Clinical features and prognostic factors of elderly patients with mantle cell lymphoma / 中华血液学杂志

Objective: To examine the clinical characteristics and prognostic factors of elderly patients with mantle cell lymphoma (MCL) and the impact of nutrition and underlying diseases on the prognosis of elderly patients with MCL. Methods: retrospectively analyzed 255 elderly patients with MCL from 11 medical centers, including Peking University Third Hospital between January 2000 and February 2021. We analyzed clinical data, such as age, gender, Mantle Cell Lymphoma International Prognostic Index score, and treatment options, and performed univariate and multivariate prognostic analysis. We performed a comprehensive geriatric assessment on elderly MCL patients with medical records that included retraceable underlying disease and albumin levels, and we investigated the impact of basic nutrition and underlying disorders on MCL prognosis in the elderly. Results: There were 255 senior individuals among the 795 MCL patients. Elderly MCL was more common in males (78.4%), with a median age of 69 yr (ages 65-88), and the majority (88.6%) were identified at a late stage. The 3-yr overall survival (OS) rate was 42.0%, with a 21.2% progression-free survival (PFS) rate. The overall response rate (ORR) was 77.3%, with a 33.3% total remission rate. Elderly patients were more likely than younger patients to have persistent underlying illnesses, such as hypertension. Multivariate analysis revealed that variables related with poor PFS included age of ≥80 (P=0.021), Ann Arbor stage Ⅲ-Ⅳ (P=0.003), high LDH level (P=0.003), involvement of bone marrow (P=0.014). Age of ≥80 (P=0.001) and a high LDH level (P=0.003) were risk factors for OS. The complete geriatric assessment revealed that renal deficiency was associated with poorer OS (P=0.047) . Conclusions: Elderly MCL patients had greater comorbidities. Age, LDH, renal function, bone marrow involvement, and Ann Arbor stage are all independent risk factors for MCL in the elderly.

Correlation between collateral circulation and cerebral hemodynamics in moyamoya disease and moyamoya syndrome based on 4-dimensional CT angiography-CT perfusion / 中华放射学杂志

Objective:To explore the significance of four-dimensional CT angiography(4D CTA) and CT perfusion (CTP) imaging in evaluating collateral circulation grades in patients with moyamoya disease and moyamoya syndrome and their relationship with cerebral hemodynamics.Methods:The clinical and imaging data of 32 patients with moyamoya disease and moyamoya syndrome in Beijing Hospital from January 2017 to January 2022 were retrospectively analyzed. All patients underwent 4D CTA-CTP imaging. Collateral circulation was scored on CTA images by using Alberta stroke program early CT score system, and on digital subtraction angiography (DSA) images by using American society of interventional and therapeutic neuroradiology/Society of interventional radiology score system, respectively. The patients were divided into Ⅰ-Ⅲ circulation compensation grades based on collateral circulation score. Regions of interest were delineated at basal ganglia on perfusion maps and the perfusion parameters were obtained including cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), mean transit time (TTP) and delay time (DLY). The Kruskal-Wallis test was used to compare the perfusion parameters in different collateral circulation grades, and pairwise comparison was performed with Bonferroni correction. Kappa and Spearman tests were used to analyze the consistency and correlation of 4D CTA and DSA in the classification of collateral circulation.Results:4D CTA and DSA had a moderate consistency (Kappa=0.693, P<0.001) and a strong correlation ( r=0.805, P<0.001) in evaluating collateral grades. There were statistically significant differences in CBF, MTT and TTP among collateral compensation grade Ⅰ, grade Ⅱ and grade Ⅲ ( H values were 7.91, 11.69, 8.93; P values were 0.019, 0.003 and 0.012, respectively). Further pairwise comparison showed that the CBF of collateral compensation grade Ⅰ was lower than that of grade Ⅲ ( P=0.015), MTT of grade Ⅱ was higher than that of grade Ⅲ ( P=0.005), and TTP of grade Ⅰ was higher than that of grade Ⅲ ( P=0.015). There was no statistical significance of other indicators in pairwise comparison. There were no significant differences in CBV and DLY among collateral compensation grade Ⅰ, grade Ⅱ and grade Ⅲ ( P>0.05). Conclusions:4D CTA-CTP is equivalent to DSA in evaluating collateral circulation in patients with moyamoya disease and moyamoya syndrome. It can also evaluate the cerebral hemodynamics comprehensively, which has high clinical significance for disease monitoring.

