BACKGROUND:Transcranial magnetic stimulation has been used in the treatment of Alzheimer's disease,but its mechanism has not been fully clarified. OBJECTIVE:To explore the mechanism of repetitive transcranial magnetic stimulation to increase neural excitability in mice with Alzheimer's disease. METHODS:Sixteen C57BL/6 mice were randomized into control group (n=8) and control+magnetic stimulation group (n=8). Another 16 APP/PS1 mice were randomized into dementia group (n=8) and dementia+magnetic stimulation group (n=8). Mice in the two magnetic stimulation groups were given repetitive transcranial magnetic stimulation,2 hours daily,for 14 continuous days. The water maze was then used to detect the cognitive function of mice. Whole-cell membrane-clamp technique was used to collect action potentials and analyze the effect of Alzheimer's disease on action potentials;and the potassium channe currents were collected and analyzed for the role of their kinetic properties on neural excitability. RESULTS AND CONCLUSION:The results of Morris water maze showed that normal mice could find and determine the original platform more accurately after receiving repetitive transcranial magnetic stimulation,while Alzheimer's disease led to a decrease in the learning and memory ability of mice,a decrease in the number of times they found the platform,and a degeneration of neurons in the hippocampal dentate gyrus. Repetitive transcranial magnetic stimulation could improve the learning and memory ability of mice with Alzheimer's disease. Whole-cell membrane clamp technique assay showed that repetitive transcranial magnetic stimulation could trigger neuronal depolarization and enhance neuronal excitability in Alzheimer's disease mice. Analysis of potassium channel currents showed that Alzheimer's disease caused an increase in the transient outward potassium channel half-activation voltage. The inactivation curve was shifted in the direction of depolarization and the resuscitation time constant was prolonged,causing the delayed rectifier potassium channel activation curve to be shifted in the direction of depolarization. Whereas repetitive transcranial magnetic stimulation delayed the opening and closing of the potassium channel and inhibit the efflux of intracellular potassium ions,which resulted in the retention of a higher intracellular potassium concentration and increased neuronal excitability. To conclude,repetitive transcranial magnetic stimulation may alleviate cognitive decline by increasing neuronal excitability in the hippocampal dentate gyrus.

BACKGROUND:Transcranial magnetic stimulation has been used in the treatment of Alzheimer's disease,but its mechanism has not been fully clarified. OBJECTIVE:To explore the mechanism of repetitive transcranial magnetic stimulation to increase neural excitability in mice with Alzheimer's disease. METHODS:Sixteen C57BL/6 mice were randomized into control group (n=8) and control+magnetic stimulation group (n=8). Another 16 APP/PS1 mice were randomized into dementia group (n=8) and dementia+magnetic stimulation group (n=8). Mice in the two magnetic stimulation groups were given repetitive transcranial magnetic stimulation,2 hours daily,for 14 continuous days. The water maze was then used to detect the cognitive function of mice. Whole-cell membrane-clamp technique was used to collect action potentials and analyze the effect of Alzheimer's disease on action potentials;and the potassium channe currents were collected and analyzed for the role of their kinetic properties on neural excitability. RESULTS AND CONCLUSION:The results of Morris water maze showed that normal mice could find and determine the original platform more accurately after receiving repetitive transcranial magnetic stimulation,while Alzheimer's disease led to a decrease in the learning and memory ability of mice,a decrease in the number of times they found the platform,and a degeneration of neurons in the hippocampal dentate gyrus. Repetitive transcranial magnetic stimulation could improve the learning and memory ability of mice with Alzheimer's disease. Whole-cell membrane clamp technique assay showed that repetitive transcranial magnetic stimulation could trigger neuronal depolarization and enhance neuronal excitability in Alzheimer's disease mice. Analysis of potassium channel currents showed that Alzheimer's disease caused an increase in the transient outward potassium channel half-activation voltage. The inactivation curve was shifted in the direction of depolarization and the resuscitation time constant was prolonged,causing the delayed rectifier potassium channel activation curve to be shifted in the direction of depolarization. Whereas repetitive transcranial magnetic stimulation delayed the opening and closing of the potassium channel and inhibit the efflux of intracellular potassium ions,which resulted in the retention of a higher intracellular potassium concentration and increased neuronal excitability. To conclude,repetitive transcranial magnetic stimulation may alleviate cognitive decline by increasing neuronal excitability in the hippocampal dentate gyrus.

