Jianpi Peiyuan acupoint thread embedding therapy for perimenopausal obesity: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical efficacy and safety of Jianpi Peiyuan acupoint thread embedding therapy on perimenopausal obesity (PMO).@*METHODS@#Ninety-six patients of PMO were randomly divided into an observation group (48 cases) and a control group (48 cases). The control group received health education and lifestyle intervention. On the basis of the treatment in the control group, the observation group was treated with acupoint thread embedding at the main acupoints of Shangwan (CV 13), Zhongwan (CV 12), Xiawan (CV 10), Yinlingquan (SP 9) and Fenglong (ST 40), etc. as well as the supplementary acupoints in accordance with the syndrome differentiation, once every 2 weeks for 8 weeks (4 times in total). The indexes of obesity (body mass index [BMI], waist circumference, hip circumference and body mass), modified Kupperman score, insomnia severity index (ISI) score, self-rating anxiety scale (SAS) score, and self-rating depression scale (SDS) score of the two groups were observed before and after treatment, and the safety was evaluated.@*RESULTS@#After treatment, BMI, waist circumference, hip circumference and body mass in the two groups were lower than before treatment (P<0.05), and those in the observation group were lower than the control group (P<0.05). After treatment, Kupperman, ISI and SAS scores in the observation group were lower than before treatment (P<0.05), and ISI score in the control group was lower than before treatment (P<0.05). Kupperman, ISI and SAS scores in the observation group were lower than those in the control group (P<0.05). There was no significant difference in SDS between the two groups or within groups (P>0.05). No serious adverse reactions occurred during the experiment.@*CONCLUSION@#Jianpi Peiyuan acupoint thread embedding therapy can reduce the degree of obesity in PMO patients, and improve patients' the perimenopausal symptoms, insomnia and anxiety, with good safety.

Three-dimensional visualization on the relationship between tubules after macula densa and afferent arterioles in mouse kidney / 解剖学报

Objective To establish the spatial course of distal tubule and afferent arterioles after macula densa, and to locate and detect the proteins in the adjacent parts by using three-dimensional visualization technology of microstructure. Methods C57 BL/6J mice were fixed by perfusion and embedded in epon 812. Tissue blocks were cut perpendicular to the longitudinal axis of the kidney. And a total of 720, 2. 5 μm-thick consecutive sections were obtained from the renal capsule to the outer stripe of the renal outer medulla. After aligning the digital microscopic images through computer registration procedures, the tubules and vessels were traced by 3D reconstruction program edited by C Language. Selecting the tissue sections of the contact site and applying the improved immunoperoxidase staining method to detect H

Morphometry of the ureteric bud branching in the developing mouse kidney / 解剖学报

[Abstract] Objective To investigate the branching pattern of the ureteric bud and the number of the nephron induced by each ureteric bud tip, through the three-dimensional tracing of the ureteric tree, combined with the morphological analysis and measurement of the ureteric tree. Methods The kidneys were obtained from three mice at various developing time points and prepared for paraffin and epoxy sections. Then the microscopic images were digitized and aligned from these sections. Based on the computer-assisted tracing and visualization of ureteric tree, the number of branches and the nephron induced by each ureteric bud tip were obtained by counting. In addition, paraffin sections were stained with HE staining for morphological observation of nephrogenic zone and ureteric bud, while in order to reflect the density of the ureteric bud tips at nephrogenic zone, the distance between two neighboring ureteric bud tips was measured aided with the Claudin-7 immunohistochemical staining. Results The ureteric bud branching tree revealed that the initial bifid iterative branching formed the framework of renal medulla, the branching became complicated and dense in cortex and nephrogenic zone, while the distance between ureteric bud tips were also decreasing. The number of the nephron induced by each ureteric bud tip increased from one (E14. 5) to two (E17. 5), and occasionally to three. Conclusion Threedimeasional Visualization of ureteric bud branching tree reveals regional complication, suggesting molecules in different regions drive different branching patterns; While the density of the ureteric bud tips at nephrogenic zone increases corresponding to decreasing of thickness of the nephrogenic zone, and the disappearance of the ureteric bud tips after birth is also consistent with the gradual consumption of nephron progenitor cells.