Advances and challenges in using nirmatrelvir and its derivatives against SARS-CoV-2 infection / 药物分析学报

On December 22,2021,the United States Food and Drug Administration approved the first main protease inhibitor,i.e.,oral antiviral nirmatrelvir(PF-07321332)/ritonavir(Paxlovid),for the treatment of early severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Nirmatrelvir inhibits SARS-CoV-2 infection,but high doses or long-term treatment may cause embryonic developmental toxicity and changes in host gene expression.The chiral structure of nirmatrelvir plays a key role in its antiviral activity.Ritonavir boosts the efficacy of nirmatrelvir by inactivating cytochrome P450 3A4 expression and occupying the plasma protein binding sites.Multidrug resistance protein 1 inhibitors may increase the efficacy of nirmatrelvir.However,Paxlovid has many contraindications.Some patients treated with Paxlovid experience a second round of coronavirus disease 2019(COVID-19)symptoms soon after re-covery.Interestingly,the antiviral activity of nirmatrelvir metabolites,such as compounds 12-18,is similar to or higher than that of nirmatrelvir.Herein,we review the advances and challenges in using nirmatrelvir and its derivatives with the aim of providing knowledge for drug developers and physicians in the fight against COVID-19.

Doctors’ Professional Ethics in the Perspective of Marx’s "Industrial Pathology" / 中国医学伦理学

In Das Kapital, Marx cited the Public Health Report of Dr. Simon, the promoter of the British public health reform, and developed Marx’s "industrial pathology", which not only directly demonstrated the oppression and exploitation of capitalism on the working class, but also indirectly raised expectations and construction of doctors’ professional ethics and social values. Marx believed that the doctors should have professional, fair and resolute ethic, and only by placing their value in the working people and putting the health and interests of the people first, can they better save the dying, heal the wounded, and play a greater role of value and advantage. Reviewing the professional ethics and social values of doctors from the perspective of Marx’s "industrial pathology" not only enlightens people on how to better respond to the COVID-19, but also has important reference significance for the construction of contemporary medical ethics.

Analysis of heart rate variability during blood donation / 中国输血杂志

【Objective】 To observe the regulation of autonomic nerves in blood donors during blood donation by heart rate variability analysis and explore the possible mechanism of donation related vasovagal reaction. 【Methods】 Electrocardiogram (ECG) of 90 blood donors was monitored by Fontaine Ⅰlead during the whole process of blood donation, and the 5-min heart rate variation before, during and after blood donation was analyzed. 【Results】 During the whole process of blood donation, the sympathetic HRV index (LF nu) and the sympathetic and vagal balance ability index (LF/HF) increased, whereas the vagal nerve index (pNN50, RMSSD, HFnu) and heart rate variability index (SDNN, Total power) decreased. For baseline heart rate variability of different blood donors (first-time vs. repeated, male vs. female, 18-24 years old vs. ≥25 years old, <400 mL vs. 400 mL) before blood donation, the pNN50, RMSSD and Total power of 18-24 years old blood donors were higher, but other indicators showed no significant difference. There were differences in HRV indexes of different types of blood donors during blood donation compared with before blood donation. The decrease of pNN50 and HFnu and the increase of LF/HF were larger in experienced blood donors than in first-time blood donors. The decrease of RMSSD was larger in male blood donors than in female blood donors; the change of LF/HF was larger in blood donors aged≥25 years than in blood donors aged 18-24 years; other indicators had no significant difference. 【Conclusion】 Blood donation leads to reflex readjustment of the cardiac autonomic tone: the sympathetic nerve is excited while the vagal nerve is suppressed. The cardiac autonomic nerve function of first-time blood donors, female donors and low-age (18-24 years old) donors to blood donation stress is not fully regulated. Donation related vasovagal reaction may be related to the autonomic nerve regulation function of blood donors.

Study on RHD and RHCE gene mRNA based on three generation sequencing technology / 中国输血杂志

【Objective】 To establish RH gene mRNA sequencing method based on nanopores sequencing and to explore the RHD and RHCE mRNA transcripts in D positive and Del individuals. 【Methods】 From March 2021 to May 2022, 5 RhD positive samples and 5 Del samples screened out by hospitals in Chengdu were sent to our laboratory for futher examination. The erythrocytes and buff coat were isolated, then DNA and RNA were extracted.All 10 samples were genotyped by PCR-SSP. After the mRNA was reversely transcribed into cDNA, the full-length mRNA of RHD and RHCE genes were simultaneously amplified by a pair of primers. Sanger sequencing and third-generation sequencing technology based on Nanopore were used to sequence the amplified products, and the types and expressions of different splices of RHD and RHCE gene mRNA transcripts were analyzed. 【Results】 The method established in this study can simultaneously amplify the full length transcripts of RHD and RHCE. Ten different RHD gene mRNA transcripts and nine RHCE gene mRNA transcripts were detected in 10 samples. RHD full-length transcript (RHD-201) can be detected in RhD Del type, but the expression amount was significantly lower than that in RhD positive samples. The expression amount of transcript RHD-207 (Del789) in Del samples was significantly higher than that in RhD positive samples. The transcript RHD-208 (Del8910+ 213) was only detected in RhD Del type individuals, and no significant difference was found between other RHD transcripts and all RHCE transcripts in the two phenotypes. 【Conclusion】 In this study, an analytical method for sequencing full-length transcript isomers of RHD and RHCE mRNA via the third generation was successfully established, and complex alternative splicing patterns were found in RHD and RHCE genes, providing a new method for the study of alternative splicing of blood group gene variants mRNA.