Objective:To investigate the treatment outcome of chemotherapy regimens containing azacitidine and mitoxantrone liposome in the treatment of angioimmunoblastic T-cell lymphoma (AITL).Methods:The clinical data of 1 AITL patient with severe clinical symptoms admitted to Weihai Municipal Hospital in July 2021 were retrospectively analyzed, and the relevant literatures were reviewed.Results:The 74-year-old male patient was presented with the manifestations of rash, lymph node enlargement, bloating and fever. He was pathologically diagnosed as AITL by lymph node biopsy. In the early stage of treatment, due to severe clinical symptoms and poor therapeutic effect, the treatment regimens were constantly adjusted. CHOPE, etoposide + chidamide + thalidomide +dexamethasone + cyclosporine, brentuximab vedotin + bendamustine + dexamethasone + cyclosporine + thalidomide +chidamide regimens were used successively, and the disease progressed after short-term complete remission. Finally complete remission was obtained again after a multi-drug combination regimens containing azacitidine and mitoxantrone liposome, following the maintenance treatment of azacitidine combined with chidamide, and the disease condition of the patient remained stable.Conclusions:The chemotherapy regimens containing azacitidine and mitoxantrone liposome can achieve a good therapeutic effect for relapsed/refractory AITL.

Closed-loop hospital management can effectivly cope with the COVID-19 pandemic. In order to ensure the continuity of treatments for hemodialysis patients under closed-loop management and minimize possible medical and infection risks, Huashan Hospital affiliated to Fudan University and 9 hospitals in Shanghai established a hemodialysis alliance in January 2021.The alliance optimized hemodialysis resources within the region through overall planning by preparing sites, materials and personnel shifts in advance, and establishing management systems and work processes to ensure that patients could be quickly and orderly diverted to other blood dialysis centers for uninterrupted high-quality hemodialysis services, in case that some hemodialysis centers in the alliance under closed-loop management.From November 2021 to April 2022, 317 of 1 459 hemodialysis patients in the alliance were diverted to other centers for treatment, accumulating 1 215 times/cases of treatments without obvious adverse reactions. The practice could provide a reference for medical institutions to quickly establish mutual support mode under major public health events.

Background Noise has multiple negative effects on the organism, and gut microbes are influenced by the environment and are closely associated with the development of diseases. Currently, the effects of chronic noise exposure on intestinal microbiota are poorly understood. Objective To investigate the effects of noise exposure on the structure of rat gut microbiota and to make predictions of gut microbiota function. Methods Male Wistar rats (6 weeks old, 160-180 g) were randomly divided into control, NE_95dB, and NE_105dB groups, 10 rats in each group. Rats in the NE_95dB and the NE_105dB groups were exposed to noise at 95 dB sound pressure level (SPL) and 105 dB SPL, respectively, 4 h per day for consecutive 30 d, while the control group was exposed to background noise. Feces were collected after the last noise exposure for intestinal microbiota detection. Based on the 16S ribosomal RNA (rRNA) gene sequencing method, the diversity and structure of microbiota in rat intestinal contents were analyzed and compared. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was applied to predict functions of the identified intestinal microbiota genes. Results Significant differences were found in the microbial structure of the rat gut after the designed noise exposure. In the α diversity results, there was a statistically significant difference in the Chao1 index between the NE_95dB group and the NE_105dB group (P=0.02), while there were no statistically significant differences in the Shannon and Simpson indexes between the noise exposure groups and the control group (P>0.05). The β diversity analysis results showed significant differences in species abundance between the control group and the noise exposure groups (P=0.001). Further species analysis results showed that the relative abundances of the Ruminococcaceae_NK4A214_group (P<0.05) and Peptococcaceae_unclassified (P<0.01) at the genus level were significantly higher in the NE_105dB group, and the relative abundance of Parasutterella (P<0.05) was significantly higher in the NE_95dB group compared to the control group. In addition, the Ruminococcaceae_NK4A214_group (P<0.05) was also significantly higher in the NE_105dB group compared to the NE_95dB group. The PICRUSt functional prediction analysis results showed that there were eight differential pathways between the control group and the NE_95dB group, in which D-arginine and D-ornithine metabolism, ascorbate and aldarate metabolism, carotenoid biosynthesis, glycerophospholipid metabolism, mineral absorption, NOD-like receptor signaling pathway and non-homologous end-joining were significantly down-regulated, and nucleotide metabolism was significantly up-regulated. There were 38 differential pathways between the control group and the NE_105dB group. Among them, D-arginine and D-ornithine metabolism, and mineral absorption were the differential metabolic pathways in both noise exposure groups, and both were down-regulated relative to the control group. Conclusion Chronic noise exposure could alter structure of rat gut microbiota and may affect metabolic functions of multiple microbiota genes.

