Dual-responsive supramolecular photodynamic nanomedicine with activatable immunomodulation for enhanced antitumor therapy

A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8+ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.

Improving mechanism of Buyang huanwu decoction on idiopathic pulmonary fibrosis model rats / 中国药房

OBJECTIVE To study the improving mechanism of Buyang huanwu decoction （BYHW） on idiopathic pulmonary fibrosis （IPF） model rats. METHODS Ninety-six Wistar rats were randomly divided into blank group， model group， positive control group， and BYHW low-dose， middle-dose and high-dose groups， with 16 rats in each group. Except for the blank group， the IPF model was induced in other groups by intratracheal instillation of bleomycin （5 mg/kg）. Starting from the day of modeling， the blank group and model group were given normal saline （10 mL/kg） intragastrically， while the rats in the positive control group were given dexamethasone solution （5 mg/kg） intragastrically， BYHW low-dose， middle-dose and high-dose groups were treated with BYHW （2.5， 5， 10 g/kg， by crude drug） intragastrically， once a day， for 28 consecutive days. The body mass of rats in each group was measured on days 0， 7， 14， 21 and 28 after modeling. The number of adherent white blood cells in pulmonary veins was observed by a dynamic visualization system. The contents of TNF-α and IL-6 in serum and TNF-α， IL-6， HYP and TGF-β1 in lung tissue were detected； the protein expression of ZO-1 was also detected. The pathomorphological changes in lung tissue were observed. RESULTS Compared with the model group， the body weight of rats all increased significantly in BYHW high-dose and middle-dose groups， positive control group， while the number of adherent white blood cells in pulmonary veins was decreased significantly； the contents of TNF-α （except for serum in BYHW middle-dose group） and IL-6 in serum and lung tissue， the contents of HYP and TGF-β1 in lung tissue were decreased significantly， while the protein expression of ZO-1 in the lung tissue was increased significantly （P＜0.05 or P＜0.01）. The pathological changes of lung tissue were improved to varying degrees. CONCLUSIONS BYHW may play anti-pulmonary fibrosis role by improving leukocyte adhesion， anti-inflammatory， anti-fibrosis， and other aspects of pulmonary microcirculation.

Mechanism of nitidine chloride inducing apoptosis of cervical cancer cells by inhibiting p53 ubiquitination degradation / 中国药理学通报

Aim To investigate the effect of nitidine chloride (NC) on the apoptosis of cervical cancer cells and its mechanism. Methods Cervical cancer cell lines HeLa and SiHa were selected as subjects. The cytotoxicity of NC and its inhibitory effect on cell growth were detected by CCK-8 assay and clone formation assay. The effect of NC on the apoptosis of cervical cancer cells was detected by TUNEL assay, and the expression of apoptosis-related proteins was detected by Western blot. The effects of NC on the interaction between p53 and E6AP protein, the level of p53 ubiquitination modification and the stability of p53 protein in cervical cancer cells were analyzed by immunoprecipi-tation assay, ubiquitination assay and Western blot assay. Results NC could significantly inhibit the proliferation and induce apoptosis of cervical cancer cells. NC could inhibit the interaction between tumor suppressor protein p53 and E6AP in cervical cancer cells, reduce the level of p53 ubiquitination modification, delay the degradation of p53 and increase the expression level of p53 protein. Conclusions NC can inhibit the ubiquitination and degradation of p53, improve the expression level of p53 protein, restore its tumor suppressor function, and thus play an anti -cervical cancer role.

Advances in traditional Chinese medicine treatment of non-alcoholic fatty liver disease via farnesoid X receptor / 中国中药杂志

Non-alcoholic fatty liver disease(NAFLD) is a chronic metabolic condition with rapidly increasing incidence, becoming a public health issue of worldwide concern. Studies have shown that farnesoid X receptor(FXR)-based modulation of downstream targets can improve liver function and metabolic status in the patients with NAFLD and may be a potential drug target for treating this di-sease. Great progress has been achieved in the development of drugs targeting FXR for the treatment of NAFLD. A number of studies have explored the traditional Chinese medicine and their active ingredients for the treatment of NAFLD via FXR considering the high safety and efficacy and mild side effects. This paper systematically describes the mechanism of traditional Chinese medicines in the treatment of NAFLD via FXR and the downstream targets, aiming to provide precise targets for the drug development and clinical treatment of NAFLD.

