Targeted covalent inhibitors, primarily targeting cysteine residues, have attracted great attention as potential drug candidates due to good potency and prolonged duration of action. However, their discovery is challenging. In this research, a database-assisted liquid chromatography-tandem mass spectrometry (LC-MS/MS) strategy was developed to quickly discover potential cysteine-targeting compounds. First, compounds with potential reactive groups were selected and incubated with N-acetyl-cysteine in microsomes. And the precursor ions of possible cysteine-adducts were predicted based on covalent binding mechanisms to establish in-house database. Second, substrate-independent product ions produced from N-acetyl-cysteine moiety were selected. Third, multiple reaction monitoring scan was conducted to achieve sensitive screening for cysteine-targeting compounds. This strategy showed broad applicability, and covalent compounds with diverse structures were screened out, offering structural resources for covalent inhibitors development. Moreover, the screened compounds, norketamine and hydroxynorketamine, could modify synaptic transmission-related proteins in vivo, indicating their potential as covalent inhibitors. This experimental-based screening strategy provides a quick and reliable guidance for the design and discovery of covalent inhibitors.

Objective To analyze the trajectory categories of fatigue development in middle-aged and elderly stroke patients and explore its influencing factors. Methods A convenient sampling method was used to select 230 middle-aged and elderly stroke patients in the Luzhou People's Hospital from January 2021 to January 2023 as the research subjects. A self-compiled general information-questionnaire, the Fatigue Severity Scale (FSS), the Pittsburgh Sleep Quality Index (PSQI), and the Beck Depression Inventory (BDI) were used to investigate the sociodemographic and clinical data, fatigue, sleep quality, and depression status of patients at 2 days after admission and 3 and 6 months after discharge. The latent growth curve model was used to fit the categories and trajectories of fatigue development, and the unordered multinomial Logistic regression model was used to analyze the influencing factors of trajectory categories of fatigue development. Results The fatigue development trajectory of middle-aged and elderly stroke patients showed three potential categories, namely the low-level fatigue stability group (33.04%), the medium-level fatigue rapid aggravation group (42.17%), and the high-level fatigue slow aggravation group (24.79%). The results of unordered multinomial Logistic regression analysis showed that age, marital status, education level, disease severity, the Activity of Daily Living (ADL) score, PSQI score, and BDI score were the influencing factors of fatigue development trajectory in middle-aged and elderly stroke patients (all P < 0.05). Conclusion The fatigue development trajectory of middle-aged and elderly stroke patients is heterogeneous. Nurses should understand the evolution characteristics of fatigue in different patients and implement targeted management measures according to patients'symptoms to improve their health outcomes.

Objective:To systematically review the teaching effect of problem-based learning (PBL) combined with evidence-based medicine (EBM) teaching mode on the standardized residency training.Methods:CNKI, Wanfang database, VIP database, SinoMed, Embase, PubMed and Web of SCI databases were searched, and the randomized controlled trial (RCT) studies of the application of EBM combined with PBL teaching in standardized residency training were collected. The retrieval time was from the establishment to 1st July, 2018. Two investigators independently extracted data and assessed the quality of the studies. After assessing the risk of bias of included studies, Meta-analysis was performed on RevMan 5.3.Results:In total, 4 studies were included in the review. Narrative assessment was adopted, because outcome indicators of these study were varied and the quality of the literatures could not meet the requirement of Meta-analysis. Our study suggested that the residents who were in PBL combined with EBM teaching mode group got higher scores in the standardized residency training, compared with those in the lecture-based learning (LBL) teaching mode group, especially in case analysis score, total score of examination, improvement of clinical thinking ability, communication and expression ability, organization and cooperation ability, etc.Conclusion:The current evidence suggests that the application of EBM combined with PBL teaching mode has a positive effect on the standardized residency training. Compared with the traditional LBL teaching, EBM can improve students' ability. However, limited by the quantity and quality of included studies, the above conclusions still need to be verified by more studies with larger samples and higher quality.

