Effects of polysorbates on stability of monoclonal antibody drugs / 中国生物制品学杂志

@#Objective To evaluate the effects of various polysorbates(PS)on the stability of different types of monoclonal antibody(mAb)drugs.Methods Three types of monoclonal antibodies mAbA(IgG1 proantibody drug),mAbB(IgG1 mAb)and mAbC(IgG1 mAb with Fc N297A mutation)were used as model proteins,and different kinds or contents of PS were added into the mAb formulations respectively to investigate the influencing factors.The effects of PS on the stability of mAb drugs were evaluated comprehensively by detecting the changes of quality attributes,such as protein aggregates and insoluble particles.Results PS20 and PS80 showed no significant difference in inhibiting the formation of aggregates and charge variants in the three mAbs(P>0.05),while the addition of PS80 in mAbB and PS20 in mAbC significantly inhibited the increase of insoluble particles respectively(P<0.05);The content of PS20 showed a significant effect on the detection indexes of charge variants and insoluble particles in mAbC(P<0.05).Conclusion Different types of mAbs have different sensitivities to various kinds and contents of PS.Therefore,when designing the formulation of mAbs,it is necessary to select appropriate kinds and contents of PS to further improve the stability of mAb drugs.

Dignity status of lymphoma patients during perichemotherapy and its influencing factors / 白血病·淋巴瘤

Objective:To investigate the dignity status of lymphoma patients during perichemotherapy, and to analyze the influencing factors.Methods:The convenience sampling method was used to investigate 230 lymphoma patients during perichemotherapy in Affiliated Tumor Hospital of Xinjiang Medical University from August 2020 to February 2021 by using general data questionnaire and patient dignity scale. Dual logistic regression was used to analyze the influencing factors of dignity.Results:The dignity score of patients with malignant lymphoma during perichemotherapy was 42.1±16.8, and 30.0% (69/230) patients had obvious dignity impairment. Among 5 dimensions of patient dignity, the scores of physical and mental pain, self-cognition, social role function independence and social support were 1.8±0.8, 1.8±0.9, 1.7±0.9, 1.6±0.7 and 1.2±0.5, respectively. Each patient had an average of 4.1 dignity problems, and five items with the highest score were worrying about their future (physical and mental pain dimension) [(2.1±1.1) scores, 50.4% (116/230)], feeling uncomfortable (physical and mental pain dimension) [(2.0±1.1) scores, 56.5% (130/230)], feeling a burden to others (self-perception dimension) [(2.0±1.1) scores, 33.5% (77/230)], feeling depressed (physical and mental pain dimension) [(1.9±1.0) scores, 53.5% (123/230)], feeling like a different person (self-perception dimension) [(1.9±1.1) scores, 49.1% (113/230)]. Logistic regression analysis showed that widowed (compared with unmarried: OR = 2.108, 95% CI 1.562-3.570), barely affordable and difficult to afford (compared with fully affordable: OR = 2.163, 4.307, respectively; 95% CI 1.120-7.469, 1.374-12.807), disease acceptance and negative (compared with positive: OR = 2.003, 3.694, respectively; 95% CI 1.358-6.599, 1.221-9.061), Eastern Cooperative Oncology Group (ECOG) score 2-4 (compared with score 0: OR = 3.753, 4.720, 5.044, respectively; 95% CI 1.352-9.506, 1.514-12.793, 2.221-15.539), patients with B symptom (compared with those without B symptom: OR = 1.962, 95% CI 1.100-3.501), patients with severe chemotherapy reaction (compared with those without severe chemotherapy reaction: OR = 4.814, 95% CI 2.714-8.539) were independent risk factors for obvious dignity loss of patients during perichemotherapy (all P < 0.05), and married was an independent protective factor compared with unmarried ( OR = 0.192, 95% CI 0.036-0.807, P < 0.05). Conclusion:Patients with lymphoma have impaired dignity during perichemotherapy. Medical staff should pay attention to the influencing factors of impaired dignity and develop targeted intervention programs to reduce the impaired dignity of patients.

Effects of bisphenol A exposure at different circadian time on hepatic lipid metabolism in mice / 环境与职业医学

Background Lipid metabolism in liver shows circadian-dependent profiles. The hepatotoxicity of environmental chemicals is dependent on circadian time. Objective To observe the effects of bisphenol A (BPA) exposure at different zeitgeber time (ZT) on hepatic and blood lipid metabolism and decipher the underlying mechanisms related to circadian rhythm in mice. Methods Thirty-five female C57BL/6J mice were sacrificed every 4 h in a light-dark cycle (12 h/12 h). The liver tissues were collected to describe the circadian profiles of hepatic Rev-erba, Bmal1, Clock, Srebp1c, and Chrebp mRNA expression levels within 24 h. Thirty female mice were divided into 6 groups by the timing (ZT3 represents the 3 h after light on, ZT15 represents the 3 h after light off) and dose (50 or 500 μg·kg−1·d−1) of BPA exposure to observe hepatotoxicity. Mice were gavaged with designed doses of BPA once per day for 4 weeks. Mice were maintained with ad libitum access to food and water and measured body weight weekly. After the experiment, mice were euthanatized and liver tissues were separated to determine the biochemical indicators of lipid metabolism and lipid metabolism- and circadian-related gene mRNA expressions. Results Hepatic Rev-erba, Bmal1, Clock, Srebp1c, and Chrebp mRNA expression levels were rhythmic during a 24 h period in mice. At ZT3 and ZT15, BPA did not alter body weight, plasma glucose, plasma total cholesterol, plasma low density lipoprotein cholesterol, and plasma triglycerides (P>0.05). The plasma high density lipoprotein cholesterol decreased in the 50 μg·kg−1·d−1 BPA group at ZT3 by 14.56% compared with the control group (P<0.05). The liver triglycerides increased in the 50 μg·kg−1·d−1 BPA group at ZT15 by 115.20% compared with the control group (P<0.05). BPA decreased Srebp1c mRNA expression level when dosing at ZT3 and increased Chrebp, Srebp1c, and Acc1 mRNA expression levels when dosing at ZT15 compared with the control group (P<0.05). BPA increased Bmal1 mRNA expression level and decreased Rev-erbα mRNA expression level at ZT3 exposure and decreased Bmal1 and increased Rev-erbα mRNA expression level at ZT15 exposure (P<0.05). Conclusion BPA exposure at light or dark period has different effects on hepatic lipid metabolism in mice. Hepatic lipid deposit appears when BPA is dosed at dark period. Rev-erbα-Bmal1 regulation circuits and the subsequent upregulation of Srebp1c and Chrebp and the target gene Acc1 may be involved.