Activation of Cannabinoid Receptor 1 in GABAergic Neurons in the Rostral Anterior Insular Cortex Contributes to the Analgesia Following Common Peroneal Nerve Ligation / 神经科学通报·英文版

The rostral agranular insular cortex (RAIC) has been associated with pain modulation. Although the endogenous cannabinoid system (eCB) has been shown to regulate chronic pain, the roles of eCBs in the RAIC remain elusive under the neuropathic pain state. Neuropathic pain was induced in C57BL/6 mice by common peroneal nerve (CPN) ligation. The roles of the eCB were tested in the RAIC of ligated CPN C57BL/6J mice, glutamatergic, or GABAergic neuron cannabinoid receptor 1 (CB1R) knockdown mice with the whole-cell patch-clamp and pain behavioral methods. The E/I ratio (amplitude ratio between mEPSCs and mIPSCs) was significantly increased in layer V pyramidal neurons of the RAIC in CPN-ligated mice. Depolarization-induced suppression of inhibition but not depolarization-induced suppression of excitation in RAIC layer V pyramidal neurons were significantly increased in CPN-ligated mice. The analgesic effect of ACEA (a CB1R agonist) was alleviated along with bilateral dorsolateral funiculus lesions, with the administration of AM251 (a CB1R antagonist), and in CB1R knockdown mice in GABAergic neurons, but not glutamatergic neurons of the RAIC. Our results suggest that CB1R activation reinforces the function of the descending pain inhibitory pathway via reducing the inhibition of glutamatergic layer V neurons by GABAergic neurons in the RAIC to induce an analgesic effect in neuropathic pain.

Study on the correlation between ceramic and chronic obstructive pulmonary disease in Foshan City / 中华劳动卫生职业病杂志

Objective: To study the correlation between ceramic and chronic obstructive pulmonary disease (COPD), and explore its related risk factors. Methods: In January 2021, five representative ceramic enterprises were selected from Chancheng District, Nanhai District, Gaoming District and Sanshui District of Foshan City. The ceramic workers who came to Chancheng Hospital of Foshan First People's Hospital for physical examination from January to October 2021 were selected as the research objects, and 525 people were included. Conduct questionnaire survey and pulmonary function test. Logistic regresion was performed to analyze the influencing facters of COPD among ceramic workers. Results: The subjects were (38.51±1.25) years old, 328 males and 197 females, and the detection rate of COPD was 9.52% (50/525). The incidence of respiratory symptoms such as dyspnea, chronic cough, wheezing and chest tightness, the detection rates of abnormal lung age, abnormal lung function and COPD in males were higher than those in females (P<0.05). The logistic regression analysis showed that male, age, working years, smoking status and family history of COPD were the risk factors for COPD among ceramic workers (P<0.05) . Conclusion: The ceramic workers are the high risk population of COPD. We should do a good job in health education, and do a regular physical examination to find the changes of lung function in time, and prevent the occurrence of COPD as soon as possible.

