Traditional Chinese medicine in osteoporosis: from pathogenesis to potential activity.

Osteoporosis characterized by decreased bone density and mass, is a systemic bone disease with the destruction of microstructure and increase in fragility. Osteoporosis is attributed to multiple causes, including aging, inflammation, diabetes mellitus, and other factors induced by the adverse effects of medications. Without treatment, osteoporosis will further progress and bring great trouble to human life. Due to the various causes, the treatment of osteoporosis is mainly aimed at improving bone metabolism, inhibiting bone resorption, and promoting bone formation. Although the currently approved drugs can reduce the risk of fragility fractures in individuals, a single drug has limitations in terms of safety and effectiveness. By contrast, traditional Chinese medicine (TCM), a characteristic discipline in China, including syndrome differentiation, Chinese medicine prescription, and active ingredients, shows unique advantages in the treatment of osteoporosis and has received attention all over the world. Therefore, this review summarized the pathogenic factors, pathogenesis, therapy limitations, and advantages of TCM, aiming at providing new ideas for the prevention and treatment of OP.

The regulation of tolerogenic dendritic cells by a Chinese herb formula improves abortion prone in mice.

BACKGROUND: Abortion prone (AP) is a common clinical event. The underlying mechanism remains unclear. Traditional Chinese formulas are known to be efficient in the management of abortion. The purpose of this study is to observe the effects of Anzitiaochongtang (AZT), a traditional formulation of Chinese medicine, on improving AP in mice by regulating immune tolerance. METHODS: An established abortion model (CBA/J×DBA/2) was employed. AZT was prepared and administered to mice in a manner consistent with clinical practice. Tolerogenic dendritic cells (tDC) and type 1 regulatory T cells (Tr1 cell) in mice were analyzed by immunological approaches to be used as representative immune tolerant parameters. RESULTS: An AP model was established with CBA/J × DBA/2 mice. The expression of IL-10 in tDC and Tr1 cell frequency in the mouse decidua tissues were lower in the AP group than that in the normal pregnancy (NP) group. Administration of AZT up regulated the expression of IL-10 in tDCs and Tr1 cell generation in the decidua tissues, and improved the pregnancy and tissue structure in AP mice. The main mechanism by which AZT improves pregnancy in AP mice is that AZT enhanced the expression of galectin-9 in the epithelial cells of decidua tissues. Galectin 9 activates TIM3 on DCs to promote the IL-10 expression. The DCs induced more Tr1 cells in the decidua tissues. CONCLUSIONS: Dysfunctional tDCs were detected in the AP decidua tissues. Administration of AZT improved pregnancy in AP mice by regulating tDC function and generation of Tr1 cells in the maternal-fetal interface.

Optimizing Processing Technology of Cornus officinalis: Based on Anti-Fibrotic Activity.

Cornus officinalis, a kind of edible herbal medicine, has been widely used in the protection of liver and kidney due to its medicinal and nutritional effect. Its anti-inflammatory, anti-tumor, and anti-oxidant activities can be enhanced by wine-steamed (WS) processing. Based on the activations of hepatic stellate cells-T6 (HSC-T6) and HK-2, our study used single-factor plus orthogonal design to investigate the anti-fibrosis of C. officinalis processed with steamed (S), high-pressure steamed (HPS), WS, high-pressure wine-steamed (HPWS), wine-dipped (WD), and wine-fried (WF). The chemical constituents in processed C. officinalis with higher anti-fibrotic activities were detected by ultra-high performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). Results showed that C. officinalis with HPWS significantly inhibited the activations of HSC-T6 and HK-2. Moreover, compounds in C. officinalis with HPWS were obtained via UHPLC-Q-TOF-MS/MS, indicating that 27 components were changed compared with raw C. officinalis. These results demonstrated that HPWS is the optimal processing technology for anti-fibrosis of C. officinalis.

Effects of Acupuncture on Endometrium and Pregnancy Outcomes in Patients with Polycystic Ovarian Syndrome Undergoing in vitro Fertilization-Embryo Transfer: A Randomized Clinical Trial.