The protective effect of cuminaldehyde on gastric mucosa in Rattus norregicus of experimental gastric ulcer / 中国药理学通报

Aim To explore the effect of cuminaldehyde in cumin fruit on gastric ulcer and the protective mechanism via establishing the gastric ulcer model of rats was by ethanol injury. Methods Thirty-six male R. norregicus were divided into six groups: control group, model group, omeprazole positive control group and cuminaldehyde low, medium and high dosage groups. After seven days of continuous intragastric administration, the acute gastric ulcer of R. norregicus was tested by absolute alcohol. Gastric ulcer area, inhibition rate, gastric tissue antioxidant activity, serum inflammatory factors and gastric mucosal protective factors were detected in different groups. Results The results showed that cuminaldehyde significantly reduced the area of gastric ulcer and increased the inhibition rate of gastric ulcer. The inhibition rate of cuminaldehyde at high dose group was up to 74.65%, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH) in gastric tissue significantly increased, and the contents of serum prolandin E

The regulation mechanism of phloroglucinol in urinary smooth muscle spasm / 中国药理学通报

Aim To study the regulation and mechanism of phloroglucinol in bladder smooth muscle spasm. Methods In vitro the experiment used bladder muscle strip to verify the relieving effect of phloro-glucinol on bladder spasm by different drugs. At the same time,RT-qPCR and Western blot were used to detect the expression levels of genes involved in the calcium signaling pathway caused by the antispasmodic effect of phloroglucinol. Results Phloroglucinol could relieve bladder spasm, and the antispasmodic effect was enhanced with the increase of concentration, and the expression of calponin 1 and MYLK3 in tissue cells increased. The results of RT-qPCR showed that the expression of Gprc5b G,Ppp2r5a, Chptl, Prkar2b ,Abcd2 and Rasdl genes in mouse bladder tissue significantly decreased, which was consistent with the sequencing results of RNA-seq.Conclusions Phloroglucinol can relieve bladder smooth muscle spasm, and its mechanism is related to calcium signaling pathway. Meanwhile, phloroglucinol also inhibits the expression of Rasdl gene, suggesting that it may be related to cell cycle , protein phosphorylation, choline metabolism, ATP synthesis and tumor-related pathways.

The protective effect of terpinen-4-ol on inflammatory injury of VSMCs induced by high glucose through improving autophagic flux disorder / 中国药理学通报

Aim To investigate the effect of terpinen-4-ol (T40) on inflammatory injury of vascular smooth muscle cells (VSMCs) induced by high glucose based on the improvement of autophagic flow disorder and involved molecular signals. Methods The scratch test was used to analyze the migration ability of VSMCs, the levels of IL-1β and IL-6 in cell culture supernatant were measured by ELISA, the expression levels of inflammation-related proteins NF-κb p65, p-NF-κb p65, IL-1β, IL-18 and autophagy-related proteins p62, LC3-HYLC3-I, Beclinl, p-Beclinl were de-tected by Western blot. Results T40 inhibited migration of VSMCs induced by high glucose, reduced the secretion and release of pro-inflammatory factors IL-1β and IL-6, inhibited the expression of p-NF-κb p65/ NF-κb p65, IL-1β, IL-18, downregulated the expression of p62, LC3-TJ/LC3- I and p-Beclinl at same time. After interfering the autophagic flux of VSMCs with autophagy inhibitor chloroquine (CQ) , T40 pre-treatment significantly inhibited the protein expression levels of the above inflammatory factors and autophagy-related signals which mediated by CQ. Conclusion T40 inhibits the inflammatory injury of VSMCs induced by high glucose through improving the autophagic flow disorder.

Expression, purification and functional verification of recombinant human α-galactosidase A in suspension CHO-S / 中国药理学通报

Aim To express and purify rhα-Gal A with a 6 X His tag via using a serum-free expression system in high-density suspension culture of Chinese hamster ovary cells ( CHO-S) , and to verify the scavenging effect of rhα-Gal A on globular trisaccharide ceramide (Gb3 or GL3) . Methods The construction of recombinant protein expression vector, pcDNA4-GLA, was achieved by fusing the human α-galactosidase cDNA, gla, with 6 X His tag and artificial DNA synthesis. The expression plasmid was transfected into the suspended CHO-S to express rhα-Gal A and then purified. Following this procedure, we determined rhα-Gal A's expression, the enzymatic activity, and the glycosylation of the recombinant enzyme. Co-incubation with cultured cells was performed to examine whether rhα-Gal A could be taken up into the cells and effectively remove Gb3 substrates. Results rhα-Gal A was successfully expressed and purified after transiently transfecting pcDNA4-GLA into the suspended CHO-S, and the yield was up to (100 ±20. 6) mg • L