Tumor cell-based glycolytic metabolism and single-cell sequencing of urinary exfoliated cells for the diagnosis and molecular profiling of urothelial carcinoma / 中华病理学杂志

Objective: To explore the diagnostic values of HK2 testing and single-cell sequencing in the urothelial carcinoma (UC). Methods: The qualified urine specimens of 265 suspected UC patients or postoperative patients from the Cancer Hospital of Chinese Academy of Medical Sciences, Beijing, China were collected. Both exfoliative cytology and HK2 testing were performed on clinically suspected UC or postoperative patients. The performance of diagnostic cytology and HK2, including consistency, sensitivity, specificity, positive predictive value and negative predictive value, was evaluated based on histopathological, clinical and imaging diagnosis. Isolated HK2 metabolically abnormal cells were subject to single-cell sequencing to verify the reliability of HK2 detection performance and to explore the molecular characteristics of UC. Results: The concordance rate of HK2 testing and cytology for detecting UC was 90.3% (102/113, Kappa=0.604). Compared with cytology, the sensitivity of HK2 was significantly higher (85.2% versus 75.6%, P=0.024). The detection sensitivity of combined HK2 testing and cytology was increased to 91.1%. HK2 testing was significantly more sensitive than cytology for diagnosing UC in the upper urinary tract (81.8% versus 65.5%, P=0.022). It was also more sensitive than cytology for diagnosing early-stage UC (82.6% versus 69.5%, P=0.375) and low-grade UC (69.6% versus 47.8%, P=0.125). Single-cell sequencing of the ten patients, whose samples were positive for HK2, demonstrated highly concordant copy number variations (CNVs) in tumor cells from the same UC patient, with heterogeneity in CNV profiles among different patients. Deletion of chromosome 8p was found in 3 of the 4 urine samples of renal pelvis UC. The 2 patients with benign lesions had no CNVs in all sequenced cells. Conclusions: The test for abnormal urinary glycolytic HK2 metabolism can assist urine cytology to improve the sensitivity of UC diagnosis, and it provides a novel and reliable approach for early detection of upper urinary tract UC and lower grade UC. Meanwhile, this study has preliminarily revealed the feasibility of single-cell sequencing in urinary samples, which is expected to improve the diagnostic specificity of HK2 testing.

Gene Mutation Types of Thalassemia in Chongzuo Childbearing-age Population of Guangxi Zhuang Autonomous Region of China / 中国实验血液学杂志

OBJECTIVE@#To investigate the gene mutation and genotype distribution of thalassemia in the population of childbearing age in Chongzuo area of Guangxi.@*METHODS@#Six α-thalassemia and 17 β-thalassemia gene mutations common in Chinese were detected by gap-polymerase chain reaction (gap-PCR) combined with agarose gel eletrophoresis and reserve dot bolt hybridization in 29 266 cases of child-bearing age suspected of thalassemia.@*RESULTS@#A total of 19 128 (65.36%) cases were identified with thalassemia. The detection rate of α-thalassemia, β-thalassemia and α-combining β-thalassemia was 45.25% (13 242/29 266), 15.47% (4 526/29 266) and 4.65% (1 360/29 266), respectively. A total carrying rate of 8 kinds of α-thalassemia gene mutations was 26.74% (15 649/58 532), including 12.51% for --SEA, followed by 5.70% for -α3.7, and 0.24% for --Thai. Among 32 α-thalassemia genotypes, the most common five were --SEA/αα, -α3.7/αα, αCSα/αα, -α4.2/αα and αWSα/αα, accounting for 47.27%, 18.31%, 8.56%, 8.52% and 7.91%, respectively, as well as 0.97% for --Thai/αα. A total carrying rate of 13 kinds of β-thalassemia gene mutations was 10.07% (5 897/58 532), including 3.63% for CD41-42, followed by 2.55% for CD17, and 0.003% for -50 (G>A). Among 17 β-thalassemia genotypes, the most common six were CD41-42/N, CD17/N, CD71-72/N, CD26/N, 28/N and IVSI-1/N, accounting for 36.15%, 25.81%, 9.43%, 8.18%, 8.09% and 7.75%. The homozygous genotype CD26/CD26 [hemoglobin (Hb): 121 g/L] and -28/-28 (Hb: 56 g/L) were respectively detected in one case, and double heterozygous genotype were detected in 5 cases, including 3 cases of CD41-42/CD26 (Hb: 41 g/L, 51 g/L, 63 g/L, respectively), 1 case of -28/IVSI-1 (Hb: 53 g/L), and 1 case of CD71-72/CD26 (Hb: 89 g/L), in which patients with moderate or severe anemia had a history of blood transfusion. Among 104 α-combining β-thalassemia genotypes, the most common were --SEA/αα, -α3.7/αα combining CD41-42/N and --SEA/αα combining CD17/N, accounting for 12.13%, 9.63% and 9.26%, respectively. In addition, 1 case of --SEA/-α3.7 combining -28/IVSI-1 (Hb: 83 g/L) and 1 case of -α3.7/αα combining CD41-42/ CD41-42 (Hb: 110 g/L) were detected without history of blood transfusion, while 1 case of αWSα/αα combining CD41-42/CD17 (Hb: 79 g/L) and 1 case of --SEA/αα combining CD17/-28 (Hb: 46 g/L) were detected with history.@*CONCLUSIONS@#The detection rate of thalassemia genes is high and the mutations are diverse in the population of childbearing age in Chongzuo area of Guangxi. The common deletion genotype is --SEA/αα in α-thalassemia and CD41-42/N in β-thalassemia, and deletion genotype --Thai is not rare. There is a certain incidence of intermediate and severe β-thalassemia, and most patients require transfusion therapy. The results are beneficial for genetic consultation and intervention of thalassemia.