Effect of FTY720 on transfusion-related acute lung injury: a preliminary investigation / 中国输血杂志

【Objective】 To investigate the effects and mechanisms of different doses of fingolimod (FTY720) on non-antibody-mediated transfusion-related acute lung injury (TRALI). 【Methods】 A TRALI mouse model was constructed using lipopolysaccharide (LPS) pre-stimulation and platelets (Plt) of different storage days for second strike. The success of the modeling was determined by protein concentration in lung tissue homogenates, myeloperoxidase (MPo) activity, lung wet/dry weight ratio (W/D ratio), lung tissue damage score and pathological sections. Ceramide and sphingosine-1-phosphate (S1P) contents in platelets of different storage days were detected. FTY720 was administered 1 h after LPS injection to investigate the role of FTY720 in TRALI. The expression levels of vascular endothelial cadherin (VE-cadherin) and zonula occludens-1 (ZO-1) were analyzed by WB. 【Results】 Mice infused with stored 5-day Plt (d5Plt group) exhibited typical signs of TRALI, and the differences in lung tissue homogenate protein concentration (6 546.38±409.50) μg/mL, MPO activity (49.38±4.43) U/L, W/D ratio 4.79±0.21, and lung tissue damage score 7.24±0.38 from the rest of the groups were statistically significant (P<0.05). With the increase of platelet storage time, the ceramide content gradually increased and S1P content gradually decreased, and the ratio of the two was imbalanced. d5Plt showed statistically significant differences (P<0.01) in ceramide content (58.37±5.69) μmol/L and S1P content (149.81±4.86) nmol/L from the rest of the groups. After preventive administration of FTY720, 1 mg/kg FTY720 had no significant effect on TRALI mice, whose lung tissue homogenate protein concentration (6 170.26±545.50) μg/mL, MPO activity (45.97±4.79) U/L, W/D ratio 4.88±0.25, and lung tissue damage score 7.92±0.65 were significantly higher than those of the normal and LPS control groups (P<0.01). The low-dose (0.5, 0.2, and 0.1 mg/kg) FTY720 group alleviated lung injury, and its protein concentration, MPO activity, W/D ratio, and lung tissue injury score were significantly lower than those of the d5Plt group (P<0.05). Pathological sections also showed similar results. In terms of endothelial intercellular junction protein expression, the VE-cadherin expression levels in the 1 mg/kg FTY720 group were significantly lower than those in the normal and LPS control groups (P<0.05), and the VE-cadherin and ZO-1 expression levels in the low-dose (0.5, 0.2, and 0.1 mg/kg) FTY720 group were significantly higher than those in the d5Plt group (P<0.05), which tended to be normalized. 【Conclusion】 In this study, a TRALI mouse model was successfully established by one strike of LPS and two strikes of d5Plt. Low doses of FTY720 (0.5, 0.2, 0.1 mg/kg) were protective against TRALI, while high doses of FTY720 (1 mg/kg) may aggravate the symptoms of TRALI. This protective effect may be somewhat dependent on the expression of VE-cadherin and ZO-1.

Screening and clinical significance of intestinal colonization of carbapenem-resistant Enterobacteriaceae (CRE) in patients before haploidentical hematopoietic stem cell transplantation / 中国输血杂志

【Objective】 To investigate the situation of carbapenem-resistant Enterobacteriaceae(CRE) colonization in patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT). 【Methods】 A total of 241 consecutive patients who underwent haplo-HSCT in the First Affiliated Hospital of Soochow University from June 1, 2021 to June 1, 2022 were enrolled. Anal swab screening was performed within 48 hours of admission and blood cultures were taken when the patient developed fever. Univariate and multivariate analysis were used to analyze the colonization rate, distribution, risk factors and the correlation between CRE colonization and post-transplant bloodstream infection(BSI). 【Results】 Among 241 patients with haplo-HSCT, there were 90 cases in CRE colonization positive group, with a colonization rate of 37.3% (90/241). Multivariate logistic regression analysis showed that sex (OR 2.42, 95% CI 1.38-4.22, P<0.05) and history of infection within 30 days before transplantation (OR 3.37, 95% CI 1.59-7.17, P<0.05) may be independent risk factors for CRE intestinal colonization. Of the 95 CRE strains, the top five species were carbapenem-resistant Klebsiella pneumoniae (38/95, 40.0%), carbapenem-resistant Escherichia coli (29/95, 30.5%), carbapenem-resistant Enterobacter cloacae (13/95, 13.6%), carbapenem-resistant Klebsiella acidophilus (6/95, 6.3%) and carbapenem-resistant Proteus mirabilis (3/95, 3.1%). The incidence of post-transplant BSI was 12.0% (29/241) in the CRE-colonized group and 3.3% (8/241) in the non-colonized group. In the colonization group, 100% of the pathogens of BSI were identical with those of CRE colonization. 【Conclusion】 Bacterial culture of anal swab during haplo-HSCT is helpful for detection of CRE colonization in intestinal tract, which provides some clinical basis for active monitoring of key flora, prevention and control of infection.