Effect of chemogenetic manipulation of PVN corticotropin-releasing factor-expressing neurons on excitability of presympathetic neurons in SHR / 中国药理学通报

Aim To observe the effect of corticotropin-releasing factor ( CRF) -expressing neurons on presympathetic neurons in hypothalamic paraventricular nucleus ( PVN) of normotensive Wistar Kyoto ( WKY) rats or spontaneously hypertensive rats (SHR) , and to elucidate the underlying neuronal circuit mechanism of central sympathetic hyperexcitability. Methods The expression levels of CRF protein in WKY rats and SHR PVN were determined by Western blot. Meanwhile, the WKY and SHR PVN CRF-expressing neurons and presympathetic neurons were observed by immunofluo-rescent staining. Adult WKY rats and SHR were used in this study. By microinjection of Cre-dependent ade-no-associated viruses ( AAV) that specifically recognized the CRF promoter and AAV of chemogenetics into the PVN, CRF-expressing neurons expressed designer receptors exclusively activated by designer drugs (DREADDs). Human M3 muscarinic DREADD coupled to Gq receptor ( hM3 Dq) was specifically expressed in PVN CRF-expressing neurons in WKY rats, while human M4 muscarinic DREADD coupled to Gi receptor ( hM4Di) was specifically expressed in PVN CRF-expressing neurons in SHR. Clozapine-N-oxide (CNO) , as a designer ligand, would couple to excitatory hM3Dq or inhibitory hM4Di to regulate the excitability of PVN CRF-expressing neurons. Then the PVN presympathetic neurons were retrogradely labeled by microinjection of fluosecent tracer into the intermedio-lateral column (IML) of spinal cord. Lastly, whole cell patch clamp was used to determine the effect of CNO (10 jjumol L~ ) on spontaneous excitatory postsynaptic currents ( sEPSCs) and current-evoked firing of PVN presympathtic neurons of WKY rats and SHR. Results The expression of CRF protein in the PVN of SHR was significantly higher than that of WKY rats, and the activity and number of CRF-expressing neurons in the PVN of SHR were increased. PVN CRF-expressing neurons were expressed with chemogenetic DREADDs and PVN presympathetic neurons were retrogradely labeled with fluorescent tracer in WKY rats and SHR. In SHR expressed with chemogenetic inhibitory hM4Di-mCherry of PVN CRF-expressing neurons, bath application of CNO to the brain slices resulted in a significant decrease in sEPSCs frequency, but no change in their amplitude of labeled PVN presympathetic neurons. In contrast, in WKY rats expressed with excitatory hM3Dq-eGFP of PVN CRF-expressing neurons, CNO had no obvious effect on the sEPSCs frequency and amplitude in PVN presympathetic neurons. Furthermore, bath application of CNO had no significant effect on current-evoked firing of PVN presympathetic neurons of either WKY rats with hM3Dq-eGFP expression in CRF neurons or SHR with hM4Di-mCherry expression in CRF neurons. Conclusions The activity and number of PVN CRF-expressing neurons are increased in SHR, and CRF-expressing neurons enhance the excitability of presympathetic neurons, which acts as a regulatory neuronal microcircuit between CRF neurons and presympathetic neurons in the PVN.