OBJECTIVE: To investigate the complications of tourniquet in the clinical application of lower tibiofibular fracture. METHODS: From June 2018 to September 2019, 33 cases of closed lower tibiofibular fractures (AO type 43A) were treated with plates and screws and were divided into two groups according to whether pueumatic tourniquet was used:16 cases in the observation group, 13 males and 3 females, aged 18 to 69 (38.8±17.0) years, the operation time after injury was (6.9±1.7) days, and tourniquet was not used during operation. There were 17 cases in the control group, 13 males and 4 females, aged from 21 to 71 (43.8±12.4) years, the operation time after injury was (6.5±1.0) days, automatic pneumatic tourniquetwas routinely used in the operation. The operation time, blood loss, postoperative swelling, pain and other complications were compared between two groups. RESULTS: Total of 33 patients were followed up for an average of 15 months. There was no significant difference in operation time and blood loss between two groups ( CONCLUSION The fracture of lower tibiofibular segment is superficial and easy to be exposed and fixed during operation. In order to avoid tourniquet complications, it is not recommended to use air bag tourniquet routinely or minimize the application time of tourniquet.
Adolescent ; Adult ; Aged ; Female ; Fracture Fixation, Internal ; Fractures, Bone/surgery* ; Humans ; Male ; Middle Aged ; Operative Time ; Retrospective Studies ; Tourniquets ; Treatment Outcome ; Young Adult

Objective:To investigate the multilocus sequence typing feature of the virulence-associated genes of Staphylococcus aureus(S. aureus) separated from the clinical specimens of a multi-center cohort children in Guangzhou area. Methods:A total number of 412 Staphylococcus aureus strains isolated from 2 059 non-repeated fecal specimens of children by three groups′ researchers in Guangzhou Women and Children′s Medical Center from August 2018 to November 2018. While collecting specimens, patient clinical information is also properly collected and preserved. After extracting the DNA of the strain, the virulence-associated genes were detected by polymerase chain reaction (PCR), including the staphylococcal enterotoxin (SE) genes ( sea, seb, sec, sed, see) and the Panton-Valentine leucocidin-encoding gene ( pvl).The multi-locus sequence typing (MLST) method was performed to reveal the MLST feature of these genes and the statistical difference were examined by the the χ 2 test. Results:Among the 412 isolates of S. aureus, 256 strains (256/412, 62.1%) contains at least one SE gene. Among the enterotoxin gens, the sec (125/412, 30.3%), seb(98/412, 23.8%)and sea (66/412, 16.0%)genes were the three most prevalent members of SEs. The frequency of pvl gene in Staphylococcus aureus was 18.7%(77/412).Among them, the frequency of Staphylococcus aureus sea gene isolated from patients with gastroenteritis (58/319, 18.2%) was significantly higher than that from the non-gastroenteritis group (8/93, 8.6%)(χ2=4.912, P=0.027). The frequency of Staphylococcus aureus pvl gene isolated from the patients with pneumonia (8/21, 38.1%) was greater than that from the non-pneumonia group (6/47, 12.8%)(χ2=4.252, P=0.039). In addition, the virulence-associated gene of S. aureus was closely related to the specific ST type, 82.4% (28/34) of ST6 carried sea gene, all ST338 and ST59 carried seb gene, 96% (48/50) ST45 carried sec gene, and the pvl gene carrying rate of ST338 was 5/5. Conclusions:The SEA toxin produced by ST6 Staphylococcus aureus may be closely related to the diagnosis of gastroenteritis in children. The frequency of pvl virulence gene in Staphylococcus aureus in children with community-acquired pneumonia was higher than that in the non-pneumonia group, and closely related to the CC59.

Objective To investigate the diet-related influencing factors in patients with gallbladder stone. Methods Forty patients with gallbladder stone who were admitted to the Third Affiliated Hospital of Sun Yat-sen University between July 2015 and September 2015 were enrolled in this prospective study, as the stone group. Another 40 healthy people were selected as the control group. The informed consents of patients in two groups were obtained and the local ethical committee approval was received. A cross-sectional survey was conducted to compare the baseline data, body mass index, serum lipid level, dietary composition, living habit and dietary intake between two groups. Normally-distributed data of two groups were compared by t test, and the rates were compared by Chi-square test or Fisher's exact probability test. Results A majority of patients in the stone group were farmers with junior education background, living in rural areas. The high-density lipoprotein cholesterol (HDL-C) level in the stone group was (1.1±0.3) mmol/L, significantly lower than (1.4±0.4) mmol/L in the control group (t= -3.616, P<0.05). The apolipoprotein A (apoA) level in the stone group was (1.27±0.16) g/L, significantly higher than (1.09±0.27) g/L in the control group (t=2.947, P<0.05). The percentage of eating fat pork in the stone group was 80% (32/40), significantly higher than 35% (14/40) in the control group (χ2=8.286, P<0.05). The percentage of eating cereals and dairy products in the stone group was respectively 10% (4/40) and 20% (8/40), significantly lower than 80% (32/40) and 90% (36/40) in the control group (χ2=19.789, 19.789; P<0.05). There were significant differences in the preference for fatty diet, dietary composition, drinking habit, breakfast habit, eating habit, smoking habit, hand-washing habit and exercise time between two groups (P<0.05). The daily intake of water, dairy products and fruits in the stone group was respectively (743±379) ml, (33±4) g and (128±39) g, significantly less than (1 410±406) ml, (233±88) g and (275±43) g in the control group (t=-5.373, -7.790, -3.293; P<0.05). The daily intake of poultry and edible oil in the stone group was respectively (112±35) and (43±12) g, significantly higher than (21±8) and (22±9) g in the control group (t=4.706, 8.854; P<0.05). Conclusions Lack of diet-related knowledge, high-fat and low-protein diet, irregular eating habit, insufficient drinking water and lack of exercise may probably be correlated with the incidence of gallbladder stone.

