This article systematically analyzes the historical evolution of the name， origin， quality evaluation， harvesting， processing and other aspects of Picrorhizae Rhizoma by referring to the medical books， prescription books， and other documents of the past dynasties， combined with relevant modern research materials， in order to provide a basis for the development and utilization of famous classical formulas containing this medicinal herb. The research results indicate that Picrorhizae Rhizoma was first recorded in New Revised Materia Medica from the Tang dynasty. Throughout history， Huhuanglian has been used as its official name， and there are also aliases such as Gehu Luze， Jiahuanglian and Hulian. The main source of past dynasties is the the rhizomes of Picrorhiza kurrooa and P. scrophulariiflora. In ancient times， Picrorhizae Rhizoma was mainly imported by foreign traders via Guangzhou and other regions， and also produced in China， mainly in Xizang. In ancient times， it was harvested and dried in early August of the lunar calendar， while in modern times， it is mostly harvested from July to September， with the best quality being those with thick and crispy rhizomes without impurities， and bitter taste. Throughout history， Picrorhizae Rhizoma was collected， washed， sliced， and dried before being used as a raw material for medicine， it has a bitter and cold taste， mainly used to treat bone steaming， hot flashes， infantile chancre fever， and dysentery. There is no significant difference in taste and efficacy between ancient and modern times. Based on the research results， it is recommended that the rhizomes of P. scrophulariiflora in the 2020 edition of Chinese Pharmacopoeia， or the rhizomes of P. kurrooa， can be used in famous classical formulas containing this medicinal herb， which can be processed according to the processing requirements marked by the original formula. For those without clear processing requirements， the dried raw products are used as medicine.

Objective To explore the regulatory effect of moderate intensity aerobic exercise on glu-cose and lipid metabolism disordersafter immune stimulation in high-fat diet induced insulin resistance(IR)mice by inducing tolerance of trained immunity.Methods Eighteen of 70 male C57BL/6 male mice were randomly selected as the control group(CON group),while the remaining mice were subjected to high-fat diet intervention(HFD group)for 8 weeks.After modeling,six of the CON group and HFD group were measured their glucose and lipid metabolism and inflammation levels.The remaining mice in the HFD group were randomly divided into HFD sedentary group(HS group)and HFD exer-cise group(HE group),each of 16.The HE groups underwent a daily 60-minute running on a hori-zontal treadmill at 12 m/min,5 days a week for 8 weeks.After that,the CON,HS and HE groups were randomly divided into an immune stimulation group(lipopolysaccharides,LPS group)and a con-trol group(phosphate buffered saline,PBS group),with 6 in CON-PBS and CON-LPS groups,and 8 in HS-PBS,HS-LPS,HE-PBS and HE-LPS groups.The LPS group received intraperitoneal injec-tion of LPS as an immune stimulus,and were taken samples 24 hours after intervention.During the intervention period,the body weight,food intake,fasting blood glucose(FBG),glucose tolerance,and insulin tolerance were tested for all groups.Then,the serum blood lipid level was tested.More-over,the levels of tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1β)and interleukin-10(IL-10)in serum were detected by using the enzyme-linked immunosorbent assay,while the protein expression of IL-1β,IL-10,induciblenitricoxidesynthase(iNOS)andarginase-1(Arg-1)were measured by using Western Blot.Results(1)After 8 weeks of high-fat diet intervention,compared with the CON group,there was a significant increase in the body weight,food intake,and FBG,the level of TNF-α and IL-1β in serum and expressions of IL-1β and iNOS in liver,skeletal muscle and adipose tissue,but a significant decrease in glucose and insulin tolerance,the level of anti-in-flammatory factor IL-10,as well as IL-10 and Arg-1 in liver and Arg-1 in adipose tissues in group HFD(P<0.01,P<0.05).