Stability study of umbilical cord mesenchymal stem cells formulation in large-scale production / 药学学报

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

Based on LC-MS technology explored the metabolomics of Agrimonia pilosa intervening in non-small cell lung cancer A549 cells / 药学学报

The objective of this study was to analyze the effects on cell viability, apoptosis, and cell cycle of non-small cell lung cancer (NSCLC) A549 cells after intervention with Agrimonia pilosa (AP) and investigate Agrimonia pilosa anti-tumor activity in vitro. Meanwhile, liquid chromatography mass spectrometry (LC-MS) metabolomics technology was used to analyze the changes of cellular metabolites and metabolic pathways. The results of this study will provide a theoretical and experimental basis for investigating the mechanism of the effect of Agrimonia pilosa on non-small cell lung cancer A549 cells. The results showed that the cell nucleus of A549 cells crumpled and apoptosis occurred with the increase of drug concentration. The survival rate of the cells decreased, and the inhibition rate reached 21.5% and 91.74% under the low and high dose conditions, respectively. Lactate dehydrogenase (LDH) content increased (P < 0.05). Metabolomics results showed significant differences in metabolism between groups, thirty-three distinct metabolites including LysoPC(24:0/0:0), LysoPC(17:0/0:0) and PC(O-40:5) were deduced. The pathway enrichment showed that the Agrimonia pilosa plays an anti-tumor role mainly by regulating the metabolism of glycerophosphate and purine in A549 cells, in which the effect on glycerophosphate metabolism pathway was most significant. The results of combined pharmacodynamics suggested that Agrimonia pilosa might induce apoptosis and inhibit the growth of A549 cells by regulating LysoPC(24:0/0:0), LysoPC(17:0/0:0) and PC(O-40:5) metabolites in A549 cells.

Clinicopathologic Characteristics and Prognosis of Oligodendroglioma with IDH Mutation and 1p/19q Codeletion / 肿瘤防治研究

Objective To analyze the clinicopathological characteristics and prognosis of oligodendroglioma with IDH mutation and 1p/19q codeletion. Methods We collected the data of 54 oligodendroglioma patients with IDH mutation and 1p/19q codeletion.The patients'clinicopathological data, including age, histological grade, and tumor site, were analyzed for the effects on progression-free and overall survival. Results Among the 54 patients, 46 cases were with tumor sites in one lobe, and eight cases involved tumor sites in more than two lobes.A total of 12 and 42 cases had WHO grades 2 and 3 oligodendroglioma, respectively.Detection by fluorescence in situ hybridization showed 1p/19q co-deletion in all cases.Immunohistochemical tests revealed diffuse and strong positive results for Olig2.All glial fibrillary acidic proteins were positive.p53 was strongly positive in six cases.ATRX was expressed in all 48 cases.Ki-67 proliferation index ranged from 5% to 60%.Sanger sequencing showed that all 54 cases had IDH gene mutations (40 cases were IDH1 mutations, and 14 were IDH2 mutations), and 33 cases had telomerase reverse transcriptase promoter mutations.Relapse and metastasis occurred in 16 patients during treatment.Univariate analysis indicated that the postoperative recurrence and metastasis interval of more than two years can prolong the progression-free and overall survival of patients.All 54 patients had a mean progression-free survival of 33.5 months and the mean overall survival of 40.7 months. Conclusion For oligodendroglioma with IDH mutation and 1p/19q codeletion, precision chemoradiotherapy after surgery can reduce the risk of progression, and the postoperative recurrence and metastasis interval is associated with the prognosis.

Characteristics and relationship between the development of gross motor skills and executive function in children with attention deficit hyperactivity disorder / 中国康复理论与实践

ObjectiveTo investigate the developmental characteristics of gross motor skills and executive functions, and the correlation between them in school-age children with attention deficit hyperactivity disorder (ADHD). MethodsFrom November, 2020 to May, 2021, 90 children with ADHD were recruited from Peking University Sixth Hospital and Beijing Haidian Wanquan Primary School, and other 90 children with normal development from this primary school were recruited matched their age and gender. Gross motor skills were assessed with the Test of Gross Motor Development in Children, Third Edition (TGMD-3), and inhibitory control, working memory, and cognitive flexibility were assessed with Stroop Color Words Test (SCWT), Rey-Osterrich Complex Figure Test (ROCFT) and Trail Making Test (TMT), respectively. ResultsThe TGMD-3 score was significantly lower in children with ADHD than in normal children (t = -6.275, P < 0.001), while the test results of SCWT, ROCFT and TMT were worse (|t| ≥ 1.986, P ≤ 0.05). The TGMD-3 score of children with ADHD was negatively correlated with the word sense reaction time (r = -0.261), the number of word sense errors (r = -0.404) and the number of color errors (r = -0.326) (P < 0.05), positively correlated with the delayed structural memory scores (r = 0.228) (P < 0.05), and negatively correlated with the TMT-A reaction time (r = -0.255), the number of TMT-A errors (r = -0.329), TMT-B reaction time (r = -0.214) and the number of TMT-B errors (r = -0.474) (P < 0.05). Stratified linear regression analyses showed that the TGMD-3 score of children with ADHD was significant only in predicting test results for inhibitory control and cognitive flexibility (P < 0.05), with explanations of 8.7% and 22.5%, respectively. ConclusionDevelopments of both gross motor skills and executive function delay in children with ADHD, and there is a relation between them, especially the level of gross motor skills relating to the developments of inhibitory control and cognitive flexibility.

