Metabolomics-based study on the improvement mechanism of the Mongolian drug Sugemule-4 on insomnia rats / 中国药房

OBJECTIVE To study the effects of the Mongolian medicine Sugemule-4 on the metabolism of insomnia rats， and to preliminarily explore its possible mechanisms for improving insomnia. METHODS The rat model of chronic stress insomnia was established by tail clipping stimulation and intraperitoneal injection of p-chlorophenyl alanine solution. Twenty-four male rats were randomly divided into the normal group， model group， diazepam group （positive control， 0.92 mg/kg）， and Sugemule-4 group （5.2 g/kg）， with 6 rats in each group. Since the 7th day of tail clipping stimulation， the Sugemule-4 group and diazepam group began to be intragastrically administered with relevant medicine； the normal group and model group were intragastrically administered with an equal volume of distilled water， once a day， for 14 consecutive days. The learning and memory abilities of rats were tested using a water maze experiment， and the non-invasive sleep activity monitoring system was used to monitor the 24- hour sleep time of rats. A metabolomics study was conducted on rat serum and hippocampal tissue by using ultra-high-performance liquid chromatography-tandem mass spectrometry. The multivariate statistical analysis method was adopted to analyze the differential metabolites in serum and hippocampal tissue of rats， and screen for differential metabolites and metabolic pathways among those groups. RESULTS Compared with the normal group， the escape latency of rats in the model group was significantly increased， the times of crossing platforms were significantly reduced， and the percentage of average 24-hour sleep time was significantly reduced （P＜0.05）. Compared with the model group， the levels of the above indicators were significantly reversed in the diazepam group and Sugemule-4 group （P＜0.05）. Metabolomics studies found that a total of 9 differential metabolites were identified in rat serum and hippocampal tissue， including 5-hydroxyindoleacetic acid， canine urate， canine urinary quinolinic acid， 5-hydroxytryptamine， phenol sulfate， 1-carboxyethyltyrosine， 3-（4-hydroxyphenyl） lactate， N-acetyl tyrosine， tyrosine and phenol sulfate， mainly involving 2 metabolic pathways of tryptophan and tyrosine.CONCLUSIONS Sugemule-4 can improve the sleep time and behavioral performance of insomnia rats， and its mechanism may be associated with affecting amino acid metabolic pathways such as tryptophan and tyrosine.

Rapid Determination of 32 Kinds of Veterinary Drug Residues in Eggs Using Modified QuEChERS Based on Reduced Graphene Oxide-coated Melamine Sponge by Ultra-High Liquid Chromatography-Tandem Mass Spectrometry / 分析化学

A rapid analytical method for simultaneous determination of 32 kinds of multi-residue veterinary drugs in eggs was developed using a modified QuEChERS technique based on a reduced graphene oxide-coated melamine sponge(r-GO@MeS)by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).The influences of graphene oxide(GO)concentrations,sponge dosages,and purification modes on drug recoveries were investigated during the purification process.The optimal purification conditions involved using a GO concentration of 0.5 mg/mL,a sponge dosage of 6.0 cm3/mL,and a dynamic purification mode of 5 extrusion cycles.Separation was achieved using an Agilent Eclipse Plus C18 RRHD column(100 mm×2.1 mm,1.8 μm),and quantitative analysis was performed by the external standard method using an electrospray ionization source(ESI)in multiple reaction monitoring(MRM)mode.The results showed that all 32 kinds of veterinary drugs exhibited good linear correlation with coefficients greater than 0.999,and matrix effects(MEs)ranging from?7.8%to 18.9%.The limits of detection(LODs)and quantification(LOQs)ranged from 0.2 to 10.2 μg/kg and from 0.6 to 28.0 μg/kg,respectively.The recoveries for the three spiked levels were in the range of 66.5%?117.5%,with intra-day and inter-day precision(Relative standard deviation)below 13.3%and 16.3%,respectively.The synthetic r-GO@MeS exhibited efficient matrix purification without the need of high-speed centrifugation or strong magnetic field assistance.This significantly shorted the sample pretreatment time and improved the convenience of the matrix purification process.Combined with UPLC-MS/MS,the method was suitable for the rapid determination of multi-residue veterinary drugs in eggs.