Blood transfusion compatibility in patients with delayed serologic transfusion reaction: a retrospective analysis of 6 cases / 中国输血杂志

【Objective】 To retrospectively analyze the characteristics of blood transfusion compatibility detection in patients with delayed serologic transfusion reaction ( DSTR), in order to provide reference for safe and effective blood transfusion in clinical practice. 【Methods】 From April 2020 to July 2021, 6 samples of patients who applied for blood type identification, unexpected antibody screening and transfusion from the Third People′s Hospital of Chengdu or People′s Hospital of Sichuan Province were collected. Microcolumn method was used for identification of ABO and RhD blood type of patients; unexpected antibody screening, blood cross-match, antibody identification and direct anti-human globulin tests were also conducted. The sensitizing antibodies on the surface of red blood cells were identified by acid release solution, and the antigen-antibody reaction was enhanced by polyethylene glycol. The patients′ own red blood cells and input red blood cells were separated by capillary high-speed centrifugation, and the surface antigens of red blood cells were detected by serological method. Meanwhile,the characteristics of patients before and after transfusing antigen-positive red blood cells were summarized. 【Results】 Anti-E was detected in the plasma of patients 1 and 2, and anti-c,-E were detected in the red blood cell release solution, while anti-C, anti-E, anti-JKa and anti-Fyb were detected in the plasma and red blood cell release solution of patients 3, 4, 5 and 6, respectively. After capillary high-speed centrifugation, antigen-positive red blood cells were detected in the distal end of the blood samples of 6 patients. 【Conclusion】 For patients with multiple blood transfusions and a recent history of blood transfusion, when newly emerging erythrocyte antibodies with clinically significance, direct anti-human globulin test(+) or erythrocyte antibody screening(+) are detected, and the patient has no clinical symptoms of hemolysis, it should be suspected as DSTR occurrence, and the transfusion reaction investigation procedure should be initiated in time.

Perioperative allogenic blood transfusion for single disease in patients undergoing spinal deformity correction surgery:a longitudinal observational study / 中国输血杂志

【Objective】 To analyze the profile of perioperative allogenic blood transfusion for single disease in patients who underwent spinal deformity correction surgery and risk factors of the blood transfusion, in order to provide reference for clinical decision making. 【Methods】 Clinical data from medical record homepage of 292 patients who underwent elective spinal deformity correction surgery at Chengdu Third People′s Hospital from January 2015 to December 2017 were retrospectively analyzed. Statistical analysis of the transfusion profile of allogeneic blood based on the type of single disease in patients undergoing correction surgery was performed. Multiple factor linear regression analysis was used to identify the risk factors of perioperative allogenic blood transfusion in patients with spinal deformity correction surgery. Hospital length of stay and discharge status were compared between transfusion group and non-transfusion group using Mann Whitney U test and chi-square test respectively. 【Results】 The year prevalence of perioperative allogeneic blood transfusion from 2015 to 2017 were 90.38%(47/52), 93.62%(44/47) and 81.35%(157/193), respectively. The prevalence of perioperative allogeneic blood transfusion in patients with kyphotic deformity in ankylosing spondylitis, kyphosis, adolescent idiopathic scoliosis, scoliosis and spinal stenosis were 89.08%(106/119)、79.49%(62/78)、95.24%(40/42)、84.38%(27/32) and 61.90%(13/21), respectively. Multivariate linear regression analysis showed that the regression coefficients for age and osteotomy were -0.060 (P<0.05) and 2.060 (P<0.05), respectively. Compared with non-transfusion group, the transfusion group had longer hospital length of stay (P<0.05). 【Conclusion】 Perioperative allogeneic blood transfusion in patients with spinal deformity correction surgery is closely related to the type of single disease. Age is a protective factor for perioperative allogeneic blood transfusion, while osteotomy is a risk factor for perioperative allogeneic blood transfusion in patients undergoing the spinal deformity correction surgery. Perioperative blood transfusion can also prolong the hospital length of stay of the patients.