Research progress on mTOR signaling pathway and regulatory T cell nutrition metabolic regulation mechanism / 细胞与分子免疫学杂志

In the tumor microenvironment, metabolic reprogramming can impact metabolic characteristics of T cells, thus inducing immunosuppression to promote tumor immune escape. The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in regulating diverse functions of various immune cells. This review mainly focuses on the molecular mechanism of mTOR signaling in regulating cellular energy metabolism process, and the activation status of mTOR signaling under different nutritional environments. In addition, it also summarizes the role of the mTOR signaling in regulatory T cell (Tregs) metabolism and function in current studies, and evaluates the potential of mTOR as a clinical immunotherapeutic target and its current application challenges.

An evaluation of carrier detection for Spinal muscular atrophy using digital PCR assay / 中华医学遗传学杂志

OBJECTIVE@#To assess the effectiveness and feasibility of carrier detection for Spinal muscular atrophy (SMA) by using digital PCR assay.@*METHODS@#Peripheral blood samples were collected from 214 pregnant women who were routinely screened for SMA carriers, of which 204 were randomly selected samples and 10 were samples with known copy numbers of SMN1 exons 7 and 8. Samples with known copy numbers of SMN1 exons 7 and 8 were randomly mixed into the experiment to validate the performance of the digital PCR assay.@*RESULTS@#The copy numbers of SMN1 exons 7 and 8 and SMN2 exons 7 and 8 in peripheral blood samples were detected by digital PCR assay. The results of SMN1 exons 7 and 8 were compared with those of the quantitative PCR method to assess the reliability and clinical performance of the digital PCR assay. Among the 204 random samples, digital PCR has detected five samples with simultaneous heterozygous deletion of SMN1 exons 7 and 8, three samples with heterozygous deletion of SMN1 exon 8 only, and 196 samples with no deletion of SMN1 exons 7 and 8. Ten samples with known SMN1 exons 7 and 8 copy numbers were detected with the expected values. The digital PCR test results were fully consistent with that of the quantitative PCR.@*CONCLUSION@#The results of digital PCR for the detection of copy number variation of SMN1 exons 7 and 8 were consistent with qPCR. Digital PCR assay was able to clearly distinguish the copy number of the target genes, therefore can be used for SMA carrier screening. Moreover, it can also detect copy number of SMN2 exons 7 and 8, which can provide more information for genetic counseling.

Meta-analysis of the role of fibular fixation in tibiofibular fractures / 中国骨伤

OBJECTIVE@#To compare the role and importance of fibular fixation in tibiofibular fractures by Meta-analysis.@*METHODS@#The literature related to the comparison of the efficacy of fixation of the fibula with or without fixation on the treatment of tibiofibular fractures was searched through the databases of China Knowledge Network, Wipu, Wanfang, The Cochrane Library, Web of science and Pubmed, and statistical analysis was performed using RevMan 5.3 software. The rates of malrotation, rotational deformity, internal/external deformity, anterior/posterior deformity, non-union, infection, secondary surgery and operative time were compared between the fibula fixation and non-fixation groups.@*RESULTS@#A total of 11 publications were included, six randomised controlled trials and five case-control trials, eight of which were of high quality. A total of 813 cases were included, of which 383 were treated with fibula fixation and 430 with unfixed fibulae.Meta-analysis results showed that fixation of the fibulae in the treatment of tibiofibular fractures reduced the rates of postoperative rotational deformity[RR=0.22, 95%CI(0.10, 0.45), P<0.000 1] and internal/external deformity[RR=0.34, 95%CI(0.14, 0.84), P=0.02] and promoted fracture healing [RR=0.76, 95%CI(0.58, 0.99), P=0.04]. In contrast, the rates of poor reduction [RR=0.48, 95% CI(0.10, 2.33), P=0.36], anterior/posterior deformity[RR=1.50, 95%CI(0.76, 2.96), P=0.24], infection[RR=1.43, 95%CI(0.76, 2.72), P=0.27], secondary surgery[RR=1.32, 95%CI(0.82, 2.11), P=0.25], and operative time[MD=10.21, 95%CI(-17.79, 38.21), P=0.47] were not statistically significant (P>0.05) for comparison.@*CONCLUSION@#Simultaneous fixation of the tibia and fibula is clinically more effective in the treatment of tibiofibular fractures.