Study of Danshen decoction on colon cancer based on network pharmacology and molecular docking / 中国药理学通报

Aim To explore the mechanism of Danshen decoction in the treatment of colon cancer using network pharmacology and molecular docking.Methods The active components and corresponding target proteins of Salvia miltiorrhiza, Santalum album and Amo-mum villosum in Danshen decoction were screened based on Traditional Chinese Medicine Systems Pharmacology database and analysis platform.The targets of colon cancer were searched by using Genecards database, and the common targets were selected.The network diagram of traditional Chinese medicine-active components-target-disease was constructed by using Cytoscape 3.7.0.The protein protein interaction network of common targets was constructed by using STRING database.The gene ontology(GO)and Kyoto Encyclopedia of Genes and Gnomes(KEGG)enrichment analysis were carried out based on R4.0.2.The important targets in the key pathways and the important active components in the network diagram of traditional Chinese medicine-active ingredients-target-disease network were selected for Surflex Dock.Results A total of 78 active components, 142 targets, 3 239 colon cancer targets, 105 overlapping targets and 69 corresponding active components were screened out.KEGG analysis showed that the key signaling pathway was PI3K/AKT.Luteolin and Tanshinone IIA with high correlation were selected to dock with protein kinase B(AKT1).Both active components had hydrogen bonding with AKT1.Conclusions Danshen decoction plays a positive role in colon cancer treatment.The mechanism may be related to the regulation of PI3K/AKT signaling pathway.

Plasma microfibrillar associated protein 5 level in patients with polycystic ovary syndrome / 中华内分泌代谢杂志

Objective:To assess plasma microfibrillar associated protein 5(MFAP5) level in patients with polycystic ovary syndrome(PCOS), and to explore its relationship with glucose and lipid metabolism as well as sex hormones.Methods:Fifty PCOS patients and 65 healthy female subjects were selected as PCOS group and control group, respectively. Clinical data and plasma MFAP5 levels between the two groups were compared.Results:The plasma MFAP5 level in PCOS group was significantly higher than that in control group( P<0.01), and the plasma MFAP5 level in PCOS overweight subgroup was higher than that in control subgroup( P<0.01). No difference was observed in plasma MFAP5 level between the two non-overweight subgroups( P>0.05). Correlation analysis showed that plasma MFAP5 level was positively correlated with waist circumference, low density lipoprotein-cholesterol, fasting insulin, homoeostasis model assessment of insulin resistance index(HOMA-IR), HbA 1C, testosterone, LH/FSH ratio, and leukocyte( P<0.05 or P<0.01). There was no significant correlation of MFAP5 with body weight, body mass index(BMI), hip circumference, waist hip ratio, high density lipoprotein-cholesterol(HDL-C), triglyceride, total cholesterol, and blood glucose( P>0.05). In PCOS group, plasma MFAP5 level was positively correlated with body weight, BMI, waist circumference, hip circumference, total cholesterol, and leukocyte( P<0.05 or P<0.01). There was no significant correlation of MFAP5 with waist hip ratio, HDL-C, triglyceride, blood glucose, fasting insulin, HOMA-IR, leukocyte, and sex hormones( P>0.05). Multivariate logistic regression analysis showed that MFAP5 was an independent risk factor for PCOS( P<0.05). Conclusion:Plasma MFAP5 level is increased in PCOS patients and is closely related to BMI, waist circumference, hip circumference, and total cholesterol. Plasma MFAP5 is an independent risk factor for PCOS, which may be involved in the pathogenesis of PCOS.