(2)After 8 weeks of diet intervention,the body weight of group HS-PBS was still significantly higher than group CON-PBS(P<0.01).However,no significant differences were found between group CON-PBS and HS-PBS in other indicators(P>0.05).After LPS intervention,the food intake of both CON-LPS and HS-LPS groups was significantly lower than the corresponding PBS group(P<0.05).However,the levels of FBG,TG,TC,LDL-C,TNF-α and IL-1β in serum,IL-1β and iNOS in liver and adipose tissues,and iNOS in skeletal muscles of group HS-LPS were signif-icantly higher compared with group HS-PBS and CON-LPS(P<0.05).Meanwhile,the levels of IL-10 in serum,skeletal muscles and adipose tissues,and Arg-1 in skeletal muscles and adipose tissues of group HS-LPS decreased significantly compared with group HS-PBS and CON-LPS(P<0.05).(3)Af-ter simultaneous aerobic exercise intervention,there were no significant differences between group HE-LPS and HE-PBS in FBG,TC,LDL-C,TNF-α,IL-1β and IL-10 in serum,as well as IL-1β,iN-OS and IL-10 in the liver,skeletal muscles and adipose tissues(P>0.05).Moreover,thelevels of FBG,TG,TC,TNF-α,IL-1β in serum,and IL-1β and iNOS in the liver,skeletal muscle and adi-pose tissue decreased significantly in group HE-LPS compared with group HS-LPS(P<0.05).Howev-er,the levels of IL-10 in the serum and liver,and IL-10 and Arg-1 in skeletal muscles and adi-pose tissues increased significantly in group HE-LPS compared with group HS-LPS(P<0.05).Conclu-sion Eight-week aerobic exercise can effectively relieve the glucose and lipid metabolism disorder after immune stimulation in IR mice,which may be related to the stimulation of immunologic tolerance in innate immune cells,thereby reducing the excessive inflammatory response caused by secondary im-mune stimulation.

Objective To explore the regulatory effect of moderate intensity aerobic exercise on glu-cose and lipid metabolism disordersafter immune stimulation in high-fat diet induced insulin resistance(IR)mice by inducing tolerance of trained immunity.Methods Eighteen of 70 male C57BL/6 male mice were randomly selected as the control group(CON group),while the remaining mice were subjected to high-fat diet intervention(HFD group)for 8 weeks.After modeling,six of the CON group and HFD group were measured their glucose and lipid metabolism and inflammation levels.The remaining mice in the HFD group were randomly divided into HFD sedentary group(HS group)and HFD exer-cise group(HE group),each of 16.The HE groups underwent a daily 60-minute running on a hori-zontal treadmill at 12 m/min,5 days a week for 8 weeks.After that,the CON,HS and HE groups were randomly divided into an immune stimulation group(lipopolysaccharides,LPS group)and a con-trol group(phosphate buffered saline,PBS group),with 6 in CON-PBS and CON-LPS groups,and 8 in HS-PBS,HS-LPS,HE-PBS and HE-LPS groups.The LPS group received intraperitoneal injec-tion of LPS as an immune stimulus,and were taken samples 24 hours after intervention.During the intervention period,the body weight,food intake,fasting blood glucose(FBG),glucose tolerance,and insulin tolerance were tested for all groups.Then,the serum blood lipid level was tested.More-over,the levels of tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1β)and interleukin-10(IL-10)in serum were detected by using the enzyme-linked immunosorbent assay,while the protein expression of IL-1β,IL-10,induciblenitricoxidesynthase(iNOS)andarginase-1(Arg-1)were measured by using Western Blot.Results(1)After 8 weeks of high-fat diet intervention,compared with the CON group,there was a significant increase in the body weight,food intake,and FBG,the level of TNF-α and IL-1β in serum and expressions of IL-1β and iNOS in liver,skeletal muscle and adipose tissue,but a significant decrease in glucose and insulin tolerance,the level of anti-in-flammatory factor IL-10,as well as IL-10 and Arg-1 in liver and Arg-1 in adipose tissues in group HFD(P<0.01,P<0.05).