Analysis of urine Alzheimer-associated neuronal thread protein level and related factors of middle-aged and elderly people in Mianyang / 四川精神卫生

ObjectiveTo investigate the Alzheimer-associated neurofilament protein （AD7c-NTP） in urine of middle-aged and elderly people and its correlation between common metabolites. MethodsA total of 1 150 middle-aged and elderly people who did their physical exmanination in the health examination center of the Sichuan Science City Hospital and the Third Hopital of Mianyang were recruited from March 2017 to March 2020. The level of urine AD7c-NTP were measured by enzyme-linked immunosorbent assay （ELISA）， and common metabolites in blood were measured by biochemical analyzer. Based on urine AD7c-NTP level ≤1.5 ng/mL， the objects was divided into normal group （n=956） and elevated group （n=194）. Thier demographic data and blood biochemical indicators were collected. ResultsThe urine AD7c-NTP level in middle-aged and elderly people was 0.60（0.30~1.20） ng/mL. The urine AD7c-NTP level was higher in women than that in men ［1.04（0.40~1.30） ng/mL vs. 0.84（0.30~1.00） ng/mL， Z=4.202， P˂0.01］. And the urine AD7c-NTP level was lower in the normal group than that in the elevated group ［0.50（0.30~0.90） ng/mL vs. 2.10（1.70~2.10） ng/mL， Z=22.035， P˂0.01］. The results of the univariate comparison showed that， the differences between the two groups in age （Z=6.545）， fasting glucose （Z=3.506）， blood uric acid （Z=2.574）， urea nitrogen （Z=2.891）， creatinine （Z=2.243）， total bilirubin （Z=3.936）， glutathione （Z=0.969）， total cholesterol （t=3.956） and low density lipoprotein （Z=-5.678） were were statistically significant （P˂0.05 or 0.01）. Spearman correlation analysis showed that， the urine AD7c-NTP level was positively correlated with age and the levels of urea nitrogen， glucose， total cholesterol and low density lipoprotein （r=0.177， 0.178， 0.171， 0.109， 0.149， P˂0.01）， and negatively correlated with the level of total bilirubin （r=-0.172， P˂0.01）. Conclusionthe urine AD7c-NTP level in middle-aged and elderly females was signifitcantly higher than in middle-aged and elderly males.The urine AD7c-NTP level of middle-aged and elderly people was positively correlated with age， urea nitrogen， glucose， total cholesterol and low density lipoprotein， and negatively correlated with total bilirubin.

Sjögren's syndrome combined with cold agglutinin disease: A case report / 北京大学学报(医学版)

Sjögren's syndrome(SS)is a chronic autoimmune disease that affects exocrine glands, especially salivary and lacrimal glands. The main clinical manifestations are dry mouth and dry eyes, but also multi-organ and multi-system can be involved. Cold agglutinin disease(CAD)is an autoimmune disease characterized by red blood cell agglutination in the blood vessels of extremities caused by cold agglutinin at low temperature, resulting in skin microcirculation disturbance, or hemolytic anemia. Cold agglutinin disease is divided into two categories, primary cold agglutinin disease and secondary cold agglutinin disease. Primary cold agglutinin disease is characterized with cold agglutinin titer of 1 ∶4 000 or more and positive Coomb's test. However, the Coomb's test is not necessarily positive and the cold agglutinin titer is between 1 ∶32 and 1 ∶4 000 in secondary cold agglutinin disease. Here, we reported an elderly patient admitted to hospital due to fever. He was diagnosed with respiratory infection, but he showed incompletely response to the anti-infection treatment. Further laboratory tests showed the patient with positive ANA and anti-SSA antibodies. Additionally, the patient complained that he had dry mouth and dry eyes for 1 year. Schirmer test and salivate gland imaging finally confirmed the diagnosis Sjogren's syndrome. During the hospital stay, the blood clots were found in the anticoagulant tubes. Hemolytic anemia was considered as the patient had anemia with elevated reticulocytes and indirect bilirubin. In addition, further examination showed positive cold agglutination test with a titer of 1 ∶1 024, and cold agglutinin disease was an important type of cold-resistant autoimmune hemolytic anemia. Furthermore, the patient developed cyanosis after ice incubating at the tip of the nose. Hence, the patient was diagnosed as CAD and he was successfully treated with glucocorticoids instead of anti-infection treatments. Hence, the patient was diagnosed with SS combined with secondary CAD. SS combined CAD are rarely reported, and they are both autoimmune diseases. The abnormal function of B lymphocytes and the production of autoantibodies might be the common pathogenesis of them. Cold agglutinin disease can lead to severe hemolytic anemia, even life-threatening. In clinical practice, timely recognizing and dealing with CAD might promote the prognosis of the patient.

