Research progress on endogenous small-molecule phenolics and the proposal of "phenolomics" / 药学学报

Small-molecule phenolic substances widely exist in animals and plants, and have some shared biological activities. The metabolism of phenylalanine and tyrosine in the human body, and especially the metabolism of catecholamine neurotransmitters, produces endogenous small-molecule phenols. Endogenous small-molecule phenolic substances are functionally related to the important physiological processes and the occurrence of mental diseases in humans and some animals, which are systematically sorts and summarized in this review. Integrating the previous experimental research and literature analysis on natural small-molecule phenols by our research group, the understanding of the hypothesis that "small-molecule phenol are pharmacological signal carriers" was deepened. Based on above, the concept of "phenolomics" was further proposed, analyzed the research direction and research content which can bring into the knowledge framework of phenolomics. The induction of phenolomics will provide wider perspectives on explaining the pharmacological mechanism of drugs, discovering new drug targets, and finding biomarkers of mental diseases.

Effects of estradiol on depressive-like behavior of ovariectomized rats and its possible mechanism / 解剖学报

Objective To examine the effect of estradiol (E2) treatment on ovariectomy (OVX) induced depressive-like behavior and possible mechanism by measuring inflammatory biomarkers levels oi interleukin-6 (IL-6) and tumor necrosis tactor-(x (TNF-ot) and brain-derived neurotrophic factor (BDNF) expression in amygdaia nucleus. Methods Thirty nine healthy aduit 缶male SD rats were randomly divided into three groups : sham operation group (SO), ovariectomized group (OVX) and ovariectomized estradiol treatment group (OVX + E2). After 6 weeks of E2 treatment, depressive like behavior was evaluated by opening field test (OFT) and sugar water preference test (SPT). The levels of inflammatory factors IL-6 and TNF-a in amygdala were measured by ELESA, and the expression of BDNF in rat amygdala was detected by immunohistochemical staining. Results The result of the SPT showed that OVX significantly decreased the sugar intake and sugar preference rate of rats, and E2 treatment significantly increased sugar water intake and sugar water preference rate of rats. The result of the OFT showed that OVX significantly decreased the numbers of crossing and rearing of rats, and reduced the time spent in the centre ; E2 treatment significantly increased the numbers of crossing and rearing of rats, and prolonged the time spent in the centre. ELESA and immunohistochemical analysis found the levels of IL-6 and TNF-a in amygdala increased significantly, while the average absorbance (AA) of BDNF in the amygdala reduced significantly (P<0.01 respectively) of rats in OVX group when compared with the SO group. And the levels of IL-6 and TNF-a in amygdala decreased significantly (P<0.01 respectively), while the A4 of BDNF increased significantly (P< 0.05) in the amygdala of rats in the OVX+EX group when compared with the OVX group. The difference was statistically significant. Conclusion E2 treatment improved depression-like behavior of OVX rats is partly due to increased antiinflammatory and activated the BDNF expression in amygdaloid nucleus, thus enhancing the neuroprotective effect of OVX rats.

Effects of treadmill exercise on learning and memory of the vascular dementia rats and its mechanism / 解剖学报

Objective To observe the effects of 4-week low intensity treadmill exercise on the learning and memory, amino acid levels and the protein expression of protein kinase A ( PKA) , cyclic adenosine monophosphate response element binding protein( CREB) and brain-derived neurotrophic factor(BDNF) in the prefrontal cortex (PFC) of the vascular dementia (VD) rats. Methods Thirty-nine SD rats were randomly allocated to 3 groups, sham group (sham, n= 13) , vascular dementia group (VD, n= 13) and vascular dementia treaded with exercise group (VD + EX, n= 13). Chronic cerebral ischemia model in VD group and VD+EX group rats were established by permanent ligation of bilateral, then VD+EX group rats were submitted to 4-week low intensity treadmill exercise. After exercise, spatial learning and memory ability were evaluated by Moms water maze test ( MWM ) , glutamic ( Glu ) and gamma-aminobutyric acid (GABA) levels in the PFC were measured by high performance liquid chromatography( HPLC) ; the protein expression of PKA, CREB and BDNF in the PFC of rats were detected by Western blotting. Results The result of the MWM showed the average escape latency of rats in the VD group on the 1 -5 days was significantly higer than sham group, the time to first find the original platform was significantly prolonged and the platform crossings decreased significantly ( P 0. 05 ) between the two groups. Conclusion Four-week low-intensity running exercise improves the learning and memory ability of VD rats through enhancing the Glu level and activating PKA-CREB-BDNF signaling in the PFC of rats.