OBJECTIVE: To observe the effect of acupuncture on endometrium and pregnancy outcomes in patients with polycystic ovary syndrome (PCOS) infertility undergoing in vitro fertilization-embryo transfer (IVF-ET). METHODS: Eighty-three patients were randomly assigned to observation group (40 cases) and control group (43 cases) according to the random numbers generated by SPSS software. The patients of the two groups received GnRH agonist long protocol as a routine treatment. In the observation group, acupuncture was given at two acupoint groups for 30 min once every other day. Group 1 included Guanyuan (CV 4), Qihai (CV 6), Zhongji (CV 3), bilateral acupoints Zigong (EX-CA1). Group 2 included Mingmen (GV 4), Yaoyangguan (GV 3), bilateral Shenshu (BL 23) and Ciliao (BL 32). The two groups of acupoints were used alternately. The whole needling process was performed at the time of ovulation induction until the transplantation day and consisted of 3 courses, while the control group did not receive acupuncture interventions. The Gn dosage and Gn stimulation time, endometrial thickness and type (A, B, and C), serum oestradiol (E2) and progesterone (P) levels on the day of injection of human chorionic gonadotropin (hCG), clinical pregnancy rate, as well as live birth rate were observed. Adverse reactions were also be recorded. All patients were followed up for the pregnant rate 14 days after IVF-ET and live birth rate after pregnancy. All adverse reactions (AEs) of acupuncture were recorded during the trial. RESULTS: The Gn dosage and Gn stimulation time in the observation group were lower in the observation group than in the control group (P<0.01). The proportion of type A endometrium in the observation group were higher than that in the control group (P<0.05). The serum E2 and P levels on the day of hCG injection was lower and the clinical pregnancy rate was higher in the observation group compared to those in the control group (P<0.05). There was no serious AEs during this trial. CONCLUSION: Acupuncture can improve the proportion of type A endometrium, regulate the levels of serum E2 and P on the day of hCG injection, and improve the pregnancy rate in patients with PCOS infertility undergoing IVF-ET.

A Reasonable Evaluation of Chuanxiong Rhizoma Processing with Wine through Comparative Pharmacokinetic Study of Bioactive Components: Dominant Effect on Middle Cerebral Artery Occlusion Model Rats.

According to the ancient documents and Chinese herbal medicine processing experience, Chuanxiong Rhizoma was usually processed with yellow rice wine to improve efficacy. However, the relevant mechanisms are still unclear so far. In this study, a validated ultrahigh-performance liquid chromatography tandem mass spectrometry method was used to compare the pharmacokinetics of four representative components in middle cerebral artery occlusion rats after oral administration of raw and wine-processed Chuanxiong Rhizoma. The neurobehavioral scores and 2,3,5-triphenyltetrazolium chloride staining were employed to evaluate the model. Biological samples were prepared by protein precipitation with methanol. All analytes were separated on an ACQUITY BEH C18 column through gradient elution using acetonitrile and 0.01% of formic acid as mobile phase, and the flow rate was 0.3 mL/min. The results showed that the maximum plasma concentrations, the area values under the concentration-time curves of senkyunolide A, and ferulic acid in wine-processed Chuanxiong Rhizoma were all higher than in raw Chuanxiong Rhizoma, which were completely opposite to our previous studies in normal rats. Compared with normal rats, the theory that wine processing could enhance the efficacy of Chuanxiong Rhizoma may be better reflected in model rats.

RNF144A exerts tumor suppressor function in breast cancer through targeting YY1 for proteasomal degradation to downregulate GMFG expression.