Meta-analysis of the efficacy of intravitreal Ranibizumab combined with compound trabeculectomy and panretinal photocoagulation in the treatment of neovascular glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To systematically evaluate the efficacy and safety of intravitreal ranibizumab combined with compound trabeculectomy and panretinal photocoagulation(PRP)compared with compound trabeculectomy combined with PRP in the treatment of neovascular glaucoma(NVG).METHODS: Databases including Wanfang database, China National Knowledge Infrastructure(CNKI), PubMed, EMbase, China Biomedical Document Service System(CBM), Clinicalkey, and Cochrane Library were retrieved. Literatures about intravitreal ranibizumab combined with compound trabeculectomy and PRP in the treatment of NVG in the experimental group and compound trabeculectomy and PRP in the treatment of NVG in the control group from creation of database to July 20, 2022 were searched. At the same time, relevant reference were consulted. The best corrected visual acuity, intraocular pressure, occurrence of complications and the success rate of the surgery were systematically evaluated.RESULTS: A total of 8 clinical studies were included, with 864 patients(864 eyes)with NVG. Meta-analysis showed that the intraocular pressure of patients in the experimental group was lower than that in the control group at 1wk, 1 and 3mo after surgery(1wk: MD=-4.00, 95%CI: -4.62～-3.38, P&#x0026;#x003C;0.05; 1mo: MD=-4.11, 95%CI: -4.66～-3.56, P&#x0026;#x003C;0.05; 3mo: MD=-4.58, 95%CI: -5.61～-3.55, P&#x0026;#x003C;0.05). The best corrected visual acuity of the experimental group was better than that of the control group at 1mo after surgery(MD=0.17, 95%CI: 0.11～0.23, P&#x0026;#x003C;0.05), but there was no significant difference at 1wk after surgery(MD=0.08, 95%CI: -0.13～0.29, P=0.47). The patients in the experimental group had fewer complications(OR=0.30, 95%CI: 0.18～0.52, P&#x0026;#x003C;0.05)and higher surgical success rate(OR=5.15, 95%CI: 2.78～9.53, P&#x0026;#x003C;0.05).CONCLUSION:With decreased intraocular pressure, improved visual acuity and surgical success rate, intravitreal ranibizumab combined with compound trabeculectomy and PRP was better than the compound trabeculectomy and PRP in the treatment of NVG.

Determination of monosaccharide composition of polysaccharide and free monosaccharides in Cistanches Herba by ion chromatography-integral pulsed amperometry / 药学学报

Polysaccharides and free monosaccharides are important active components in Cistanches Herba, which have functions of anti-aging and immunological activity regulation. The study of monosaccharide composition in polysaccharide and free monosaccharide can lay a foundation for the study of primary structure, spatial structure of Cistanche polysaccharide and biological activity of Cistanches Herba. In this study, a method of water extraction and alcohol precipitation was used to extract Cistanche polysaccharide. Trifluoroacetic acid was selected as the hydrolytic acid for polysaccharide hydrolysis. An orthogonal experimental method is established. Three levels of acid concentration, hydrolysis temperature and hydrolysis time were selected to investigate the optimal hydrolysis condition. The optimal hydrolysis condition was 0.08 mol·L-1 trifluoroacetic acid hydrolysis at 100 ℃ for 3 h. The free monosaccharides of Cistanches Herba were extracted by water extraction. The established ion chromatogram integrated pulsed amperometry method can efficiently separate 11 monosaccharides in a short time. The method has good repeatability and high sensitivity, methodological experiment results meet the requirements of quantitative determination. It can accurately determine the monosaccharide composition of Cistanche polysaccharide and free monosaccharide content. Ion chromatography does not require derivatization operation and the pre-treatment steps are simple. This method can measure fructose, but PMP derivation-HPLC method can't. The monosaccharide composition of Cistanche polysaccharide include fucose, arabinose, rhamnose-galactose, glucose, xylose, mannose, fructose, ribose and glucuronic acid, among which the contents of glucose and fructose are relatively high. The free monosaccharides in the water extract of Cistanches Herba include glucose, fructose and mannose.

Analysis of the of Pb, Cd and As in decoction of Lindera aggregata (Sims) Kosterm. by PBET digestion in vitro/Caco-2 cell model and their cumulative risk assessment / 药学学报

Inductively coupled plasma mass spectrometry (ICP-MS) was applied to determine the concentrations of lead (Pb), cadmium (Cd) and arsenic (As) in Lindera aggregata (Sims) Kosterm. The physiologically based extraction test (PBET) digestion in vitro/Caco-2 cell model was established to investigate the bioaccessible contents of Pb, Cd and As in decoction of Lindera aggregata (Sims) Kosterm. The target-organ toxicity dose modification of HI method (TTD) was used to evaluate the cumulative risk caused by the combined exposure of the total levels of Pb, Cd and As in Lindera aggregata (Sims) Kosterm. and the bioaccessible contents in the decoction. The results showed that the total contents of Pb, Cd and As in 4 batches of samples were in the range of 2.901-3.872, 1.299-1.800 and 0.062-0.216 mg·kg-1, respectively. After transportation by Cacco-2 cells, the bioaccessible contents of Pb, Cd, and As in the decoction were in the range of 0.045-0.080, 0.070-0.112 and 0.004-0.018 mg·kg-1. The results of risk assessment showed that calculated by the total amounts of heavy metals in the Lindera aggregata (Sims) Kosterm., for the end points of nervous system, the cumulative risks of co-exposure of heavy metals in 3 batches of samples were of concern. After decoction and transportation by Caco-2 cells, for the end points of cardiovascular system, blood, nervous system, kidney and testis, the TTD modification of HI values of all batches of samples were less than 1, and the health risks were acceptable. The study provided methodology basis for a more objective assessment of the health risks of heavy metals and harmful elements in traditional Chinese medicine and for a more scientific limit standard of heavy metals and harmful elements.

