OBJECTIVE To observe the auxiliary analgesic effect of electroacupuncture at Hegu and Neiguan combined with in-domethacin suppository in patients undergoing transvaginal ultrasound-guided oocyte retrieval(TUGOR and its effect on the outcome of in vitro fertilization(IVF.METHODS 64 IVF-ET patients undergoing TUGOR were randomly divided into a treatment group and a control group,32 cases in each group.One case dropped out of the treatment group during the treatment.The control group was given indomethacin suppository rectal administration,and the treatment group was given electroacupuncture at Hegu and Neiguan in addition to the treatment of the control group.The patients'tenderness threshold,VAS score,pain grade score,respiratory rate,and pulse rate were evaluated before and after TUGOR operation.The number of oocytes obtained,the rate of two pronuclei(2PN,embryo utiliza-tion rate,and high-quality embryo rate were evaluated after TUGOR operation.The adverse reactions of the two groups were monitored during and after operation.RESULTS After TUGOR operation,the VAS score and pain grade of the treatment group were signifi-cantly lower than those of the control group(P<0.01;the tenderness threshold of the two groups was significantly reduced after opera-tion(P<0.05,P<0.01,and the treatment group was better than the control group(P<0.05;the incidence of nausea during opera-tion,abdominal distension and nausea 48 h after operation in the treatment group were better than those in the control group(P<0.05;the high-quality embryo rate in the treatment group was better than that in the control group(P<0.05.CONCLUSION Electroacupuncture at Hegu and Neiguan combined with indomethacin suppository can effectively assist in analgesia,and can reduce the incidence of adverse reactions during and after TUGOR to varying degrees,and may have certain advantages in improving the rate of high-quality embryos.

Objective To explore the characteristics and influencing factors of adverse reactions of apheresis plasma do-nation in 27 domestic plasma donation stations,and put forward targeted preventive measures.Methods A total of 6 275 plasma donors with adverse reactions from 2018 to 2020 in 27 plasma donation stations in China were selected as the re-search objects.The types of adverse reactions,ages,time of plasma donation and other related characteristics were counted and retrospectively analyzed.Results From January 2018 to December 2020,the incidence of adverse reactions of aphere-sis plasma donation in 27 plasma collection stations was 1.37‰,including vasovagal reaction/hypovolemia(3 208 cases,0.700‰),sodium citrate allergy/hypocalcemia(1 205 cases,0.263‰),hypoglycemia(1 020 cases,0.223‰),syncope(796 cases,0.174‰),hematoma(8 cases,0.002‰),other reactions(36 cases,0.008‰),all of which were non-se-vere adverse reactions.There were significant differences in the incidence of different types of adverse reactions(P＜0.001).The adverse reactions in 2018,2019 and 2020 were compared,and the difference was statistically significant(P＜0.001),with the highest incidence of 1.51‰(2 143/1 414 162)of adverse reactions in 2019 and the lowest incidence of 1.29‰(1 818/1 410 506)in 2020.The difference in the incidence of adverse reactions in different age groups was statistically sig-nificant(P＜0.001),with the highest incidence of 2.61‰(224/85 733)of 18-25 years old,and the lowest incidence of 1.05‰(465/439 786)of 56-60 years old.The incidence of different types of adverse reactions was compared according to different age groups,and significant differences were noticed in the incidence of vasovagal reaction/hypovolemia(P＜0.001),sodium citrate allergy/hypocalcemia(P＜0.05),hypoglycemia(P＜0.001),and syncope(P＜0.001)among dif-ferent age groups,while no significant difference was found in hematoma and other adverse reactions among different age groups(P＞0.05).Conclusion The incidence of adverse reactions in plasma donation is low in China.In the process of plasma donation,attention should be paid to first-time and young(18-25 years old)donors.The incidence of adverse reac-tions in 56-60 years old donors is the lowest,which can provide data support for the age revision of plasma donors in China.