(2)After 8 weeks of diet intervention,the body weight of group HS-PBS was still significantly higher than group CON-PBS(P<0.01).However,no significant differences were found between group CON-PBS and HS-PBS in other indicators(P>0.05).After LPS intervention,the food intake of both CON-LPS and HS-LPS groups was significantly lower than the corresponding PBS group(P<0.05).However,the levels of FBG,TG,TC,LDL-C,TNF-α and IL-1β in serum,IL-1β and iNOS in liver and adipose tissues,and iNOS in skeletal muscles of group HS-LPS were signif-icantly higher compared with group HS-PBS and CON-LPS(P<0.05).Meanwhile,the levels of IL-10 in serum,skeletal muscles and adipose tissues,and Arg-1 in skeletal muscles and adipose tissues of group HS-LPS decreased significantly compared with group HS-PBS and CON-LPS(P<0.05).(3)Af-ter simultaneous aerobic exercise intervention,there were no significant differences between group HE-LPS and HE-PBS in FBG,TC,LDL-C,TNF-α,IL-1β and IL-10 in serum,as well as IL-1β,iN-OS and IL-10 in the liver,skeletal muscles and adipose tissues(P>0.05).Moreover,thelevels of FBG,TG,TC,TNF-α,IL-1β in serum,and IL-1β and iNOS in the liver,skeletal muscle and adi-pose tissue decreased significantly in group HE-LPS compared with group HS-LPS(P<0.05).Howev-er,the levels of IL-10 in the serum and liver,and IL-10 and Arg-1 in skeletal muscles and adi-pose tissues increased significantly in group HE-LPS compared with group HS-LPS(P<0.05).Conclu-sion Eight-week aerobic exercise can effectively relieve the glucose and lipid metabolism disorder after immune stimulation in IR mice,which may be related to the stimulation of immunologic tolerance in innate immune cells,thereby reducing the excessive inflammatory response caused by secondary im-mune stimulation.

The study was designed to investigate the peripheral anti-inflammatory effect of nicotinamide riboside(NR)in experimental autoimmune encephalomyelitis(EAE)mice and its mechanisms.Female C57BL/6 mice were induced by MOG35-55 to prepare EAE model,which then randomly divided into EAE model group and NR treatment group.Mice in EAE model group were given normal saline at a dose of 200 μl/d and mice in NR treatment group were given NR at a dose of 500 mg/kg(200 μl/d)by intragastric administration.Clinical score and body weight of mice in each group were observed and recorded.After mice were sacrificed on the 28th day after immunization,frozen sections of spleen and spinal cord were prepared and proteins of spinal cord were extracted.HE staining was used to detect peripheral inflammatory cells infiltrating spinal cord;immunofluorescence staining was used to detect the number of CD4+T cells and CD68+macrophages in spinal cord of mice;Western blot was used to detect the expression of IFN-γ and IL-1β in spinal cord of mice;immunofluorescence staining was used to detect the number of ROCK-Ⅰ+cells,TLR4+cells,p-NF-κB+cells,TNF-α+cells,IL-1β+cells,IFN-γ+cells,IL-6+cells,IL-10+cells,IL-17+cells,iNOS+cells and Arg-1+cells in spleen of mice.Data showed that compared with EAE model group,NR significantly delayed the onset time of EAE mice(P<0.05),decreased clinical score(P<0.05 or P<0.01),alleviated weight loss,prevented peripheral inflammatory cells from infiltrating spinal cord,decreased the number of CD4+T cells and CD68+macrophages in spinal cord(P<0.01),down-regulated the expression of IFN-γ and IL-1β of spinal cord(P<0.05),inhibited the expression of ROCK-Ⅰ,TLR4 and p-NF-κB in spleen of mice(P<0.01),reduced the secretion of IFN-γ,iNOS,IL-6 and other pro-inflammatory factors in spleen(P<0.05 or P<0.01),and increased the secretion of anti-inflammatory factors Arg-1 and IL-10 in spleen(P<0.05 or P<0.01).In conclusion,NR can effectively alleviate the clinical symptoms of EAE mice and significantly reduce inflammatory response of peripheral and central nervous system,and its mechanism may be related to the inhibition of Rho/ROCK signaling pathway and TLR4/NF-κB signaling pathway in spleen of EAE mice.