Effect and mechanism of Bovis Calculus on ulcerative colitis by inhibiting IL-17/IL-17RA/Act1 signaling pathway / 中国中药杂志

This study aimed to elucidate the effect and underlying mechanism of Bovis Calculus in the treatment of ulcerative colitis(UC) through network pharmacological prediction and animal experimental verification. Databases such as BATMAN-TCM were used to mine the potential targets of Bovis Calculus against UC, and the pathway enrichment analysis was conducted. Seventy healthy C57BL/6J mice were randomly divided into a blank group, a model group, a solvent model(2% polysorbate 80) group, a salazosulfapyridine(SASP, 0.40 g·kg~(-1)) group, and high-, medium-, and low-dose Bovis Calculus Sativus(BCS, 0.20, 0.10, and 0.05 g·kg~(-1)) groups according to the body weight. The UC model was established in mice by drinking 3% dextran sulfate sodium(DSS) solution for 7 days. The mice in the groups with drug intervention received corresponding drugs for 3 days before modeling by gavage, and continued to take drugs for 7 days while modeling(continuous administration for 10 days). During the experiment, the body weight of mice was observed, and the disease activity index(DAI) score was recorded. After 7 days of modeling, the colon length was mea-sured, and the pathological changes in colon tissues were observed by hematoxylin-eosin(HE) staining. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), and interleukin-17(IL-17) in colon tissues of mice were detected by enzyme-linked immunosorbent assay(ELISA). The mRNA expression of IL-17, IL-17RA, Act1, TRAF2, TRAF5, TNF-α, IL-6, IL-1β, CXCL1, CXCL2, and CXCL10 was evaluated by real-time polymerase chain reaction(RT-PCR). The protein expression of IL-17, IL-17RA, Act1, p-p38 MAPK, and p-ERK1/2 was investigated by Western blot. The results of network pharmacological prediction showed that Bovis Calculus might play a therapeutic role through the IL-17 signaling pathway and the TNF signaling pathway. As revealed by the results of animal experiments, on the 10th day of drug administration, compared with the solvent model group, all the BCS groups showed significantly increased body weight, decreased DAI score, increased colon length, improved pathological damage of colon mucosa, and significantly inhibited expression of TNF-α,IL-6,IL-1β, and IL-17 in colon tissues. The high-dose BCS(0.20 g·kg~(-1)) could significantly reduce the mRNA expression levels of IL-17, Act1, TRAF2, TRAF5, TNF-α, IL-6, IL-1β, CXCL1, and CXCL2 in colon tissues of UC model mice, tend to down-regulate mRNA expression levels of IL-17RA and CXCL10, significantly inhibit the protein expression of IL-17RA,Act1,and p-ERK1/2, and tend to decrease the protein expression of IL-17 and p-p38 MAPK. This study, for the first time from the whole-organ-tissue-molecular level, reveals that BCS may reduce the expression of pro-inflammatory cytokines and chemokines by inhibiting the IL-17/IL-17RA/Act1 signaling pathway, thereby improving the inflammatory injury of colon tissues in DSS-induced UC mice and exerting the effect of clearing heat and removing toxins.

The preventive effect and mechanism of Dayuanyin in hypoxic pulmonary hypertension through NF-κB signaling pathway / 药学学报

Dayuanyin (DYY) has been shown to reduce lung inflammation in both coronavirus disease 2019 (COVID-19) and lung injury. This experiment was designed to investigate the efficacy and mechanism of action of DYY against hypoxic pulmonary hypertension (HPH) and to evaluate the effect of DYY on the protection of lung function. Animal welfare and experimental procedures are approved and in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Science. Male C57/BL6J mice were randomly divided into 4 groups: control group, model group, DYY group (800 mg·kg-1), and positive control sildenafil group (100 mg·kg-1). The animals were given control solvents or drugs by gavage three days in advance. On day 4, the animals in the model group, DYY group and sildenafil group were kept in a hypoxic chamber containing 10% ± 0.5% oxygen, and the animals in the control group were kept in a normal environment, and the control solvent or drugs continued to be given continuously for 14 days. The right ventricular systolic pressure, right ventricular hypertrophy index, organ indices and other metrics were measured in the experimental endpoints. Meantime, the expression levels of the inflammatory factors in mice lung tissues were measured. The potential therapeutic targets of DYY on pulmonary hypertension were predicted using network pharmacology, the expression of nuclear factor kappa B (NF-κB) signaling pathway-related proteins were measured by Western blot assay. It was found that DYY significantly reduced the right ventricular systolic pressure, attenuated lung injury and decreased the expression of inflammatory factors in mice. It can also inhibit hypoxia-induced activation of NF-κB signaling pathway. DYY has a protective effect on lung function, as demonstrated by DYY has good efficacy in HPH, and preventive administration can slow down the disease progression, and its mechanism may be related to inhibit the activation of NF-κB and signal transducer and activator of transcription 3 (STAT3) by DYY.