Risk Factors of Multiple Myeloma Complicated with Venous Thromboembolism / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical characteristics of venous thromboembolism (VTE) in patients with multiple myeloma (MM) and to identify the risk factors of VTE in MM patients.@*METHODS@#179 newly diagnosed MM (NDMM) patients admitted to The Second Hospital of Shanxi Medical University from January 2014 to December 2020 who were followed up for more than 6 months were collected, and they were divided into VTE group and control group according to whether combined with VTE. The clinical and laboratory data were compared between the two groups. Mann-whitney U test was used for inter-group comparison of measurement data, Chi-square test or Fisher's exact test was used for inter-group comparison of count data, and multivariate logistic regression analysis was performed to explore the risk factors of VTE in MM patients.@*RESULTS@#Compared with control group, the serum albumin (ALB) level in VTE group was significantly lower (P =0.033), the fibrinogen (FIB) level was significantly higher (P =0.016), and the proportion of patients with D-dimer≥2 000 ng/ml was significantly higher than that in the control group (26.3% vs 4.4%, P =0.002). There was a significant difference in M-component type between the two groups (P =0.028), and the proportion of IgG type in VTE group was higher. There were no statistically significant differences between two groups in age, sex, body mass index (BMI), the proportions of patients with hypertension, diabetes, coronary heart disease and cerebral infarction, white blood cell (WBC) count, platelet (PLT) count, liver and kidney function, plasma cells ratio in bone marrow, serum globulin (GLO), lactate dehydrogenase (LDH), β2-microglobulin (β2-MG) level, C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), prothrombin time (PT), activated partial thromboplastin time (APTT), disease stage, thrombosis prevention and the use of immunomodulators (P >0.05). Multivariate logistic regression analysis showed that FIB level (OR=1.578, 95%CI:1.035-2.407, P =0.034), D-dimer≥2 000 ng/ml (OR=5.467, 95%CI:1.265-23.621, P =0.023) and IgG type (OR=4.780, 95%CI: 1.221-18.712, P =0.025) were independent risk factors for VTE in MM patients.@*CONCLUSION@#MM patients are prone to VTE, and FIB level, D-dimer≥2 000 ng/ ml and IgG type are independent risk factors for VTE in MM patients.

High-Throughput Sequencing Technology for Detection of Gene Mutations in Myeloid Malignancies and Its Clinical Prognostic Significance / 中国实验血液学杂志

OBJECTIVE@#To detect the gene mutations in patients with myeloid malignancies by high-throughput sequencing and explore the correlation between gene mutations and prognosis.@*METHODS@#A retrospective analysis was performed on 56 patients with myeloid malignancies who were hospitalized in the department of hematology, Peking University International Hospital from January 2020 to May 2021. The genetic mutations of the patients were detected by next-generation sequencing technology, and the correlation between the genetic mutations and prognosis of myeloid malignancies was analyzed.@*RESULTS@#In 56 patients, the number of mutated genes detected in a single patient is 0-9, with a median of 3. Sequencing results showed that the most common mutated genes were RUNX1(21.4%), TET2(17.9%), DNMT3A(17.9%), TP53(14.3%) and ASXL1(14.3%), among which the most common mutations occurred in the signaling pathway-related genes (23.3%) and the transcription factor genes (18.3%). 84% of the patients carried multiple mutated genes (≥2), and correlation analysis showed there were obvious co-occurring mutations between WT1 and FLT3, NPM1 and FLT3-ITD, and MYC and FLT3. TP53 mutation was more common in MDS patients.The overall survival time of patients with NRAS mutation was significantly shortened (P =0.049). The prognosis of patients with TP53 mutation was poor compared with those without TP53 mutation, but the difference wasn't statistically significant (P =0.08).@*CONCLUSION@#The application of next-generation sequencing technology is of great significance in myeloid malignancies, which is helpful to better understand the pathogenesis of the disease, to judge the prognosis and to find possible therapeutic targets.