Ring finger protein 144A (RNF144A), a poorly characterized member of the RING-in-between-RING family of E3 ubiquitin ligases, is an emerging tumor suppressor, but its underlying mechanism remains largely elusive. To address this issue, we used Affymetrix GeneChip Human Transcriptome Array 2.0 to profile gene expression in MDA-MB-231 cells stably expressing empty vector pCDH and Flag-RNF144A, and found that 128 genes were differentially expressed between pCDH- and RNF144A-expressing cells with fold change over 1.5. We further demonstrated that RNF144A negatively regulated the protein and mRNA levels of glial maturation factor γ (GMFG). Mechanistical investigations revealed that transcription factor YY1 transcriptionally activated GMFG expression, and RNF144A interacted with YY1 and promoted its ubiquitination-dependent degradation, thus blocking YY1-induced GMFG expression. Functional rescue assays showed that ectopic expression of RNF144A suppressed the proliferative, migratory, and invasive potential of breast cancer cells, and the noted effects were partially restored by re-expression of GMFG in RNF144A-overexpressing breast cancer cells. Collectively, these findings reveal that RNF144A negatively regulates GMFG expression by targeting YY1 for proteasomal degradation, thus inhibiting the proliferation, migration, and invasion of breast cancer cells.

Network Pharmacology Approach for Predicting Targets of Zishen Yutai Pills on Premature Ovarian Insufficiency.

METHODS: A comprehensive strategy based on several Chinese herb databases and chemical compound databases was established to screen active compounds of ZSYTP and predict target genes. For network pharmacological analysis, network construction and gene enrichment analysis were conducted and further verified by molecular docking. RESULTS: A total of 476 target genes of ZSYTP were obtained from 205 active compounds. 13 herbs of ZSYTP overlapped on 8 active compounds based on the compound-target-disease network (C-T network). 20 biological processes and 9 pathways were strongly connected to the targets of ZSYTP in treating POI, including negative regulation of gene expression, mRNA metabolic process, hypoxia-inducible factor 1 (HIF-1) signaling pathway, and gluconeogenesis. Finally, molecular docking was visualized. CONCLUSION: Intriguingly, the signal pathways and biological processes uncovered in this study implicate inflamm-aging and glucose metabolism as potential pathological mechanisms of POI. The therapeutic effect of ZSYTP could be mediated by regulating glucose metabolism and HIF-1 signal pathway. Collectively, this study sheds light on the therapeutic potential of ZSYTP on POI.

[Pelvic-sacral tendon-regulation needling technique of acupuncture combined with manipulative reduction in treatment of postpartum pelvic girdle pain: a randomized controlled trial].

OBJECTIVE: To observe the effect on postpartum pelvic girdle pain treated with the combined therapy of pelvic-sacral tendon-regulation needling technique of acupuncture and manipulative reduction and the simple manipulative therapy. METHODS: A total of 80 patients with postpartum pelvic girdle pain were randomized into an observation group and a control group, 40 cases in each one. In the control group, the manipulative reduction was simply adopted. In the observation group, on the base of the treatment as the control group, the pelvic-sacral tendon-regulation needling technique of acupuncture was applied at Mingmen (GV 4), Dachangshu (BL 25), Yaoyangguan (GV 3), Ciliao (BL 32), Zhongliao (BL 33), Huantiao (GB 30) and Yanglingquan (GB 34). In either group, the treatment was given once every two days, three times a week and 3 treatments taken as one course. Totally, 3 courses of treatment were required. The clinical therapeutic effect was compared in the patients between the two groups. The changes in the scores of the pain visual analogue scale (VAS), Oswestry dysfunction index (ODI) and Japanese Orthopaedic Association (JOA), as well as the pelvic floor distress inventory-short form 20 (PFDI-20), the pelvic floor impact questionnaire (PFIQ-7) and the sex life index (the frequency of intercourse and orgasm) were recorded in the patients of the two groups before and after treatment. RESULTS: The total effective rate was 95.0% (38/40) in the observation group, higher than 77.5% (31/40) in the control group (P<0.01). After treatment, the scores of VAS, ODI, PFDI-20 and PFIQ-7 were lower than those before treatment respectively in the patients of the two groups (P<0.01). JOA score and the sex life index were increased after treatment as compared with those before treatment in the two groups (P<0.01). The difference value of each of the above indexes in the observation group was higher than the control group (P<0.01). CONCLUSION: The combined therapy of pelvic-sacral tendon-regulation needling technique of acupuncture and manipulative reduction effectively alleviates pain and improves the muscle strength of pelvic floor muscle fibers in the patients with postpartum pelvic girdle pain. Its therapeutic effect is better than that of the simple manipulative therapy.