Differences in related indicators after Toric intraocular lens implantation in cataract patients with different axial lengths / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the differences in visual recovery, corneal astigmatism, and rotation stability of Toric intraocular lens(TIOL)implantation in cataract patients with different axial lengths.METHODS: Retrospective analysis. A total of 132 patients(132 eyes)with age-related cataract and corneal astigmatism who underwent phacoemulsification cataract extraction combined with TIOL implantation in our hospital's ophthalmology department from February 2021 to September 2022 were selected. They were divided into two groups based on the axial length: the group with axial length ≤24mm(79 cases, 79 eyes)and the group with axial length &#x003E;24mm(53 cases, 53 eyes). Compare the best corrected distance visual acuity(BCDVA), corneal astigmatism, and TIOL rotation between the two groups of patients at 3mo after surgery.RESULT: After 3mo of surgery, both groups of patients had improved BCDVA and significantly decreased corneal astigmatism compared to those before surgery(P&#x003C;0.001). However, there was no difference in BCDVA and corneal astigmatism between the two groups(P&#x003E;0.05), and there was no significant difference in TIOL rotation between the two groups [(5.24±3.72)° vs.(6.36±4.21)°, P=0.110].CONCLUSION: There is no significant difference in visual recovery, corneal astigmatism, and TIOL rotational stability after TIOL implantation in cataract patients with different axial lengths.

Protective effects of three kinds of borneol on different brain regions in acute cerebral ischemia/reperfusion model rats / 中国中药杂志

This study compared the ameliorating effects of L-borneol, natural borneol, and synthetic borneol on the injury of different brain regions in the rat model of acute phase of cerebral ischemia/reperfusion(I/R) for the first time, which provides a reference for guiding the rational application of borneol in the early treatment of ischemic stroke and has important academic and application values. Healthy specific pathogen-free(SPF)-grade SD male rats were randomly assigned into 13 groups: a sham-operation group, a model group, a Tween model group, a positive drug(nimodipine) group, and high-, medium-, and low-dose(0.2, 0.1, and 0.05 g·kg~(-1), respectively) groups of L-borneol, natural borneol, and synthetic borneol according to body weight. After 3 days of pre-administration, the rat model of I/R was established by suture-occluded method and confirmed by laser speckle imaging. The corresponding agents in different groups were then administered for 1 day. The body temperature was monitored regularly before pre-administration, days 1, 2, and 3 of pre-administration, 2 h after model awakening, and 1 d after model establishment. Neurological function was evaluated based on Zea-Longa score and modified neurological severity score(mNSS) 2 h and next day after awakening. The rats were anesthetized 30 min after the last administration, and blood was collected from the abdominal aorta. Enzyme-linked immunoassay assay(ELISA) was employed to determine the serum levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-4, and transforming growth factor-beta1(TGF-β1). The brain tissues were stained with triphenyltetrazolium chloride(TTC) for the calculation of cerebral infarction rate, and hematoxylin-eosin(HE) staining was used for observing and semi-quantitatively evaluating the pathological damage in different brain regions. Immunohistochemistry was employed to detect the expression of ionized calcium binding adapter molecule 1(IBA1) in microglia. q-PCR was carried out to determine the mRNA levels of iNOS and arginase 1(Arg1), markers of polarization phenotype M1 and M2 in microglia. Compared with the sham-operation group, the model group and the Tween model group showed significantly elevated body temperature, Zea-Longa score, mNSS, and cerebral infarction rate, severely damaged cortex, hippocampus, and striatum, increased serum levels of IL-6 and TNF-α, and decreased serum levels of IL-4 and TGF-β1. The three borneol products had a tendency to reduce the body temperature of rats 1 day after modeling. Synthetic borneol at the doses of 0.2 and 0.05 g·kg~(-1), as well as L-borneol of 0.1 g·kg~(-1), significantly reduced Zea-Longa score and mNSS. The three borneol products at the dose of 0.2 g·kg~(-1) significantly reduced the cerebral infarction rate. L-borneol at the doses of 0.2 and 0.1 g·kg~(-1) and natural borneol at the dose of 0.1 g·kg~(-1) significantly reduced the pathological damage of the cortex. L-borneol and natural borneol at the dose of 0.1 g·kg~(-1) attenuated the pathological damage of hippocampus, and 0.2 g·kg~(-1) L-borneol attenuated the damage of striatum. The 0.2 g·kg~(-1) L-borneol and the three doses of natural borneol and synthetic borneol significantly reduced the serum level of TNF-α, and the 0.1 g·kg~(-1) synthetic borneol reduced the level of IL-6. L-borneol and synthetic borneol at the dose of 0.2 g·kg~(-1) significantly inhibited the activation of cortical microglia, and 0.2 g·kg~(-1) L-borneol up-regulated the expression of Arg1 and down-regulated the expression level of iNOS. In conclusion, the three borneol products may alleviate inflammation to ameliorate the pathological damage of brain regions of rats in the acute phase of I/R by inhibiting the activation of microglia and promoting the polarization of microglia from M1 type to M2 type. The protective effect on brain followed a trend of L-borneol > synthetic borneol > natural borneol. We suggest L-borneol the first choice for the treatment of I/R in the acute phase.