BACKGROUND:In the initial stage of multiple sclerosis,central immune cells activate and release a large number of inflammatory factors,causing white matter demyelination and even involving gray matter neurons.The equilibrium of differentiation between different subsets of CD4+ T cells plays an important role in the progression of experimental autoimmune encephalomyelitis.The previous results of the research group showed that the active ingredient astragalus glycoprotein in astragalus can regulate the immune response in experimental autoimmune encephalomyelitis mice,and whether it has a regulatory effect on the differentiation of T cell subsets has not been determined. OBJECTIVE:To explore the therapeutic effects and immune regulatory mechanisms of astragaloside IV on experimental autoimmune encephalomyelitis mice. METHODS:Female C57BL/6 mice were divided into the normal control group,experimental autoimmune encephalomyelitis disease model group,and astragaloside IV treatment group(n=8 per group).Myelin oligodendrocyte glycoprotein peptides 35-55 were used for experimental autoimmune encephalomyelitis model induction in the last two groups.On day 10 to 28 after immunization,the astragaloside IV treatment group was treated with 40 mg/kg per day astragaloside IV intragastrically.Body weight and clinical scores of mice in each group were recorded from the immunization day to the 28th day.On the 28th day after immunization,the mouse spinal cord was taken and made into frozen sections for hematoxylin-eosin staining and Lux fast blue staining to observe pathological changes in the spinal cord.Percentage of splenic T cell subsets was detected using flow cytometry.Western blot assay was used to determine the protein expression of interferon-γ,interleukin-17 and interleukin-6 in the spinal cord.Levels of interferon-γ,interleukin-17,interleukin-6 and interleukin-4 in supernatants of cultured splenocytes were determined by ELISA. RESULTS AND CONCLUSION:(1)Compared with the experimental autoimmune encephalomyelitis disease model group,astragaloside IV could reduce the degree of weight loss in experimental autoimmune encephalomyelitis mice(P<0.05),ameliorate clinical symptoms(P<0.05),inhibit the infiltration of inflammatory cells and alleviate myelin loss(P<0.01,P<0.05).(2)Compared with the experimental autoimmune encephalomyelitis disease model group,astragaloside IV could inhibit the proportion of CD4+T cell subsets expressing interferon-γ(P<0.001)and interleukin-17(P<0.001),but increase percentages of CD4+ interleukin-10+(P<0.001)and CD4+ transforming growth factor-β+(P<0.01)T cell subsets.(3)Astragaloside IV could inhibit the expression of interferon-γ(P<0.05,P<0.01),interleukin-17(P<0.05,P<0.05),and interleukin-6(P<0.05,P<0.05)in the spinal cord and spleen,and up-regulate the expression of interleukin-4(P<0.01)in spleen.(4)These findings confirm that astragaloside IV alleviates clinical symptoms in experimental autoimmune encephalomyelitis mice,which may be related to regulating the splenic T cell subsets,therefore,inhibiting the infiltration of inflammatory cells into the center and reducing the demyelination.

Objective:To explore the effect of adaptive nursing based on one point and two sources on the psychological resilience and self-care of patients with arrhythmia.Methods:From December 2020 to May 2021, patients with arrhythmias in Beijing Anzhen Hospital affiliated to Capital Medical University were selected by convenience sampling as research objects. The patients admitted from December 2020 to February 2021 were set in the control group ( n=163) , and the patients admitted from March to May 2021 were set in the observation group ( n=175) . The control group received routine nursing, while the observation group received adaptive nursing based on one point and two sources on the basis of the control group. The scores of the Chinese version of Connor-Davidson Resilience Scale (CD-RISC) and Exercise of Self-care Agency (ESEA) were compared between the two groups before and after intervention. Results:Before the intervention, there were no significant differences in the scores of CD-RISC and ESEA between the two groups ( P>0.05) . After intervention, the scores of CD-RISC and ESEA in the observation group were statistically higher than those in the control group ( P<0.01) . Conclusions:Adaptive nursing based on one point and two sources can effectively improve the psychological resilience of patients with arrhythmia, and improve their self-care, which is worth popularizing in clinical practice.

