Design strategy and research progress of multifunctional nanoparticles in lung cancer therapy.

INTRODUCTION: Lung cancer is one of the cancer types with the highest mortality rate, exploring a more effective treatment modality that improves therapeutic efficacy while mitigating side effects is now an urgent requirement. Designing multifunctional nanoparticles can be used to overcome the limitations of drugs and conventional drug delivery systems. Nanotechnology has been widely researched, and through different needs, suitable nanocarriers can be selected to load anti-cancer drugs to improve the therapeutic effect. It is foreseeable that with the rapid development of nanotechnology, more and more lung cancer patients will benefit from nanotechnology. This paper reviews the merits of various multifunctional nanoparticles in the treatment of lung cancer to provide novel ideas for lung cancer treatment. AREAS COVERED: This review focuses on summarizing various nanoparticles for targeted lung cancer therapy and their advantages and disadvantages, using nanoparticles loaded with anti-cancer drugs, delivered to lung cancer sites, enhancing drug half-life, improving anti-cancer drug efficacy and reducing side effects. EXPERT OPINION: The delivery mode of nanoparticles with superior pharmacokinetic properties in the in vivo circulation enhances the half-life of the drug, and provides tissue-targeted selectivity and the ability to overcome biological barriers, bringing a revolution in the field of oncology.

Early autoimmunity and outcome in virus encephalitis: a retrospective study based on tissue-based assay.

To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. METHODS: A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). RESULTS: Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], p=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). CONCLUSIONS: Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.

Ultrasensitive quantification of trace amines based on N-phosphorylation labeling chip 2D LC-QQQ/MS.

Trace amines (TAs) are metabolically related to catecholamine and associated with cancer and neurological disorders. Comprehensive measurement of TAs is essential for understanding pathological processes and providing proper drug intervention. However, the trace amounts and chemical instability of TAs challenge quantification. Here, diisopropyl phosphite coupled with chip two-dimensional (2D) liquid chromatography tandem triple-quadrupole mass spectrometry (LC-QQQ/MS) was developed to simultaneously determine TAs and associated metabolites. The results showed that the sensitivities of TAs increased up to 5520 times compared with those using nonderivatized LC-QQQ/MS. This sensitive method was utilized to investigate their alterations in hepatoma cells after treatment with sorafenib. The significantly altered TAs and associated metabolites suggested that phenylalanine and tyrosine metabolic pathways were related to sorafenib treatment in Hep3B cells. This sensitive method has great potential to elucidate the mechanism and diagnose diseases considering that an increasing number of physiological functions of TAs have been discovered in recent decades.

Structure bionic topology design method based on biological unit cell.

The mechanical structure topology design based on substructure always adopts the traditional substructure design method, which often comes from the experience and is limited by the inherent or stereotyped design thinking. A substructure design method based on biological unit cell (UC) is proposed, which draws inspiration from the biological efficient load-bearing topology structure. Especially, the thought of the formalized problem-solving of extension matter-element is introduced. Through the matter-element definition of UC substructure, the process model for the structure bionic topology design method based on biological UC is formed, which avoids the random or wild mental stimulation of the structure topology design method based on traditional substructure. In particular, in this proposed method, aiming at the problem about how to achieve the integration of high-efficiency load-bearing advantage of different organisms, furthermore, a biological UC hybridization method based on the principle of inventive problem solving theory (TRIZ) is proposed. The typical case is used to illustrate the process of this method in detail. The results from simulations and experiments both show that: the load-bearing capacity of structure design based on biology UC is improved than the initial design; on this basis, the load-bearing capacity of structure design is improved further through UC hybridization. All these show the feasibility and correctness of the proposed method.

Lipolysis and gestational diabetes mellitus onset: a case-cohort genome-wide association study in Chinese.