Mechanisms by which high-intensity interval training influences bone health in a rat model of postmenopausal osteoporosis / 中国组织工程研究

BACKGROUND:Resistance training and weight-bearing exercise are recommended modes for patients with osteoporosis to improve bone health.High-intensity interval training is a high-impact weight-bearing exercise with obvious time-efficient characteristics;however,little attention has been paid to its impact on bones. OBJECTIVE:To observe the effect of high-intensity interval training on the bone health of ovariectomized rat models. METHODS:Thirty-six female Sprague-Dawley rats were randomly divided into sham group,model group and model exercise group(n=12 per group).Bilateral ovariectomy was used to prepare an osteoporosis rat model in the latter two groups.Six weeks after modeling,the model exercise group was subjected to a high-intensity interval training on an electric treadmill at 90%peak running speed for 2 minutes and 50%peak running speed for 1 minute as one session,a total of nine sessions,3 days per week,for 6 weeks.Rats in the sham and model groups were raised quietly in the mouse cage during the same period.The relevant indexes were tested 48-72 hours after the final training. RESULTS AND CONCLUSION:Compared with the sham group,bone mineral density,maximal load,stiffness,elasticity,trabecular volume fraction,and trabecular number decreased(P<0.05),while trabecular separation increased(P<0.05);the level of irisin in the serum,gastrocnemius and femur decreased(P<0.05);the expression of peroxisome proliferator-activated receptor γ coactivator-1α protein and fibronectin type Ⅲ domain-containing protein 5 mRNA and protein in the gastrocnemius muscle decreased(P<0.05);the expression of type I collagen,Osterix,and Runx2 mRNA in the femur decreased(P<0.05);and the expression of anti-tartrate acid phosphatase,receptor activator of nuclear factor κB ligand,and osteoclast-associated receptor mRNA increased in the model group(P<0.05).Compared with the model group,bone mineral density,fracture load,maximal load,stiffness,elasticity,average trabecular thickness,and trabecular number increased(P<0.05),and trabecular separation decreased(P<0.05);the level of irisin in the serum,gastrocnemius and femur increased(P<0.05);the expression of peroxisome proliferator-activated receptor γ coactivator-1α protein and fibronectin type Ⅲ domain-containing protein 5 mRNA and protein in gastrocnemius increased(P<0.05);the expression of type I collagen,Osterix,and Runx2 mRNA in the femur increased(P<0.05);and the expression of anti-tartrate acid phosphatase,receptor activator of nuclear factor κB ligand,and osteoclast-associated receptor mRNA decreased in the model exercise group(P<0.05).To conclude,short-term high-intensity interval training may improve bone health of ovariectomized rats through up-regulating the irisin level.

Thin slice CT signs combined with multiplanar reformation for diagnosing tracheobronchial tuberculosis / 中国医学影像技术

Objective To observe value of thin slice CT multiple signs combined with multiplanar reformation(MPR)for diagnosing tracheobronchial tuberculosis(TBTB).Methods Data of 234 TBTB patients who underwent chest thin slice CT scanning were retrospectively analyzed.MPR was performed,the direct signs and indirect signs of TBTB were observed.The diagnostic efficacy of axial plain CT images(direct observation)and of MPR combined with the former(combined observation)were compared.Results The sensitivity,specificity,positive predictive value,negative predictive value and accuracy of direct observation was 38.88％(201/517),98.13％(1 789/1 823),85.53％(201/235),84.99％(1 789/2 105)and 85.04％(1 990/2 340),respectively,of combined observation was 91.10％(471/517),98.85％(1 802/1 823),95.54％(471/493),97.51％(1 802/1 848)and 97.14％(2 273/2 340),respectively.Significant differences of sensitivity,positive predictive value,negative predictive value and accuracy were found(all P＜0.001),whereas no significant difference of specificity was found between 2 methods(P＞0.05).Conclusion Thin slice CT multiple signs combined with MPR could be used to effectively diagnose TBTB.