Objective To investigate the safety of regular plasma donors aged 55 to 60,so as to provide reference for retention and recruitment of elderly plasma donors in China.Methods Plasma donors from 9 blood products manufacturing enterprises from 2018 to 2020 and the local general population were selected as the research objects.The total protein level,albumin and globulin ratio(ALB/GLB,A/G)and adverse reactions of plasma donation of regular plasma donors and local general population were retrospectively analyzed.Results The total protein level(g/L)and A/G of plasma donors aged 56 to 60 and the general population were 61.21±5.62 vs 60.04±6.93 and 1.610±0.299 vs 1.635±0.330,respectively,and the differences were statistically significant.The total protein level of regular plasma donors was higher than that of general popu-lation,but A/G was slightly lower than that of general population.From 2018 to 2020,there were a total of 23 056 302 plas-ma donations in 108 plasma stations,and adverse reactions occurred in 20 932 donations,with a total incidence of 0.09%,with no serious adverse reactions.Conclusion It is safe for regular plasma donors aged 55 to 60 to donate plasma,and the retention of them can alleviate the pressure of plasma supply.

Kashin-Beck disease (KBD) is an endemic and degenerative osteoarthropathy that can cause damage to the endochondral ossification of the limbs during development. The etiology is still unclear. In recent years, scholars at home and abroad have studied the mechanism of T-2 toxin and its metabolites causing KBD cartilage damage from the perspectives of immunotoxicity, oxidative stress, inflammatory response, cell apoptosis, etc., mainly including transforming growth factor-β receptor (TGF-βRs) signaling pathway, immune regulatory factor, inflammatory factor IL-1β and apoptosis enzyme activating factor 1 (APAF1), which promote the progression of KBD by inducing human chondrocyte injury, inhibiting matrix synthesis and accelerating cellular catabolism. This article reviews the research progress on the immunotoxicity of T-2 toxin and its toxic effects on KBD cartilage injury at the molecular level, in order to provide a scientific basis for prevention and treatment of KBD.

OBJECTIVE To investigate the effect of Jiawei Tianwang Buxin Dan(JWBXD)on insomnia in rats exposed to simulated high-altitude conditions.METHODS ① Thirty SD rats were randomly divided into the normal control,model,model+Jiawei Tianwang Buxin Dan(JWBXD,9.6 mg·kg-1),model+Tianwang Buxin Dan(TWBXD,9.6 mg·kg-1),and model+diazepam(DZP,3 mg·kg-1)groups.Rats,except for the normal control group,were subjected to a low-pressure,low-oxygen animal experimental chamber simulating a 5000 m altitude.Respective drugs were ig administrated once daily at 9:00 for seven days,and signal acquisition and sleep analysis were conducted by a wireless physiological sig-nal telemetry system.②Forty rats were randomly divided into five groups as described in ①.Through-out the experiment,the general condition and body mass of the rats were observed daily.Drug adminis-tration lasted for seven days,and grip strength was tested one hour after the final administration.ELISA was used to measure the levels of corticotropin-releasing hormone(CRH),adrenocorticotropic hor-mone(ACTH),corticosterone(CORT),and melatonin(MLT)in serum.Western blotting was performed to measure the expression levels of core clock proteins period circadian regulator 2(Per2),circadian locomotor output cycles(Clock),cryptochrome 2(Cry2),brain-muscle arnt-like protein 1(Bmal1),nuclear receptor subfamily 1,group D member 1(NR1D1),glycogen synthase kinase-3β(GSK-3β),as well as acetylserotonin O-methyltransferase(ASMT)in the hypothalamus and pineal gland,respectively.RESULTS ① Compared with the normal control group,the model group exhibited a decrease in total sleep time(P<0.01),an increase in wakefulness(P<0.01),a significant reduction in slow wave sleep(SWS)(P<0.05)and the mean bouts duration(P<0.05).Compared with the model group,both DZP and JWBXD(P<0.01)prolonged sleep time and suppressed wakefulness(P<0.01)in the hypoxic envi-ronment.DZP and JWBXD prolonged SWS(P<0.05,P<0.01),while TWBXD had no significant effect.JWBXD improved the mean bouts duration of SWS in the model rats(P<0.01),whereas no such improvement was observed in model+DZP and model+TWBXD groups.② Compared with the normal control group,the model group showed a significant decrease in forelimb grip strength(P<0.01),increased levels of serum ACTH(P<0.05),CRH,and CORT(P<0.01),and decreased MLT levels(P<0.05).The expression levels of Per2,Cry2,GSK-3β,and NR1D1 in the hypothalamus were downregu-lated(P<0.05,P<0.01),while Bmal1 and Clock were upregulated(P<0.05,P<0.01).ASMT expression in the pineal gland was decreased(P<0.05).Compared with the model group,JWBXD and TWBXD enhanced forelimb grip strength(P<0.01),reduced serum CORT and ACTH levels(P<0.05),decreased CRH levels(P<0.01),and restored MLT levels(P<0.01).JWBXD upregulated the expression levels of Per2,Cry2,GSK-3β and NR1D1 in the hypothalamus(P<0.05,P<0.01),but downregulated Bmal1 and Clock expression(P<0.05,P<0.01).TWBXD downregulated Bmal1 expression in the hypothalamus(P<0.01)and increased NR1D1 expression(P<0.05).DZP significantly enhanced the expression levels of Per2,Cry2 and NR1D1 in the hypothalamus(P<0.01).JWBXD,TWBXD and DZP improved ASMT expression in the pineal gland(P<0.05).CONCLUSION JWBXD can improve sleep structure and prolong the duration of SWS in rats exposed to simulated high-altitude conditions.The mechanisms may involve the regulation of core clock protein expressions in the hypothalamus,promotion of mela-tonin secretion,and inhibition of HPA axis hyperactivity.