BACKGROUND: Genetic knowledge of gestational diabetes mellitus (GDM) in Chinese women is quite limited. This study aimed to identify the risk factors and mechanism of GDM at the genetic level in a Chinese population. METHODS: We conducted a genome-wide association study (GWAS) based on single nucleotide polymorphism (SNP) array genotyping (ASA-CHIA Bead chip, Illumina) and a case-cohort study design. Variants including SNPs, copy number variants (CNVs), and insertions-deletions (InDels) were called from genotyping data. A total of 2232 pregnant women were enrolled in their first/second trimester between February 2018 and December 2020 from Anqing Municipal Hospital in Anhui Province, China. The GWAS included 193 GDM patients and 819 subjects without a diabetes diagnosis, and risk ratios (RRs) and their 95% confidence intervals (CIs) were estimated by a regression-based method conditional on the population structure. The calling and quality control of genotyping data were performed following published guidelines. CNVs were merged into CNV regions (CNVR) to simplify analyses. To interpret the GWAS results, gene mapping and overexpression analyses (ORAs) were further performed to prioritize the candidate genes and related biological mechanisms. RESULTS: We identified 14 CNVRs (false discovery rate corrected P values < 0.05) and two suggestively significant SNPs (P value < 0.00001) associated with GDM, and a total of 19 candidate genes were mapped. Ten genes were significantly enriched in gene sets related to lipase (triglyceride lipase and lipoprotein lipase) activity (LIPF, LIPK, LIPN, and LIPJ genes), oxidoreductase activity (TPH1 and TPH2 genes), and cellular components beta-catenin destruction complex (APC and GSK3B genes), Wnt signalosome (APC and GSK3B genes), and lateral element in the Gene Ontology resource (BRCA1 and SYCP2 genes) by two ORA methods (adjusted P values < 0.05). CONCLUSIONS: Genes related to lipolysis, redox reaction, and proliferation of islet ß-cells are associated with GDM in Chinese women. Energy metabolism, particularly lipolysis, may play an important role in GDM aetiology and pathology, which needs further molecular studies to verify.

Simple changes to the reporting environment produce a large reduction in the frequency of interruptions to the reporting radiologist: an observational study.

BACKGROUND: Interruptions are a cause of discrepancy, errors, and potential safety incidents in radiology. The sources of radiological error are multifactorial and strategies to reduce error should include measures to reduce interruptions. PURPOSE: To evaluate the effect of simple changes in the reporting environment on the frequency of interruptions to the reporting radiologist of a hospital radiology department. MATERIAL AND METHODS: A prospective observational study was carried out. The number and type of potentially disruptive events (PDEs) to the radiologist reporting inpatient computed tomography (CT) scans were recorded during 20 separate 1-h observation periods during both pre- and post-intervention phases. The interventions were (i) relocation of the radiologist to a private, quiet room, and (ii) initial vetting of clinician enquiries via a separate duty radiologist. RESULTS: After the intervention there was an 82% reduction in the number of frank interruptions (PDEs that require the radiologist to abandon the reporting task) from a median 6 events per hour to 1 (95% confidence interval [CI] = 4-6; P < 0.00001). The overall number of PDEs was reduced by 56% from a median 11 events per hour to 5 (95% CI = 4.5-11: P < 0.00001). CONCLUSION: Relocation of inpatient CT reporting to a private, quiet room, coupled with vetting of clinician enquiries via the duty radiologist, resulted in a large reduction in the frequency of interruptions, a frequently cited avoidable source of radiological error.

Curative effect of percutaneous screw-rod system combined with sacroiliac screw internal fixation in the treatment of types II-IV fragility fracture of the pelvis / 中华创伤杂志