Objective: To investigate the expression of eukaryotic translation initiation factor 2B1(eIF2B1) in HCC and its correlation with clinical prognosis. Methods: Through the follow⁃up of the clinical data of 743 hepatocellular carcinoma patients in the specimen bank ,91 HBV⁃related liver cancer patients with complete follow⁃up information were screened out , and their postoperative tumor tissues were selected. Meanwhile , the adjacent tumor tissues with a distance of more than 2 cm from the tumor margin were collected to make tissue chips. Western blot and immunohistochemical experiments were performed. Image J was used to analyze the proportion of positive cells stained by tissue chip and the gray value of Western blot results. Clinical data and follow⁃up data of included patients were statistically analyzed by R4. 0. 5 software. Results: Immunohistochemical results suggested that eIF2B1 was more strongly expressed in HCC than in para⁃cancerous tissues. Western blot results showed that eIF2B1 was more strongly expressed in HepG2. 2. 15 cells than in HepG2 cells. The expression of eIF2B1 in HCC tissues was correlated with tumor number (P < 0. 05) . Cox multivariate regression analysis showed that the expression of eIF2B1 was an independent risk factor for the overall clinical prognosis of HBV⁃DNA positive patients (HR = 4. 28 ,P = 0. 018) . Conclusion The expression of eIF2B1 is significantly enhanced in HBV⁃associated HCC tissues and is significantly associated with overall survival in HBV DNA positive patients.

Objective:To explore the efficacy, adverse reactions, and feasibility of high-definition transcranial direct current stimulation(HD-tDCS) treating major depressive disorder(MDD) patients with anxious distress.Methods:Sixty cases of MDD with anxious distress admitted to Zhenjiang Mental Health Center were recruited as participants. All patients were allocated into either the active treatment group or the sham group based on the random number table method. HD-tDCS was utilized in both groups to stimulate the left dorsolateral prefrontal cortex on the basis of conventional antidepressant treatment. In the active group, 2mA current stimulation was used for 20 min, and in the sham group, a 30-sceond stimulation was adopted at the beginning and the end of the stimulation. Participants in both group were treated once a day, five times a week for two consecutive weeks. Anxiety and depression symptoms of the patients were assessed respectively by the Hamilton depression scale(HAMD 17), the Montgomery-Asberg Depression Rating Scale(MARDS), the Hamilton Anxiety Scale(HAMA), and the Beck Anxiety Inventory(BAI) at the baseline, 2nd, 4th, and the 6th weekend of the treatment. The differences between active treatment and sham groups were analyzed by repetitive measure analysis of variance and simple effect analysis. Fisher′s exact probability test was used to compare the effective rate, remission rate and adverse reaction rate between the two groups. Results:(1) The interaction of times and groups was significant in HAMD 17( F=3.29, P<0.05) and BAI( F=2.99, P<0.05). In all measurement instruments, the main effects of groups( F=4.40-7.94) and times( F=35.42-247.59) were significant( P<0.05).(2) Findings from the simple effect analysis showed that: there were no significant differences in the scores of HAMD 17 at baseline and the 2 nd assessment between the two groups. Similarly, no significant differences were found in BAI at baseline, the 2nd and the 6th weekend of the treatment between two groups( P>0.05).(3) The scores of HAMD 17 at the 4th and the 6th week, BAI at the 4th weekend of the treatment in the active group were significantly lower than that in the sham group( P<0.05).(4) At the 4th weekend of the treatment, the active group had a remission rate of 16/20 and a response rates of 19/20, which were higher than 9/19 and 13/19, respectively, in the sham group( P<0.05). Also, the remission rate(18/20) in the active group was higher than that in the sham group(11/19) at the 6th weekend of the treatment.( P<0.05). As for the response rates, differences were not found between the two groups at the 6th weekend of the treatment.(5) The overall dropout rate had no significant differences in-between( P>0.05). As for the safety outcome, the rate of adverse events(e.g., itching, tingling and headache) showed no significant differences between the two groups. Additionally, no severe adverse events or mania was reported. Conclusions:This study indicated that HD-tDCS has significant efficacy and high safety in the treatment among MDD patient with anxious distress. Nevertheless, further large sample clinical studies are warranted to confirm the findings of the current investigation.