Trend in resistance to beta-cypermethrin in Aedes albopictus and preliminary strategies of beta-cypermethrin use in Xuhui District， Shanghai / 上海预防医学

ObjectiveTo investigate the resistance to beta-cypermethrin in Aedes albopictus in Xuhui District， Shanghai， China， and determine the effects of insecticide components， concentration and distance on eliminating resistant population of Aedes albopictus in ultra-low volume （ULV） spray， which would provide scientific evidence for effective mosquito control strategy and rational use of beta-cypermethrin. MethodsLarval impregnation method recommended by the World Health Organization was used to determine the drug resistance in Aedes albopictus larvae to calculate the median lethal concentration （LC50） of insecticides to Aedes albopictus larvae. The resistance to insecticides in female adults of Aedes albopictus was measured by the adult mosquito contact tube method recommended by the World Health Organization， and the 24-hour mortality （%） of female mosquitoes caused by insecticides was measured. Then the 24-hour mortality （%） of resistant female adults of Aedes albopictus due to beta cypermethrin monotherapy and compound agents was calculated by ULV spray. ResultIn 2016， 2017， 2019 and 2021， the resistance ratio in Aedes albopictus larvae to beta-cypermethrin was 9.22， 68.22， 37.33 and 59.22， respectively. In 2021， the 24-hour mortality of Aedes albopictus female adults was 62.07%. ULV sprayer experiments were performed using 4.5% beta-cypermethrin （single dose） and 12.0% beta-cypermethrin-chlorpyrifos （compound dose）. The 24-hour mortality increased with the concentration of the insecticides. The overall mortality caused by compound was higher than that by single dose. The mortality were 24.24%， 31.60% and 97.83% at the concentrations of 0.045 0%， 0.067 5% and 0.090 0% for single dose， respectively， and 58.87%， 61.62% and 90.00% at the concentrations of 0.12%， 0.18% and 0.24% for compound dose， respectively. There was no significant difference in mortality when spraying distance was 10 m， 30 m and 50 m. ConclusionAedes albopictus in Xuhui District is developed varying resistance to beta-cypermethrin. It warrants to strengthen the monitoring on insecticide resistance to formulate scientific and reasonable strategy for insecticide use. and reduce the resistance level of the Aedes albopictus to beta-cypermethrin. Compound dose is recommended to improve the effect. In addition， comprehensive treatment may be adopted to reduce the resistance.

Observation on chromosome aberration of peripheral blood lymphocytes in children with vascular diseases after interventional procedure / 中华放射医学与防护杂志

Objective:To evaluate the effect of ionizing radiation on chromosome aberration of peripheral blood lymphocytes in children with vascular interventional procedure.Methods:The chromosome aberration of peripheral blood lymphocytes was analyzed before and after vascular interventional procedure to assess the effect of low-dose ionizing radiation on chromosomes. Peripheral blood (PB) was collected using heparin as an anticoagulant from 26 patients before and after (within 10 minutes) vascular interventional surgery. Informed consent was obtained from the patients′ parents.Results:Dicentric + centric ring (dic+ r) formation increased significantly ( U=647, P<0.01) in peripheral blood lymphocytes of children after interventional operation. No correlation was observed between the rate of dic+ r and the cumulative dose (CD), dose area product (DAP), age, body weight, gender and the estimated effective dose E ( P>0.05). There was no significant difference in dic+ r rate of children between different genders, ages and lesion sites ( P>0.05). The dic+ r rate after interventional operation exceeded 40×10 -3 in 4 of 26 cases with the highest of 95.83×10 -3. Conclusions:The ionizing radiation during children′s vascular interventional procedure might lead to the increase of chromosome aberration of peripheral blood lymphocytes and some children are abnormally sensitive. Great attention should be paid to the justification and radiation protection during interventional procedure for children.

Application value evaluation of bedside non-invasive hemodynamic monitoring in the perioperative management of neonatal gastrointestinal surgery / 中国小儿急救医学