Objective:To compare the effect of percutaneous screw-rod system combined with sacroiliac screw internal fixation and non-operation of type II-IV fragility fracture of the pelvis (FFP).Methods:A retrospective multicentral cohort study was performed to analyze the clinical data of 74 patients with FFP treated in Jiangjin Central Hospital of Chongqing and Hechuan People′s Hospital of Chongqing from January 2017 to June 2021, including 23 males and 51 females, aged 62-95 years [(79.3±7.3)years]. A total of 41 patients received non-surgical treatment (non-operation group). and 33 patients received percutaneous screw-rod system combined with sacroiliac screw internal fixation (operation group). The time to get out of bed, visual analog scale (VAS) and Majeed score on admission and at 1, 3, 6, 12 months after treatment, fracture healing time and complications were evaluated in the two groups.Results:Except for 9 patients who died at 3-9 months after treatment, the remaining patients were followed up for 12-24 months [(13.5±3.2)months]. The time to get out of bed was (11.4±2.8)days in operation group and was (67.4±4.4)days in non-operation group ( P<0.01). The VAS and Majeed score at 1, 3, 6 and 12 months after treatment were significantly improved in both groups compared with those on admission (all P<0.05). There was no significant difference in VAS and Majeed score between the two groups on admission (all P>0.05). The VAS was (3.2±0.7)points in operation group compared to (4.2±0.8)points in non-operation group at 1 month after treatment, and was (1.8±0.5)points in operation group compared to (2.9±0.7)points in non-operation group at 3 months after treatment (all P<0.01). The Majeed score was (56.0±2.4)points in operation group compared to (40.4±2.7)points in non-operation group at 1 month after treatment; the score was (77.3±2.6)points in operation group compared to (57.7±4.2)points in non-operation group at 3 months after treatment; the score was (86.5±1.8)points in operation group compared to (79.6±2.8)points in non-operation group at 6 months after treatment (all P<0.01). In contrast, the two groups had no statistically significant difference in VAS at 6 months and 12 months after treatment and Majeed score at 12 months after treatment (all P>0.05). There was no statistically significant difference in the fracture healing time between the two groups ( P>0.05). There was no statistically significant difference in the incidence of complications related to fixation methods between the two groups ( P>0.05). The incidence of bed-related complications was 24.2% (8/33) in operation group and was 51.2% (21/41) in non-operation group ( P<0.05). The 1-year fatality rate was 3.0% (1/33) in operation group and 19.5% (8/41) in non-operation group ( P<0.05). Conclusion:Compared with non-operative treatment, percutaneous screw-rod system combined with sacroiliac screw internal fixation in the treatment of type II-IV FFP can allow early off-bed movement, effectively relieve pain, improve quality of life of the patients, and reduce complication rate.

Application of 3D digital modeling combined with 3D printed model in classroom theoretical teaching of orthopedics / 中华医学教育探索杂志

Objective:To investigate the application effect of 3D digital modeling combined with 3D printed model in assisting the classroom theoretical teaching of orthopedics in five-year undergraduate students majoring in clinical medicine.Methods:In May 2022, 33 five-year undergraduate students majoring in clinical medicine in the class of 2018 in Southwest Medical University were selected and divided into experimental group with 17 students and control group with 16 students according to the odd or even student number. The students in the experimental group were taught by traditional PPT+3D digital modeling combined with 3D printed model, and those in the control group were taught by the traditional PPT teaching method. The teaching effect was evaluated by theoretical examination and a questionnaire survey on the degree of satisfaction with teaching. SPSS 25.0 was used to perform the t-test, the Mann-Whitney U test, the rank sum test, and the chi-square test. Results:The experimental group had a significantly higher score of theoretical examination than the control group (86.24±4.16 vs. 82.50±6.06). The questionnaire survey on the degree of satisfaction with teaching showed that compared with the control group, the experimental group had a significantly higher degree of satisfaction with the understanding and learning of orthopedic diseases [3 (2, 3) vs. 2 (2, 2), P < 0.05], the improvement in learning interest [2 (2, 3) vs. 2 (1, 2), P < 0.05], classroom innovation [3 (3, 3) vs. 2 (1.5, 2), P < 0.05], and overall classroom teaching [3 (2, 3) vs. 2 (2, 2), P < 0.05]. Conclusion:In assisting the classroom theoretical teaching of orthopedics in undergraduate students majoring in clinical medicine, 3D digital modeling combined with 3D printed model can provide concrete 3D models, reduce the difficulties in learning, improve the awareness of orthopedic diseases, strengthen learning interest, and increase the degree of satisfaction with teaching and academic scores.

