were included, and the filiform needling therapy was optimal in treatment of OSAHS. The acupoints included Lianquan (CV23), Danzhong (CV17), Zhongwan (CV12), and bilateral Kongzui (LU6), Pishu (BL20), Fenglong (ST40), Zusanli (ST36), Yinlingquan (SP9) and Zhaohai (KI6). Zusanli (ST36) received the reinforcing method, Pishu (BL20) and Fenglong (ST40) were stimulated with the reducing technique, and the rest acupoints with the uniform reinforcing-reducing. Each acupoint was manually manipulated once every 10 min during the needle retention for 30 min. Acupuncture was delivered once a day, 5 times a week and for consecutive 4 weeks. Among the included literature, the severity of disease was not reported in detail, the filiform needling was the dominant intervention, the local acupoints such as Lianquan (CV23) and Panglianquan (Extra) were mainly selected. The apnea-hypopnea index and the minimum oxygen saturation were taken as the evaluation indexes, and the effect was evaluated in reference to the generally accepted standards. The attention to safety evaluation was insufficient, the report on methodology was not adequate and the quality was low. CONCLUSION Filiform needling is the dominant therapy of acupuncture and moxibustion for OSAHS, and the local acupoints are considered specially. But the quality of clinical research should be improved.
Humans ; Moxibustion ; Acupuncture Therapy ; Sleep Apnea, Obstructive/therapy* ; Acupuncture Points ; Randomized Controlled Trials as Topic

Gene therapy, harnessing the power of CRISPR-Cas9 and/or DNAzyme systems, stands as a pivotal approach in cancer therapy, enabling the meticulous manipulation of genes pivotal to tumorigenesis and immunity. However, the pursuit of precise gene therapy encounters formidable hurdles. Herein, a near-infrared upconversion theranostic nanomachine is devised and tailors for CRISPR-Cas9/DNAzyme systems mediate precise gene therapy. An ingenious logic DNAzyme system consists of Chain 1 (C1)/Chain 2 (C2) and endogenous lncRNA is designed. We employ manganese modified upconversion nanoparticles for carrying ultraviolet-responsive C1-PC linker-C2 (C₂P) chain and Cas9 ribonucleoprotein (RNP), with outermost coats with hyaluronic acid. Upon reaching tumor microenvironment (TME), the released Mn²⁺ ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS-STING signaling, and enabling T1-magnetic resonance imaging. Under near-infrared irradiation, Cas9 RNP/C₂P complex dissociates, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing. This strategy remodels the TME by activating cGAS-STING signaling and dual immune checkpoints blockade, thus realizing tumor elimination. Our theranostic nanomachine armed with the CRISPR-Cas9/DNAzyme logic systems, represents a resourceful and promising strategy for advancing cancer systemic immunotherapy and precise gene therapy.

Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy (SAE). OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury. However, its regulatory function in microglial pyroptosis and involvement in SAE remains unclear. In this study, we demonstrated that OGT deficiency augmented microglial pyroptosis and exacerbated secondary neuronal injury. Furthermore, OGT inhibition impaired cognitive function in healthy mice and accelerated the progression in SAE mice. Mechanistically, OGT-mediated O-GlcNAcylation of ATF2 at Ser44 inhibited its phosphorylation and nuclear translocation, thereby amplifying NLRP3 inflammasome activation and promoting inflammatory cytokine production in microglia in response to LPS/Nigericin stimulation. In conclusion, this study uncovers the critical role of OGT-mediated O-GlcNAcylation in modulating microglial activity through the regulation of ATF2 and thus protects against SAE progression.
Animals ; Microglia/metabolism* ; Pyroptosis/physiology* ; Mice ; Sepsis-Associated Encephalopathy/prevention & control* ; Activating Transcription Factor 2/metabolism* ; N-Acetylglucosaminyltransferases/genetics* ; Mice, Inbred C57BL ; Male ; Mice, Knockout