Objective:To explore the value of ultrasonic cardiac output monitor(USCOM) in guiding perioperative hemodynamic management of neonatal gastrointestinal surgery.Methods:Seventy-five neonates with hemodynamic changes after gastrointestinal surgery admitted to the Department of Neonatology, Xiamen Children′s Hospital from January 2017 to December 2020 were enrolled, of which the non-USCOM group had 34 cases from January 2017 to December 2018, mainly based on clinical indicators such as heart rate, blood pressure, blood lactate acid to evaluate the hemodynamic status of children after surgery.The USCOM group had 41 cases from January 2019 to December 2020, used USCOM to assist in the evaluation of hemodynamics of children after surgery dynamic state.Another 40 cases were set up as the control group, included neonates with hyperbilirubinemia.The USCOM group and the control group were examined by USCOM to record cardiac output(CO), cardiac index(CI), and systemic vascular resistance(SVR). The changes in CO, CI, SVR between the USCOM group and the control group, the changes in USCOM group before and after the operation were compared, respectively.Changes in heart rate, blood pressure, and lactic acid in the USCOM group before and after the operation were compared.And the differences of vasoactive drug dosage and time of first use after operation, postoperative first expansion time, volume expansion, incidence of anuria or oliguria within 24 hours after operation, and length of hospital stay between USCOM group and non-USCOM group were analyzed.Results:The CO, CI, SVR, heart rate, blood pressure before operation in USCOM group were not significantly different compared with those in the control group and 12 h after the operation.The CO and CI in USCOM group at 1 h after operation were lower than those before operation, and the lactic acid increased, the differences were statistically significant( P<0.05). The SVR of USCOM group at 1 h after operation was higher than that before operation, but there was no significant difference ( P>0.05). The CO and CI at 12 h after operation in USCOM group were higher than those at 1 h after operation, and the SVR at 12 h was lower than that at 1 h after operation , the differences were all statistically significant( P<0.05). There were no significant differences in heart rate and blood pressure in USCOM group before and 1 h after operation ( P>0.05). The blood pressure at 12 h after operation was significantly higher than that at 1 h after operation( P<0.05). The time of first volume expansion and use of vasoactive drugs in USCOM group were significantly earlier than those in non-USCOM group[0.75(0.50, 1.37)h vs.7.00(5.00, 13.25)h, Z=-7.041, P<0.001; (1.39±1.33)h vs.(8.61±5.15)h, t=-7.917, P<0.001], the total volume of expansion was significantly reduced[17.50(10.00, 30.00)mL vs.30.00(20.00, 30.00)mL, t=-3.045, P=0.002], the dosage of dopamine was significantly reduced[8.40(6.20, 10.40)mg/kg vs.8.90(7.20, 14.40)mg/kg, Z=-2.475, P=0.013], the incidence of oliguria or anuria within 24 hours after operation was significantly reduced(12.2% vs.32.3%, t=4.500, P=0.034), the length of hospital stay was significantly shortened[25.00(15.50, 31.00)d vs.28.00(21.75, 34.00)d, Z=-1.985, P=0.047], and the dosage of dobutamine and epinephrine was not significantly changed( P>0.05). Conclusion:Non-invasive hemodynamic monitoring can monitor the hemodynamic changes of the neonatal gastrointestinal tract in real time during the perioperative period, which is helpful to guide the management of vasoactive drugs and fluids after surgery.

HucMSC-cm protects lipopolysaccharide-induced acute lung injury by activating AMP-activated protein kinase / 中华急诊医学杂志

Objective:To investigate the protective effect of human umbilical cord mesenchymal stem cell conditioned medium (HucMSC-cm) against lipopolysaccharide (LPS)-induced acute lung injury (ALI) and relevant mechanism of action.Methods:Forty 6-week-old male C57BL/6 mice were selected and randomized (random number) into the sham group, LPS group, LPS + HucMSC-cm (LPS+cm) group, and LPS+HucMSC-cm+Compound C (LPS+cm+cc) group, with 10 mice in each group. Mice were intratracheally injected with LPS (5 mg/kg) to establish ALI model, and intratracheally injected with hucMSC-CM (50 μL) 4 h after LPS treatment. Mice in the LPS+cm+cc group were intraperitoneally treated with Compound C (15 mg/kg) prior to LPS treatment. Neutrophils in peripheral blood were counted with the automated hematology analyzer 72 h after LPS administration. After that, mice were sacrificed, and the lung tissue pathology was observed using hematoxylin eosin (HE) staining. Besides, the expressions of IL-6, ICAM-1, VCAM-1 and P-AMP-activated protein kinase (P-AMPK) in the lung tissues were analyzed by Western blot and immunohistochemical assay. In vitro, human lung microvascular endothelial cells (HuLEC-5a) were cultured and divided into three groups: control group, LPS group (10 μg/ mL), and LPS + HucMSC-cm group. After 24 h of treatment, the expressions of p-AMPK and AMPK were detected by Western blot, and the expressions of IL-6 and IL-8 were detected by real-time fluorescence quantitative PCR. Oneway analysis of variance was used to compare the mean values of normally distributed measurement data between groups. Comparisons between two groups were performed using the Tukey’s multiple comparison test. Results:Compared with the sham group, the LPS group showed lungs with congestion and swelling, thickened pulmonary septum, and inflammatory cell infiltration. Moreover, in the LPS group, the protein expressions of IL-6 ( P=0.003), ICAM-1 ( P<0.001) and VCAM-1 ( P=0.001) were increased significantly, while the expression of p-AMPK was decreased ( P=0.013), accompanied by an increase in the proportion of neutrophils in peripheral blood ( P<0.001). Compared with the LPS group, the LPS+HucMSC-cm group demonstrated eased congestion, edema and pathological injury of lung tissue, reversed protein expressions of IL-6 ( P=0.003), ICAM-1 ( P=0.002), VCAM-1 ( P=0.006) and P-AMPK ( P=0.002), as well as decreased proportion of neutrophils in peripheral blood ( P<0.005). Compared with the LPS+HucMSC-cm group, the LPS+cm+cc group exhibited more severe lung histopathological injury, significantly increased protein expressions of IL-6, ICAM-1 and VCAM-1 in lung tissues, as well as decreased expression of P-AMPK protein. The results of immunohistochemistry were consistent with those of protein. In vitro experiment, after LPS treatment, the mRNA expressions of IL-6 ( P<0.001) and IL-8 ( P=0.027) were increased and p-AMPK protein expression ( P=0.005) was decreased as compared with the control group. In comparison with the LPS group, the LPS+HucMSC-cm group showed decreased mRNA expression levels of IL-6 ( P=0.003) and IL-8 ( P=0.002), but increased protein level of p-AMPK ( P=0.003). Conclusions:HucMSC-cm has a protective effect against LPS-induced acute lung injury, which is mainly attributed to the inhibited expression of adhesion molecules and inflammatory factors under the activation of AMPK.