Construction， reliability and validity of a professional identity questionnaire for psychiatrists / 四川精神卫生

BackgroundDomestic researches on the professional identity of psychiatrists are still relatively rare up to now， and effective evaluation tools remain inadequate. ObjectiveTo construct a professional identity questionnaire for psychiatrists with high reliability and validity， so as to provide an effective tool for the evaluation of professional identity of psychiatrists. MethodsA self-designed questionnaire titled "Professional Identity Questionnaire" was compiled. After preliminary screening of items and expert consultation， an initial questionnaire was formed and administered to a sample of 400 psychiatrists， and the final questionnaire was assessed by item analysis， reliability analysis and validity analysis. ResultsThe Cronbach's α coefficient was 0.930 for the final questionnaire， and ranged from 0.817 to 0.920 for each dimension. The value of KMO was 0.904 （χ2=2 931.652， P<0.01）. The cumulative variance contribution rate of factors extracted from exploratory factor analysis was 68.306%. Confirmatory factor analysis showed that the integrity of fit indexes were χ2/df=1.234， GFI=0.905， NFI=0.916， RMSEA=0.036， CFI=0.983， IFI=0.983. The final version of the professional identity questionnaire for psychiatrists consisted of 23 items relating to 4 dimensions， namely， professional cognition， professional behavior， professional emotion and professional values. ConclusionThe professional identity questionnaire for psychiatrists has good reliability and validity， and can be used as an effective tool to evaluate the professional identity of psychiatrists. ［Funded by Foundation of Sichuan Research Center of Applied Psychology of Chengdu Medical College （number， CSXL-22304）； Science and Technology Guiding Plan Project of Guangyuan City （number， 22ZDYF0072）］

Rudimentary horn pregnancy: clinical analysis of 12 cases and literature review / 中华妇产科杂志

Objective: To investigate the clinical characteristics, treatments and fertility recovery of rudimentary horn pregnancy (RHP). Methods: The clinical data of 12 cases with RHP diagnosed and treated in Peking University Third Hospital from January 1, 2010 to December 31, 2022 were retrospectively analyzed. Clinical informations, diagnosis and treatments of RHP and the pregnancy status after surgery were analyzed. Results: The median age of 12 RHP patients was 29 years (range: 24-37 years). Eight cases of pregnancy in residual horn of uterus occurred in type Ⅰ residual horn of uterus, 4 cases occurred in type Ⅱ residual horn of uterus; among which 5 cases were misdiagnosed by ultrasound before surgery. All patients underwent excision of residual horn of uterus and affected salpingectomy. After surgery, 9 patients expected future pregnancy, and 3 cases of natural pregnancy, 2 cases of successful pregnancy through assisted reproductive technology. Four pregnancies resulted in live birth with cesarean section, and 1 case resulted in spontaneous abortion during the first trimester of pregnancy. No uterine rupture or ectopic pregnancy occurred in subsequent pregnancies. Conclusions: Ultrasonography could aid early diagnosis of RHP while misdiagnosis occurred in certain cases. Thus, a comprehensive judgment and decision ought to be made based on medical history, physical examination and assisted examination. Surgical exploration is necessary for diagnosis and treatment of RHP. For infertile patients, assisted reproductive technology should be applied when necessary. Caution to prevent the occurrence of pregnancy complications such as uterine rupture, and application of cesarean section to terminate pregnancy are recommended.

Diagnosis and treatment principles of liver injury induced by antithyroid drugs / 临床肝胆病杂志

Pharmacotherapy is the primary treatment method for hyperthyroidism. Antithyroid drugs can induce liver injury， and the diagnosis of drug-induced liver injury is mostly exclusive based on medical history collection， clinical symptoms， serum biochemistry， radiological examination， and histology. According to the severity of liver injury， drug-induced liver injury can be classified into mild， moderate， severe， and fatal degrees. Drug withdrawal may not be necessary for patients with mild liver injury， but regular monitoring of liver function is required； in severe cases， patients may develop liver failure， which may lead to a mortality rate， and early identification， timely drug withdrawal， and reasonable pharmacotherapy can help to avoid fatal consequences. The treatment principles of liver injury induced by antithyroid drugs include promoting the recovery of liver injury， preventing the severe exacerbation and chronicity of liver injury， and reducing the risk of death. Standardized medication， timely monitoring， early identification， and early treatment are important measures for the prevention and treatment of liver injury induced by antithyroid drugs.