Ultrasensitive quantification of trace amines based on N-phosphorylation labeling chip 2D LC-QQQ/MS / 药物分析学报

Trace amines(TAs)are metabolically related to catecholamine and associated with cancer and neuro-logical disorders.Comprehensive measurement of TAs is essential for understanding pathological pro-cesses and providing proper drug intervention.However,the trace amounts and chemical instability of TAs challenge quantification.Here,diisopropyl phosphite coupled with chip two-dimensional(2D)liquid chromatography tandem triple-quadrupole mass spectrometry(LC-QQQ/MS)was developed to simul-taneously determine TAs and associated metabolites.The results showed that the sensitivities of TAs increased up to 5520 times compared with those using nonderivatized LC-QQQ/MS.This sensitive method was utilized to investigate their alterations in hepatoma cells after treatment with sorafenib.The significantly altered TAs and associated metabolites suggested that phenylalanine and tyrosine metabolic pathways were related to sorafenib treatment in Hep3B cells.This sensitive method has great potential to elucidate the mechanism and diagnose diseases considering that an increasing number of physiological functions of TAs have been discovered in recent decades.

The effects of natural polysaccharide supramolecular hydrogel on bacteriostatic activity and biofilm clearance of berberine / 药学学报

Taking berberine (BBR) as an example, to study whether the supramolecular hydrogel formed by berberine and lotus root starch (Nelumbo nucifera Gaertn; LRS), a natural polysaccharide, affects the inhibition to Staphylococcus aureus and the ability of biofilm clearance. The chemical structure and rheological properties of BBR@LRS gel were characterized by infrared spectroscopy and rheometer. The in vitro release of supramolecular hydrogel was observed at pH = 1.2 and pH = 7.4. Broth dilution method and biofilm clearence experiment were used to observe the bacteriostasis and biofilm clearance respectively. Cytotoxicity test and in vitro hemolysis test were used to evaluate the biosafety preliminarily. The results showed that the LRS polysaccharide hydrogel could encapsulate BBR, and there was an interaction between them. The BBR@LRS gel had good rheological properties and biosafety, and played a role in solubility enhancement and slow release of BBR, which was stronger than BBR in inhibiting the growth of Staphylococcus aureus and clearing biofilm. This study provides reference for the effect of natural polysaccharide supramolecular hydrogels on biological functions of active components of traditional Chinese medicine.

Research Progress in Noninvasive Early Diagnosis of Hepatocellular Carcinoma / 肿瘤防治研究

Liver cancer is a common tumor that seriously threatens human life and health. Given that the early onset of liver cancer is insidious and lacks specific symptoms, hence it is difficult to screen through routine examination. Thus, clinical diagnosis of liver cancer is mostly in the advanced stage. However, advanced liver cancer has few treatment options, poor prognosis and high relapse rate, thereby causing a high mortality rate. Therefore, early diagnosis of liver cancer is particularly important. Currently, non-invasive screening of liver cancer widely used in clinical setups lacks sufficient sensitivity and specificity, hence, a more reliable diagnostic method needs to be found urgently. This article reviews the research progress of noninvasive early diagnosis of liver cancer to provide a reference for raising the early diagnosis rate of liver cancer.

Research and exploration of salivary biological markers for hepatitis B-related hepatocellular carcinoma / 中华肝脏病杂志

Objective: To study using isotope-labeled relative and absolute quantitative proteomics methodologies to screen for salivary biological markers as a simple, non-invasive tool for identifying hepatitis B-related HCC at an early stage. Methods: Saliva samples were collected to extract salivary proteins. Isotope-labeled relative and absolute quantitative proteomics were used to analyze the differentially expressed proteins between the hepatocellular carcinoma (HCC) and non-HCC groups. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were used to verify differential proteins and identify markers in liver cancer tissues and saliva. Statistical analysis was used to analyze the diagnostic efficiency of salivary biomarkers. Results: 152 differentially expressed salivary proteins were screened out between the HCC and non-HCC groups. Western blot, immunohistochemistry, and enzyme-linked immunosorbent assays validated that the expressions of α-1-acid glycoprotein 1 (ORM1) and alpha-fetoprotein (AFP) were significantly increased in HCC (P < 0.05). There was a significant correlation between salivary AFP and serum AFP (P < 0.05). HCC was diagnosed when salivary α-1-acid glycoprotein 1 combined with AFP. The area under the receiver operating characteristic curve was 0.8726 (95% confidence interval: 0.8104 ~ 0.9347), the sensitivity was 78.3%, and the specificity was 88%. Conclusion: Salivary AFP and α-1-acid glycoprotein 1 can serve as potential biomarkers for hepatitis B-related hepatocellular carcinoma.