Objective:To investigate the effect of virus inactivation on weak positive result of 2019 novel coronavirus(2019-nCoV) nucleic acid test.Methods:A retrospective study was conducted on the nasopharyngeal swabs of three patients with positive PCR nucleic acid test for 2019-nCoV at different concentrations in the Second affiliated Hospital of Zhejiang University Medical College from January to February 2020.The virus in nasopharyngeal swab specimens were inactivated by water bath at 56 ℃ for 30 min, dry bath at 56 ℃ for 60 min and dry bath at 60 ℃ for 30 min respectively. After treatment, these samples RNA were extracted and then detected by three new commercial quantitative real-time polymerase chain reaction reagent kits for 2019-nCoV.Cycle threshold (Ct) value was used to evaluate the effect of virus inactivation on nucleic acid detection of 2019-nCoV.Results:There was no significant difference between the groups before and after inactivation. Ct values of ORF1ab gene before inactivation were 23.28±0.28, 25.25±0.25, 28.93±0.44, 32.06±0.47, 35.20±0.38, 32.89±0.38, 36.24±0.23, 33.30±0.46, and those after inactivation were, group 1:23.60±0.20, 27.29±0.30, 31.83±0.51, 37.41±0.46, group 2: 24.25±0.34, 27.18±0.42, 31.84±0.61, 34.99±1.01, 34.89±0.45,group 3: 23.37±0.17, 26.89±0.52, 32.05±0.50.Ct value of N gene before inactivation were 24.38±0.09, 26.64±0.11, 30.35±0.12, 33.29±0.33, 36.93±0.11, 34.50±0.12, 35.63±0.12, those after inactivation were, group 1: 24.66±0.11, 28.52±0.14, 32.71±0.14, 37.00±0.13;group 2: 25.41±0.10, 28.79±0.15, 33.29±0.28; group 3: 23.37±0.11, 28.68±0.11, 33.54±0.13, 37.18±0.23(ORF1ab gene: t=-1.416; N gene: t=-1.379, P>0.05). There was no significant difference among the three inactivation groups, the specific Ct values are shown above(ORF1ab gene: t=-0.460; N gene: t=-0.132, P>0.05). However, the Ct values of the inactivated groups (1,2,3) and the non-inactivated group at different dilution times were different (10 ×:Ct value of ORF1ab was 25.25±0.25 in the non-inactivated group, and 27.29±0.30, 27.18±0.42 and 26.89±0.52 in the inactivated group1,2 and 3, t(ORF1ab)=-7.327, P<0.01.Ct value of N gene in the non-inactivated group was26.64±0.11, those in inactivated group 1, 2 and 3 were 28.52±0.14, 28.79±0.15 and 28.68±0.11, respectively, t (N)=-19.340, P<0.01. 100 ×:Ct value of ORF1ab was 28.93±0.44 in the non-inactivated group, and 31.83±0.51,31.84±0.61 and 32.05±0.50 in the inactivated group1,2 and 3, t (ORF1ab)=-9.462, P<0.01. Ct value of N gene in the non-inactivated group was 30.35±0.12, those in the inactivated group 1, 2 and 3 were 32.71±0.14, 33.29±0.28 and 33.54±0.13, respectively, t (N)=-18.583, P<0.01. The positive detection rate of the non-inactivated group (7/11, 8/11, 5/11) was significantly different from that of the inactivated group (inactivated group 1:4/11, 4/11, 3/11, inactivated group 2:3/11, 3/11, 3/11, and inactivated group 3:3/11, 3/11, 2/11) ( Z=-2.670, P<0.01). There were no significant difference among the inactivated groups(inactivated group 1:4/11, 4/11, 3/11, inactivated group 2:3/11, 3/11, 3/11, inactivated group 3:3/11, 3/11, 2/11) ( Z=4.413, P>0.05) and among the three reagents(reagent 1:7/11, 4/11, 3/11, 3/11, reagent 2:8/11, 4/11, 3/11, 3/11, reagent 3:5/11, 3/11, 3/11, 2/11)(χ 2=1.199, P>0.05). Conclusion:The virus inactivation can degrade the nucleic acid of the 2019-nCoV, resulting in the decrease of the Ct value and the false negative results of the low-concentration specimens.