Analysis and discussion on the subject complaint in clinical drug trials / 中华医学科研管理杂志

Objective:By exploring the management of subject complaints by the ethics committee, to identify and correct the problems that damage the rights of subjects in clinical drug trials, in order to improve the ability of the ethics committee of protecting the rights and interests of the subjects.Methods:We conducted a retrospective analysis of 13 cases of subject complaints accepted by the Ethics Committee of Peking University People′s Hospital from January to December 2021, analyzed the causes of complaints, and proposed countermeasures and suggestions.Results:Problems exist in the subject complaints regarding the payment of compensation, investigators′ communication attitude and skills, subjects′ understanding bias, etc.Conclusions:The ethics committee should attach great importance to subject complaints, adopt a closed-loop management process, carry out hierarchical management, strict ethical review, improve the ability of continuous supervision, conduct targeted training for investigators, and provide counseling services for subjects, to improve the communication between investigators and subjects, effectively reduce and avoid the occurrence of complaints. Relevant functional departments of medical and health institutions should work together to protect the rights and interests of the subjects.

Establishment of a new strategy to correct the interference of chyle blood on the detection of hemoglobin and mean red blood cell hemoglobin concentration / 中华检验医学杂志

Objective:To establish a new strategy for rapid correction of the interference of chyle blood on hemoglobin (HGB) and related indexes by reticulocyte (RET) channel research parameters (HGB-O, MCHC-O) from automatic hematological analyzer.Methods:With the diagnostic experimental design, a total of 90 impatient samples were sequential picked from Fuwai Hospital, which had routine blood testing from June 1 to July 31, 2021. The selected samples were free of hemolysis, jaundice, chylo. The age of the patients was (49.2±5.7) years, with 47 males and 43 females. Three different contents(25, 50, 75 μl) of fat emulsion injection were used to replace plasma in equal amounts to prepare chyle blood samples with mild, medium and heavy degrees of average red blood cell hemoglobin concentration (MCHC). The research parameters (HGB-O, MCHC-O) obtained by the RET channel detection of the automatic blood analyzer were used as the corrected HGB and its related index values (RET method), and the original values (the detection values before adding fat emulsion) and the formula correction values were paired with t-test or Wilcoxon signed rank test, single factor analysis of variance or Kruskal-Wallis rank-sum test, Bland-Altman and correlation analysis to evaluate the correction effect of RET method.Results:There was no significant difference ( H=0.035, P=0.983; H=0.097, P=0.953; H=0.112, P=0.945) between the RET correction values of HGB (g/L) [104.0(83.8, 132.8), 109.0(87.78, 128.25), 104.0(87.8, 131.8)] and the original values [104.0(83.0, 133.0), 107.5(86.75, 129.25), 103.5(85.8, 131.3)] and the formula correction values [104.0(84.0, 133.8), 106.0(86.75, 131.25), 102.5(86.8, 131.3)] in the samples of chythemia with varying degrees of MCHC (g/L) elevation; meanwhile, the RET correction values [366.5(325.8, 341.5), 333.5(323.8, 340.0), 333.5(327.0, 341.25)] and the original values [336.0(324.8, 342.0), 333.0(323.5, 342.3), 332.0(326.75, 340.5)] and the formula correction values [333.5(323.5, 343.3), 331.0(321.0, 338.3), 329.5(325.25, 337.25)] were also not statistically significant ( H=0.049, P=0.976; H=3.149, P=0.207; H=0.883, P=0.643). The detection values of HGB and related indexes corrected by RET method were in good agreement with the original values [96.7% (29/30) of the points were within the 95% consistency limit], and the two were positively correlated (the correlation coefficients were all higher than 0.919, P<0.01). Conclusion:The RET method based on the research parameters of RET channel of automatic hematological analyzer can serve as a new strategy to correct the interference of chyle blood on the detection of HGB and related indexes.

Calf tissue flap combined with artificial bone of antibiotics loaded calcium sulphate in treatment of tibia osteomyelitis / 中华显微外科杂志