Acupoint Autohemotherapy Attenuates Atopic Dermatitis Lesions by Regulating Th1/Th2 Balance in DNCB-Induced BALB/c Mice / 中国结合医学杂志

OBJECTIVE@#To evaluate the therapeutic effects of acupoint autohemotherapy (A-AHT) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD) in mice focusing on regulating T helper 1/T helper 2 (Th1/Th2) immune responses.@*METHODS@#Thirty BALB/c mice were divided into 5 groups by a random number table, including normal control (NC), AD model (AD), A-AHT, sham A-AHT (sA-AHT), and acupoint injection of normal saline (A-NS) groups, 6 mice per group. Mice were challenged by DNCB for the establishment of experimental AD model. On the 8th day, except for the NC and AD groups, the mice in the other groups received management once every other day for a total of 28 days. For the A-AHT and sA-AHT groups, 0.05 mL of autologous whole blood (AWB) was injected into bilateral Zusanli (ST 36) and Quchi (LI 11) and sham-acupoints (5 mm lateral to ST 36 and LI 11), respectively. The A-NS group was administrated with 0.05 mL of normal saline by acupoint injection into ST 36 and LI 11. Dermatitis severity for dorsal skin of mice was determined using the Severity Scoring of Atopic Dermatitis (SCORAD) every week. The total immunoglobulin E (IgE), interleukin-4 (IL-4), and interferon-gamma (IFN-γ) cytokine levels in serum were examined by enzyme-linked immunosorbent assay (ELISA). Spleen Th1/Th2 expression were analyzed via flow cytometry and immunohistochemical assay was used to detect T-box expressed in T cell (T-bet) and GATA-binding protein 3 (GATA3) expressions in skin lesions of mice.@*RESULTS@#Compared with the AD group, both A-AHT and sA-AHT reduced the SCORAD index and serum IgE level (P<0.05 or P<0.01); A-AHT, sA-AHT and A-NS down-regulated serum IL-4 level and upregulated IFN-γ/IL-4 ratio (P<0.05 or P<0.01); A-AHT regulated the Th1/Th2 shift specifically and increased the related transcription factors such as T-bet expression and T-bet/GATA3 ratio (P<0.05).@*CONCLUSION@#A-AHT showed significant effectiveness on the AD model mice, through regulating Th1/Th2 immune responses.

Application of extracorporeal membrane oxygenation in the treatment of persistent pulmonary hypertension of the newborn / 中国当代儿科杂志

OBJECTIVES@#To study the clinical value of extracorporeal membrane oxygenation (ECMO) in the treatment of persistent pulmonary hypertension of the newborn (PPHN).@*METHODS@#A retrospective analysis was performed on the medical data of 11 neonates with PPHN who were treated with ECMO in the Neonatal Intensive Care Unit of Zhongshan People's Hospital from January 2015 to December 2021, involving the neonates' general information, clinical diagnosis, laboratory results, duration of ECMO treatment, complications during ECMO treatment, length of hospital stay, and outcome.@*RESULTS@#Of the 11 neonates, 10 (91%) had successful weaning from ECMO, and 8 (73%) survived. For the 11 neonates, the mean duration of ECMO treatment was (81±50) hours (range: 26 to 185 hours), the mean duration of ventilator use was (198±105) hours (range: 57 to 392 hours), and the mean length of hospital stay was (22±15) days (range: 2 to 49 days). The oxygenation index and blood lactate level were significantly improved after 24 hours of ECMO treatment among the 11 neonates (P<0.05). Ten neonates had significantly reduced pulmonary artery pressure after 24 hours of ECMO treatment (P<0.05). One neonate had a progressive increase in the pulmonary artery pressure during EMCO treatment, succumbing to death. This neonate was diagnosed with alveolar capillary dysplasia based on the histopathological findings of the lung tissue and whole-exome sequencing results. Among the 11 children, 5 had intracranial hemorrhage, 1 had disseminated intravascular coagulation, 1 had gastric hemorrhage, 2 had pulmonary hemorrhage, 1 had renal insufficiency, and 3 had bleeding at the puncture site during ECMO treatment.@*CONCLUSIONS@#ECMO is effective for the treatment of PPHN, however, the high incidence of complications of ECMO treatment suggests that it is important to carefully assess the indications and timing of ECMO treatment and improve the management of ECMO, which can improve the weaning rate and survival rate.

Study on the spatial distribution and related factors of medical insurance designated retail pharmacies in Guiyang / 中国药房

OBJECTIVE To pr ovide theoretic support for Guiyang to scientifically guide the development of drug retail industry and implement national health policies . METHODS The data were collected through statistical yearbook ，data cloud ， coordinate acquisition device of Application Programming Interface of Baidu map and so on. The spatial distribution characteristics and accessibility of medical insurance designated retail pharmacies （shorted for “designated pharmacies ”）in Guiyang were analyzed by spatial analysis based on Geographic Information System. The related factors for the distribution of designated pharmacies in Guiyang were analyzed by statistical method. RESULTS The number of designated pharmacies ，designated pharmacies per thousand people and designated pharmacies per 10 km2 in Guiyang increased from 2 018，0.41 and 2.51 in 2020 to 2 500，0.42 and 3.11 in 2021，with growth rates of 23.89％，2.44％ and 23.90％ respectively. The service area of the designated pharmacies that residents of Guiyang reached within 15 minutes on foot was 10.27％ of the total service area of designated pharmacies in Guiyang. The results of correlation analysis showed that the correlation coefficients between the regional gross regional production ，total retail sales of consumer goods ，population，urban per capita disposable income and the number of designated pharmacies in Guiyang were 0.999，0.999，0.977 and 0.992，respectively （all P＜0.05）. CONCLUSIONS The distribution of designated pharmacies is insufficient in Guiyang ，the development of designated pharmacies in various administrative regions is uneven ，and the layout of pharmacies is significantly affected by economic and demographic factors. It is suggested that the local government should explore the strategy of scientifically and reasonably expanding the coverage of designated pharmacies in urban and rural areas，promote the rational layout of pharmacies with appropriate economic and demographic policies ，and pay attention to improving the service capacity of designated pharmacies ，so as to improve the quality of life of the people and guide the healthy and high-quality development of drug retail industry.

