No Incidence of Liver Cancer Was Observed in A Retrospective Study of Patients with Aristolochic Acid Nephropathy / 中国结合医学杂志

OBJECTIVE@#To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN).@*METHODS@#A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014.@*RESULTS@#A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer.@*CONCLUSIONS@#No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.

Development of an in vitro screening method for idiosyncratic hepatotoxic components in traditional Chinese medicine: a case study with Epimedii Folium and Psoraleae Fructus / 药学学报

Idiosyncratic drug-induced liver injury (IDILI) has long posed a challenging and pivotal concern in pharmaceutical research. The complex composition of traditional Chinese medicine (TCM) has introduced a bottleneck in current research, hindering the elucidation of the component basis associated with IDILI in TCM. Using Epimedii Folium (EF) and Psoraleae Fructus (PF) as illustrative examples, this study endeavors to establish an in vitro evaluation model, providing a high-throughput and preliminary assessment method for screening components related to TCM-induced IDILI. A TNF-α-mediated HepG2 susceptible model was first established in this study, with the focus on the index components present in EF and PF. The release of lactate dehydrogenase (LDH) in the cell supernatant served as the detection index. A concentration-toxicity response curve was constructed, and the hepatotoxic components of EF and PF were identified utilizing the synergistic toxicity index. The LDH results unveiled the hepatotoxic effects of bavachin, backuchiol, isobavachin, neobavaisoflavone, psoralidin, isobavachalcone, icarisid I, and icarisid II on both normal and susceptible cells, categorizing these 8 components as both direct hepatotoxicity components and idiosyncratic hepatotoxicity components. Bavachin and neobavaisoflavone exhibited no hepatotoxicity on normal cells but demonstrated significant effects on susceptible cells, designating them as potential idiosyncratic susceptible hepatotoxicity components. The study further delineated that 10 EF components and 3 PF components were direct immune-promoting hepatotoxicity components. Additionally, 14 idiosyncratic immune-promoting hepatotoxicity components were identified, encompassing 10 EF components and 4 PF components, with neobavaisoflavone, bavachinin, and isobavachin being potential idiosyncratic susceptible immune-promoting hepatotoxicity components. Synergistic toxicity index results indicated that 13 idiosyncratic immune-promoting hepatotoxicity components (except anhydroicaritin) combined with bavachin demonstrated synergistic hepatotoxicity on susceptible cells. Notably, 3 idiosyncratic susceptible immune-promoting hepatotoxicity components combined with bavachin exhibited synergistic hepatotoxicity, with neobavaisoflavone displaying the highest synergistic toxicity index and bavachinin the lowest. In summary, this methodology successfully screens hepatotoxic and immune-promoting hepatotoxic components in EF and PF, distinguishing the types of components inducing hepatotoxicity, evaluating the hepatotoxicity degree of each component, and elucidating the synergistic relationships among them. Importantly, these findings align with the characteristics of IDILI. The method provides an effective model tool for the fundamental research of TCM-related IDILI components.

New outlook on safety of traditional Chinese medicine: concept and practice / 中国中药杂志

Profound changes have taken place in human disease spectrum, constitution spectrum, and drug use behavior, and the safety of traditional Chinese medicine(TCM) faces new trends and problems. In particular, serious adverse reactions/events such as liver injury and kidney injury caused by non-toxic TCM have been frequently reported, overturning people's understanding of TCM safety, and even shaking the public's confidence in the development of TCM. In the new era of globalization, correctly understanding the situation and problems of TCM safety and addressing the dilemmas in safety evaluation and risk prevention of TCM are the key missions to be undertaken by TCM practitioners. This paper suggests that the situation and problems of TCM safety should be viewed objectively and dialectically, and the use standard of TCM should be advanced with the times. Furthermore, this paper puts forward the new conception and methodology of TCM safety(including one innovative understanding, two types of evaluation modes, tri-elements injury hypothesis; four-quadrant risk decision processes, and five-grade safety evidence body) for the first time, hoping to provide new theories, new strategies, new methods and successful examples for solving the safety problems of TCM.