As human microbiome research advances, a large body of evidence shows that microorganisms are closely related to human health. Probiotics were discovered and used as foods or dietary supplements with health benefits in the last century. Microorganisms have shown broader application prospects in human health since the turn of the century, owing to the rapid development of technologies such as microbiome analysis, DNA synthesis and sequencing, and gene editing. In recent years, the concept of "next-generation probiotics" has been proposed as new drugs, and microorganisms are considered as "live biotherapeutic products (LBP)". In a nutshell, LBP is a living bacterial drug that can be used to prevent or treat certain human diseases and indications. Because of its distinct advantages, LBP has risen to the forefront of drug development research and has very broad development prospects. This review introduces the varieties and research advances on LBP from a biotechnology standpoint, followed by summarizing the challenges and opportunities for LBP clinical implementations, with the aim to facilitate LBP development.
Humans ; Probiotics ; Dietary Supplements ; Bacteria ; Drug Development ; Biotechnology

OBJECTIVES: Major depressive disorder (MDD) patients with anhedonia tend to have a poor prognosis. The underlying imaging basis for anhedonia in MDD remains largely unknown. The relationship between nodal properties and anhedonia in MDD patients need to be further investigated. Herein, this study aims to explore differences of cerebral functional node characteristics in MDD patients with severe anhedonia (MDD-SA) and MDD patients with mild anhedonia (MDD-MA) before and after the antidepressant treatment. METHODS: Ninety participants with current MDD were recruited in this study. 24-Item Hamilton Depression Scale (HAMD-24) and Snaith-Hamilton Pleasure Scale (SHAPS) were used to assess the severity of depression and anhedonia at baseline and the end of 6-months treatment. The MDD patients who scored above the 25th percentile on the SHAPS were assigned to an MDD-SA group (n=19), while those who scored below the 25th percentile were assigned to an MDD-MA group (n=18). All patients in the 2 groups received antidepressant treatment. Functional magnetic resonance imaging (fMRI) images of all the patients were collected at baseline and the end of 6-months treatment. Graph theory was applied to analyze the patients' cerebral functional nodal characteristics, which were measured by efficiency (e_i) and degree (k_i). RESULTS: Repeated measures 2-factor ANCOVA showed significant main effects on group on the e_i and k_i values of left superior frontal gyrus (LSFG) (P=0.003 and P=0.008, respectively), and on the e_i and k_i values of left medial orbital-frontal gyrus (LMOFG) (P=0.004 and P=0.008, respectively). Compared with the MDD-MA group, the significantly higher e_i and k_i values of the LSFG (P=0.015 and P=0.021, respectively), and the significantly higher e_i and k_i values of the LMOFG (P=0.015 and P=0.037, respectively) were observed in the MDD-SA group at baseline. Meanwhile, higher SHAPS scores could result in higher e_i and k_i values of LSFG (P=0.019 and P=0.026, respectively), and higher e_i value of LMOFG (P=0.040) at baseline; higher SHAPS scores could result in higher e_i values of LSFG (P=0.049) at the end of 6-months treatment. The multiple linear regression analysis revealed that sex were negatively correlated with the e_i and k_i values of LSFG (r= -0.014, P=0.004; r=-1.153, P=0.001, respectively). The onset age of MDD was negatively correlated with the k_i value of LSFG (r=-0.420, P=0.034) at the end of 6-months treatment. We also found that SHAPS scores at baseline were positively correlated with the HAMD-24 scores (r=0.387, P=0.022) at the end of 6-months treatment. CONCLUSIONS There are obvious differences in nodal properties between the MDD-SA and the MDD-MA patients, such as the high e_i of LSFG in the MDD-SA patients, which may be associated with the severity of anhedonia. These nodal properties could be potential biomarkers for the prognosis of MDD. The increased e_i and k_i values in the LSFG of MDD-SA patients may underlie a compensatory mechanism or protective mechanism. The mechanism may be an important component of the pathological mechanism of MDD-SA. The poor prognosis in the MDD-SA patients suggests that anhedonia may predict a worse prognosis in MDD patients. Sex and onset age of MDD may affect the nodal properties of LSFG at baseline and the end of 6-months treatment.
Anhedonia ; Antidepressive Agents/therapeutic use* ; Depressive Disorder, Major/drug therapy* ; Humans ; Infant ; Infant, Newborn ; Magnetic Resonance Imaging ; Prefrontal Cortex