Relationships between lead-induced learning and memory impairments and gut microbiota disturbance in mice / 中华劳动卫生职业病杂志

Objective: To explore the effect of lead exposure on the neurobehavior and gut microbiota community structure in mice. Methods: In August 2019, 64 C57BL/6 mice were randomly divided into 4 groups: control group (0 ppm) , low lead exposure group (20 mg/l) , medium lead exposure group (100 mg/l) and high lead exposure group (500 mg/l) . During the experiment, they were free to eat and drink. The drinking water of the lead exposure group was mixed with lead acetate, and sodium acetate was added in the control group. After 10 weeks of exposure, the Morris water maze was used to test the learning and memory ability of each group of mice, and then they were sacrificed for sampling. ICP-MS was used to detect lead content in whole blood and brain tissue. ELISA was used to determine the level of IL-1β in mouse serum. 16S rRNA sequencing was used to detect the structural diversity of the intestinal flora in feces, and then the correlation between the flora and behavior indicators was analyzed. Results: In the Morris water maze experiment, compared with the control group, there was no significant difference in the body weight and swimming speed of the mice in the lead exposure groups. The escape latency of the mice in the 100 mg/l and 500 mg/l dose groups was prolonged, and the number of platform crossings decreased (P<0.05) ; meanwhile, the staying time of the mice in the 500 mg/l Pb-treated group in the target quadrant was lower than that of the control group, and the difference was statistically significant (P<0.05) . Compared with the control group, the blood lead content of the mice in each lead exposure group was significantly increased, and the brain lead content of mice in the 500 mg/l dose group was significantly elevated (P<0.05) . The serum IL-1β levels of mice in each lead exposure group were higher than those of the control group (P<0.05) . At the phylum level, the relative abundance of the Proteobacteria phylum in all of Pb-treated groups was significantly increased (P<0.05) ; at the genus level, Allobaculum, Desulfovibrio, Lachnospiraceae_NK4A136_group, Turicibacter and Ureaplasma were significantly increased (P<0.05) . Among them. The relative abundance of Desuffaoibrio, Turici bacter, and Ureaplasma was negatively correlated with the residence time of mice in the quadrant of the platform (r=-0.32, -0.29, -0.44, P<0.05) . Conclusion: Lead exposure induced learning and memory impairments in mice, which may be related to the disturbance of the gut microbiota.

Association of Increased Amygdala Activity with Stress-Induced Anxiety but not Social Avoidance Behavior in Mice / 神经科学通报·英文版

Chronic stress leads to many psychiatric disorders, including social and anxiety disorders that are associated with over-activation of neurons in the basolateral amygdala (BLA). However, not all individuals develop psychiatric diseases, many showing considerable resilience against stress exposure. Whether BLA neuronal activity is involved in regulating an individual's vulnerability to stress remains elusive. In this study, using a mouse model of chronic social defeat stress (CSDS), we divided the mice into susceptible and resilient subgroups based on their social interaction behavior. Using in vivo fiber photometry and in vitro patch-clamp recording, we showed that CSDS persistently (after 20 days of recovery from stress) increased BLA neuronal activity in all the mice regardless of their susceptible or resilient nature, although impaired social interaction behavior was only observed in susceptible mice. Increased anxiety-like behavior, on the other hand, was evident in both groups. Notably, the CSDS-induced increase of BLA neuronal activity correlated well with the heightened anxiety-like but not the social avoidance behavior in mice. These findings provide new insight to our understanding of the role of neuronal activity in the amygdala in mediating stress-related psychiatric disorders.