Analysis of pathogens of mucosal candidiasis and their resistance to drugs in a third-grade class-A hospital in Taiyuan, Shanxi / 中华皮肤科杂志

Objective:To analyze types of mucosal candidiasis and drug resistance of relevant pathogens in a dermatology outpatient clinic in Taiyuan.Methods:Clinical data were collected from 172 patients with mucosal candidiasis, who had positive fungal culture results, in the dermatology outpatient clinic of Shanxi Bethune Hospital from 2019 to 2020. Pathogens were identified by a molecular biological approach, and in vitro drug sensitivity test was performed. Results:Among the 172 patients with mucosal candidiasis, 142 (82.6%) had vulvovaginal candidiasis, 24 (14.0%) had candidal balanoposthitis, and 6 (3.5%) had oral candidiasis; 3 patients were aged ≤ 18 years, 155 were aged 19 - 59 years, and 14 were aged ≥ 60 years, and the proportion of patients with vulvovaginal candidiasis significantly differed among the above 3 age groups (2/3, 134/155[86.45%], 6/14, respectively; χ2 = 14.29, P < 0.05) . Molecular biological identification showed that all the 172 isolated strains belonged to the genus Candida, including 165 strains of Candida albicans (95.9%) , 5 strains of Candida glabrata (2.9%) , and 2 strains of Candida parapsilosis (1.2%) ; the sensitivity to common antifungal agents including flucytosine, amphotericin B, fluconazole, itraconazole and voriconazole was 95.9%, 100.0%, 62.2%, 47.1% and 56.4%, respectively. Conclusion:In the dermatology outpatient clinic of Shanxi Bethune Hospital, vulvovaginal candidiasis was the most common type of mucosal candidiasis, and the main pathogen was Candida albicans; the Candida isolates showed high sensitivity to flucytosine and amphotericin B.

Finite element analysis of 14-year-old adolescent after spinal foraminoplasty at L / 解剖学报

Objective To establish the three-dimensional finite element model of lumbar spine(L) 3-5 segments of the normal spine of 14-year-old adolescents to analyze the biomechanical changes of the lumbar spine after different degrees of lumbar foraminal plasty, and to provide reference for improvement of adolescent foraminoplasty. Methods A14-year-old female volunteer with no previous history of lumbar spine was selected to collect lumbar CT image data and we imported it into Mimics 16.0 software for modeling. ABAQUS software was used to conduct finite element model force analysis. Models M

Mechanism of heroin promoting addiction and relapse in progeny of male rats by inhibiting promoter methylation of imprinted gene H19 by down-regulating DNMT3a / 中国药理学通报

Aim To investigate the effect of heroin use in male rats of F0 generation on heroin addiction and relapse in rats of Fl generation and the underlying mechanism. Methods Male rats of F0 generation were treated with different doses of heroin (1, 3, 9 mg • kg

Research progress on cellular and molecular mechanism of keloids / 中国药理学通报

Keloid is a fibrous proliferative disease of the skin, and its pathological essence is excessive wound healing caused by excessive fibrosis. Its pathological mechanism is complex and unclear. At present, it is believed that the cellular mechanism of keloids mainly involves inflammatory cells and fibrosis-related cells, as well as cytokines such as growth factors, interleukins, tumor necrosis factor, and matrix metalloproteinase; the molecular mechanism mainly involves TGF-p/Smad pathway, NF-Mo- lecular mechanisms such as kB pathway, STAT3 signaling pathway, MAPK signaling pathway, and focal adhesion kinase. This article reviews the latest research progress on the pathological mechanism of keloids from the perspectives of cells, cytokines, and molecular signaling pathways.

ACSL5, a prognostic factor in acute myeloid leukemia, modulates the activity of Wnt/β-catenin signaling by palmitoylation modification / 医学前沿

Acyl-CoA synthetase long chain family member 5 (ACSL5), is a member of the acyl-CoA synthetases (ACSs) family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs. The dysregulation of ACSL5 has been reported in some cancers, such as glioma and colon cancers. However, little is known about the role of ACSL5 in acute myeloid leukemia (AML). We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors. ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients. In AML cells, the ACSL5 knockdown inhibited cell growth both in vitro and in vivo. Mechanistically, the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a. Additionally, triacsin c, a pan-ACS family inhibitor, inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199, the FDA approved BCL-2 inhibitor for AML therapy. Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML.