The influence of HBsAg expression in liver tissue on the postoperative recurrence of HCC patients / 中华肿瘤杂志

Objective: To investigate the influence of HBsAg expression in peritumoral tissue of hepatocellular carcinoma (HCC) patients on their postoperative recurrence. Methods: The HCC patients treated in Shanghai Eastern Hepatobiliary Surgery Hospital from October 2009 to August 2010 were selected. The clinicopathological data and adjacent tissues of 718 patients were collected, and dextran polymer immunohistochemical staining was used to detect the expression of HBsAg in adjacent tissues. According to the expression of HBsAg in adjacent tissues, the tissues were divided into HBsAg positive group and HBsAg negative group. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for multivariate analysis. Results: Among the 718 patients in the whole group, 153 were HBsAg negative and 565 were HBsAg positive. There was a statistically significant difference in serum HBV DNA level between HBsAg-positive and HBsAg-negative patients (P<0.001). The number of patients with serum DNA≥2 000 IU/ml and<2 000 IU/ml in HBsAg negative group were 52 and 93, while the patients in HBsAg positive group were 325 and 205. The cumulative recurrence rates of all patients at 1, 3, and 5 years after surgery were 30.2%, 54.3%, and 62.7%, respectively. The expression of HBsAg was related to the recurrence (P=0.038). Multivariate analysis showed that γ-GT, PT, multiple tumors, tumor length, and portal vein invasion were independent risk factors for recurrence of HCC (P<0.05). In HBeAg-negative patients with low viral load (HBV DNA <2 000 IU/ml) and without cirrhosis, the recurrence rates of HBsAg-positive patients were 14.3% and 31.0% at 3 and 5 years, respectively, compared with HBsAg negative patients (all 0), the difference was statistically significant (P=0.021). Conclusion: The positive expression of HBsAg in peritumoral tissue increases the postoperative recurrence risk of HCC patients.

Adjuvant transcatheter arterial chemoembolization for curative hepatectomy of hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To explore the effect of transcatheter chemoembolization (TACE) on recurrence and survival time of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) following curative resection.Methods:Of 724 HBV-related HCC patients who underwent curative resection in the Third Affiliated Hospital of Naval Military Medical University from October 2009 to August 2010 were retrospectively analyzed. Patients who underwent resection only and no recurrence within 3 months after surgery were classified into control group, while those received adjuvant TACE were classified into intervention group. The patients were further divided into 4 sub-groups according to tumor size, tumor number and tumor thrombus which were defined as risk factors for recurrence. Tumor diameter ≤5 cm with low or high risk factors (tumor number ≥2 or presence tumor thrombus) were in group 1 and group 2 respectively, tumor diameter >5 cm with low or high risk factors for recurrence were in group 3 and group 4 respectively.Results:A total of 354 patients were classified in the control group and 370 patients were classified in the TACE group. Adjuvant TACE showed an overall survival benefit in patients with tumor diameter >5 cm and presenting high risk factors, the 1-, 3-, and 5-year cumulative survival rates were 90.1%, 67.6%, and 46.5%, respectively, for the lip-TACE group 83.3%, 52.4%, and 33.3%, respectively, for the control group ( P<0.05). Patients with the tumor diameter ≤5 cm, there was no significant difference in cumulative survival between the TACE group and the control group regardless of the risk level ( P>0.05). There was no significant difference in recurrence curve between TACE group and control group in each stratum. Conclusions:Adjuvant TACE had no preventive effect on recurrence, but TACE can prolong the survival time of HCC patients with high risk factors for recurrence.