E.faecium QH06 alleviates TNBS-induced colonic mucosal injury in rats / 南方医科大学学报

OBJECTIVE@#To investigate the effect of Enterococcus faecium QH06 on TNBS-induced ulcerative colitis (UC) in rats and explore the mechanisms in light of intestinal flora and intestinal immunity.@*METHODS@#Thirty-six male Wistar rats were randomized equally into control group, UC model group, and E.faecium QH06 intervention group. The rats in the latter two groups were subjected to colonic enema with 5% TNBS/ethanol to induce UC, followed by treatment with intragastric administration of distilled water or E.faecium QH06 at the dose of 0.21 g/kg. After 14 days of treatment, the rats were examined for colon pathologies with HE staining. The mRNA and protein expression levels of IL-4, IL-10, IL-12, and IFN-γ in the colon tissues were detected using RT-qPCR and ELISA, and the expression of TLR2 protein was detected with immunohistochemistry and ELISA. Illumina Miseq platform was used for sequencing analysis of the intestinal flora of the rats with bioinformatics analysis. The correlations of the parameters of the intestinal flora with the expression levels of TLR2 and cytokines were analyzed.@*RESULTS@#The rats with TNBS- induced UC showed obvious weight loss (P < 0.01) and severe colon tissue injury with high pathological scores (P < 0.01). The protein expression levels of IFN-γ, IL-12, and TLR2 (P < 0.01) and the mRNA expression levels of IFN-γ, IL-12 and IL-10 (P < 0.05) were significantly increased in the colon tissues of the rats with UC. Illumina Miseq sequence analysis showed that in UC rats, the Shannon index (P < 0.05) ACE (P < 0.01)and Chao (P < 0.05) index for the diversity of intestinal flora both decreased with a significantly increased abundance of Enterobacteriaceae (P < 0.01) and a lowered abundance of Burkholderiaceae (P < 0.05). Compared with the UC rats, the rats treated with E. faecium QH06 showed obvious body weight gain (P < 0.05), lessened colon injuries, lowered pathological score of the colon tissue (P < 0.05), decreased protein expressions of IFN- γ, IL- 12, and TLR2 and mRNA expressions of IFN- γ and IL-12 (P < 0.01 or 0.05), and increased protein expressions of IL- 4 (P < 0.05). The Shannon index ACE (P < 0.05) and Chao (P < 0.05) index of intestinal microflora were significantly increased, the abundance of Enterobacteriaceae was lowered and that of Burkholderiaceae and Rikenellaceae was increased in E.faecium QH06- treated rats (P < 0.01 or 0.05). Correlation analysis showed that IFN-γ was positively correlated with the abundance of Enterobacteriaceae, and IFN-γ was negatively correlated with the abundance of Prevotellaceae, Desulfovibrionaceae, norank_o_Mollicutes_RF39 and Clostridiales_vadinBB60_group; TLR2 was negatively correlated with Clostridiales_vadinBB60_group, norank_o_Mollicutes_RF39 and Prevotellaceae.@*CONCLUSION@#E.faecium QH06 can alleviate TNBS-induced colonic mucosal injury in rats, and its effect is mediated possibly by increasing the abundance of SCFA-producing bacteria such as Prevotellaceae and inhibiting abnormal immune responses mediated by TLR2.

Clinical characteristics and long-term follow-up results of radiofrequency ablation for the treatment of ventricular tachycardia in patients with arrhythmogenic left ventricular cardiomyopathy / 中华心血管病杂志

Objective: To investigate the acute and long-term outcome of catheter ablation for the treatment of ventricular tachycardia (VT) in patients with arrhythmogenic left ventricular cardiomyopathy (ALVC). Methods: This retrospective, cross-sectional study enrolled ALVC patients undergoing radiofrequency ablation for the treatment of VT at the First Affiliated Hospital of Nanjing Medical University from January 2011 to December 2018 and collected their clinical characteristics and intraoperative electrophysiological examination. Patients were followed up every 6 months after radiofrequency ablation until August 2021. Echocardiographic results and VT recurrence post radiofrequency ablation were analysed. Results: Totally 12 patients were enrolled (mean age: (42±15) years, 11 males(11/12)). The mean of left ventricular end diastolic diameter (LVDd) and left ventricular ejection fraction (LVEF) were (51±5)mm and (65±5)%, respectively. Twelve VTs were induced in 10 patients during the electrophysiological study, and the mean tachycardia cycle length was (293±65) ms. Three-dimensional substrate mapping revealed the diseased area at endocardial site in one patient, at epicardial sites in the other 11 patients (involved endocardial sites in 2 cases) with the basal part near the mitral annulus being the predilection for the substrate (10/11). After the catheter ablation at the endocardial and epicardial sites respectively, the complete procedure endpoint was achieved in all patients (VT cannot be induced post ablation). The median follow-up time was 65 (25, 123) months. One patient was lost to follow-up, and the other 11 patients survived without VT. No significant cardiac function deterioration was detected by the echocardiographic examination ((51±5)mm vs. (52±5)mm, P>0.05 for LVDd, (65±5)% vs. (60±6)%, P>0.05 for LVEF) at the end of follow-up. Conclusion: After radiofrequency ablation, the complete procedure endpoint is achieved in ALVC patients, and the catheter ablation provides long-term ventricular tachycardia control during the long-term follow-up.

Comparative study of femoral head replacement and internal fixation in the treatment of unstable intertrochanteric fractures in the elderly / 中国骨伤

OBJECTIVE@#To compare the clinical efficacy of femoral head replacement and internal fixation in the treatment of unstable intertrochanteric fractures in the elderly.@*METHODS@#Retrospective analysis of 70 cases of unstable intertrochanteric fractures treated from January 2016 to January 2019 and meeting the inclusion and exclusion criteria, 39 cases were fixed with closed reduction and new proximal femoral intramedullary nail(InterTAN), and 31 cases were treated with open trochanter reconstruction and artificial femoral head replacement. The operation time, intraoperative bleeding, hospital stay, weight bearing time, postoperative complication rate and hip function recovery (Harris score) were compared between two groups.@*RESULTS@#All cases were followed up for 12 to 24 months. There were no significant differences in intraoperative bleeding and hospital stay between the two groups (@*CONCLUSION@#InterTAN and femoral head replacement can treat unstable intertrochanteric fractures in the elderly, but femoral head replacement can move down early, improve the quality of life at the end of life, reduce postoperative complications and facilitate the treatment of coexisting diseases in internal medicine.

Bone marrow mesenchymal stem cells protect myocardial ischemia-reperfusion injury by inducing regulatory T cells in mice / 中华急诊医学杂志

Objective:To investigate the protective effect and mechanism of bone marrow-derived mesenchymal stem cell (BM-MSC) on myocardial ischemia-reperfusion injury (MIRI) in mice.Methods:Twenty four C57 MIRI mice were randomly(random number) divided into four groups: SO group, RI group, MSC+RI group, and MSC + RI+ PC61 group. The ratio of Treg were detected by flow cytometry. Serum levels of CK, TNI, BNP, IL-10 and TGF-β were measured by ELISA. The histological changes of myocardium were observed by HE staining. The number of cardiomyocyte apoptosis was measured by TUNEL staining, and the area ratio of myocardial infarction were determined by TTC staining. One-way ANOVA was used to analyze the data.Results:In the MSC + RI group, the ratio of Treg and the levels of IL-10 and TGF-β were the highest, while CK, TNI and BNP were the lowest ( P<0.01) .The number of myocardial apoptotic cells, infarct size and tissue fibrosis were the least ( P<0.01) . Conclusions:MSC can induce the production of Treg, increase the release of anti-inflammatory cytokines IL-10 and TGF-β, and reduce the inflammatory injury after myocardial ischemia-reperfusion.