Interpretation on Consensus on drug-induced liver injury by CIOMS Working Group:liver injury attributed to herbal and dietary supplements / 中国中药杂志

With the increase in the medical level, the improvement of adverse drug reaction(ADR) monitoring systems, and the enhancement of public awareness of safe medication, drug safety incidents have been frequently reported. Drug-induced liver injury(DILI), especially liver injury attributed to herbal and dietary supplements(HDS), has globally attracted high attention, bringing great threats and severe challenges to the people for drug safety management such as clinical medication and medical supervision. Consensus on drug-induced liver injury had been published by the Council for International Organizations of Medical Sciences(CIOMS) in 2020. In this consensus, liver injury attributed to HDS was included in a special chapter for the first time. The hot topics, including the definition of HDS-induced liver injury, epidemiological history, potential risk factors, collection of related risk signals, causality assessment, risk prevention, control and management were discussed from a global perspective. Based on the previous works, some experts from China were invited by CIOMS to undertake the compilation of this chapter. Meanwhile, a new causality assessment in DILI based on the integrated evidence chain(iEC) method was widely recognized by experts in China and abroad, and was recommended by this consensus. This paper briefly introduced the main contents, background, and characteristics of the Consensus on drug-induced liver injury. Significantly, a brief interpretation was illustrated to analyze the special highlights of Chapter 8, "Liver injury attributed to HDS", so as to provide practical references for the medical staff and the researchers who worked on either Chinese or Western medicine in China.

Study on the objectivity and biological mechanism of Psoralea corylifolia Linn.'s 'Great dryness damages the liver' / 药学学报

According to the theory of 'Xingben Dazao' of Psoralea corylifolia Linn. (BL), the susceptible syndromes and biomarkers of liver injury caused by BL were searched. Rat models of kidney-yin deficiency syndrome (M_yin) and kidney-yang deficiency syndrome (M_yang) were established, and all animal experimental operations and welfare following the provisions of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Traditional Chinese Medicine (No. YFYDW2020017). The results showed that BL significantly decreased the body weight, water intake, and urine weight of M_yin rats and increase the organ indexes of the liver, testis, adrenal gland, and spleen and the expression of alanine aminotransferase (ALT). Meantime, BL significantly increased the urine weight of M_yang rats and decreased the expression of ALT and aspartate aminotransferase (AST). Hematoxylin and eosin (HE) staining showed that BL could aggravate inflammatory infiltration of hepatocytes in rats with M_yin and alleviate liver injury in rats with M_yang. Metabolomics identified 17 BL co-regulated significant differential metabolic markers in M_yin and M_yang rats. Among them, 8 metabolites such as glutamine, quinolinate, biliverdin, and lactosylceramide showed opposite trends, mainly involving cysteine and methionine metabolism, tyrosine metabolism, tryptophan metabolism, purine metabolism, sphingolipid metabolism, glycerol phospholipid metabolism, glutamine metabolism, and other pathways. M_yin/M_yang may be the susceptible constitution of BL for liver damage or protection, which may be related to the regulation of amino acid metabolism and sphingolipid metabolism. The study can provide some experimental data support for the safe and accurate use of BL in the clinical practice of traditional Chinese medicine.

Monoterpenoids from Paeoniae Radix Rubra based on UPLC-Q-TOF-MS / 中国中药杂志

The ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to conduct the qualitative analysis of the monoterpene chemical components from Paeoniae Radix Rubra. Gradient elution was performed on C_(18) HD(2.1 mm×100 mm, 2.5 μm) column with a mobile phase of 0.1% formic acid(A) and acetonitrile(B). The flow rate was 0.4 mL·min~(-1) and the column temperature was 30 ℃. MS analysis was conducted in both positive and negative ionization modes using electrospray ionization(ESI) source. Qualitative Analysis 10.0 was used for data processing. The identification of chemical components was realized by the combination of standard compounds, fragmentation patterns, and mass spectra data reported in the literature. Forty-one monoterpenoids in Paeoniae Radix Rubra extract were identified. Among them, 8 compounds were reported in Paeoniae Radix Rubra for the first time and 1 was presumed to be the new compound 5″-O-methyl-galloylpaeoniflorin or its positional isomer. The method in this study realizes the rapid identification of monoterpenoids from Paeoniae Radix Rubra and provides a material and scientific basis for quality control and further study on the pharmaceutical effect of Paeoniae Radix Rubra.