Regulatory Mechanism of Traditional Chinese Medicine in Mitochondrial Quality Control for Diabetic Cardiomyopathy： A Review / 中国实验方剂学杂志

Diabetic cardiomyopathy occurs in diabetic patients and is different from hypertensive heart disease， coronary atherosclerotic heart disease， and other cardiac abnormalities. The main clinical symptoms are systolic and diastolic cardiac dysfunction， myocardial fibrosis， congestive heart failure， and angina pectoris. As one of the main complications of diabetes， its incidence and fatality rates have been on the rise year by year. However， modern medicine still fails to figure out its pathogenesis and no specific drug is available， which has seriously affected the survival and quality of life of patients. Cardiomyocytes contain a large number of mitochondria， which participate in cardiac energy metabolism and other biological activities and occupy an important position in the development of diabetic cardiomyopathy. Mitochondrial quality control mainly involves mitochondrial oxidative stress， mitochondrial dynamics， mitochondrial autophagy， and intracellular calcium regulation， which is an important condition for stabilizing the normal mitochondrial structure and exerting normal mitochondrial functions. In recent years， the efficacy of traditional Chinese medicine in intervening in mitochondrial quality control through multiple angles， pathways， and targets to affect the structure and function of myocardial mitochondria and significantly improve the clinical symptoms of patients with diabetic cardiomyopathy has attracted wide attention from scholars. Therefore， this paper reviewed the experimental studies and/or clinical observations concerning the treatment of diabetic cardiomyopathy with effective compounds of Chinese herbs and/or Chinese herbal compounds in the past ten years to further explain the pathogenesis of diabetic cardiomyopathy， clarify the regulatory mechanism of traditional Chinese medicine in mitochondrial quality control， and summarize the scientific connotations and shortcomings of traditional Chinese medicine in the treatment of diabetic cardiomyopathy， hoping to provide certain ideas and methods for further clinical application of traditional Chinese medicine in the treatment of diabetic cardiomyopathy.

Biotransformation of α-asarone by Alternaria longipes CGMCC 3.2875 / 中国天然药物

Biotransformation of α-asarone by Alternaria longipes CGMCC 3.2875 yielded two pairs of new neolignans, (+) (7S, 8S, 7'S, 8'R) iso-magnosalicin (1a)/(-) (7R, 8R, 7'R, 8'S) iso-magnosalicin (1b) and (+) (7R, 8R, 7'S, 8'R) magnosalicin (2a)/(-) (7S, 8S, 7'R, 8'S) magnosalicin (2b), and four known metabolites, (±) acoraminol A (3), (±) acoraminol B (4), asaraldehyde (5), and 2, 4, 5-trimethoxybenzoic acid (6). Their structures, including absolute configurations, were determined by extensive analysis of NMR spectra, X-ray crystallography, and quantum chemical ECD calculations. The cytotoxic activity and Aβ

Research Progress on Computer-Aided Skeleton-Based Individual Identification in Forensic Radiology / 法医学杂志

Individual identification based on imaging data of the skeleton of a corpse is a key technique for forensic identification. To reduce the influence of artificial factors, computer-aided semi-automatic or automatic individual identification has become one of the research directions of skeleton-based individual identification in forensic radiology. Therefore, this paper reviews and summarizes literatures related to estimation of anthropological information such as, age and sex by computer-aided forensic radiology bone characteristics and individual identification based on bone imaging characteristics, in order to provide reference on skeleton-based individual identification in forensic radiology.