Effect of Bushen Huatan Prescription on Serum LPS and TLR4/MyD88/NF-κB Signaling Pathway in Rats with Ovariectomy-induced Osteoporosis / 中国实验方剂学杂志

Objective:To explore the effect of Bushen Huatan prescription on serum lipopolysaccharide （LPS） and Toll-like receptor 4 （TLR4）/ myeloid cell differentiation protein 88 （MyD88）/nuclear transcription factor-<italic>κ</italic>B （NF-<italic>κ</italic>B） signaling pathway in rats with ovariectomy-induced osteoporosis. Method:Sixty SPF 6-month-old female rats were randomly divided into sham operation group， model group， estradiol valerate group and Bushen Huatan prescription low， medium and high dose groups.One week after modeling by bilateral ovariectomy， 8 rats in each group were selected to receive intragastric administration.The estradiol valerate group was given 0.184 mg·kg^-1 by gavage， and Bushen Huatan prescription low， middle and high dose groups were given 4.7， 9.4 and 18.8 g·kg^-1 by gavage， sham operation group and model group were given 0.9% saline 4 mL by gavage respectively.After 12 weeks of intervention， the rats were sacrificed for detection.Serum LPS was detected by enzyme linked immunosorbent assay （ELISA）， while protein expressions of TLR4， MyD88 and phosphorylated （p）-NF-<italic>κ</italic>B p65 in bone tissue were detected by Western blot， and the mRNA expressions of TLR4， MyD88， NF-<italic>κ</italic>B p65， IL-1<italic>β</italic>， and IL-6 in bone tissue were detected by quantitative real-time polymerase chain reaction（PCR）. Result:Compared with sham operation group， the serum LPS level as well as protein expression of TLR4， MyD88， p-NF-<italic>κ</italic>B p65 and mRNA expression of TLR4， MyD88， NF-<italic>κ</italic>B p65， IL-1<italic>β</italic>， and IL-6 significantly increased in model group（<italic>P</italic><0.05）.Compared with the model group， serum LPS level， protein expression of TLR4， MyD88， and p-NF-<italic>κ</italic>B p65， mRNA levels of TLR4， MyD88， and NF-<italic>κ</italic>B p65 in bone tissues as well as downstream inflammatory factors IL-1<italic>β</italic>， IL-6 mRNA expression decreased to different degrees in estradiol valerate group and Bushen Huatan prescription high dose group（<italic>P</italic><0.05）. Conclusion:Bushen Huatan prescription can reduce serum LPS content， regulate mRNA and protein expression of TLR4， MyD88， NF-<italic>κ</italic>B p65 and p-NF-<italic>κ</italic>B p65 in TLR4/MyD88/NF-<italic>κ</italic>B pathway， and down-regulate mRNA levels of IL-1<italic>β</italic> and IL-6 in bone tissues to improve bone microstructure and inhibit the development of postmenopausal osteoporosis （PMOP）.

Mechanism of Bushen Huatan Prescription in Regulating Th17/Treg Balance in Ovariectomized Osteoporosis Rats / 中国实验方剂学杂志

Objective:To study the effect of Bushen Huatan prescription on helper T cell 17 （Th17）/T regulatory cells （Treg） balance of immune T cell subsets in the prevention and treatment of postmenopausal osteoporosis. Method:Sixty 6-month-old female SD rats were randomly divided into sham operation group， model group， estradiol valerate group （0.184 mg·kg^-1） and Bushen Huatan prescription low， medium and high groups （4.7， 9.4， 18.8 g·kg^-1） according to the random number table. All the groups except the sham operation group received ovariectomy to make postmenopausal osteoporosis model. Intragastric administration was started 1 week after operation， and the rats in model group and sham operation group received equal volume of normal saline， once a day for 12 weeks. Microcomputed tomography （Micro CT） was then used to detect bone mass and microstructure of rats， the contents of Forkhead box protein （Foxp3） and retinoic acid related nuclear orphan receptor （ROR<italic>γ</italic>t） in serum were detected by enzyme-linked immunosorbent assay （ELISA）， the mRNA expression levels of Foxp3 and ROR<italic>γ</italic>t in bone tissues were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot was used to detect the protein expression of Foxp3 and ROR<italic>γ</italic>t in bone tissues， the number of Th17 and Treg cells in each group was analyzed and compared by flow cytometry. Result:Compared with the sham operation group， the bone mass and trabeculae of the model group decreased （<italic>P</italic><0.01）， the bone microstructure was destroyed， the concentration of Foxp3 in serum decreased， the concentration of ROR<italic>γ</italic>t increased （<italic>P</italic><0.01）， the mRNA and protein expression levels of Foxp3 in bone tissues decreased， ROR<italic>γ</italic>t increased， the number of Treg cells in bone tissues decreased， number of Th17 cells increased （<italic>P</italic><0.01）， and Th17/Treg ratio increased （<italic>P</italic><0.01） in model group. Compared with the model group， the bone mass in each treatment group increased （<italic>P</italic><0.05， <italic>P</italic><0.01）， Foxp3 concentration in serum increased， ROR<italic>γ</italic>t concentration decreased （<italic>P</italic><0.01）， the mRNA and protein expression levels of Foxp3 in bone tissues increased significantly （<italic>P</italic><0.05， <italic>P</italic><0.01）， but no statistical difference was shown in mRNA expression between low dose group and the model group. In addition， the mRNA and protein expression of ROR<italic>γ</italic>t decreased （<italic>P</italic><0.05， <italic>P</italic><0.01）， number of Treg cells increased， number of Th17 cells decreased （<italic>P</italic><0.05， <italic>P</italic><0.01）， and Th17/Treg ratio decreased in treatment groups （<italic>P</italic><0.01）. Conclusion:Bushen Huatan prescription can increase bone mass， improve bone microstructure， increase the number of Treg cells and decrease the number of Th17 cells in ovariectomized rats. It is concluded that Bushen Huatan prescription may play a role in preventing and treating postmenopausal osteoporosis by regulating Th17/Treg balance.