Objective:To observe the surgical method and clinical efficacy of applying calf tissue flap combined with artificial bone of antibiotics loaded calcium sulphate in treatment of tibia osteomyelitis.Methods:From July 2018 to January 2021, calf tissue flaps combined with artificial bone of antibiotics loaded calcium sulphate (or mixed with iliac bone) were applied to treat 16 cases with tibia osteomyelitis in the Department of Hand and Microsurgery of Baoji Third Hospital. There were 10 males and 6 females, aged 15 to 64 years old, with a mean age of 41 years old. For the 5 cases with acute osteomyelitis caused by wound infection, local dressing changes and drainage or VSD wound management were applied after debridement, together with primary systemic anti-infection treatment. After the acute infection period had been under control and stabilised, the wounds were then thoroughly exposed and cavities were filled and covered with the surgical reconstruction procedure with antibiotics-loaded artificial bone of calcium sulphate in combination with calf tissue flaps. For the 11 cases with chronic and hypotoxicity osteomyelitis, calf tissue flaps combined with antibiotics-blended artificial bone of calcium sulphate were applied to fill the cavity and cover the wound in phase I surgical reconstruction after thorough debridement. For the 7 cases with large bone defects or larger cavities after debridement, a mixed bone grafts of antibiotics-loaded artificial bone of calcium sulphate and autologous iliac bone were employed, with muscle flaps or myocutaneous flaps for an embedding repair. Sizes of the tissue flaps were 2.0 cm×3.5 cm to 12.0 cm×23.0 cm. Clinical outcomes were evaluated through follow-ups at outpatient clinic. The therapeutic effect was evaluated by the method described by McKee et al.Results:Except for 1 case of distal necrosis of tissue flap and survived after dressing change, the other tissue flap survived successfully. Postoperative follow-ups lasted for 12 to 40(mean 18) months. All the osteomyelitis were successfully cured, except 1 that had recurrence of osteomyelitis 1 year later, and treated with antibiotics-loaded artificial bone of calcium sulphate combined with autologous iliac bone implants after thorough debridement, and then healed well. The shape and texture of flaps were good. Protective sensations were restored to vary levels after 6 months. The calf regained weight-bearing and walking functions at 1 year after surgery. According to McKee et al., the therapeutic effect was evaluated: 11 cases were cured, 4 cases were improved, and 1 case relapsed, with an effective rate of 93.8%.Conclusion:Application of calf tissue flap combined with antibiotics-loaded artificial bone of calcium sulphate in the treatment of tibia osteomyelitis has a high cure rate and remarkable efficacy. It can significantly reduce the number of surgeries and shorten the course of disease.

Combining repeated transcranial magnetic stimulation with psychological intervention can synergistically relieve depression among those with Parkinson′s disease / 中华物理医学与康复杂志

Objective:To explore any effect of supplementing psychological intervention with repeated transcranial magnetic stimulation (rTMS) in the rehabilitation of depressed persons with Parkinson′s disease (dPD).Methods:A total of 120 dPD patients were randomly divided into a psychological intervention group, an rTMS treatment group and an observation group, each of 40. In addition to conventional anti-Parkinson′s treatment and anti-depressant treatment, the psychological intervention group received such treatment and the rTMS group received 10Hz rTMS applied over the left dorsolateral prefrontal cortex for 8 weeks. The observation group received both interventions. Before and after the treatment, depression, neurological functioning and life quality were evaluated in all of the subjects using the 24-item Hamilton Depression Scale, the Movement Disorder Society′s unified Parkinson′s disease rating scale and the SF-36 questionnaire.Results:After the intervention, significant improvement was observed in all of the quantitative evaluations as well as in the remission rate (40%) and the reaction rate (90%). On average, the observation group′s results were significantly better than those of the other two groups.Conclusion:Psychological intervention and rTMS a have synergistic effect in treating dPD patients and their combination is worthy of clinical promotion and application, as it can relieve their depression and improve their neurological functioning and life quality.

Nephrotic syndrome associated with coenzyme Q10 deficiency due to coenzyme Q2 gene mutation: a case report / 中华肾脏病杂志

The paper reports a case of coenzyme Q10 deficiency nephrotic syndrome associated with coenzyme Q2 gene mutation and reviews the literature on this topic. The patient presented with hematuria, proteinuria, and a diminution of vision as clinical manifestations. But the proteinuria was not relieved after sufficient doses of glucocorticoids for over 2 months. The patient′s birth history was unremarkable, and his parents were both healthy and not consanguineous. Whole exome sequencing revealed that the patient had a mutation of coenzyme Q2 gene at c.973A>G(p.T325A) and c.517C>T(p.R173C). Combined with renal biopsy pathology, the patient was diagnosed with hereditary nephropathy and started the supplements of coenzyme Q10 after stopping glucocorticoid treatments immediately. After 5 weeks of therapy, the patient′s 24-h urine protein quantification decreased from 6.01 g to 1.53 g.