Impact of CSF3R Mutation on Treatment Response and Survival of Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of CSF3R mutation in acute myeloid leukemia (AML) and analyze its clinical characteristics and prognosis.@*METHODS@#A retrospective study was conducted in 212 patients with AML who were newly diagnosed in the Second Hospital of Shanxi Medical University from January 1th 2018 to June 30th 2021, including 22 patients with CSF3R mutations as mutation group and 190 patients with CSF3R wild type ［66 cases of them were screened by propensity score matching (PSM), as control group］. The early efficacy and survival between the two groups were compared.@*RESULTS@#The median age of patients in the mutation group was 50(17-73) years old, and the ratio of male to female was 1.2:1 The main types were AML with maturation (11 cases) and acute myelomonocytic leukemia (9 cases). Prognostic stratification was carried out according to the risk stratification system of the European leukemia network in 2017, with 16 cases (72.73%) in the middle and high-risk group. At the initial diagnosis, the median count of white blood cell (WBC) was 44.75(1.30-368.71)×109/L, among which 15 cases (68.18%) were >10×109/L, and the median count of platelet (PLT) was 24(4-55)×109/L. CSF3R T618I (68.18%) was a common mutation site, which had concomitant gene mutations, in which CEBPA mutation was the most common (10 cases, 45.45%), but only existed in CSF3R T618I mutation. The CR/CRi rate was 68.18% and 71.21% in the mutant group and the control group (P >0.05), the median over all survival time was 15 months and 9 months (P >0.05), and the median disease-free survival time was 8 months and 4 months (P >0.05), respectively.@*CONCLUSION@#Most AML patients with CSF3R mutation are middle-aged patients, the main types are AML with maturation and acute myelomonocytic leukemia, and most of them have middle and high-risk prognosis. CSF3R mutation may not be an independent prognostic marker for newly diagnosed AML patients.

Role and mechanism of platelet-derived growth factor BB in thrombocytosis in Kawasaki disease / 中国当代儿科杂志