Effects of total flavonoids of Pterocarya hupehensis Skan on migration,invasion and ferroptosis of non-small-cell lung cancer A549 cells / 中国病理生理杂志

AIM:To investigate the impact of total flavonoids of Pterocarya hupehensis Skan(PHSTF)on the migration,invasion,and ferroptosis of non-small-cell lung cancer A549 cells.METHODS:The A549 cells were divided into control group,low-,medium-and high-dose(100,150 and 200 μg/mL)PHSTF groups,ferroptosis inhibitor liprox-statin-1(Lip-1)group,and high-dose PHSTF combined with Lip-1 group,each cultured in corresponding media.Cell via-bility was assessed using the CCK-8 assay,while cell migration and invasion abilities were determined through scratch and Transwell assays.Cell lipid peroxidation levels were measured using the glutathione(GSH)assay kit.RT-qPCR was em-ployed to assess the mRNA expression of solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),while Western blot was utilized to examine the protein expression of SLC7A11,GPX4,Kelch-like epichlorohy-drin-associated protein-1(Keap-1),nuclear factor E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1).RE-SULTS:Compared with control group,PHSTF significantly diminished the viability of A549 cells in a time-and dose-de-pendent manner(P＜0.01),and the cell migration and invasion were also reduced(P＜0.01),along with a significant de-crease in GSH level(P＜0.01).Treatment with PHSTF inhibited the mRNA and protein expression levels of ferroptosis-re-lated proteins,including SLC7A11 and GPX4(P＜0.01),suppressed the protein expression of Nrf2 and HO-1(P＜0.01),and enhanced the expression of Keap-1(P＜0.01).The Lip-1 partially restored the decrease in cell viability in-duced by PHSTF(P＜0.01),significantly up-regulated the protein expression levels of SLC7A11,GPX4,Nrf2 and HO-1,and suppressed the protein expression of Keap-1(P＜0.01).CONCLUSION:Total flavonoids of Pterocarya hupehen-sis Skan can inhibit the migration and invasion of non-small-cell lung cancer A549 cells,and induce the cell ferroptosis by regulating the Keap-1/Nrf2/HO-1 pathway.

Quantitative study on high-touch surface in oral diagnosis and treatment procedures / 中国感染控制杂志

Objective To clarify the high-touch surface in oral diagnosis and treatment procedures,provide basis and guidance for cleaning and disinfection.Methods The direct observation method was used to investigate the tou-ch time and frequency of environmental surfaces in 7 outpatient departments of a tertiary stomatology hospitals in Beijing.The average touch frequency,95％confidence interval and cumulative touch rate were calculated.Results In oral diagnosis and treatment procedures,the average touch frequency of the environmental surface was 26.75 times per procedure,with the highest in endodontics(46.25 times per procedure)and the lowest in the oral mucosal specialty(10.19 times per procedure).The high-touch surface consisted of the shadowless lamp handle,manipula-tion panel and handle on dental unit(doctor's side),computer keyboard and mouse,handle and line front end of three way syringe,as well as dental high speed handpiece and line front end,with average touch frequencies of 3.99,3.85,2.65,1.86,and 1.40 times per procedure.The high-touch surface in all stomatology specialties in-cluded the manipulation panel and handle on dental unit(doctor's side),75％of specialties included computer key-board and mouse,and the shadowless lamp handle has the highest touch frequency in 50％of specialties.The ave-rage touch frequency of the environmental surface was highest(113.50 times per procedure)during crown prepara-tion procedure,and the lowest(8.50 times per procedure)during the orthodontic consultations.Conclusion The high-touch surface of different dental specialties and different diagnosis and treatment procedures are different.Me-dical institutions should take corresponding cleaning,disinfection and management measures according to the actual situation of high-touch surface in stomatology departments,so as to effectively improve the quality of environmental cleaning and disinfection.