Analysis of risk factors for intradialytic hypotension in elderly maintenance hemodialysis patients / 中华肾脏病杂志

Objective:To analyze the risk factors for the occurrence of intradialytic hypotension (IDH) in elderly maintenance hemodialysis (MHD) patients based on longitudinal multidimensional data.Methods:This was a single-center, retrospective observational study. Data of MHD patients were retrospectively analyzed from April 3, 2017 to December 31, 2021 in the blood purification center of National Clinical Research Center for Kidney Diseases, General Hospital of Eastern Theater Command. IDH defined by the Kidney Disease Outcomes Quality Initiative was used as outcome indicator. Generalized estimating equations were used for univariate and multivariate regression analysis. The importance of each factor on the occurrence of IDH was evaluated by chi-square statistic minus degrees of freedom, and sensitivity analysis was performed by 5-fold interpolation of missing data.Results:A total of 156 elderly patients were enrolled, 91(58.3%) of whom were male, and 2 681 dialysis data recordings were included. The incidence of IDH from 2017 to 2021 fluctuated from 8.3% to 13.2%, with an average incidence of 11.0% by 2021. The results of multivariate regression showed pre-dialysis systolic pressure of 140-159 mmHg (1 mmHg=0.133 kPa, 90-139 mmHg as reference: OR=0.482, 95% CI 0.273-0.851, P=0.012), pre-dialysis diastolic pressure ≥ 90 mmHg (60-89 mmHg as reference, 90-99 mmHg: OR=4.081, 95% CI 2.132-7.809, P < 0.001; ≥ 100 mmHg: OR=8.547, 95% CI 3.233-22.597, P < 0.001), albumin (34-48 as reference, < 34 g/L: OR=2.677, 95% CI 1.592-4.502, P < 0.001; > 48 g/L: OR=2.692, 95% CI 1.102-6.577, P=0.030), C-reactive protein ≥ 8 mg/L (< 8 mg/L as reference: OR=1.787, 95% CI 1.216-2.628, P=0.003), hemodiafiltration as the dialysis mode (hemodialysis as the reference: OR=2.256, 95% CI 1.395-3.648, P=0.001), actual ultrafiltration volume/dry body mass (per 1% increase, OR=1.539, 95% CI 1.139-2.080, P=0.005), and ultrafiltration rate (per 100 ml/h increase, OR=1.641, 95% CI 1.389-1.939, P < 0.001) were independently associated with the occurrence of IDH. Contribution analysis showed that the top three factors related to IDH were ultrafiltration rate ( χ 2- df=32.798), pre-dialysis diastolic pressure ( χ 2- df=20.757) and albumin ( χ 2- df=19.971). The sensitivity analysis showed that the regression results were robust. Conclusions:The risk factors of IDH in elderly MHD patients are increasing ultrafiltration rate, higher pre-dialysis diastolic pressure(≥ 90 mmHg), lower albumin (< 34 g/L), HDF, higher c-reactive protein(≥ 8 mg/L) and increasing actual ultrafiltration volume/dry body mass. Higher pre-dialysis systolic pressure (140-159 mmHg) is a protective factor.

Incidence and risk factors of postoperative delirium in liver transplantation recipients: a Meta-analysis / 中华器官移植杂志

Objective:To clarify the incidence and the related risk factors of postoperative delirium in liver transplantation (LT) recipients to provide rationales for early identification of delirium and constructing the related models.Methods:The authors used the "肝移植""移植术""肝移植手术""肝脏移植""移植肝""谵妄""谵语""危险因素""相关因素""影响因素"and "liver transplantation""liver transplant""delirium""delirious""delirium confusion""risk factors""relevant factors""root cause analysis"as the Chinese and English keywords, searching Wanfang data, China Biomedical Literature Database, CNKI, PubMed, Embase, Web of Science, Cochrane Library, BMJ and the literature for the incidence or risk factors of postoperative delirium in LT recipients. The researchers independently performed literature screening, methodological evaluation and data extraction. And RevMan 5.4 and State16.0 software were employed for data processing.Results:A total of 19 articles involving 5003 samples were retrieved and 22 risk factors identifies. Meta-analysis showed that the incidence of POD was 23%(1151/5003). The statistically significant risk factors included preoperative blood ammonia concentration >46 mmol/L ( OR=3.51, 95% CI: 1.53-8.09, P<0.001), model for end-stage liver disease (MELD) score >15 points ( OR=4.24, 95% CI: 2.51-7.16, P<0.001), preoperative hepatic encephalopathy ( OR=3.00, 95% CI: 2.09-4.31, P<0.001), preoperative dosing of diuretics ( OR=2.36, 95% CI: 1.38-4.04, P<0.001), history of alcoholism ( OR=3.16, 95% CI: 1.06-9.40, P=0.040), longer anhepatic period ( OR=1.04, 95% CI: 1.03-1.06, P<0.001) and elevated aspartate transaminase concentration at Day 1 post-operation ( OR=1.33, 95% CI: 1.15-1.53, P<0.001). Conclusions:Preoperative blood ammonia concentration >46 mmol/L, MELD score >15, hepatic encephalopathy, dosing of diuretic, a history of alcoholism, longer anhepatic period and elevated aspartate transaminase at Day 1 post-operation are risk factors for postoperative delirium after LT. Postoperative reintubation is not a risk factor for postoperative delirium.