Objective: To compare the consistency of thyroid stimulating hormone (TSH) results from four chemiluminescence assays. Methods: A total of 102 fresh serum samples from Peking Union Medical College Hospital during March 2018 and April 2018 were collected for precision evaluation and methodological comparison referring to CLSI EP15-A2 and EP9-A2 protocols. The levels of serum TSH were detected by Abbott i2000 (system A), Beckman DXI800 (system B), Siemens ADVIA Centaur XP (system C) and Roche e601 (system D) automatic chemiluminescence analyzers and their matching reagents, respectively. The obtained results were compared with the passing-bablok and Bland Altman methods. Taking 0.27 μIU/mL and 5.33 μIU/mL as the medical decision level, the expected bias of each detection system was compared. Results: The precisions of systems A,B,C and D were 1.7%-3.3%， 2.3%- 3.9%，0.7%-2.3% and 0.6%-1.5%,respectively. The median (P 25,P 75) of TSH concentrations detected by systems A,B,C and D were 1.898 (0.518,4.809)μIU/mL, 2.819 (0.719,7.020)μIU/mL,2.502 (0.692,6.888)μIU/mL and 3.105 (0.886, 7.905)μIU/mL, respectively. The coefficients of determination (R 2 ) of regression equation were above 0.975 for 4 detection systems. The correlation coefficients (r), intercepts and slopes of 4 detection systems were 0.993 5-0.997 1, 0-0.06 and 0.59-1.15, respectively, and systems B and C had the best correlations with 1.02 of slope and 0 of intercept. The deviation plot showed that the bias% of 4 detection systems was between -48.1% and 17.3%. Among them, systems A and D had the largest bias, while systems B and C had the lowest bias. The expected bias of 4 detection systems at the medical decision level was -40.7%-37.2%. Conclusion The consistency between Beckman and Siemens TSH detection systems is good, while those of Roche and Abbott TSH detection systems are different from the other two.

Objective To investigate the prevalence and possible factors of hypouricemia in Peking Union Medical College Hospital.Methods A retrospective investigation.Serum uric acid, lipids, glucose and other chemistry tests were analyzed among 83176 outpatients(Male:30795,Female:52381), 15849 inpatients(Male:7402,Female:8447)and 24081 healthy subjects(Male:11859,Female:12222)in Peking Union Medical College Hospital from December 2015 to April 2016.Grouped by gender and age, the prevalence of hypouricemiawas analyzed in all subjects and the etiology and possible risk factors of hypouricemia were explored among all patients.Results The serum uric acid of outpatients,inpatients and healthy subjects were 286(235-348)μmol/L, 282(226-348)μmol/L and 298(244-358)μmol/L, respectively.And the prevalence were 0.6%(499/83176),2.5%(390/15849)and 0.2%(39/24081), respectively.The prevalence of hypouricemia ofwomen was significantly higher than that ofmen(outpatients:0.7%vs 0.4%,P<0.001;inpatients:2.8%vs 2.1%,P=0.004;healthy subjects:0.30%vs 0.04%, P<0.001).After analyzing 507 hypouricemia patients, the top three clinical diagnoses that related with hypouricemia were kidney diseases, tumor and rheumatic diseases.Compared with the control group, the prevalence of hypouricemia in hypertriglyceridemia group and group with eGFR higher than 90 ml/(min· 1.73 m2)were lower(OR:0.33, 95% CI:0.21-0.50; OR:0.16, 95% CI:0.09-0.29), and the prevalence of hypouricemia in hyperglycemia group was higher(OR:1.62, 95% CI:1.12-2.35). Conclusion The prevalence of hypouricemia of Chinese women was higher than that of men and may be related with TG,Glu and eGFR.