Application of bilateral facial perforator artery flap in repairing large area defect in middle and lower part of nose / 中国修复重建外科杂志

OBJECTIVE@#To investigate the feasibility and effectiveness of bilateral facial perforator artery flap in repairing large area defect in middle and lower part of nose.@*METHODS@#The clinical data of 18 patients with large area defect in middle and lower part of nose repaired by bilateral facial perforator artery flap between January 2019 and December 2022 were retrospectively analyzed. Among them, there were 13 males and 5 females, the age ranged from 43 to 81 years, with an average of 63 years. There were 3 cases of nasal trauma, 4 cases of basal cell carcinoma, 8 cases of squamous cell carcinoma, 1 case of lymphoma, and 2 cases of large area solar keratosis. The size of the defect ranged from 3.0 cm×3.0 cm to 4.5 cm×4.0 cm; the size of unilateral flap ranged from 3.0 cm×1.3 cm to 3.5 cm×2.0 cm, and the size of bilateral flaps ranged from 3.3 cm×2.6 cm to 4.5 cm×4.0 cm.@*RESULTS@#One patient developed skin flap necrosis after operation, and a frontal skin flap was used to repair the wound; 1 case gradually improved after removing some sutures due to venous congestion in the skin flap, and the wound healing was delayed after dressing change; the remaining 16 cases of bilateral facial perforator artery flaps survived well and all wounds healed by first intention, without any "cat ear" malformation. All 18 patients had first intention healing in the donor area, leaving linear scars without obvious scar hyperplasia, and no facial organ displacement. All patients were followed up 3-12 months, with an average of 6 months. Due to the appropriate thickness of the flap, none of the 18 patients underwent secondary flap thinning surgery. All flaps had good blood circulation, similar texture and color to surrounding tissues, symmetrical bilateral nasolabial sulcus, and high patient satisfaction.@*CONCLUSION@#The bilateral facial perforator artery flaps for repairing large area defect in middle and lower part of nose can achieve good appearance and function, and the operation is relatively simple, with high patient satisfaction.

Exploring the safe and rational use of Epimedii Folium based on the evolution of efficacy/toxicity records in ancient and modern literature / 药学学报

Epimedii Folium is a traditional non-toxic Chinese herbal medicine. However, liver injury caused by Chinese herb preparations, including Epimedii Folium, is frequently reported over the years. Based on ancient and modern literature, this paper systematically summarized and analyzed the safe application of Epimedii Folium from the perspectives of varieties, processing methods, clinical adverse reactions, pharmacological effects and toxic mechanism. Combined with our team work, we build the comprehensive prevention and control system "human-drug-application", for the safe and rational application of Epimedii Folium. This study is expected to provide support for scientific evaluation and precise prevention and control of the safety risk of Epimedii Folium.

Thoughts on path of R&D and registration of innovative traditional Chinese medicine with synchronous transformation of "series prescriptions" / 中国中药杂志

Since the implementation of drug registration in China, the classification of Chinese medicine has greatly met the needs of public health and effectively guided the transformation, inheritance, and innovation of research achievements on traditional Chinese medicine(TCM). In the past 30 years, the development of new Chinese medicine has followed the registration transformation model of " one prescription for single drug". This model refers to the R&D and registration system of modern drugs, and approximates to the " law-abiding" medication method in TCM clinic, while it rarely reflects the sequential therapy of syndrome differentiation and comprehensive treatment with multiple measures. In 2017, Opinions on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices released by the General Office of the CPC Central Committee and the General Office of the State Council pointed out that it is necessary to " establish and improve the registration and technical evaluation system in line with the characteristics of Chinese medicine, and handle the relationship between the traditional advantages of Chinese medicine and the requirements of modern drug research". Therefore, based on the development law and characteristics of TCM, clinical thinking should be highlighted in the current technical requirements and registration system of research and development of Chinese medicine. Based on the current situation of registration supervision of Chinese medicine and the modern drug research in China, the present study analyzed limitations and deficiency of " one prescription for single drug" in the research and development of Chinese medicine. Additionally, a new type of " series prescriptions" was proposed, which was consistent with clinical thinking and clinical reality. This study is expected to contribute to the independent innovation and high-quality development of the TCM industry.