Chrysin alleviates cerebral ischemia-reperfusion injury by inhibiting ferroptosis in rats / 中国中药杂志

The purpose of this study is to investigate whether chrysin reduces cerebral ischemia-reperfusion injury(CIRI) by inhi-biting ferroptosis in rats. Male SD rats were randomly divided into a sham group, a model group, high-, medium-, and low-dose chrysin groups(200, 100, and 50 mg·kg~(-1)), and a positive drug group(Ginaton, 21.6 mg·kg~(-1)). The CIRI model was induced in rats by transient middle cerebral artery occlusion(tMCAO). The indexes were evaluated and the samples were taken 24 h after the operation. The neurological deficit score was used to detect neurological function. The 2,3,5-triphenyl tetrazolium chloride(TTC) staining was used to detect the cerebral infarction area. Hematoxylin-eosin(HE) staining and Nissl staining were used to observe the morphological structure of brain tissues. Prussian blue staining was used to observe the iron accumulation in the brain. Total iron, lipid pero-xide, and malondialdehyde in serum and brain tissues were detected by biochemical reagents. Real-time quantitative polymerase chain reaction(RT-qPCR), immunohistochemistry, and Western blot were used to detect mRNA and protein expression of solute carrier fa-mily 7 member 11(SLC7A11), transferrin receptor 1(TFR1), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long chain family member 4(ACSL4), and prostaglandin-endoperoxide synthase 2(PTGS2) in brain tissues. Compared with the model group, the groups with drug intervention showed restored neurological function, decreased cerebral infarction rate, and alleviated pathological changes. The low-dose chrysin group was selected as the optimal dosing group. Compared with the model group, the chrysin groups showed reduced content of total iron, lipid peroxide, and malondialdehyde in brain tissues and serum, increased mRNA and protein expression levels of SLC7A11 and GPX4, and decreased mRNA and protein expression levels of TFR1, PTGS2, and ACSL4. Chrysin may regulate iron metabolism via regulating the related targets of ferroptosis and inhibit neuronal ferroptosis induced by CIRI.

Effect of Erjing Pills on alleviating neuroinflammation of AD rats based on TLR4/NF-κB/NLRP3 pathway and its mechanism / 中国中药杂志

This paper aimed to study the effect of Erjing Pills on the improvement of neuroinflammation of rats with Alzheimer's di-sease(AD) induced by the combination of D-galactose and Aβ_(25-35) and its mechanism. SD rats were randomly divided into a sham group, a model control group, a positive drug group(donepezil, 1 mg·kg~(-1)), an Erjing Pills high-dose group(9.0 g·kg~(-1)), and an Erjing Pills low-dose group(4.5 g·kg~(-1)), with 14 rats each group. To establish the rat model of AD, Erjing Pills were intragastrically administrated to rats for 5 weeks after 2 weeks of D-galactose injection. D-galactose was intraperitoneally injected into rats for 3 weeks, and then Aβ_(25-35) was injected into the bilateral hippocampus. The new object recognition test was used to evaluate the learning and memory ability of rats after 4 weeks of intragastric administration. Tissues were acquired 24 h after the last administration. The immunofluorescence method was used to detect the activation of microglia in the brain tissue of rats. The positive expressions of Aβ_(1-42) and phosphory protein Tau~(404)(p-Tau~(404)) in the CA1 area of the hippocampus were detected by immunohistochemistry. The levels of inflammatory factors interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) in the brain tissue were determined by enzyme-linked immunosorbent assay(ELISA). Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)/nucleotide-binding oligomerization domain-like receptors 3(NLRP3) pathway-associated proteins in the brain tissue were determined by Western blot. The results showed that as compared with the sham group, the new object recognition index of rats in the model control group decreased significantly, the deposition of Aβ_(1-42) and p-Tau~(404) positive protein in the hippocampus increased significantly, and the levels of microglia activation increased significantly in the dentate gyrus. The levels of IL-1β, TNF-α, and IL-6 in the hippocampus of the model control group increased significantly, and the expression levels of TLR4, p-NF-κB p65/NF-κB p65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus increased significantly. Compared with the model control group, the Erjing Pill groups enhanced the new object recognition index of rats, decreased the deposition of Aβ_(1-42) and the expression of p-Tau~(404) positive protein in the hippocampus, inhibited the activation of microglia in the dentate gyrus, reduced the levels of inflammatory factors IL-1β, TNF-α, and IL-6 in the hippocampus, and down-regulated the expression levels of TLR4, p-NF-κB P65/NF-κB P65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus. In conclusion, Erjing Pills can improve the learning and memory ability of the rat model of AD presumably by improving the activation of microglia, reducing the expression levels of neuroinflammatory factors IL-1β, TNF-α, and IL-6, inhibiting the TLR4/NF-κB/NLRP3 neuroinflammation pathway, and decreasing hippocampal deposition of Aβ and expression of p-Tau, thereby restoring the hippocampal morphological structure.