Objective To observe the value of gastrointestinal ultrasound contrast agents for evaluating gastric emptying status in patients with superior mesenteric artery syndrome(SMAS).Methods Gastrointestinal ultrasound was prospectively performed in 30 SMAS patients(SMAS group)and 24 healthy subjects(control group).The diameter of proximal duodenum(D),the maximum diameter of duodenum at the angle between superior mesenteric artery and abdominal aorta(d),as well as the degree of duodenum compression(D-d/D)were measured after gastrointestinal contrast agents passing through immediately.Gastric residual volume(GRV)at 5 min(T0),30 min(T1),60 min(T2),90 min(T3)and 120 min(T4)after taking contrast agent were recorded,and the ratio of T1-T4 GRV to T0 GRV(GRV1-GRV4)were calculated and compared between groups.Pearson correlation analysis was performed to explore the correlation of(D-d)/D with GRV1-GRV4 in SMAS patients.Results D,(D-d)/D,GRV1,GRV2,GRV3 and GRV4 in SMAS group were all higher,while d in SMAS group was lower than those in control group(all P＜0.05).(D-d)/D in SMAS patients was moderately and positively correlated with GRV4(r=0.509,P=0.007),but not significantly correlated with GRV1-GRV3(all P＞0.05).Conclusion Gastrointestinal ultrasound contrast agents could be used to real-time dynamically observe gastric emptying status in patients with SMAS and quantitatively analyze GRV.

Objective:To explore the clinical value of synovial fluid calprotectin for the diagnosis of periprosthetic joint infection (PJI).Methods:Based on prospective cohort study design, a total of 82 patients suspected of PJI after hip and knee arthroplasty in the First Medical Center of the PLA General Hospital from July 2021 to June 2022 were selected. Patients were divided into infection group (PJI, n=39) and non-infection group (non-PJI, n=43) according to the diagnostic criteria proposed by the Second International Consensus Conference in 2018. The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used for double-blind detection of calprotectin and internal reference standard (IRS) in synovial fluid of patients. The peaks of target protein and IRS were recorded for further analysis. Mann-Whitney U test was used to compare the concentrations of S100A8 and S100A9 between the two groups, and receiver operating characteristic curve (ROC) was used to analyze the diagnostic efficacy of S100A8 and S100A9 for PJI. Results:Calprotectin was detected as monomers S100A8 and S100A9. Synovial fluid S100A8 was significantly higher in the PJI group than that in the non-PJI group [1.57 (0.48, 4.17) vs 0.00 (0.00, 0.05), Z=?7.221, P<0.05]. Synovial fluid S100A9 was also significantly higher in the PJI group than that in the non-PJI group [0.74 (0.29, 1.70) vs 0.06 (0.00, 0.10), Z=?6.255, P<0.05]. When using S100A8 and S100A9 to diagnose PJI, the sensitivity were 97.4% and 87.2%, the specificity were 86.0% and 88.4%, and the area under the ROC were 0.964 (95% CI 0.929-0.998) and 0.902 (95% CI 0.924-0.996), respectively. Conclusion:The detection of synovial fluid S100A8 and S100A9 by MALDI-TOF MS can make a satisfactory diagnosis for PJI.

Liquid band-aid is a new type of wound dressing that has emerged in recent years. Compared with traditional band-aid, it has the advantages of convenient use, natural shedding, good waterproof and breathable effect, and easy fitting for irregular wounds. It has brought a great convenience to the wound treatment in our daily life. This paper reviews the current research status of liquid band-aids at home and abroad and summarizes the research progress on film forming materials for liquid band-aids with the purpose to provide references for the further development and improvement of liquid band-aids.