Effect of endoscopic injection of norepinephrine on cerebral infarction complicated by stress-induced gastrointestinal bleeding / 中国基层医药

Objective:To investigate the clinical effect of endoscopic injection of norepinephrine on cerebral infarction complicated by stress-induced gastrointestinal bleeding.Methods:A total of 150 patients with cerebral infarction complicated by stress-induced gastrointestinal bleeding who were admitted to the Intensive Care Unit of Lishui City People's Hospital from October 2020 to October 2021 were included in this study. These patients were randomly divided into a control group and an observation group using the random number table method, with 75 patients in each group. Patients in the control group received routine clinical treatment, while those in the observation group received endoscopic injection of norepinephrine in addition to routine clinical treatment. The hemostatic time, blood transfusion volume, and length of hospital stay were compared between the two groups. The stress index and inflammatory index were compared between the two groups before and after treatment. The hemostatic effect and adverse reactions were evaluated in each group.Results:The hemostatic time, blood transfusion volume, and length of hospital stay in the observation group were (16.16 ± 4.36) hours, (385.35 ± 41.28) mL, and (5.35 ± 1.28) days, respectively, which were significantly shorter or less than (27.27 ± 6.34) hours, (447.07 ± 32.07) mL, and (7.07 ± 2.07) days in the control group ( t = 12.50, 10.22, 6.12, all P < 0.001). After treatment, the levels of cortisol, norepinephrine, antidiuretic hormone, high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-α in the observation group were (288.33 ± 19.53) mmol/L, (29.17 ± 4.26) μg/L, (4.08 ± 1.08) mU/L, (38.27 ± 8.72) ng/L, (6.69 ± 1.35) μg/L, and (6.37 ± 1.51) mg/L, respectively, which were significantly lower than (327.22 ± 22.01) mmol/L, (39.32 ± 5.54) μg/L, (5.36 ± 1.22) mU/L, (51.24 ± 13.23) ng/L, (8.67 ± 2.29) μg/L, and (11.44 ± 3.13) mg/L in the control group ( t = 11.44, 12.57, 6.80, 7.08, 6.45, 12.63, all P < 0.001). The overall response rate of hemostasis in the observation group was 94.67% (71/75), which was significantly higher than 82.67% (62/75) in the control group ( χ2 = 5.37, P < 0.05). The incidence of adverse reactions in the observation group was 8.00% (6/75), which was slightly, but not significantly, lower than 14.67% (11/75) in the control group ( χ2 = 1.66, P > 0.05). Conclusion:Endoscopic injection of norepinephrine for the treatment of cerebral infarction complicated by stress-induced gastrointestinal bleeding can rapidly stop bleeding, effectively reduce inflammation,improve stress index, and be highly safe.

Coronary intravascular lithotripsy for calcified coronary artery calcification-systematic review of researches / 中国介入心脏病学杂志

Coronary artery calcification commonly results in reduced vascular compliance,facilitating incomplete stent expansion and in-stent restenosis after stent implantation,thereby leading to the failure of interventional treatment.Conventional approaches to managing calcified lesions are constrained by the intricate nature and properties of calcified plaques,which frequently pose challenges in their manipulation,consequently giving rise to numerous approaches complications and an elevated likelihood of adverse cardiovascular events following the procedure.Percutaneous coronary intraluminal shock wave balloon catheter angioplasty,also known as coronary intravascular lithotripsy,utilizing a balloon catheter system,demonstrates the capacity to safely and efficiently modify superficial and deep-seated calcifications,regardless of their concentric or eccentric nature.This intervention significantly enhances vascular compliance,thereby facilitating subsequent interventional therapies.Presently,coronary intravascular lithotripsy has emerged as a crucial approach in the management of coronary artery calcification.This article primarily offers a comprehensive examination of the mechanism of intravascular lithotripsy and the research pertaining to the treatment of coronary artery calcification.

Construction of evaluation index system of entrustable professional activities in psychiatric residents / 中国心理卫生杂志

Objective:To construct an evaluation the index system of entrustable professional activities for resident training doctors in psychiatric department,and to provide reference for formulating training strategies and assessment standards.Entrustable professional activities refers to the ability of trainees to perform and complete spe-cific clinical tasks independently after they have been trusted.Methods:Through documental analysis and semi-structured interviews,the item database of entrustable professional activities for psychiatric resident training physi-cians was established.Delphi consultation was conducted among 63 experts in the field of psychiatry from 7 national resident training bases and 3 medical colleges in China.Indicators were comprehensively screened and sorted out,and indicators at all levels and their weights were determined by the analytic hierarchy process.Results:A hierarchi-cal evaluation index system of entrustable professional activities for psychiatric resident training doctors was con-structed,including 4 first-level indicators,17 second-level indicators and 68 third-level indicators.The weights of the first-level,second-level and third-level indicators were determined.Conclusion:The evaluation index system of en-trustable professional activities is comprehensive and systematic,which is suitable for clinical work and convenient for practical application.It could provide quantitative standards for the assessment of psychiatric residents and pro-mote the improvement of training quality.