Objective To investigate the changes of prevalence of hyperuricemia ( HUA) and its correlations with blood glucose and lipid in healthy adults receiving physical examination at Peking Union Medical College Hospital (PUMCH) from 2012 to 2017. Meth-ods An observational approach was adopted for the data analysis.The test results of uric acid (UA),fasting blood glucose (FBG),to-tal cholesterol (TC),triacylglycerol (TG),low density lipoprotein cholesterol (LDL-C),high density lipoprotein cholesterol (HDL-C), creatinine (Cr) and Urea of 399 089 cases (206 881 males and 192 208 females) at PUMCH from January 2012 to December 2017 were collected and statistically analyzed.Results The total prevalence of HUA was 17.4% in which the prevalence of males was signif-icantly higher than that of females (25.6% vs 8.5%,χ2＝20 234.850,P＜0.01).During the years of 2012 to 2017,the prevalence of HUA was 26.5%,24.7%,28.6%,23.9%,24.8% and 24.5% in males,and 13.8%,6.3%,7.9%,6.1%,6.2% and 6.8% in females for each year respectively.The prevalence of HUA in males aged 18 to 64 years old was significantly higher than that in the age-matched fe-males (all P＜0.05).However, the prevalence of HUA in males aged≥65 years old was similar to the age-matched females.There was no statistically significant difference of HUA prevalence between males and females aged ≥65 in 2013,2015,2016 and 2017 ( χ2＝1.792,0.017,1.440 and 0.205 respectively;all P＞0.05).The percentages of hyperlipidemia in both males and females of HUA group were higher than those of non-HUA group respectively (all P＜0.01).The percentage of hyperglycemia in males of non-HUA group was higher than that of HUA group,but the percentage of hyperglycemia in females of non-HUA group was lower than that of HUA group ( all P＜0.01).High levels of TC,TG and FBG were risk factors of HUA with increased OR values in increased concentrations of TC,TG and FBG,respectively.Conclusion During the recent 6 years, in healthy adults receiving physiced examination at PVMCH, the preva-lence of male HUA diagnosed was at overall high level,but the prevalence of female HUA was in decreasing and relatively stable trend. Hyperlipidemia and hyperglycemia should be the risk factors of HUA.

Objective To analyze the role of telehealth?based dialysis registration systems in real?time and dynamic reflection of renal anemia in hemodialysis (HD) patients, and discuss the prospect of its application in dialysis registration management. Methods The Red China project was to build up a dialysis registration system based on the WeChat mobile terminal platform. Demographic and baseline laboratory parameters such as age, gender, primary disease, dialysis age, creatinine were recorded in this system. Hemoglobin (Hb) level was monthly recorded. The platform generated Hb statistics report for each HD center monthly, including the detection rate, target rate and the distribution level of Hb, and released it to physicians through the WeChat terminal of mobile phone. After that, physicians could change the treatment of anemia individually on basis of this report. Here the demographic and baseline laboratory parameters, the detection rate, target rate, the average level and the distribution of Hb from June 2015 to October 2017 after the project launched were analyzed. Results From June 2015 to October 2017, 8392 maintenance HD patients from 28 HD centers in Shanghai were enrolled, of whom 5059(60.3％) were male.The average rate age was (60.5 ± 13.7) years old. Baseline average Hb was (108.3±16.0) g/L. Baseline detection rate and target rate were 54.2％and 47.5％, respectively. After 28 months follow?up, the detection rate of Hb increased from 54.2％ to 73.6％ (P<0.001), the target rate of Hb increased from 47.5％ to 56.1％ (P<0.001), and the level of average Hb rose from (108.3±16.0) g/L to (110.7±16.0) g/L. The difference between average Hb in two consecutive months was less than 1.3 g/L. Conclusions The telehealth?based dialysis registration system can timely report the anemia situation of HD patients, which may improve the awareness rate of anemia, the degree of attention and the compliance of anemia monitoring, so as to improve the detection rate and target rate of Hb and reduce the fluctuation of Hb, which helps to maintain the HD patients to correct anemia in a timely, stable and long?term way. The telehealth?based dialysis registration system, as an improved mode of dialysis registration is a promising way for long?term management of renal anemia in dialysis patients.