Efficacy of dexmedetomidine on painless gastroenteroscopy in patients recovered from COVID-19 / 中华麻醉学杂志

Objective:To evaluate the efficacy of dexmedetomidine on painless gastroenteroscopy in the patients recovered from COVID-19.Methods:Eighty patients of either sex, aged 18-64 yr, with body mass index <30 kg/m 2, undergoing elective painless gastroenteroscopy, of American Society of Anesthesiologists physical statusⅠor Ⅱ, within 2nd to 7th weeks after diagnosis of COVID-19, who had a negative nucleic acid test or antigen test at present and presented with no respiratory symptoms in our hospital from January to February 2023, were selected and divided into 2 groups ( n=40 each) using a random number table method: dexmedetomidine group (group D) and control group (group C). Sufentanil 0.1 μg/kg was intravenously injected in two groups. Dexmedetomidine 0.2 μg/kg was intravenously injected in group D, and the equal volume of normal saline was given instead in group C. Propofol 1.5-2.0 mg/kg was intravenously injected after 2-3 min observation, and propofol 5-7 mg·kg -1·h -1 was intravenously infused to maintain sedation during operation. The development of bucking and hypoxemia during operation, total consumption of propofol, emergence time, time of hospital discharge, development of bradycardia and hypotension during operation, and scores for patients′ and endoscopic physicians′ satisfaction with anesthesia were recorded. Results:Compared with group C, the incidence of bucking and hypoxemia was significantly decreased, scores for endoscopic physicians′ satisfaction with anesthesia were increased ( P<0.05), and no significant change was found in the other parameters in group D ( P>0.05). Conclusions:Low-dose dexmedetomidine can reduce the risk of bucking and hypoxemia during operation and raise the quality of anesthesia in the patients recovered from COVID-19 undergoing painless gastroenteroscopy.

Efficacy and safety of thrombolytic therapy with intravenous alteplase in elderly patients with acute cerebral infarction on maintenance dialysis / 中华老年医学杂志

Objective:To investigate the efficacy and safety of thrombolytic therapy with intravenous alteplase(rt-PA)for elderly acute ischemic stroke patients on maintenance hemodialysis.Methods:In this retrospective study, data of 165 elderly patients with acute cerebral infarction on maintenance dialysis, aged 65-85, treated at the Stroke Center of the Fourth Central Hospital Affiliated to Nankai University between May 2018 and March 2021, were collected.Based on whether intravenous thrombolysis with alteplase(rt-PA)was used and differences in thrombolytic schemes, patients were divided into a conservative treatment group( n=58, receiving only standardized secondary stroke prevention), a low-dose rt-PA group( n=57, receiving rt-PA intravenous thrombolysis, 0.6 mg/kg)and a standard-dose rt-PA group( n=50, receiving rt-PA intravenous thrombolysis, 0.9 mg/kg). The safety and efficacy of rt-PA treatment were assessed. Results:The rate of effectiveness at 24 h and the rate of good prognosis at 7 d were 64.9%(37/57)and 70.2%(40/57)for the low-dose rt-PA group and 68.0%(34/50)and 74.0%(37/50)for the standard dose group, respectively.There was no significant difference between the two groups( χ2=0.417, P=0.518; χ2=0.636, P=0.425), but these rates were better than 29.3%(17/58)and 41.4%(24/58)for the conservative treatment group( χ2=10.583、16.714, P<0.001). The good prognosis rate at 90 days were 73.7%(42/57), 78.0%(39/50)and 69.0%(40/58)for the three groups, respectively, with no significant difference( χ2=1.126, P=0.569), but the fatality rate for the low-dose rt-PA group was 7.0%(4/57), lower than 18.0%(9/50)( χ2=5.420, P=0.020)for the standard dose rt-PA group and 20.0%(8/58)for the conservative treatment group( χ2=5.048, P=0.025). The incidence of intracranial hemorrhage was 8.8%(5/57)for the low-dose rt-PA group, lower than 24.0%(12/50)for the standard-dose rt-PA group( P=0.032). The incidence of extracranial complications was 15.8%(9/57)for the low-dose rt-PA group, lower than 36.0%(18/50)for the standard-dose group( P=0.017). Conclusions:For elderly patients with acute cerebral infarction on maintenance hemodialysis, intravenous thrombolytic therapy with low dose rt-PA should be considered with caution.