Critical hubs of renal ischemia-reperfusion injury: endoplasmic reticulum-mitochondria tethering complexes / 中华医学杂志(英文版)

Mitochondrial injury and endoplasmic reticulum (ER) stress are considered to be the key mechanisms of renal ischemia-reperfusion (I/R) injury. Mitochondria are membrane-bound organelles that form close physical contact with a specific domain of the ER, known as mitochondrial-associated membranes. The close physical contact between them is mainly restrained by ER-mitochondria tethering complexes, which can play an important role in mitochondrial damage, ER stress, lipid homeostasis, and cell death. Several ER-mitochondria tethering complex components are involved in the process of renal I/R injury. A better understanding of the physical and functional interaction between ER and mitochondria is helpful to further clarify the mechanism of renal I/R injury and provide potential therapeutic targets. In this review, we aim to describe the structure of the tethering complex and elucidate its pivotal role in renal I/R injury by summarizing its role in many important mechanisms, such as mitophagy, mitochondrial fission, mitochondrial fusion, apoptosis and necrosis, ER stress, mitochondrial substance transport, and lipid metabolism.

Molecular cloning and functional characterization of multiple ApOSCs from Andrographis paniculata / 中国天然药物

Triterpenoids have been described in Andrographis paniculata. Oleanolic acid exhibits high biological activity and is widely used in the clinic, and β-sitosterol not only has good biological activity but also plays an important physiological role in plants. However, analysis of the biosynthetic pathway of triterpenoids in Andrographis paniculata has not been reported. Here, we provide the first report of the isolation and identification of nine 2, 3-oxidosqualene cyclases (ApOSC3 to ApOSC11) from A. paniculata. The results showed that ApOSC4 represented a monofunctional synthase that could convert 2, 3-oxidosqualene to β-amyrin. ApOSC5 as a bifunctional 2, 3-oxidosqualene cyclases, could transfer 2, 3-oxidosqualene to β-amyrin and α-amyrin. ApOSC6 to ApOSC8 composed the multifunctional 2, 3-oxidosqualene cyclases that could convert 2, 3-oxidosqualene to β-amyrin, α-amyrin and one or two undetermined triterpenoids. This study provides a better understanding of the biosynthetic pathway of triterpenoids in A. paniculata, and the discovery of multifunctional 2, 3-oxidosqualene cyclases ApOSC5 to ApOSC8 of the facilitates knowledge of the compounds diversity in A. paniculata.

Effect of acupuncture on patients with cancer-related fatigue and serum levels of CRP, IL-6, TNF-α and sTNF-R1 / 中国针灸

OBJECTIVE@#To observe the therapeutic effect of acupuncture on cancer-related fatigue (CRF) and to explore its possible mechanism.@*METHODS@#A total of 80 patients with CRF were randomized into an observation group and a control group, and finally 67 patients completed the trial (36 patients in the observation group, 31 patients in the control group). Patients in the control group were treated with conventional chemoradiotherapy and symptomatic treatment, while no particular anti-fatigue intervention was adopted. On the basis of treatment in the control group, acupuncture was applied at Baihui (GV 20), Guanyuan (CV 4), Qihai (CV 6), Fengchi (GB 20), Zusanli (ST 36), Sanyinjiao (SP 6) in the observation group, once a day, 5 times as one course, with 2 days interval between each course, totally 4 courses were required. Before and after treatment, scores of functional assessment of cancer therapy-fatigue (FACT-F) in Chinese and McGill quality of life questionnaire (MQOL), serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α) and soluble TNF receptor-1 (sTNF-R1) were observed in the two groups.@*RESULTS@#①Compared before treatment, the FACT-F score was decreased after treatment in the observation group (<0.05), while there was no significant difference in the control group (<0.05). The change of the FACT-F score in the observation group was larger than that in the control group (<0.05). ②In the observation group, scores of physiological and psychological dimension were decreased (<0.05), score of social support dimension was increased after the treatment (<0.05). The score changes of physiological, psychological and social support dimension in the observation group were larger than those in the control group (all <0.05). ③After treatment, the serum levels of IL-6, TNF-α and sTNF-R1 were decreased in the observation group (<0.05), while the serum levels of CPR and IL-6 were increased in the control group (<0.05). The serum levels of CPR, IL-6 and TNF-α in the observation were lower than those in the control group (<0.05).@*CONCLUSION@#①Acupuncture can improve the related symptoms of depression, weakness and headache in patients with CRF, strengthen their cognition of the support from society and family, and boost the confidence in curing the disease. ②Acupuncture can effectively down-regulate serum levels of the relative inflammatory factors, which may be its possible mechanism on treating CRF.