Objective:To investigate the changes of blood pressure and serum circadian clock protein levels after cerebral ischemia-reperfusion in spontaneously hypertensive rat (SHR) and their correlation.Methods:The middle cerebral artery occlusion method was used to prepare the SHR cerebral ischemia-reperfusion model at zero point of Zeitgeber Time (ZT), and the systolic blood pressure within 24 h was continuously monitored after the model was made. The tail vein blood of rats was taken every 3 h, and the changes in serum circadian clock proteins (CLOCK, BMAL1, PER1 and CRY1) levels were detected by enzyme-linked immunosorbent assay. Pearson correlation analysis was used to determine the relationship between blood pressure circadian rhythm pattern and circadian clock protein level fluctuation after cerebral ischemia-reperfusion.Results:In the sham operation group, there were various blood pressure patterns, including dipper (53%), non-dipper (27%), super dipper (13%), and reverse dipper (7%), and the main pattern was dipper. In contrast, the degree of blood pressure disorder in the model group was aggravated, and the non-dipper was the main type, with the proportion as high as 40%. The proportion of super dipper and reverse dipper increased to 27% and 13% respectively; proportion of dipper blood pressure decreased to 20%. The serum level of CLOCK in the model group was relatively stable, while the circadian rhythm of BMAL1, PER1 and CRY1 was significantly changed compared with the sham operation group. Pearson analysis showed that PER1 was negatively correlated with the dipper ( r=-0.565, P=0.002) and super dipper ( r=-0.531, P=0.001) blood pressure patterns, and positively correlated with the non-dipper blood pressure pattern ( r=0.620, P<0.001). Conclusion:The circadian rhythm pattern of blood pressure in SHR after cerebral ischemia-reperfusion was obviously disordered, which was closely associated with the regulation of Per1 gene.

Rhythm of blood pressure refers to the circadian variation of blood pressure, which is regulated by clock genes. However, the rhythm disorder of blood pressure increases the risk of stroke. Taking the process of blood pressure regulation as a clue and focusing on the clock gene pathway, this article explores the possible mechanism of period gene regulating renin-angiotensin-aldosterone system in rhythm of blood pressure, so as to provide reference for the in-depth study of the relevant mechanism of rhythm disorder of blood pressure and search for a new target for the primary prevention of cerebrovascular diseases.

Personalized management of ischemic stroke prevention and treatment remains a top priority in the field of neurology. The purpose of this article is to elucidate the role of nontraditional lipid profile and traditional lipids in the pathogenesis and recurrence of acute ischemic stroke in order to provide new indicators for stroke prevention, risk grading and high-risk population screening, and attempt to discuss the potential predictive value of nontraditional lipid indicators.