Objective:To explore the efficacy, adverse reactions, and feasibility of high-definition transcranial direct current stimulation(HD-tDCS) treating major depressive disorder(MDD) patients with anxious distress.Methods:Sixty cases of MDD with anxious distress admitted to Zhenjiang Mental Health Center were recruited as participants. All patients were allocated into either the active treatment group or the sham group based on the random number table method. HD-tDCS was utilized in both groups to stimulate the left dorsolateral prefrontal cortex on the basis of conventional antidepressant treatment. In the active group, 2mA current stimulation was used for 20 min, and in the sham group, a 30-sceond stimulation was adopted at the beginning and the end of the stimulation. Participants in both group were treated once a day, five times a week for two consecutive weeks. Anxiety and depression symptoms of the patients were assessed respectively by the Hamilton depression scale(HAMD 17), the Montgomery-Asberg Depression Rating Scale(MARDS), the Hamilton Anxiety Scale(HAMA), and the Beck Anxiety Inventory(BAI) at the baseline, 2nd, 4th, and the 6th weekend of the treatment. The differences between active treatment and sham groups were analyzed by repetitive measure analysis of variance and simple effect analysis. Fisher′s exact probability test was used to compare the effective rate, remission rate and adverse reaction rate between the two groups. Results:(1) The interaction of times and groups was significant in HAMD 17( F=3.29, P<0.05) and BAI( F=2.99, P<0.05). In all measurement instruments, the main effects of groups( F=4.40-7.94) and times( F=35.42-247.59) were significant( P<0.05).(2) Findings from the simple effect analysis showed that: there were no significant differences in the scores of HAMD 17 at baseline and the 2 nd assessment between the two groups. Similarly, no significant differences were found in BAI at baseline, the 2nd and the 6th weekend of the treatment between two groups( P>0.05).(3) The scores of HAMD 17 at the 4th and the 6th week, BAI at the 4th weekend of the treatment in the active group were significantly lower than that in the sham group( P<0.05).(4) At the 4th weekend of the treatment, the active group had a remission rate of 16/20 and a response rates of 19/20, which were higher than 9/19 and 13/19, respectively, in the sham group( P<0.05). Also, the remission rate(18/20) in the active group was higher than that in the sham group(11/19) at the 6th weekend of the treatment.( P<0.05). As for the response rates, differences were not found between the two groups at the 6th weekend of the treatment.(5) The overall dropout rate had no significant differences in-between( P>0.05). As for the safety outcome, the rate of adverse events(e.g., itching, tingling and headache) showed no significant differences between the two groups. Additionally, no severe adverse events or mania was reported. Conclusions:This study indicated that HD-tDCS has significant efficacy and high safety in the treatment among MDD patient with anxious distress. Nevertheless, further large sample clinical studies are warranted to confirm the findings of the current investigation.

OBJECTIVE： To study the anti-inflammatory and detumescent pharmacodynamic material basis of Jingyaokang capsule， and to provide reference for secondary development， the establishment of quality control method and technological upgrading of the preparations. METHODS： The constituents of Jingyaokang capsule were extracted and separated with different solvents and macroporous adsorption resin to obtain constituent A （overall enrichment part）， constituent B （chloroform extraction part）， constituent C （water-course part） and constituent D （elution part of 60％ ethanol）. Using dexamethasone acetate as positive control， the anti-inflammatory and detumescent effects of Jingyaokang capsule and different extraction parts （constituents A， B， C， D） were investigated by mice ear edema and rat paw edema tests to screen the active fraction. UPLC-Q-TOF-MS method was used to analyze active constituent， identify compounds and attribute medicinal material. RESULTS： Anti-inflammatory and detumescent effects of constituent B （chloroform extraction part）+constituent D （elution part of 60％ ethanol） were similar to those of Jingyaokang capsule in rats or mice， indicating both had synergistic anti-inflammatory and detumescent effects and were active constituents of Jingyaokang capsule. UPLC-Q-TOF-MS detection and identification showed that constituent B contained 13 compounds as strychnine， phellodendrine， periplogenin， tetraketone alcohol， 11-carbonyl-β-mastic acid， attributing to Strychnos nux-vomica， Stephania tetrandra， Periploca sepium， Lycopodium japonicum， Boswellia carterii， etc. Constituent D contained 7 compounds as adenine， hydroxysafflower yellow A， phellodendrine， neoeriocitrin， zingibroside R1， attributing to rainworm， Carthamus tinctorius， Stephania tetrandra， Davallia mariesii， Achyranthes bidentata， etc. CONCLUSIONS： Jingyaokang capsule shows the significant anti-inflammation and detumescent effects. The  chloroform extraction part is synergistic with 60％ ethanol elution part， which are the active constituents of anti-inflammation and detumescence，mainly including alkaloids， flavonoids and boswellic acids.