Terpine-4-ol on inhibiting vascular smooth muscle cell calcification by improving mitochondrial dynamics / 药学学报

The aim of this study was to investigate the role and mechanism of terpinen-4-ol (T4O) on high glucose (HG) -induced calcification in vascular smooth muscle cell (VSMC). To investigate the role of T4O on HG-induced calcium deposition, osteogenic phenotypic transformation and mitochondrial dynamics in VSMC, Mdivi-1, a mitochondrial dynamin-related protein 1 (Drp-1) inhibitor, was used to analyze the correlation between mitochondrial dynamics and VSMC calcification and the role of T4O. Alizarin red S staining was used to observe calcium salt deposition and flow cytometry to detect intracellular Ca2+ content; Western blot and immunofluorescence were used to detect the expression of phenotypic switching-related markers α-smooth muscle actin (α-SMA), bone morphogenetic protein 2 (BMP2) and Runt related transcription factor 2 (Runx2), and mitochondrial dynamics-related markers mitofusin 1 (MFN1), mitofusin 2 (MFN2) and Drp-1. The results showed that low and high doses of T4O could inhibit HG-induced down-regulation of α-SMA, MFN1 and MFN2 expression levels, and up-regulation of BMP2, Runx2 and Drp-1 expression levels, reduce intracellular Ca2+ content and calcium salt deposition, and effectively inhibit HG-induced VSMC calcification and mitochondrial dynamics disorders. The T4O group, Mdivi-1 group and T4O+Mdivi-1 group were able to up-regulate the expression levels of HG-induced α-SMA, MFN1 and MFN2, down-regulate the protein expression levels of BMP2, Runx2 and Drp-1, and inhibit calcium salt deposition, and there was no significant difference between the above indexes in the T4O and T4O+Mdivi-1 groups. The above findings suggest that T4O can inhibit the expression level of Drp-1, regulate the disturbance of mitochondrial dynamics, and suppress HG-induced VSMC calcification.

The PK bioanalysis method study of c-Met antibody-drug conjugate (RC108) in cynomolgus monkey / 药学学报

Antibody-drug conjugate (ADC) has the characteristics of low toxicity and high efficiency, and plays an important role in cancer treatment. However, due to the complexity of its structure, it brings difficulties in pharmacokinetic (PK) bioanalysis. This study established an analytical method for the detection of ADC (RC108) in cynomolgus monkey plasma by ligand-binding assay (LBA) and liquid chromatography tandem mass spectrometry (LC-MS/MS), which was used to analyze and quantify the total antibody, bound antibody and free drug in cynomolgus monkey plasma. Based on the LBA method, rabbit anti-RC108 Fab and mouse anti-MMAE (monomethyl auristatin E) mAb were pre-coated in 96-well plates as the total antibody and antibody binding reagents, respectively. The samples to be tested were added, and then the detection reagents were added in turn. Goat anti-human IgG (H+L)-HRP, chromogenic solution tetramethylbenzidine (TMB), H2SO4 terminate the reaction, read data at 450 nm/630 nm wavelength of microplate reader; LC-MS/MS analysis method quantifies MMAE concentration, and refer to relevant regulations for methodological validation. The analytical method for quantifying total antibody, bound antibody and free drug of RC108 drug obtained good accuracy and precision, and the selectivity, dilution linearity, hook effect, parallelism and stability were verified. Meet the requirements of biological analysis. Finally, a bioanalytical method for the determination of the concentration of the test substance RC108 (total antibody, conjugated antibody, free MMAE) in cynomolgus monkey plasma with high sensitivity and high throughput was established by LBA and LC-MS/MS method. Subsequent non-clinical research on PK research in cynomolgus monkeys will provide technical support.