Objective To investigate effect of decorin on proliferation and cell cycle of rabbit tendon cells in vitro so as to explore the role of decorin in tendon wound healing.Methods Tendon cells derived from the tissue of rabbits flexor tendon were harvested and cultured in vitro with decorin of 0.25,1.25,2.5,5 ?g/ml.After culture of 12,24 or 48 h,the cell proliferation rate was measured by MTT colorimetric determination.After 24-hour culture with 0.25?g/ml decorin,the morphology of tendon cells was obtained and the cell cycle distribution was detected by flow cytometer.Results The proliferation of tendon cells was inhibited after 12-hour culture and significantly increased after 24-hour culture with 0.25,1.25,2.5 ?g/ml decorin.However,5 ?g/ml decorin could increase the proliferation after 12-hour culture,increase after 24-hour culture,with no significant difference between 24 h and 48 h.decorin at 0.25 ?g/ml could significantly increase the cells at S phase and PI after 24-hour culture(P

OBJECTIVE:To establish a method for determining the contents of spironolactone chloramphenicol and metromidazole in Mianchi gel.METHODS:The concentrations of three main ingredients were determined by multiwavelengh coefficient spectrophotometry,the detecting wavelenghs being 239.0nm,276.0nm and 313.5nm respectively.RESULTS:The average recoveries and RSDs(n=5)were:spironolactone 99.5%,RSD=3.02%,chloramphenicol 101.61%,RSD=1.47%,metromidazole 101.47%,RSD=2.00%.CONCLUSION:This method is simple,rapid and accurate.It is good for determination of multicomponent preparation.

Objective To observe the curative effect of rhG-CSF or rhG-CSF+rhSCF mobilized peripheral blood stem cells (PBSC) on rhesus monkeys after irradiation of 7.0Gy ? ray.MethodsFifteen healthy adult rhesus monkeys were divided into placebo control, rhG-CSF, and rhG-CSF+rhSCF mobilized groups. rhSCF 20?g?kg -1 ?d -1 (?KD) was administered for 8 consecutive days. Then from the 4th day to the 8th day, animals of both rhG-CSF and rhG-CSF+rhSCF mobilized groups were also given rhG-CSF 10?KD. The placebo control animals were given 0.9% sodium chloride of the same volume per kilogram. On day 0 of the irradiation, PBSCs were collected from all subjects. 3～4 hrs after irradiation, all animals received autologous PBSC infusion. ResultsFrom day 21 to day 29 after TBI, rhG-CSF+rhSCF mobilized group showed higher WBC counts compared to placebo control and rhG-CSF mobilized group. Platelet counts of both mobilized groups recovered more quickly than those of placebo control. Bone marrow nucleated cells culture demonstrated that rhG-CSF and rhG-CSF+rhSCF mobilized PBSC had stimulated bone marrow nucleated cells to form more CFUs. Histopathological evaluation showed the number of hematopoietic cells in the bone marrow of rhG-CSF mobilized group was greater than those in placebo control but less than those in rhG-CSF+rhSCF mobilized group. ConclusionThe infusion of rhG-CSF or rhG-CSF+rhSCF mobilized PBSC can improve the hematopoietic recovery in rhesus monkeys after 7.0Gy ? ray irradiation. The combined use of two mobilizing factors gives better result than using single factor.