Distribution and transfusion efficacy of unexpected antibody / 中国输血杂志

【Objective】 To investigate the clinical characteristics and antibody distribution as well as evaluate the transfusion efficacy in unexpected antibody positive patients. 【Methods】 A total of 12 235 patients from January 1, 2022 to March 31, 2023 who hospitalized in our hospital and applied for blood transfusion were selected, and those with unexpected antibody were included. The clinical data, including gender, age, diagnosis, blood type, history of transfusion and pregnancy were collected for antibody distribution analysis. Patients who received transfusion were grouped according to the DAT results and the components of red blood cells transfused, and the Hb values of each group before and after transfusion were compared. 【Results】 Among12 235 patients, 118 were positive for antibody screening, with a prevalence of 0.96%. The antibodies from Rh system were the most common (27.43%, 48/175), followed by MNS system (8.57%, 15/175) and Lewis system (6.29%, 11/175), mainly anti-E (18.29%, 32/175), anti-M (8.00%, 14/175) and anti-Lea (5.71%, 10/175). In addition, 62 transfused patients were divided into group A with suspended red blood cell transfusion and group B with washed red blood cell transfusion for positive DAT, and group C for negative DAT. Hb values (g/L) pre- and post-transfusion were 59.19±15.67 vs 77.52±15.09 in group A, 56.35±14.08 vs 74.44±15.63 in group B, 56.00±12.06 vs 75.00±4.73 in group C, respectively. The Hb values of post-transfusion for three groups were all higher than those of pre-transfusion (P<0.05). 【Conclusion】 Anti-E from Rh system is the most common antibody in patients with unexpected antibody. Appropriate red blood cells transfusion with Hb increases by an average of 6-7 g/L per 1 U of red blood cells indicating good transfusion efficacy. For positive DAT patients, transfusion of suspended red blood cell is feasible.

Advances and applications of quantitative systems pharmacology modeling and virtual clinical trials in modern drug development / 药学学报

Quantitative systems pharmacology (QSP) modeling is an emerging computational medicine approach with growing applications and significance in modern drug development. QSP models are generally formulated based on multiscale disease mechanisms and drug-target interactions, which makes them capable of integrating multimodal data from the preclinical and clinical space. This also enables them to generate quantitative characterization of the dynamic disease progression as well as high-throughput predictions of drug-induced efficacy and toxicity signals. Therefore, QSP modeling and model-based virtual clinical trials have been widely implemented to guide drug development, in scenarios such as target identification and assessment, clinical trial design, evaluation of combination therapy and biomarkers, and personalized medicine. In US and Europe, QSP modeling has been developing rapidly in the past 10 years and is now an integral part of the model-informed drug development paradigm; however, in China it is still a nascent field. Here we will present a comprehensive review of the recent advancements of QSP and its impact in modern drug development through a number of case studies. This review will provide guidance for the future drug development efforts and the growth of QSP practice in China.

Advances in Molecular Targeted Drugs for Hepatocellular Carcinoma / 中山大学学报(医学科学版)

Being the most common solid malignant tumor in the digestive system and the third leading cause of cancer-related death worldwide， hepatocellular carcinoma （HCC） is characterized by insidious onset， early recurrence/metastasis and poor prognosis. With the advantages of targeted precision， high specificity， minimal drug resistance， remarkable therapeutic efficacy and fewer side effects， molecular targeted drugs have become the hotspot and focus of tumor therapy research in recent years. As more is learned about the mechanism and clinical efficacy， some molecular targeted drugs have been recommended by HCC treatment guidelines. This paper reviewed the mechanism of HCC targeted therapy， molecular targeted drugs， relevant therapeutic protocols and outcomes so as to provide reference and evidence for subsequent research.

Psychological and behavioral characteristics of children with autism spectrum disorder using Psycho-educational Profile (Third Edition) / 中国康复理论与实践

ObjectiveTo explore psychological and behavioral characteristics of children with autism spectrum disorder (ASD) using Psycho-educational Profile (Third Edition) (PEP3). MethodsFrom October, 2021 to October, 2022, 192 children with ASD without intervention in the Binzhou Medical University Hospital were selected as observation group, and 96 healthy children who visited at the same time were selected as control group. They were assessed with PEP3. ResultsThe development of receptive language significantly delayed behind expressive language (t = 5.383, P < 0.001) in the observation group. The cognitive, expressive language, receptive language, fine motor, gross motor, imitation and personal self-care correlated with age (r = 0.540 to 0.795, P < 0.001). The Cronbach's α of PEP3 for the observation group was 0.810 to 0.947. The original score of each subtest of PEP3 was less in the observation group than in the control group (|t| > 4.267, P < 0.001). ConclusionThe development of receptive language retards behind the expressive language in children with ASD. Cognitive and motor functions develop with age, while the correlation between maladaptive behavior and age is weak. PEP3 is reliable in internal consistency, and valid in discrimination.