Objective To avoid the accumulation of copper sulfide (CuS) nanoparticles, prepare and optimize CuS nanoparticles, analyze the factors affecting the particle size and evaluate their photothermal properties. Methods Based on the single factor study, central composite design-response surface methodology was used to optimize the CuS nanoparticle formulation process. The morphology, particle size stability, photothermal conversion efficiency, photothermal stability of optimized CuS nanoparticles were characterized. The toxicity of CuS nanoparticles on 4T1 breast cancer cells and HK2 kidney cells was evaluated by CCK-8 method. In vitro photothermal experiment was used to investigate the ability of CuS nanoparticles on killing 4T1 breast cancer cells. Results The average hydration dynamic diameter of optimized CuS nanoparticles was (10.53±1.63)nm, the actual particle size of CuS nanoparticles showed by TEM image was (3.10±0.81)nm. It had good particle size stability, good photothermal conversion efficiency and photothermal stability. Within the concentration range of 100 μg/ml and 150 μg/ml，it showed no significant toxicity on 4T1 breast cancer cells and HK2 kidney cells, indicating the good stability of CuS nanoparticles. In vitro photothermal therapy showed that CuS nanoparticles had good ability to kill 4T1 breast cancer cells by photothermal. Conclusion The prepared CuS nanoparticles have a small particle size (less than 6nm) and a good photothermal effect, which is expected to solve the problem of CuS nanoparticles accumulation in vivo and make it better for tumor treatment.

Objective To evaluate the effects of different solubilizing techniques on the in vitro dissolution and in vivo pharmacokinetics of Sirolimus (SRL). Methods Solid dispersions (SD), inclusion complex (IC), self-micro emulsifying drug delivery system (SMEDDS) and nano-structured lipid carrier (NLC) were selected as the solubilization technology for SRL. SRL-SMEDDS and SRL-NLC have obtained the optimal prescription in the previous studies. Additionally, the formulation process of SRL-SD and SRL-IC was screened by using inclusion rate and dissolution profiles as indicators. 0.4% SDS, water and buffer solutions with pH 1.2, 4.5, 6.8, 7.4 were used as dissolution media. The dissolution profile of the commercially available formulation Rapamune^® and the lab-made solubilized preparations were investigated. The in vivo absorption of the above preparations was examined using a pharmacokinetic test in Beagle dogs. Results In 0.4% SDS, the dissolution of each preparation exceeded 80% in 2 h. In the medium of pH 1.2, the dissolution of SRL-SD could not be measured while the dissolution of IC, SMEDDS and NLC increased first and then decreased. In other media, the dissolution of the SRL was reduced. The SRL-IC showed the best dissolution without a significant decrease. The relative bioavailability of APIs, SRL-SD, SRL-IC, SRL-NLC and SRL-SMEDDS were 9.1%, 18.7%, 33.2%, 78.0%, and 97.6% respectively in vivo pharmacokinetic tests. Conclusion SD, SMEDDS, NLC, and IC can improve the in vitro dissolution and in vivo absorption of SRL. Among them, SMEDDS has the most significant improvement in the bioavailability of SRL.

Chloroquine (CQ) phosphate has been suggested to be clinically effective in the treatment of coronavirus disease 2019 (COVID-19). To develop a physiologically-based pharmacokinetic (PBPK) model for predicting tissue distribution of CQ and apply it to optimize dosage regimens, a PBPK model, with parameterization of drug distribution extrapolated from animal data, was developed to predict human tissue distribution of CQ. The physiological characteristics of time-dependent accumulation was mimicked through an active transport mechanism. Several dosing regimens were proposed based on PBPK simulation combined with known clinical exposure-response relationships. The model was also validated by clinical data from Chinese patients with COVID-19. The novel PBPK model allows in-depth description of the pharmacokinetics of CQ in several key organs (lung, heart, liver, and kidney), and was applied to design dosing strategies in patients with acute COVID-19 (Day 1: 750 mg BID, Days 2-5: 500 mg BID, CQ phosphate), patients with moderate COVID-19 (Day 1: 750 mg and 500 mg, Days 2-3: 500 mg BID, Days 4-5: 250 mg BID, CQ phosphate), and other vulnerable populations (.., renal and hepatic impairment and elderly patients, Days 1-5: 250 mg BID, CQ phosphate). A PBPK model of CQ was successfully developed to optimize dosage regimens for patients with COVID-19.