Research Progress on Epigenetics in Endometriosis / 中国医学科学院学报

Epigenetics refers to heritable changes in gene expression and function without alterations in gene sequences,including DNA methylation,histone modification,and non-coding RNAs.Endometriosis is a benign gynecological disease that affects the fertility and health of reproductive-age women,the etiology of which remains unclear.The recent studies have demonstrated that epigenetics plays a key role in the occurrence and development of endometriosis.This article reviews the research progress in the regulatory mechanism and application of epigenetics in endometriosis.

Application characteristics of Qugu (CV 2) in ancient and modern literature / 中国针灸

To summarize and analyze the clinical application characteristics of Qugu (CV 2) in ancient and modern literature based on data mining technology. The Chinese Medical Code (the 5th edition) was taken as the retrieval source of ancient literature, while the CNKI, Wanfang, and VIP databases were taken as the retrieval source of modern literature. The indications of Qugu (CV 2) used alone or with compatible acupoints, compatible acupoints, acupuncture-moxibustion manipulation, etc., were systematically sorted out. As a result, a total of 140 articles of ancient literature were included. The common indications of Qugu (CV 2) used alone were urinary retention, profuse vaginal discharge and hernia. The common indications of Qugu (CV 2) used with compatible acupoints were profuse vaginal discharge, stranguria and hernia. Sixty-four acupoints were concurrently used with Qugu (CV 2), Qugu (CV 2) was mainly compatible with acupoints of conception vessel, bladder meridian and liver meridian, and the high-frequency acupoints included Zhongji (CV 3), Guanyuan (CV 4) and Sanyinjiao (SP 6); five-shu points were the most used special acupoints, and moxibustion therapy was often used. A total of 73 modern articles were included. The common indications of Qugu (CV 2) used alone were urinary retention, erectile dysfunction and chronic prostatitis; the common indications of Qugu (CV 2) used with compatible scupoints were urinary retention, erectile dysfunction and prostatic hyperplasia. Thirty-six acupoints were concurrently used with Qugu (CV 2), Qugu (CV 2) was mainly compatible with acupoints of conception vessel, kidney meridian and spleen meridian, and the high-frequency acupoints included Zhongji (CV 3), Guanyuan (CV 4) and Zusanli (ST 36); front-mu points were the most used special acupoints, and acupuncture therapy was often used. Qugu (CV 2) treats a wide range of diseases in ancient times, the distant treatment effectiveness of acupoints is emphasized; and it mainly treats local diseases in modern times, the nearby treatment effectiveness of acupoints is emphasized.

Serological biomarkers in autoimmune GFAP astrocytopathy.

Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a newly defined meningoencephalomyelitis. The pathogenesis of GFAP-A is not well understood. The present study measured the expression levels of 200 serological cytokines in GFAP-A patients, NMOSD patients and healthy controls (HCs). The correlations between serum cytokine levels and clinical information in GFAP-A patients were analyzed. A total of 147 serological proteins were differentially expressed in GFAP-A patients compared to HCs, and 33 of these proteins were not observed in NMOSD patients. Serum levels of EG-VEGF negatively correlated with GFAP antibody titers, MIP-3 alpha positively correlated with clinical severity in GFAP-A patients, and LIGHT positively correlated with WBC counts and protein levels in the CSF of GFAP-A patients. These results suggest that GFAP and AQP4 astrocytopathy share some common pathology related to TNF signaling. Serum MIP 3 alpha may be a biomarker to assess clinical severity and a potential target for therapy of autoimmune GFAP astrocytopathy.