Research on improving nurses'ethical literacy in the application of human-assisted reproductive technology / 中国医学伦理学

The role and function of nurses in the application of assisted reproductive technology were sorted out.Addressing potential ethical dilemmas,this paper analyzed the restrictive factors in dealing with difficulties in nursing practice and proposed the construction of a nursing ethics literacy system.It is suggested to improve ethical rules and education systems,strengthen case education,enhance risk prevention capabilities,and cultivate a healthy ethical culture,so as to effectively enhance nurses'ethical literacy.

Analysis of menstrual conditions and influencing factors in 281 women infected with COVID-19 / 上海预防医学

ObjectiveTo investigate the menstrual conditions of women infected with COVID-19 in Shanghai and analyze the influencing factors. MethodsFrom December 2022 to March 2023， menstrual data from 281 women infected with COVID-19 in Shanghai were collected with a questionnaire survey， including usual menstrual characteristics， the most recent menstrual period post-infection， symptoms of infection， and medication usage. According to the crossover period between the menstrual period and the infection period of the respondents， the samples were divided into two groups for comparative analysis： those whose menstrual and infection periods overlapped （positive group） and those whose menstruation started after conversion to virus-negative （negative conversion group）. ResultsAmong the 281 respondents， 196 （65.8%） experienced menstrual changes. Among them， 145 （51.6%） had changes in menstrual volume， color and texture， and 109 （38.8%） had changes in menstrual duration or cycle. Decreased menstrual volume （22.1%）， darker color （23.49%）， thicker texture （21.0%）， increased blood clots （16.7%）， and prolonged duration （21.8%） were observed in both groups. The rate of changes in menstrual volume， color， and texture was higher in the positive group （56.8%， 69/110） than that in negative group （37.3%， 76/171） （P<0.05）. Regarding the menstrual cycle changes， the rate of early onset was higher in the positive group （14.5%） compared to the negative conversion group （3.5%）（P<0.05）， while the rate of delayed menstruation was higher in the negative conversion group （25.1%） than that in the positive group （5.5%） （P<0.05）. Correlation analysis showed a weak association between sore throat and menstrual changes （r=0.154， P<0.05）. ConclusionSome women infected with COVID-19 experience short-term changes in their menstrual conditions， characterized by reduced volume， darker color， thick texture， increased clots， and prolonged menstrual duration， reflecting a pathogenesis of blood stasis. Menstruation during the infection period tends to occur earlier， while delayed menstruation is more prevalent at post-conversion.

Visualization of nasal powder distribution using biomimetic human nasal cavity model

Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.

Remifentanil Down-regulates GIRK2 Expression in Rat Dorsal Root Ganglion and Spinal Dorsal Horn / 中山大学学报(医学科学版)

ObjectiveTo observe the changes in the expression and distribution of G protein-gated inwardly rectifying potassium channel subunit 2 （GIRK2） in the dorsal root ganglion （DRG） and spinal cord dorsal horn of rats with remifentanil-induced hyperalgesia. MethodsHyperalgesia was induced by intravenous infusion of remifentanil 4 μg/kg/min for 2 h in adult male SD rats. At 6th hour and on days 1， 3 and 5 following remifentanil treatment， we used immunofluorescence to examine the changes in the GIRK2 distribution and expression. Immunoblotting was used to detect GIRK2 expression of the total protein and membrane protein in DRG and spinal dorsal horn of rats. Behavioral testing was applied to evaluate the effect of intrathecal injection of GIRK2-specific agonist ML297 on thermal nociceptive threshold on day 1 after remifentanil infusion. Resultsmmunofluorescence results showed that GIRK2 was mainly co-localized with IB4-positive small neurons in DRG and nerve fibers in spinal dorsal horn. GIRK2 expression was significantly downregulated following remifentanil treatment. Immunoblotting results revealed that on day 1 following intravenous infusion of remifentanil， compared with those in the control group， GIRK2 expression levels of the total protein and membrane protein in DRG （0.47 ± 0.10 vs. 1.01 ± 0.17， P < 0.001； 0.47 ± 0.11 vs. 1.06 ± 0.12， P < 0.001） and spinal dorsal horn （0.52 ± 0.09 vs. 1.10 ± 0.08， P < 0.001； 0.54 ± 0.10 vs. 1.01 ± 0.13， P < 0.001） were all significantly decreased. The behavioral results showed that intrathecal ML297 effect on thermal withdrawal latency was significantly reduced following remifentanil treatment （P < 0.001）. ConclusionsRemifentanil might induce hyperalgesia via down-regulating GIRK2 expression in rat DRG and spinal cord dorsal horn.