Effect of Xiaoxuming Decoction on activation of astrocytes in acute cerebral ischemia/reperfusion injury / 中国中药杂志

This study investigated the effect of Xiaoxuming Decoction(XXMD) on the activation of astrocytes after cerebral ischemia/reperfusion(I/R) injury. The model of cerebral IR injury was established using the middle cerebral artery occlusion method. Fluorocitrate(FC), an inhibitor of astrocyte activation, was applied to inhibit astrocyte activation. Rats were randomly divided into a sham group, a model group, a XXMD group, a XXMD+FC group, and a XXMD+Vehicle group. Neurobehavioral changes at 24 hours after cerebral IR injury, cerebral infarction, histopathological changes observed through HE staining, submicroscopic structure of astrocytes observed through transmission electron microscopy, fluorescence intensity of glial fibrillary acidic protein(GFAP) and thrombospondin 1(TSP1) measured through immunofluorescence, and expression of GFAP and TSP1 in brain tissue measured through Western blot were evaluated in rats from each group. The experimental results showed that neurobehavioral scores and cerebral infarct area significantly increased in the model group. The XXMD group, the XXMD+FC group, and the XXMD+Vehicle group all alleviated neurobehavioral changes in rats. The pathological changes in the brain were evident in the model group, while the XXMD group, the XXMD+FC group, and the XXMD+Vehicle group exhibited milder cerebral IR injury in rats. The submicroscopic structure of astrocytes in the model group showed significant swelling, whereas the XXMD group, the XXMD+FC group, and XXMD+Vehicle group protected the submicroscopic structure of astrocytes. The fluorescence intensity and protein expression of GFAP and TSP1 increased in the model group compared with those in the sham group. However, the XXMD group, the XXMD+FC group, and XXMD+Vehicle group all down-regulated the expression of GFAP and TSP1. The combination of XXMD and FC showed a more pronounced effect. These results indicate that XXMD can improve cerebral IR injury, possibly by inhibiting astrocyte activation and down-regulating the expression of GFAP and TSP1.

Advantage analysis of flow-through cell method in quality evaluation of Chinese patent medicine: a case study of Danshen Tablets / 中国中药杂志

To explore the quality consistency evaluation method for multi-component traditional Chinese medicine and establish a dissolution evaluation method suitable for the characteristics of multi-component Chinese patent medicine, this study discussed the characteristics and advantages of the flow-through cell method in the dissolution evaluation of Chinese patent medicine by comparing the impact of the small cup method and the flow-through cell method on the dissolution behavior of water-soluble and lipid-soluble major active components of Danshen Tablets. Dissolution tests were performed using the small cup method as described in the 2020 edition of the Chinese Pharmacopoeia and the newly introduced flow-through cell method(closed-loop method) with water solution containing 0.5% SDS as dissolution medium. Cumulative dissolution curves of the water-soluble component salvianolic acid B and the lipid-soluble component tanshinone Ⅱ_A in Danshen Tablets were plotted, and fitting and similarity analysis of the dissolution models was conducted to identify the characteristics and advantages of the flow-through cell method. For the small cup method, 150 mL of water containing 0.5% SDS was used as the dissolution medium, with a rotation speed of 75 r·min~(-1) and a temperature of(37±0.5) ℃, and 3 mL of samples were taken at 15, 30 min, 1, 2, and 4 h, with fresh dissolution medium added at the same temperature and volume. For the flow-through cell method, a closed-loop system was used. Danshen Tablets were placed in the flow-through cell with approximately 6.7 g of glass beads, and 150 mL of water containing 0.5% SDS was used as the dissolution medium. The flow rate was set at 20 mL·min~(-1), and the temperature and sampling were the same as the small cup method. The results showed that compared with the small cup method, the flow-through cell method had stronger discriminative power and higher sensitivity in distinguishing the dissolution behavior of the two components, and could better reflect the differences in formulation quality, especially for water-insoluble lipid-soluble components. Given that there were no essential differences in the in vitro release kinetics between the two methods, the flow-through cell method could not only replace the traditional small cup method but also better guide the formulation development and identify quality issues of formulations.