Phenylalanine impairs insulin signaling and inhibits glucose uptake through modification of IRß.

Whether amino acids act on cellular insulin signaling remains unclear, given that increased circulating amino acid levels are associated with the onset of type 2 diabetes (T2D). Here, we report that phenylalanine modifies insulin receptor beta (IRß) and inactivates insulin signaling and glucose uptake. Mice fed phenylalanine-rich chow or phenylalanine-producing aspartame or overexpressing human phenylalanyl-tRNA synthetase (hFARS) develop insulin resistance and T2D symptoms. Mechanistically, FARS phenylalanylate lysine 1057/1079 of IRß (F-K1057/1079), inactivating IRß and preventing insulin from promoting glucose uptake by cells. SIRT1 reverse F-K1057/1079 and counteract the insulin-inactivating effects of hFARS and phenylalanine. F-K1057/1079 and SIRT1 levels in white blood cells from T2D patients are positively and negatively correlated with T2D onset, respectively. Blocking F-K1057/1079 with phenylalaninol sensitizes insulin signaling and relieves T2D symptoms in hFARS-transgenic and db/db mice. These findings shed light on the activation of insulin signaling and T2D progression through inhibition of phenylalanylation.

Targeting mTORC2/HDAC3 Inhibits Stemness of Liver Cancer Cells Against Glutamine Starvation.

Cancer cells are addicted to glutamine. However, cancer cells often suffer from glutamine starvation, which largely results from the fast growth of cancer cells and the insufficient vascularization in the interior of cancer tissues. Herein, based on clinical samples, patient-derived cells (PDCs), and cell lines, it is found that liver cancer cells display stem-like characteristics upon glutamine shortage due to maintaining the stemness of tumor initiating cells (TICs) and even promoting transformation of non-TICs into stem-like cells by glutamine starvation. Increased expression of glutamine synthetase (GS) is essential for maintaining and promoting stem-like characteristics of liver cancer cells during glutamine starvation. Mechanistically, glutamine starvation activates Rictor/mTORC2 to induce HDAC3-mediated deacetylation and stabilization of GS. Rictor is significantly correlated with the expression of GS and stem marker OCT4 at tumor site, and closely correlates with poor prognosis of hepatocellular carcinomas. Inhibiting components of mTORC2-HDAC3-GS axis decrease TICs and promote xenografts regression upon glutamine-starvation therapy. Collectively, the data provides novel insights into the role of Rictor/mTORC2-HDAC3 in reprogramming glutamine metabolism to sustain stemness of cancer cells. Targeting Rictor/HDAC3 may enhance the efficacy of glutamine-starvation therapy and limit the rapid growth and malignant progression of tumors.

Application Progress of Massively Parallel Sequencing Technology in STR Genetic Marker Detection / 法医学杂志

In recent years, more and more forensic genetics laboratories have begun to apply massively parallel sequencing (MPS) technology, that is, next-generation sequencing (NGS) technology, to detect common forensic genetic markers, including short tandem repeat (STR), single nucleotide polymorphism (SNP), the control region or whole genome of mitochondrial DNA (mtDNA), as well as messenger RNA (mRNA), etc., for forensic practice, such as individual identification, kinship analysis, ancestry inference and body fluid identification. As the most widely used genetic marker in forensic genetics, STR is currently mainly detected by capillary electrophoresis (CE) platform. Compared with CE platform, MPS technology has the advantages of simultaneous detection of a large number of genetic markers, massively parallel detection of samples, the polymorphism of sequence detected by NGS makes STR have the advantages of higher resolution and system efficiency. However, MPS technology is expensive, there is no uniform standard so far, and there are problems such as how to integrate MPS-STR data with the existing CE-STR database. This review summarizes the current status of the application of MPS technology in the detection of STR genetic markers in forensic genetics, puts forward the main problems that need to be solved urgently, and prospects the application prospect of this technology in forensic genetics.