Comparison of Exosomes Derived from Fibroblasts and Mesenchymal Stem Cells for the Treatment of Acute Wound Healing / 中山大学学报(医学科学版)

ObjectiveTo compare the therapeutical effect of exosomes derived from fibroblasts and mesenchymal stem cells on acute wound healing. MethodsPrimary human dermal fibroblasts （hDF） were isolated， cultured and identified. Human bone marrow mesenchymal stem cell exosomes （hMSC-EXO） and hDF exosomes （hDF-EXO） were extracted by ultracentrifuga tion. After 24 h of coincubation with hDF-EXO or hMSC-EXO， hDFs proliferation and migratory capacity were evaluated by cell counting kit-8 （CCK8） assay and scratch test. Full-thickness cutaneous wounds were created on 8-week-old female C57BL/6 mice， and topically applied with PBS （control）， hDF-EXO or hMSC-EXO. Wounds were measured at day 0， 2， 4， 7， and the uptake of exosomes in wound was observed at day 1. Quantitative PCR （qPCR） analysis was performed to detect the mRNA expression levels of TNF-α， IL-6， IL-1β， IL-10 in wound at day 1. HE staining was conducted to analyze the histological structure of wounds at day 7， while immunofluorescence staining was used to examine expression of PDGFR-α、α-SMA、Ki67. ResultshDF exhibited certain fibrolast-like characteristics with respect to expression of cell surface markers and specific proteins. hDF-EXO and hMSC-EXO presented exosomal morphology， size， and markers， and both concentrations were not statistically different （P>0.05）； CCK8 assay showed that both exosomes promoted hDF cell viability， compared with the negative control （P<0.01）， and hDF-EXO group had greater cell viability than hMSC-EXO group （P<0.01）. Scratch test indicated that hDF-EXO induced a significant increase in scratch healing rate versus the negative control （P<0.01）， hMSC-EXO （P<0.05）. In vivo experiments showed wound tissues took up exosomes at day 1. qPCR detected TNF-α， IL-6， IL-1β expression levels in wound at day 1 were lower in exosomes group than in the control group， and were the lowest in hMSC-EXO group （all P<0.01）. Wound areas were measured smaller at day 7 in exosomes group than in the control group （all P<0.01） and hDF-EXO group had better closure than hMSC-EXO group （P<0.05）. HE staining revealed that compared with control group， scar， incomplete epidermis and few collagen deposition remained in the hMSC-EXO group， whereas hDF-EXO group showed re-epithelialization， continuous neo-epidermis and regenerated dermis. Immunofluorescence staining suggested that the number of fibroblasts， myofibroblasts， proliferating cells was higher in both exosomes group than that in the control group， especially the highest in hDF-EXO group. ConclusionOur study shows both exosomes accelerate wound healing， whereas hDF-EXO is more effective in promoting fibroblasts proliferation， migration， transition to myofibroblasts， and hMSC-EXO may play a role in inhibiting inflammatory reaction during early stage of wound healing.