OBJECTIVES@#To study the role and mechanism of platelet-derived growth factor BB (PDGF-BB) on platelet production in Kawasaki disease (KD) mice and human megakaryocytic Dami cells through in vitro and invivo experiments.@*METHODS@#ELISA was used to measure the expression of PDGF in the serum of 40 children with KD and 40 healthy children. C57BL/6 mice were used to establish a model of KD and were then randomly divided into a normal group, a KD group, and an imatinib group (30 mice in each group). Routine blood test was performed for each group, and the expression of PDGF-BB, megakaryocyte colony forming unit (CFU-MK), and the megakaryocyte marker CD41 were measured. CCK-8, flow cytometry, quantitative real-time PCR, and Western blot were used to analyze the role and mechanism of PDGF-BB in platelet production in Dami cells.@*RESULTS@#PDGF-BB was highly expressed in the serum of KD children (P<0.001). The KD group had a higher expression level of PDGF-BB in serum (P<0.05) and significant increases in the expression of CFU-MK and CD41 (P<0.001), and the imatinib group had significant reductions in the expression of CFU-MK and CD41 (P<0.001). In vitro experiments showed that PDGF-BB promoted Dami cell proliferation, platelet production, mRNA expression of PDGFR-β, and protein expression of p-Akt (P<0.05). Compared with the PDGF-BB group, the combination group (PDGF-BB 25 ng/mL + imatinib 20 μmol/L) had significantly lower levels of platelet production, mRNA expression of PDGFR-β, and protein expression of p-Akt (P<0.05).@*CONCLUSIONS@#PDGF-BB may promote megakaryocyte proliferation, differentiation, and platelet production by binding to PDGFR-β and activating the PI3K/Akt pathway, and the PDGFR-β inhibitor imatinib can reduce platelet production, which provides a new strategy for the treatment of thrombocytosis in KD.

MFN1 ubiquitination mediates lipopolysaccharide-induced mitochondrial dysfunction and pyroptosis in Raw264.7 mouse macrophages / 中华微生物学和免疫学杂志

Objective:To investigate the regulatory effects of mitofusin 1 (MFN1) on lipopolysaccharide (LPS)-induced Raw264.7 mouse macrophages pyroptosis and to provide reference for further study on the prevention of inflammation and fibrosis caused by macrophage dysfunction.Methods:Raw264.7 mouse macrophages were cultured in vitro and used to construct a model of LPS-induced pyroptosis. CCK-8 staining, PI staining, LDH release assay and Western blot were used to verify the Raw264.7 pyroptosis induced by LPS. MFN1 expression was detected by Western blot. DCFH-DA probe was used to detect the synthesis of total reactive oxygen species (ROS); Mito-SOX was used to detect mitochondrial ROS; JC-1 mitochondrial membrane potential was detected by fluorescence probe to reflect mitochondrial damage. Based on Ubibrowser database, it was predicted that MFN1 could bind to a variety of E3 ubiquitin ligases. Then, immunofluorescence and co-immunoprecipitation (CO-IP) were used to analyze MFN1 ubiquitination. An overexpression plasmid for MFN1 was constructed and transfected into Raw264.7 cells to detect the changes in pyroptosis and mitochondrial function. Results:LPS could induce the pyroptosis of Raw264.7 cells and mitochondrial dysfunction. MFN1 expression was decreased after LPS stimulation. Ubiquitinated MFN1 was detected by CO-IP. Ubiquitination inhibitor MG-132 inhibited LPS-induced expression of pyroptosis-related proteins including NLRP3, Pro-caspase-1, Caspase-1, IL-1β and IL-18 and improved mitochondrial function. MFN1 overexpression relieved the mitochondrial dysfunction and pyroptosis of Raw264.7 cells induced by LPS.Conclusions:The ubiquitination of MFN1 induced by LPS was involved in mitochondrial dysfunction and macrophage pyroptosis, suggesting that MFN1 was a potential target for the treatment of macrophage-induced inflammation and related diseases.

Research on diagnostic value of OCT measurement of optic disc and macular parameters in early primary open angle glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To analyze the diagnostic value of optical coherence tomography(OCT)for early primary open angle glaucoma(POAG)by measuring the thickness of macular ganglion cell complex(mGCC), peripapillary retinal nerve fiber layer(pRNFL), macular retinal nerve fiber layer(mRNFL)and retinal ganglion cell layer+inner plexiform layer(GCIP)in the macular region.METHODS:A case-control study design was used to collect 82 patients(82 eyes)with early POAG who admitted to our hospital from January 2019 to January 2020. There were 40 healthy volunteers(40 eyes)in the same period selected as the control group(20 eyes for left and right eyes, respectively). All subjects underwent tests of uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA)and equivalent spherical power. The upper, lower, nasal, temporal and average pRNFL thickness, the upper, lower and average mGCC, mRNFL and GCIP thickness in the macular region were analyzed. Spearman was used to analyze the correlation among the average thickness of eachindices, and ROC curve was used to analyze the value of mGCC, pRNFL, mRNF and GCIP thickness parameters in diagnosing early POAG.RESULTS:In the early POAG group, the thickness of upper, nasal, lower, temporal, average pRNFL and the thickness of upper, lower and average mGCC, mRNFL and GCIP were lower than those in the control group(all P&#x003C;0.05). Average thickness of pRNFL was positively correlated with average thickness of mGCC, average mRNFL and average GCIP(rs=0.582, 0.632, 0.456, all P&#x003C;0.05); average thickness of mGCC was positively correlated with average thickness of mRNFL and average GCIP(rs=0.583, 0.851, all P&#x003C;0.05); Average thickness of mRNFL was positively correlated with average thickness of GCIP(rs=0.528, all P&#x003C;0.01). ROC curve analysis shows that the AUC value of mGCC thickness and average value in early diagnosis of POAG were all above 0.8, and the diagnostic efficiency was the highest.CONCLUSION: OCT measurement of mGCC has certain value in diagnosing early POAG.