Therapeutic Effect of Ziziphi Spinosae Semen-Albiziae Flos on Depression in Rats / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Ziziphi Spinosae Semen-Albiziae Flos on the nucleotide-binding oligomerization domain，NOD-like receptor thermal protein domain associated protein 1 （NLRP1）/chemokine ligand 1 （CXCL1）/chemokine receptor 2 （CXCR2） pathway in the hippocampus of the rat model of chronic unpredictable mild stress （CUMS）-induced depression. MethodA total of 120 male SD rats were randomized into blank，CUMS，CUMS + low-，medium-，and high-dose （4，8，16 g·kg-1） Ziziphi Spinosae Semen-Albiziae Flos，and CUMS + venlafaxine hydrochloride （0.008 g·kg-1） groups，with 20 rats in each group.The rat model of depression was established by solitary feeding combined with CUMS.The behaviors and spatial learning and memory abilities of rats were examined by sugar water consumption test，tail suspension test，forced swimming test，and Morris water maze test.Quantitative real-time PCR （Real-time PCR） and Western blot were employed to determine the expression of factors associated with the NLRP1/CXCL1/CXCR2 pathway in the hippocampus.Enzyme-linked immunosorbent assay was employed to determine the levels of tumor necrosis factor-α （TNF-α），interleukin （IL）-18，IL-1β，and IL-6 in the hippocampus.The immunofluorescence assay was used to measure the levels of reactive oxygen species （ROS） in the hippocampus. ResultCompared with the blank group，the CUMS group showed decreased preference to sugar water and times of crossing the platform （P<0.01），and increased immobility time of tail suspension，forced swimming floating time，and escape latency （P<0.01）.Compared with the CUMS group，the administration of Ziziphi Spinosae Semen-Albiziae Flos and venlafaxine hydrochloride alleviated the effects of CUMS on the above-mentioned behaviors and spatial learning and memory abilities of the rats （P<0.05，P<0.01）.Compared with the blank group，the CUMS group showed up-regulated protein levels of NLRP1，CXCL1，and CXCR2 （P<0.01） and elevated levels of IL-18，IL-1β，TNF-α，and IL-6 （P<0.01） in the hippocampus.The treatment with Ziziphi Spinosae Semen-Albiziae Flos and venlafaxine hydrochloride attenuated the activation of NLRP1/CXCL1/CXCR2 signaling pathway and lowered the levels of inflammatory cytokines in the hippocampus of CUMS rats （P<0.05，P<0.01）.In addition，Ziziphi Spinosae Semen-Albiziae Flos lowered the level of ROS in the hippocampus （P<0.05，P<0.01）. ConclusionZiziphi Spinosae Semen-Albiziae Flos can mitigate the depressive behaviors of the rat model of CUMS-induced depression by inhibiting the activation of NLRP1/CXCL1/CXCR2 signaling pathway.

Comparison of the myopia control effects of orthokeratology lens and peripheral defocus spectacles / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of peripheral defocus spectacles and orthokeratology lenses on the control of axial length in children and adolescents with myopia.METHODS: Prospective study. A total of 71 cases(134 eyes)of children and adolescents with myopia who visited the Second Hospital of Longyan from June 2019 to June 2021 were selected. They were fitted with peripheral defocus spectacles for 12mo and then switched to orthokeratology lenses. The growth of axial length was observed at 3, 6, and 12mo after wearing peripheral defocus spectacles and orthokeratology lenses.RESULTS: The median axial length growth after wearing peripheral defocus spectacles and orthokeratology lenses for 12mo was 0.35 and 0.14mm, respectively. The axial growth at 3, 6, and 12mo after wearing orthokeratology lenses was lower than those after wearing peripheral defocus spectacles(P&#x0026;#x003C;0.001), and the growth rate of axial length was significantly reduced. The patients were divided into a rapid progression group(axial growth ≥0.4 mm, 29 cases, 54 eyes)and a non-rapid progression group(axial growth &#x0026;#x003C;0.4mm, 42 cases, 80 eyes)according to the axial growth of peripheral defocus spectacles for 12mo. The median axial growth after wearing peripheral defocus spectacles for 12mo in the two groups was 0.70 and 0.24mm, respectively, while the median axial growth after wearing orthokeratology lenses was 0.31 and 0.09mm, respectively. The growth rate was reduced by 56% and 63% respectively in the two groups after wearing orthokeratology lens. The axial growth of cases wearing orthokeratology lenses for 12mo in the non-rapid progression group was lower than that in the rapid progression group, and it did not change with age or diopter. There was no significant difference among different ages and different diopters in the rapid progression group(P&#x0026;#x003E;0.05). In the non-rapid progression group, axial growth of cases aged 7-12 years was higher than those aged 13-16 years(P&#x0026;#x003C;0.05), but there was no significant difference among different diopters(P&#x0026;#x003E;0.05).CONCLUSION: Orthokeratology lens is more effective than peripheral defocus spectacles in controlling axial growth in children and adolescents with myopia, and the control effect of orthokeratology lens on rapid-progressing myopia is remarkable.