Clinical study of brush liquid-based cytology combined with automatic immunohistochemistry in the classification and diagnosis of lung cancer / 中华肿瘤杂志

Objective@#To explore the feasibility of bronchoscopic brushing liquid-based slide cytology combined with automatic immunocytochemistry (ICC) for pathological typing of lung cancer.@*Methods@#A liquid-based thin-prep was prepared from 171 bronchoscopic brushing specimens of patients with pulmonary lesions. ICC was detected by automatic immunohistochemistry instrument while cytomorphological diagnosis was made. The results were compared with those of histopathological diagnosis.@*Results@#Among 171 patients, 130 (76.0%) could be classified by cell morphology alone, including 31 squamous cell carcinomas, 44 adenocarcinomas and 55 small cell carcinomas; 162 (94.7%) could be classified by cell morphology combined with ICC, including 38 squamous cell carcinomas, 61 adenocarcinomas and 63 small cell carcinomas (P<0.001). According to the gold standard of histopathological diagnosis, the coincidence rate of cytomorphology combined with ICC was higher than that of cell morphology alone. The coincidence rate of squamous cell carcinoma was increased from 85.2% to 97.1% (P=0.093), adenocarcinoma from 92.5% to 98.0% (P<0.001), and small cell carcinoma from 96.1% to 98.3% (P=0.465).@*Conclusion@#The combination of liquid-based thin-prep cytology and automatic immunohistochemistry can effectively improve the accuracy of pathological typing of brushing specimens under fiberoptic bronchoscopy, and provide more objective diagnostic results for clinical treatment.

Value of the detection of BRAFV600E gene mutation and protein expression in auxiliary cytological diagnosis of papillary thyroid carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective@#To evaluate the utility of the BRAFV600E mutation detection in different cytoloy categories and to determine if the VE1 antibody can serve as a screening tool for the detection of BRAFV600E mutation in thyroid fine needle aspiration (FNA) specimens.@*Methods@#A total of 273 FNA residual specimens were collected. BRAFV600E testing was performed on these liquid-based specimens. And also 78 specimens with enough residual cells were stained with VE1 antibody. Comparisons of molecular and immunocytochemistry results with clinicopathological outcomes were performed. SPSS 17.0 software was used to analyze the data.@*Results@#There were 70 indeterminated diagnoses in 273 cases with FNAs. Fifty-eight cases were proven to be papillary thyroid carcinoma (PTC) by histology, including 9 cases of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 3 cases of follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), and 46 cases of suspicious for malignancy (SM). BRAFV600E analysis detected PTC in 3 of 9 cases with AUS/FLUS, and in 31 (67.4%) of 46 cases with SM. The sensitivity of immunostaining with VE1 antibody was 62.8%(27/43) and the specificity was 91.4% (32/35). VE1 expression showed moderately concordance with the molecular mutation (κ=0.524, P<0.001).@*Conclusions@#Additional BRAFV600E detecting can improve the diagnostic efficacy for PTC in AUS/FLUS and SM. VE1 expression may be an alternative method for BRAFV600E detecting when molecular detecting is unavailable.