Role of Cytoglobin in Ferroptosis Regulation / 中国生物化学与分子生物学报

Ferroptosis is a recently reported iron-dependent cell death, which is induced by the broken of cellular redox homeostasis and characterized by high level of lipid peroxide. More and more studies have indicated the importance of ferroptosis during disease development and prevention. As a member of globin family, cytoglobin (CYGB), also known as stellate cell activating protein (STAP), can bind to oxygen for its transportation. Moreover, CYGB contains two cysteins within its amino acid sequence and could form the S-S bond when there has change of cellular redox which will result in downstream signaling alternation. Furthermore, CYGB has nitric oxygen dioxygenase activity to scavenge excessive nitric oxygen and prevent the production of ONOO

Advances in effect of peroxisome proliferators-activated receptors in ischemic stroke / 中国药理学通报

Ischemic stroke(IS)is one of the leading causes of mortality and disability with a high incidence and recurrence rate.However, effective therapy for treating IS is still unavailable in clinic.Peroxisome proliferation-activated receptors(PPARs)is a type of ligand-activated nuclear transcription factors that play a key role in a variety of biological processes.PPARs are close to IS, hence this study reviews that PPARs exerts the protective effect on IS through mediating neuroinflammation, oxidative stress, apoptosis, autophagy, demyelination, blood brain barrier function, encephaledema and lactic acid metabolism, which hopes to provide novel strategies for the prevention and treatment of IS.

Research progress on mechanisms and therapeutic drugs of hypoxic pulmonary hypertension / 中国药理学通报

Hypoxic pulmonary hypertension ( HPH) is a complex mechanism of HPH is complex, and it has a high mortality rate cardiopulmonary disease eaused by hypoxia.The pathological of disability.Clinically the diug of treatment for HPH is unspe-cialized, mainly relying on traditional vasomotor dnrgs, inclu¬ding prostaglandin 12 receptor agonists, endothelin receptor an¬tagonists and phosphodiesterase-5 inhibitors, but their efficacy cannot be achieved.To meet the clinical need, it is of great sig¬nificance to develop targeted anti-HPH dnigs.To provide ideas for the discovery of HPH treatment drugs, the pathophysiological mechanism of HPH and the current status of dmg development are reviewed in the paper.

Mechanism of hepatotoxicity induced by ethanol extract of Dysosma versipellis based on "quantity-weight-evidence" network toxicology / 中国中药杂志

In this study, the toxicological/pharmacological research method of "quantity-weight-evidence" network was first proposed and practiced to supplement the existing methodology of network toxicology. We transformed the traditional qualitative network into a quantitative network in this study by attributing weights to toxic component content and target frequency, which improved the reliability of data and provided a research idea for the systematic safety evaluation and toxicological research of Chinese medicinal herbs. Firstly, 50% ethanol extract of Dysosma versipellis(DV) was administrated to rats via gavage and the potential hepatotoxic components were identified by serum pharmacochemistry. Then, the component targets were obtained from SwissTargetPrediction, PharmMapper and other online databases, and the target weights were given according to the relative content of components and target fishing frequency. Meanwhile, the targets of hepatotoxicity were predicted from online databases such as Comparative Toxicology Database(CTD) and GeneCards. Subsequently, protein-protein interaction analysis and KEGG pathway enrichment were performed with the STRING database. Finally, the quantitative network of "toxic components-weighted targets-pathways" was constructed. Eleven potential toxic compounds were predicted, including podophyllotoxin, podophyllotoxone, deoxypodophyllotoxin, and 6-methoxypodophyllotoxin. A total of 106 hepatotoxic targets and 65 weighted targets(e.g., Cdk2, Egfr, and Cyp2 c9) were identified. The results of Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment showed that these targets could act on PI3 K-AKT, MAPK, and Ras signaling pathways to play a role in inflammatory response and oxidative stress. However, traditional network toxicology showed that 51 targets such as AKT1, Alb, and Stat3 may lead to hepatotoxicity by mediating inflammation and cell proliferation. In conclusion, we proposed "quantity-weight-evidence" network toxicology in this study and used it to study the mechanism of DV-induced hepatotoxicity in rats. This study confirms the feasibility of this new methodology in toxicological evaluation and further improves the systematic evaluation of the safety of Chinese medicinal herbs.