Exploration of human resource management practice for organ donation coordinators in public hospitals / 中华医院管理杂志

The human resource management of organ donation coordinators in China is still in its infancy stage, plagued by such problems as unclear career orientation, poor management and unclear career planning. In March 2010, a tertiary public hospital was approved as a medical institution in a national pilot province for organ donation. In recent years, the hospital had kept exploring human resource management of coordinators and established a relatively complete management mode for organ donation coordinators. This mode featured the establishment of full-time recruitment positions, development of human resource management plans, refinement of job descriptions, establishment of performance evaluation plans, optimization of assessment and incentive mechanisms, and innovation of talent cultivation modes. The management practice had achieved certain results, ensuring the sustainable development of hospital organ donation operation, and providing a reference for the scientific and standardized development of organ donation and transplantation in China.

Voltage-gated potassium channel-complex antibodies associated clinical syndromes with myasthenia gravis complicated with thymoma: analysis of 2 cases and literature review / 中华神经科杂志

Objective:To investigate the clinical characteristics and outcome of patients with voltage-gated potassium channel complex (VGKCc) antibody associated clinical syndromes complicated with myasthenia gravis (MG) with thymoma.Methods:The clinical history, examinations and follow-up prognosis of 2 cases of VGKCc antibodies associated clinical syndromes with MG complicated with thymoma in Qilu Hospital (Qingdao), Cheeloo College of Medicine,Shandong University in September 2020 and December 2020 were reviewed. Related literatures were summarized at the same time.Results:Case 1, a 64-year-old female clinically presented with cognitive impairment, psychosis, and epilepsy seizures, whose serum autoimmune antibody testing showed positive leucine-rich glioma-inhibited 1 (LGI1) antibody, was diagnosed as anti-LGI1 encephalitis,and had history of MG with thymoma. Her symptoms were improved by immunotherapy. Case 2, a 67-year-old male, was diagnosed as MG, and developed cognitive impairment, myokymia and autonomic dysfunction later. His serum autoimmune antibody testing showed positive contactin associated protein-like 2 antibody. Therefore, Morvan syndrome complicated with MG with thymoma was definitely diagnosed. After admission, the patient was improved with immunotherapy and thymoma resection.Conclusions:Patients with VGKCc antibody-associated clinical syndromes complicated with MG have the clinical characteristics of the two diseases simultaneously, and there is also crossover. Immunotherapy and treatment for thymoma are generally effective.

A prospective study on the development and application verification of the quantitative evaluation software for three-dimensional morphology of pathological scars based on photo modeling technology / 中华烧伤杂志

Objective: To develop a quantitative evaluation software for three-dimensional morphology of pathological scars based on photo modeling technology, and to verify its accuracy and feasibility in clinical application. Methods: The method of prospective observational study was adopted. From April 2019 to January 2022, 59 patients with pathological scars (totally 107 scars) who met the inclusion criteria were admitted to the First Medical Center of Chinese PLA General Hospital, including 27 males and 32 females, aged 33 (26, 44) years. Based on photo modeling technology, a software for measuring three-dimensional morphological parameters of pathological scars was developed with functions of collecting patients' basic information, and scar photography, three-dimensional reconstruction, browsing the models, and generating reports. This software and the clinical routine methods (vernier calipers, color Doppler ultrasonic diagnostic equipment, and elastomeric impression water injection method measurement) were used to measure the longest length, maximum thickness, and volume of scars, respectively. For scars with successful modelling, the number, distribution of scars, number of patients, and the longest length, maximum thickness, and volume of scars measured by both the software and clinical routine methods were collected. For scars with failed modelling, the number, distribution, type of scars, and the number of patients were collected. The correlation and consistency of the software and clinical routine methods in measuring the longest length, maximum thickness, and volume of scars were analyzed by unital linear regression analysis and the Bland-Altman method, respectively, and the intraclass correlation coefficients (ICCs), mean absolute error (MAE), and mean absolute percentage error (MAPE) were calculated. Results: A total of 102 scars from 54 patients were successfully modeled, which located in the chest (43 scars), in the shoulder and back (27 scars), in the limb (12 scars), in the face and neck (9 scars), in the auricle (6 scars), and in the abdomen (5 scars). The longest length, maximum thickness, and volume measured by the software and clinical routine methods were 3.61 (2.13, 5.19) and 3.53 (2.02, 5.11) cm, 0.45 (0.28, 0.70) and 0.43 (0.24, 0.72) cm, 1.17 (0.43, 3.57) and 0.96 (0.36, 3.26) mL. The 5 hypertrophic scars and auricular keloids from 5 patients were unsuccessfully modeled. The longest length, maximum thickness, and volume measured by the software and clinical routine methods showed obvious linear correlation (with r values of 0.985, 0.917, and 0.998, P<0.05). The ICCs of the longest length, maximum thickness, and volume of scars measured by the software and clinical routine methods were 0.993, 0.958, and 0.999 (with 95% confidence intervals of 0.989-0.995, 0.938-0.971, and 0.998-0.999, respectively). The longest length, maximum thickness, and volume of scars measured by the software and clinical routine methods had good consistency. The Bland-Altman method showed that 3.92% (4/102), 7.84% (8/102), and 8.82% (9/102) of the scars with the longest length, maximum thickness, and volume respectively were outside the 95% consistency limit. Within the 95% consistency limit, 2.04% (2/98) scars had the longest length error of more than 0.5 cm, 1.06% (1/94) scars had the maximum thickness error of more than 0.2 cm, and 2.15% (2/93) scars had the volume error of more than 0.5 mL. The MAE and MAPE of the longest length, maximum thickness, and volume of scars measured by the software and clinical routine methods were 0.21 cm, 0.10 cm, 0.24 mL, and 5.75%, 21.21%, 24.80%, respectively. Conclusions: The quantitative evaluation software for three-dimensional morphology of pathological scars based on photo modeling technology can realize the three-dimensional modeling and measurement of morphological parameters of most pathological scars. Its measurement results were in good consistency with those of clinical routine methods, and the errors were acceptable in clinic. This software can be used as an auxiliary method for clinical diagnosis and treatment of pathological scars.