Clinical and gene mutation characteristics of patients with hereditary ellipsocytosis: nine cases report and literature review / 中华血液学杂志

Objective: To report gene mutations in nine patients with hereditary elliptocytosis (HE) and analyze the characteristics of pathogenic gene mutations in HE. Methods: The clinical and gene mutations of nine patients clinically diagnosed with HE at Institute of Hematology & Blood Diseases Hospital from June 2018 to February 2022 were reported and verified by next-generation sequencing to analyze the relationship between gene mutations and clinical phenotypes. Results: Erythrocyte membrane protein gene mutations were detected among nine patients with HE, including six with SPTA1 mutation, one with SPTB mutation, one with EPB41 mutation, and one with chromosome 20 copy deletion. A total of 11 gene mutation sites were involved, including 6 known mutations and 5 novel mutations. The five novel mutations included SPTA1: c.1247A>C (p. K416T) in exon 9, c.1891delG (p. A631fs*17) in exon 15, E6-E12 Del; SPTB: c.154C>T (p. R52W) ; and EPB41: c.1636A>G (p. I546V) . Three of the six patients with the SPTA1 mutation were SPTA1 exon 9 mutation. Conclusion: SPTA1 is the most common mutant gene in patients with HE.

The efficacy and safety of intravenous sucrose iron therapy for recurrent iron deficiency anemia / 中华血液学杂志

Objective: To evaluate the efficacy and safety of intravenous iron supplementation in patients with recurrent iron deficiency anemia (IDA) . Methods: This retrospective analysis of 90 patients with recurrent IDA from May 2012 to December 2021 was conducted, comparing the efficacy and safety of the intravenous iron therapy group and the oral iron therapy group. Results: Among the 90 patients with recurrent IDA, 20 were males and 70 were females, with a median age of 40 (range: 14-85) years. A total of 60 patients received intravenous iron supplementation and 30 received oral iron supplementation. The hematologic response rates in the intravenous iron group were significantly higher than those in the oral iron group at 4 and 8 weeks after treatment [80.0% (48/60) vs 3.3% (1/30) and 96.7% (58/60) vs 46.7% (14/30), all P<0.001, respectively]. The median increase in hemoglobin levels was also significantly higher in the intravenous iron group than in the oral iron group [38 (4, 66) g/L vs 7 (1, 22) g/L at week 4 and 44.5 (18, 80) g/L vs 19 (3, 53) g/L at week 8, all P<0.001]. The intravenous iron group had a significantly higher proportion of patients who achieved normal hemoglobin levels than the oral iron group (55.0% vs 0 and 90% vs 43.3%, all P<0.001, respectively). Iron metabolism indicators were tested before and after 8 weeks of treatment in 26 and 7 patients in the intravenous and oral iron groups, respectively. The median increase in serum ferritin (SF) levels in the intravenous iron group 8 weeks after treatment was 113.7 (49.7, 413.5) μg/L, and 54% (14/26) of these patients had SF levels of ≥100 μg/L, which was significantly higher than the median increase in SF levels in the oral iron group [14.0 (5.8, 84.2) μg/L, t=4.760, P<0.001] and the proportion of patients with SF levels of ≥100 μg/L (P=0.013). The incidence of adverse reactions was 3.3% (2/60) in the intravenous iron group, which was significantly lower than that in the oral iron group [20.0% (6/30), P=0.015]. Conclusion: Intravenous iron supplementation is more effective for hematologic response, faster hemoglobin increase, and higher iron storage replenishment rates compared with oral iron supplementation in patients with recurrent IDA, and it is well tolerated by patients.

Research Progress of Deep Learning in Bladder Cancer Pathology / 肿瘤防治研究

The incidence of bladder cancer is increasing annually, and the gold standard for its diagnosis relies on histopathological biopsy. Whole-slide digitization technology can produce thousands of high-resolution captured pathological images and has greatly promoted the development of digital pathology. Deep learning, as a new method of artificial intelligence, has achieved remarkable results in the analysis of pathological images for tumor diagnosis, molecular typing, and prediction of prognosis and recurrence of bladder cancer. Traditional pathology relies heavily on the professional level and experience of pathologists; as such, it is highly subjective and has poor reproducibility. Deep learning can automatically extract image features. It can also improve diagnostic efficiency and repeatability and reduce missed and misdiagnosed rates when used to assist pathologists in making decisions. This technology cannot only alleviate the pressure of the current shortage of skilled workforce and uneven medical resources but also promote the development of precision medicine. This article reviews the latest research progress and prospects of deep learning in pathological image analysis of bladder cancer.