Methamphetamine: Mechanism of Action and Chinese Herbal Medicine Treatment for Its Addiction / 中国结合医学杂志

With the proliferation of synthetic drugs, research on the mechanism of action of addictive drugs and treatment methods is of great significance. Among them, methamphetamine (METH) is the most representative amphetamine synthetic drug, and the treatment of METH addiction has become an urgent medical and social problem. In recent years, the therapeutic effects of Chinese herbal medicines on METH addiction have gained widespread attention because of their non-addictiveness, multiple targets, low side effects, low cost, and other characteristics. Previous studies have identified a variety of Chinese herbal medicines with effects on METH addiction. Based on the research on METH in recent years, this article summarizes the mechanism of action of METH as the starting point and briefly reviews the Chinese herbal medicine-based treatment of METH.

Development and Application of Ontology of Cancer Hallmarks / 中国医学科学院学报

Objective To develop a traceable cancer hallmark ontology with terminology including gene mutation,cancer hallmark,and cell line for knowledge integration,standardization,correlation,and discovery.Methods The Ontology Development 101 and the current ontology development methods were employed to determine the content coverage,structural layers,reusable terms,and new terms of the cancer hallmark ontology.Taking colorectal cancer as a study case,we extracted the knowledge related with colorectal cancer hallmarks using text mining and text classification technology from PubMed,and then formalized the extracted knowledge into the cancer hallmark ontology.Moreover,we made use of existing cancer hallmark evidence in Catalogue of Somatic Mutations in Cancer and further semantic retrieval to discover new knowledge.Results The established cancer hallmark ontology comprised 9910 classes and 6138 instances,which realized the semantic representation of 2310 article abstracts about colorectal cancer and 26 pieces of evidence about genes and their cancer hallmarks.Compared with the Catalogue of Somatic Mutations in Cancer,new evidence for more genes associated with colorectal cancer hallmarks was found based on cancer hallmark ontology.Conclusion This study is of great significance to the research on the cancer pathogenesis at the molecular level,the revealing of specific roles of genes and mutations in the occurrence of cancer,and the rapid knowledge discovery of cancer hallmarks.

Endogenous corticotropin-releasing factor potentiates the excitability of presympathetic neurons in paraventricular nucleus via activation of its receptor 1 in spontaneously hypertensive rats / 生理学报

It is well established that increased excitability of the presympathetic neurons in the hypothalamic paraventricular nucleus (PVN) during hypertension leads to heightened sympathetic outflow and hypertension. However, the mechanism underlying the overactivation of PVN presympathetic neurons remains unclear. This study aimed to investigate the role of endogenous corticotropin-releasing factor (CRF) on the excitability of presympathetic neurons in PVN using Western blot, arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) recording, CRISPR/Cas9 technique and patch-clamp technique. The results showed that CRF protein expression in PVN was significantly upregulated in spontaneously hypertensive rats (SHRs) compared with normotensive Wistar-Kyoto (WKY) rats. Besides, PVN administration of exogenous CRF significantly increased RSNA, heart rate and ABP in WKY rats. In contrast, knockdown of upregulated CRF in PVN of SHRs inhibited CRF expression, led to membrane potential hyperpolarization, and decreased the frequency of current-evoked firings of PVN presympathetic neurons, which were reversed by incubation of exogenous CRF. Perfusion of rat brain slices with artificial cerebrospinal fluid containing CRF receptor 1 (CRFR1) blocker, NBI-35965, or CRF receptor 2 (CRFR2) blocker, Antisauvagine-30, showed that blocking CRFR1, but not CRFR2, hyperpolarized the membrane potential and inhibited the current-evoked firing of PVN presympathetic neurons in SHRs. However, blocking CRFR1 or CRFR2 did not affect the membrane potential and current-evoked firing of presympathetic neurons in WKY rats. Overall, these findings indicate that increased endogenous CRF release from PVN CRF neurons enhances the excitability of presympathetic neurons via activation of CRFR1 in SHRs.