Establishment and Evaluation of Intestinal Injury Model of Mouse Acute Graft Versus Host Disease Based on An Organoid Technology / 中国实验血液学杂志

OBJECTIVE@#To establish an intestinal organoid model that mimic acute graft versus host disease (aGVHD) caused intestinal injuries by using aGVHD murine model serum and organoid culture system, and explore the changes of aGVHD intestine in vitro by advantage of organoid technology.@*METHODS@#20-22 g female C57BL/6 mice and 20-22 g female BALB/c mice were used as donors and recipients for bone marrow transplantation, respectively. Within 4-6 h after receiving a lethal dose (8.0 Gy) of γ ray total body irradiation, a total of 0.25 ml of murine derived bone marrow cells (1×107/mice, n=20) and spleen nucleated cells (5×106/mice, n=20) was infused to establish a mouse model of aGVHD (n=20). The aGVHD mice were anesthetized at the 7th day after transplantation, and the veinal blood was harvested by removing the eyeballs, and the serum was collected by centrifugation. The small intestinal crypts of healthy C57BL/6 mice were harvested and cultivated in 3D culture system that maintaining the growth and proliferation of intestinal stem cells in vitro. In our experiment, 5%, 10%, 20% proportions of aGVHD serum were respectively added into the organoid culture system for 3 days. The formation of small intestinal organoids were observed under an inverted microscope and the morphological characteristics of intestinal organoids in each groups were analyzed. For further evaluation, the aGVHD intestinal organoids were harvested and their pathological changes were observed. Combined with HE staining, intestinal organ morphology evaluation was performed. Combined with Alcian Blue staining, the secretion function of aGVHD intestinal organoids was observed. The distribution and changes of Lgr5+ and Clu+ intestinal stem cells in intestinal organoids were analyzed under the conditions of 5%, 10% and 20% serum concentrations by immunohistochemical stainings.@*RESULTS@#The results of HE staining showed that the integrity of intestinal organoids in the 5% concentration serum group was better than that in the 10% and 20% groups. The 5% concentration serum group showed the highest number of organoids, the highest germination rate and the lowest pathological score among experimental groups, while the 20% group exhibited severe morphological destruction and almost no germination was observed, and the pathological score was the highest among all groups(t=3.668, 4.334,5.309,P<0.05). The results of Alican blue staining showed that the secretion function of intestinal organoids in serum culture of aGVHD in the 20% group was weaker than that of the 5% group and 10% of the organoids, and there was almost no goblet cells, and mucus was stainned in the 20% aGVHD serum group. The immunohistochemical results showed that the number of Lgr5+ cells of intestinal organoids in the 5% group was more than that of the intestinal organoids in the 10% aGVHD serum group and 20% aGVHD serum group. Almost no Clu+ cells were observed in the 5% group. The Lgr5+ cells in the 20% group were seriously injuried and can not be observed. The proportion of Clu+ cells in the 20% group significantly increased.@*CONCLUSION@#The concentration of aGVHD serum in the culture system can affect the number and secretion function of intestinal organoids as well as the number of intestinal stem cells in organoids. The higher the serum concentration, the greater the risk of organoid injury, which reveal the characteristics of the formation and functional change of aGVHD intestinal organoids, and provide a novel tool for the study of intestinal injury in aGVHD.