Meta-analysis of efficacy and safety of Liuwei Wuling Tablets combined with conventional drugs in treatment of liver fibrosis and cirrhosis in chronic hepatitis B / 中国中药杂志

The present study evaluated the clinical efficacy and safety of Liuwei Wuling Tablets combined with conventional drugs for the treatment of liver fibrosis and cirrhosis in chronic hepatitis B. CNKI, Wanfang, VIP, CBM, PubMed, EMbase and Cochrane Library were searched for the relevant randomized controlled trials(RCTs) published from database inception to February 2021. All the retrieved papers were independently screened, extracted and evaluated by two researchers, followed by Meta-analysis by Review Manager 5.4. Finally, 18 RCTs were included, involving 2 168 patients(1 106 in the treatment group and 1 062 in the control group). The Meta-analysis results showed that compared with conventional drugs alone, Liuwei Wuling Tablets combined with conventional drugs could increase the effective rate of clinical treatment by reducing serum hyaluronic acid(HA), laminin(LN), procollagen type Ⅲ(PCⅢ), and type Ⅳ collagen(Ⅳ-C) to improve liver function, decreasing the levels of total bilirubin(TBiL), alanine amino-transferase(ALT), and aspartate aminotransferase(AST), and improving the negative conversion ratio of hepatitis B virus(HBV) DNA. In terms of safety, there were no serious adverse reactions in the treatment group and the control group. The results showed that Liuwei Wuling Tablets combined with antiviral or other conventional liver-protecting drugs could improve liver function, treat liver cirrhosis, and reduce liver fibrosis with high safety. However, due to the influence of literature quality and quantity, multi-center and high-quality RCTs with large sample size are needed for verification.

Curative effect of modified Parks incision combined with rectus linear tucking on adults with concomitant strabismus / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the curative effect of modified Parks incision combined with rectus linear tucking on adults with concomitant strabismus and its influences on postoperative recovery of visual function and ocular aesthetics.METHODS: A total of 160 adults with concomitant strabismus were enrolled as the research subjects between June 2019 and June 2021. They were divided into observation group(modified Parks incision combined with rectus linear tucking, 89 cases)and control group(corneal limbal trapezoid conjunctival flap incision combined with rectus linear tucking, 71 cases)according to different surgical methods. The clinical curative effect and surgical related indexes between the two groups were compared. The changes in scores of corneal fluorescence staining, standard patient of eye dryness(SPEED), visual analogue scale(VAS)and Vancouver scar scale(VSS)before and after surgery in both groups were observed. The occurrence of complications such as poor conjunctival healing and astigmatism was statistically analyzed at 1mo after surgery.RESULTS: The total response rate of surgery in observation group was higher than that in control group, and length of surgical incision was shorter than that in control group(all P&#x003C;0.05). The scores of postoperative corneal fluorescence staining and dry eye in observation group were lower than those in control group, and VAS scores at 1wk after surgery were lower than that in control group(all P&#x003C;0.05). Postoperative divergent fusion range, strabismus angles of short-sighted 33cm and far-sighted 5m in observation group were greater than those in control group. Convergent fusion range was smaller than that in control group, and stereopsis of short-sighted 33cm and far-sighted 5m was lower than that in control group(all P&#x003C;0.05). Postoperative break-up time in observation group was longer than that in control group, lacrimal secretion was more than that in control group, and scores of corneal surface regularity index(SRI)and VSS scores were lower than those in control group(all P&#x003C;0.05). The total incidence of complications in observation group was lower than that in control group(P&#x003C;0.05).CONCLUSION: The modified Parks incision combined with rectus linear tucking can not only improve surgical effect and promote the recovery of visual function and tear film function in adults with concomitant strabismus, but also relieve dry eye and postoperative pain, improve ocular aesthetics and reduce the incidence of postoperative complications.

Discussion on Technical Evaluation Requirements of Allergen Detection Reagent Pre-marketing / 中国医疗器械杂志

In the perspective of technical evaluation, the pre-marketing regulatory requirements of allergen detection reagents in China, America, European Union were compared, and the regulatory risks and performance requirements of this product were analyzed based on the monitoring of post-marketing adverse events, reference standards and domestic and foreign regulatory documents. In view of the "neck-stuck" problems such as the difficulty of clinical trials, the difficulty of finding comparable contrast reagents and the lack of clinical diagnostic gold standards, this paper discusses and gives regulatory suggestions, with a view to providing technical reference for product R&D, production, evaluation, approval and supervision in this field.