Establishment and Application of Identification Method for Fishy Odor of Cordyceps Based on HS-SPME/GC-QQQ-MS/MS / 中国实验方剂学杂志

Objective:To establish and apply a new practical analytical method for identifying the fishy odor of Cordyceps based on headspace-solid phase microextraction-gas chromatography-triple quadrupole mass spectrometry （HS-SPME/GC-QQQ-MS/MS） technique. Method:The InertCap Pure-WAX capillary column （0.25 mm×30 m， 0.25 μm） was used for chromatographic separation. The injection port temperature was set at 250 ℃. The injection mode was split injection with a ratio of 5∶1. High purity helium was used as the carrier gas and control mode was set to constant pressure. The column flow rate was 1.43 mL∙min^-1， the linear velocity was 43.3 cm∙s^-1， and the purge flow rate was 3.0 mL∙min^-1. The chromatographic column temperature program as follows：maintained the initial temperature at 50 ℃ for 5 min， and increased the temperature at a rate of 10 ℃∙min^-1 to 250 ℃， held for 10 min. The column equilibrium time was 2.0 min. The ion source of mass spectrographic analysis was electron ionization with ion source temperature of 200 ℃， and the monitoring mode was set to multiple reaction monitoring. Result:Seven batches of Cordyceps samples were collected， including 3 batches from Sichuan， 3 batches from Qinghai and 1 batch from Tibet. There were six batches of counterfeits， including 3 batches from Sichuan， 2 batches from Guizhou and 1 batch in Xinjiang. A total of 81 volatile compounds were screened out in Cordyceps， which could be divided into 13 types （esters， ketones， aldehydes and others） according to the compound structure， indicating that the fishy odor of Cordyceps was a complex odor. There was no significant difference in the types of volatile compounds of Cordyceps from different regions， which suggested that these volatile compounds in Cordyceps produced in Tibet （Naqu）， Qinghai （Yushu and Guoluo） and Sichuan （Litang， Rangtang and Seda） were relatively consistent. However， the contents of some volatile compounds in Cordyceps produced in different regions were quite different， and 16 volatile compounds with significant difference were screened out， including 1-methoxy-2-propyl acetate， <italic>γ</italic>-octalactone， hexyl acetate and others， those compounds maybe could been used as the quality markers for identification of regions of Cordyceps. There was a large difference in volatile compounds between Cordyceps and its counterfeits， and 34 volatile compounds were screened out， including ethyl acetate， acetophenone， 2-ethyl-1-hexanol and others， those compounds maybe could been used as the quality markers for authenticity identification of Cordyceps. Conclusion:In summary， the established method for identifying the fishy odor of Cordyceps in this paper has the characteristics of high sensitivity， accuracy and simplicity， which can provide reference for the analysis of volatile compounds in other Chinese herbal medicines.

Establishment of UPLC-PDA Fingerprint of Baoyuantang Substance Benchmark and Identification of Its Chemical Constituents / 中国实验方剂学杂志

Objective:To establish the fingerprint of Baoyuantang substance benchmark， and to analyze and identify the common peaks. Method:A total of 15 batches of Baoyuantang substance benchmark were prepared， ultra performance liquid chromatography-diode array detector method （UPLC-PDA） was used to establish the fingerprint of the substance benchmark， and the methodology was developed. The chromatographic conditions were as follows：ACQUITY UPLC BEH Shield C₁₈ column （2.1 mm×100 mm， 1.7 μm）， mobile phase of 0.05% formic acid solution （A） and 0.05% formic acid acetonitrile solution （ B） for gradient elution （0-0.5 min， 5%-19%B； 0.5-6 min， 19%B； 6-10 min， 19%-27%B； 10-20 min， 27%-45%B； 20-20.1 min， 45%-95%B； 20.1-23 min， 95%B）， the flow rate of 0.4 mL·min^-1， the column temperature of 30 ℃， the detection wavelength at 203 nm and 260 nm， and the injection volume of 2 μL. Similarity evaluation system of traditional Chinese medicine fingerprint （2012 edition） was used to establish the fingerprint and generate the control fingerprint. The chemical constituents of Baoyuantang substance benchmark were identified by comparison of standard substances and UPLC-electrospray ionization tandem mass spectrometry （UPLC-ESI-MS/MS） with full information tandem mass spectrometry （MS^E） and scanning range of <italic>m</italic>/<italic>z</italic> 50-1 200. Result:The similarities of 15 batches of Baoyuantang substance benchmark were above 0.90 by comparing with the control fingerprint. There were 37 common peaks， 22 of which were identified through UPLC-ESI-MS/MS， including liquiritin， violanthin， ginsenoside Rg₁， ginsenoside Rb₁， ginsenoside Re and so on. These components were all from Astragali Radix， Ginseng Radix et Rhizoma， Zingiberis Rhizoma Recens and Glycyrrhizae Radix et Rhizoma. Conclusion:This method is accurate， stable and reliable， which will basically reflect the overall chemical composition characteristics of Baoyuantang， and it provides experimental basis for development of the granules of this famous classical formulas.