Effects of CACNA1H gene knockout on autistic-like behaviors and the morphology of hippocampal neurons in mice / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effects of CACNA1H gene knockout (KO) on autistic-like behaviors and the morphology of hippocampal neurons in mice.@*METHODS@#In the study, 25 CACNA1H KO mice of 3-4 weeks old and C57BL/6 background were recruited as the experimental group, and 26 wild type (WT) mice of the same age and background were recruited as the control group. Three-chamber test and open field test were used to observe the social interaction, anxiety, and repetitive behaviors in mice. After that, their brain weight and size were measured, and the number of hippocampal neurons were observed by Nissl staining. Furthermore, the CACNA1H heterozygote mice were interbred with Thy1-GFP-O mice to generate CACNA1H-/--Thy1+(KO-GFP) and CACNA1H+/+-Thy1+ (WT-GFP) mice. The density and maturity of dendritic spines of hippocampal neurons were observed.@*RESULTS@#In the sociability test session of the three-chamber test, the KO mice spent more time in the chamber of the stranger mice than in the object one (F1, 14=95.086, P < 0.05; Post-Hoc: P < 0.05), without any significant difference for the explored preference index between the two groups (t=1.044, P>0.05). However, in the social novelty recognition test session, no difference was observed between the time of the KO mice spend in the chamber of new stranger mice and the stranger one (F1, 14=18.062, P < 0.05; Post-Hoc: P>0.05), and the explored preference index of the KO mice was less than that of the control group (t=2.390, P < 0.05). In the open field test, the KO mice spent less time in the center of the open field apparatus than the control group (t=2.503, P < 0.05), but the self-grooming time was significantly increased compared with the control group (t=-2.299, P < 0.05). Morphological results showed that the brain weight/body weight ratio (t=0.356, P>0.05) and brain size (t=-0.660, P>0.05) of the KO mice were not significantly different from those of the control group, but the number of neurons were significantly reduced in hippocampal dentate gyrus compared with the control group (t=2.323, P < 0.05). Moreover, the density of dendritic spine of dentate gyrus neurons in the KO-GFP mice was significantly increased compared with the control group (t=-2.374, P < 0.05), without any significant difference in spine maturity (t=-1.935, P>0.05).@*CONCLUSION@#CACNA1H KO mice represent autistic-like behavior, which may be related to the decrease in the number of neurons and the increase in the density of dendritic spine in the dentate gyrus.

Application of MRI WARP sequence in periprosthetic joint infection / 中华创伤骨科杂志

Objective:To explore whether MRI WARP sequence can provide clearer musculoskeletal images to guide the operation for patients with periprosthetic joint infection (PJI) by comparing MRI WARP sequence images with conventional sequence images.Methods:The data were analyzed retrospectively of 23 PJI patients who had been diagnosed and treated at Department of Orthopedics, The First Affiliated Hospital to Fujian Medical University from January 2020 to February 2021. They were 13 females and 10 males, with an average age of 62.8 years (from 32 to 88 years). According to the MRI sequences, they were divided into a WARP group ( n=14) subjected to MRI scanning by WARP sequence and a conventional group ( n=9) subjected to MRI scanning by conventional sequence. The gender, age, erythrocyte sedimentation rate (ESR) and C-reaction protein (CRP) were recorded for both groups. The signal-to-noise ratios were compared between the 2 sequences and 2 experts evaluated the clarity and surgical guidance of the images. Results:There was no significant difference in gender, age, CRP or ESR between the 2 groups, showing comparability ( P>0.05). The 2 experts showed consistency in evaluation of image sharpness and surgical guidance ( P<0.05). The WARP group was significantly better than the conventional group in image sharpness score [2.25(2.0, 2.6) versus 1.00 (0.5, 1.0)], surgical guidance score [2.00(1.5, 2.5) versus 0.50(0, 0.8)], and signal-to-noise ratio [47.28 (32.8, 74.3) versus 21.67(13.5, 31.4)] ( P<0.05). Conclusion:MRI WARP sequence can provide clearer musculoskeletal images than conventional MRI sequence to better guide the operation for PJI patients.