A quantitative study of airway ultrasound in predicting difficult laryngoscopy: A prospective study / 中华创伤杂志(英文版)

PURPOSE@#As common clinical screening tests cannot effectively predict a difficult airway, and unanticipated difficult laryngoscopy remains a challenge for physicians. We herein used ultrasound to develop some point-of-care predictors for difficult laryngoscopy.@*METHODS@#This prospective observational study included 502 patients who underwent laryngoscopy and a detailed sonographic assessment. Patients under 18 years old, or with maxillofacial deformities or fractures, limited mouth opening, limited neck movement or history of neck surgery were excluded from the study. Laryngoscopic views of all patients were scored and grouping using the modified Cormack-Lehane (CL) scoring system. The measurements acquired comprised tongue width, the longitudinal cross-sectional area of the tongue, tongue volume, the mandible-hyoid bone distance, the hyoid bone-glottis distance, the mandible-hyoid bone-glottis angle, the skin-thyrohyoid membrane distance, the glottis-superior edge of the thyroid cartilage distance (DGTC), the skin-hyoid bone distance, and the epiglottis midway-skin distance. ANOVA and Chi-square were used to compare differences between groups. Logistic regression was used to identify risk factors for difficult laryngoscopy and it was visualized by receiver operating characteristic curves and nomogram. R version 3.6.3 and SPSS version 26.0 were used for statistical analyses.@*RESULTS@#Difficult laryngoscopy was indicated in 49 patients (CL grade Ⅲ - Ⅳ) and easy laryngoscopy in 453 patients (CL grade Ⅰ - Ⅱ). The ultrasound-measured mandible-hyoid bone-glottis angle and DGTC significantly differed between the 2 groups (p < 0.001). Difficult laryngoscopy was predicted by an area under the curve (AUC) of 0.930 with a threshold mandible-hyoid bone-glottis angle of 125.5° and by an AUC of 0.722 with a threshold DGTC of 1.22 cm. The longitudinal cross-sectional area of the tongue, tongue width, tongue volume, the mandible-hyoid distance, and the hyoid-glottis distance did not significantly differ between the groups.@*CONCLUSION@#Difficult laryngoscopy may be anticipated in patients in whom the mandible-hyoid bone-glottis angle is smaller than 125.5° or DGTC is larger than 1.22 cm.

The Mechanism of miR-1294 Targeting SOX15 to Regulate Wnt/β-catenin Signaling Pathway and Promote the Proliferation of Acute Lymphoblastic Leukemia Cells in Children / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of abnormal miRNA expression on the proliferation of pediatric acute lymphoblastic leukemia (ALL) cells and its related mechanism.@*METHODS@#15 children with ALL and 15 healthy subjects were collected from the Second Affiliated Hospital of Hainan Medical University from July 2018 to March 2021. MiRNA sequencing was performed on their bone marrow cells, and validated using qRT-PCR. MiR-1294 and miR-1294-inhibitory molecule (miR-1294-inhibitor) were transfected into Nalm-6 cells, and the proliferation of Nalm-6 cells was detected by CCK-8 and colony formation assays. Western blot and ELISA were used to detect apoptosis of Nalm-6 cells. Biological prediction of miR-1294 was performed to find the target gene, which was verified by luciferase reporter assay. Si-SOX15 was transfected into Nalm-6 cells, Western blot was used to detect the expression of Wnt signaling pathway-related proteins and to verify the effect of si-SOX15 on the proliferation and apoptosis of Nalm-6 cells.@*RESULTS@#Compared with healthy subjects, 22 miRNAs were significantly upregulated in bone marrow cells of ALL patients, of which miR-1294 was the most significantly upregulated. In addition, the expression level of SOX15 gene was significantly reduced in bone marrow cells of ALL patients. Compared with the NC group, the miR-1294 group showed increased protein expression levels of Wnt3a and β-catenin, faster cell proliferation, and more colony-forming units, while caspase-3 protein expression level and cell apoptosis were reduced. Compared with the NC group, the miR-1294-inhibitor group showed reduced protein expression levels of Wnt3a and β-catenin, slower cell proliferation, and fewer colony-forming units, while caspase-3 protein expression level was increased and apoptosis rate was elevated. miR-1294 had a complementary base-pair with the 3'UTR region of SOX15 , and miR-1294 directly targeted SOX15 . The expression of miR-1294 was negatively correlated with SOX15 in ALL cells. Compared with the si-NC group, the si-SOX15 group showed increased protein expression levels of Wnt3a and β-catenin, accelerated cell proliferation, and decreased caspase-3 protein expression level and cell apoptosis rate.@*CONCLUSION@#MiR-1294 can target and inhibit SOX15 expression, thus activating the Wnt/β-Catenin signaling pathway to promote the proliferation of ALL cells, inhibit cell apoptosis, and ultimately affect the disease progression.