A highly efficient protein corona-based proteomic analysis strategy for the discovery of pharmacodynamic biomarkers / 药物分析学报

The composition of serum is extremely complex,which complicates the discovery of new pharmaco-dynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich low-abundance proteins in serum.Here,we synthesized a silica-coated iron oxide nanoparticle and devel-oped a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis.We identified 1,070 proteins with a median coefficient of variation of 12.56％using PC-based proteomic analysis,which was twice the number of proteins iden-tified by direct digestion.There were also more biological processes enriched with these proteins.We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with MTX.This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.

Finite element analysis of facet joint between normal and lumbar disc hemiation in adolescents / 解剖学报

Objective To investigate the effect of facet joint asymmetry on lumbar biomechanics in normal and patients with adolescent lumbar disc hemiation (ALDH). Methods Mimics 21.0, 3-Matic Medical 13.0, Geomagic Wrap 2017, HyperMesh 2019 and finite element software ABAQUS 2021 were combined to establish three-dimensional finite element models of nonnal lower lumbar spine and adolescent lumbar disc hemiation. According to the difference between the left and right facet joints, three cases of nonnal and ALDH patients aged 13-18 years old were selected, with a total of 6 cases. The stress of intervertebral disc under different torque loads (neutral position, lateral flexion and rotation) was analyzed and compared. Results 1. Three dimensional finite element models of L3-L, segments were established in 6 male nonnal and adolescent patients with lumbar disc herniation, and the stress and displacement nephogram of lumbar disc hemiation in nonnal neutral position, flexion, extension, lateral flexion and rotation were obtained; 2. The stress of L4_, annulus fibrosus increased when the facet joint angle of nonnal adolescents was symmetrical in the neutral position; 3. The stress of annulus fibrosus was greater than that of nucleus pulposus under different conditions, and the stress of annulus fibrosus was flexion > neutral position > extension; 4. In patients with ALDH, the left side of the facet joint was larger than the right 10 ° model, and the stress in the posterior side of the annulus fibrosus of L4_, segment increased significantly under extension condition. Under lateral flexion condition, the left stress of the left annulus fibrosus was compared with the right stress of the right annulus fibrosus, t = l. 575, P<0. 05, the difference was statistically significant, the right stress of the right annulus fibrosus was greater than the left stress of the left annulus fibrosus. Under the rotating condition, the stress on the left and right sides of the fiber ring was greater than that on the back side. Conclusion 1. Compared with nonnal and patients with ALDH, the stress of intervertebral disc increases under different postures, which ma)' increase the shear load of intervertebral disc and aggravate the process of intervertebral disc degeneration; 2. When the degree of left-right asymmetry of facet joint is more than 10 degrees, the stress on the side with small degree is greater. Facet joint asymmetry can lead to the overload of vertebral bod)' and intervertebral disc, leading to spinal instability; 3. The stress of intervertebral disc in extension is less than that in neutral position and flexion. Extension can relieve the pressure of intervertebral disc and play an auxiliary role in the recovery of patients with ALDH.

Quantitative proteomics revealed extensive microenvironmental changes after stem cell transplantation in ischemic stroke / 医学前沿

The local microenvironment is essential to stem cell-based therapy for ischemic stroke, and spatiotemporal changes of the microenvironment in the pathological process provide vital clues for understanding the therapeutic mechanisms. However, relevant studies on microenvironmental changes were mainly confined in the acute phase of stroke, and long-term changes remain unclear. This study aimed to investigate the microenvironmental changes in the subacute and chronic phases of ischemic stroke after stem cell transplantation. Herein, induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs) were transplanted into the ischemic brain established by middle cerebral artery occlusion surgery. Positron emission tomography imaging and neurological tests were applied to evaluate the metabolic and neurofunctional alterations of rats transplanted with stem cells. Quantitative proteomics was employed to investigate the protein expression profiles in iPSCs-transplanted brain in the subacute and chronic phases of stroke. Compared with NSCs-transplanted rats, significantly increased glucose metabolism and neurofunctional scores were observed in iPSCs-transplanted rats. Subsequent proteomic data of iPSCs-transplanted rats identified a total of 39 differentially expressed proteins in the subacute and chronic phases, which are involved in various ischemic stroke-related biological processes, including neuronal survival, axonal remodeling, antioxidative stress, and mitochondrial function restoration. Taken together, our study indicated that iPSCs have a positive therapeutic effect in ischemic stroke and emphasized the wide-ranging microenvironmental changes in the subacute and chronic phases.