Relationship of serum 25- hydroxy vitamin D and systemic lupus erythematosus / 北京大学学报(医学版)

OBJECTIVE@#To investigate the application value of serum 25-hydroxy vitamin D [25(OH)D] in systemic lupus erythematosus (SLE).@*METHODS@#Data of 158 patients with SLE in Department of Rheumatology and Immunology in the People's Hospital of Xinjiang Uygur Autonomous Region from July 2016 to July 2019. All the SLE patients were divided into two groups by SLE scores of the disease activity index (SLEADI): 59 cases of active group (SLEADI > 4), 99 cases of non-active group (SLEDAI ≤4). Fifty healthy people were selected as healthy control group. The patients' general information and their laboratory data including serum 25(OH)D levels were collected. Statistical methods used were t-test, Spearman's correalation analysis and Logistic regression analysis.@*RESULTS@#(1) A total of 208 cases were included in this study. The level of 25(OH)D in SLE group [10.4(5.6, 15.8) μg/L] was significantly lower than that in healthy control group [25.5(22.8, 32.3) μg/L, P < 0.01]. 25(OH)D level in active SLE patients [6.2(3.7, 13.8) μg/L] was significantly lower than that in remission SLE patients [12.3(7.2, 16.7) μg/L, P < 0.01]. The serum 25(OH)D level in lupus nephritis [6.7 (4.4, 12.9) μg/L] was significantly lower than that in SLE without renal involvement [13.3 (7.4, 18.7) μg/L, P < 0.01]. (2) A significant negative correlation was demonstrated between the serum level of 25(OH)D and SLEDAI (r=-0.35, P < 0.01), and the 24h urinary protein excretion (r=-0.39, P < 0.01).Positive correlation was demonstrated between the serum level of 25(OH)D and C3 that decreased (r=0.249, P < 0.05). (3) Univariate analysis showed anti- dsDNA antibodies(ds-DNA), anti-Sm antibodies(Sm), IgG, C3, C4, erythrocyte sedimentation rate (ESR), 24h urinary protein quantification(24h-pro) and 25(OH)D were associated with disease activity in the SLE patients; Multivariate Logistic regression analysis showed that 25(OH)D was associated with the disease activity of the lupus patients.@*CONCLUSION@#The decrease of vitamin D level is related to the disease activity of SLE patients, and may be related to lupus nephritis, which plays an important role in the occurrence and development of SLE.

Quantitative Analysis on Immunophenotype of CD34 / 中国实验血液学杂志

OBJECTIVE@#To investigate the quantitative expression of immunophenotype of CD34@*METHODS@#Multi-parameter flow cytometry (FCM) was used to detect the proportion and mean fluorescence intensity (MFI) of each antigen of bone marrow CD34@*RESULTS@#Bone marrow blast cell proportion (P<0.01), RBC level (P<0.01), and Hb level (P<0.05) of high-risk MDS patients were higher, while EPO level (P<0.05) was lower than those of low-risk patients. The proportion of CD34@*CONCLUSION@#The immunophenotype of CD34

Discussion on clinical application of "touching-bone" acupuncture technique / 中国针灸

The value of the "touching-bone" acupuncture technique in clinical application was explained through the investigation on the origin of the theory of the "touching-bone" acupuncture technique, the analysis on the characteristics of acupoint selection, the introduction of clinical characteristics and the discussion on the mechanism of acupuncture in treatment. The "touching-bone" acupuncture technique refers to deep needling method, originated from the short needling and needling of the ancient needling methodslisted in the . The target points are the reaction sites on meridian near to bone and the attachments of soft tissues on bone. During the needle insertion, the needle tip is thrust deeply to the bone or the needle body is closely attached to the bone so as to stimulate periosteum specifically. This needling technique contributes to the satisfactory effect on spasmodic, deep-located and intractable pain disorder, motor system diseases, mental diseases and cerebral diseases, etc. Hence, this acupuncture technique deserves to be promoted in clinical application and explored in research.