Clinical observation of tuina manipulations for tic disorders in kids / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of tuina manipulations in treating different types of tic disorders (TD). Methods: Eligible TD patients were classified into three types, transient tic disorders (TTD), chronic multiple tic disorders (CMTD) and Tourette syndrome (TS), according to their disease duration and severity. The three types of children were treated with the same tuina manipulations. Changes in the Yale global tic severity scale (YGTSS) score, effective rate for tic, and cervical spine imaging examination results (including asymmetry of the lateral atlanto-dental interval, broadened anterior atlanto-dental interval, C2 spinous process deviation, occipito-atlanto-axial flexion/ extension instability) were observed after 1-month and 3-month treatments respectively. Results: The YGTSS score changed significantly after 1-month and 3-month treatments compared with that before treatment (both P<0.01); the effective rate for TD was 46.6％ and 86.7％ respectively after 1-month and 3-month treatments; there were significant differences comparing the effective rate for tic between different types of TD after 1-month and 3-month treatments (all P<0.05); comparing the effective rate for tic after 1-month treatment with that after 3-month treatment for the same type, the intra-group differences were statistically significant [TTD group (P<0.01), CMTD group (P<0.01), TS group (P<0.05)]; the abnormal parameter rates in neck imaging examination after 3-month treatment were significantly different from those before treatment (all P<0.01). Conclusion: Tuina manipulation is effective for TTD, CMTD and TS. It can correct the abnormal alterations of patients' cervical vertebrae, and its efficacy for TTD is most significant.

Comparative Study on Pharmacokinetics of Four Active Compounds in Rat Plasma after Oral Administration of Raw and Wine Processed Chuanxiong Rhizoma.

In Chinese medicine, the effect of promoting blood circulation and removing stasis could be enhanced after Chuanxiong Rhizoma is processed by wine. However, the relevant mechanism remains unclear. In this manuscript, a rapid and sensitive quantification method employing ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was established and validated to simultaneously determine butylidenephthalide, ligustilide, senkyunolide A and ferulic acid in rat plasma after oral administration of raw Chuanxiong Rhizoma (RCR) and wine-processed Chuanxiong Rhizoma (WCR) respectively. All analytes were extracted from plasma by proteins precipitation with methanol. Chromatographic separation was carried out on a Hypersil GOLD C18 column by using a gradient mobile phase system of acetonitrile and water with 0.01% formic acid, the flow rate was 0.3 mL/min. For exact mass detecting, quick switching mode was used, positive and negative ions could be detected in one injection. The pharmacokinetic profiles of four components in the two groups were evaluated and compared. The results showed that, compared to the RCR group, the Vd and AUC0→t values of four active compounds were increased and decreased respectively in WCR group, which revealed the effect of wine processing to Chuanxiong Rhizoma: the stronger the effect, the wider the distribution.

[Effect on immune factors and serum CA125 in patients of threatened abortion in early pregnancy complicated with subchorionic hematoma treated with auricular acupuncture combined with dydrogesterone].

OBJECTIVE: To evaluate the therapeutic effect of auricular acupuncture combined with dydrogesterone for threatened abortion in early pregnancy complicated with subchorionic hematoma. METHODS: A total of 80 patients were randomized into an observation group and a control group, 40 cases in each one. In the control group, dydrogesterone was taken orally twice a day, 10 mg a time until 12-week into pregnancy. In the observation group，auricular acupuncture was applied at penqiang (TF5), pizhixia (AT4), shen (CO10), xin(CO15), gan (CO12), jiaogan (AH6a) and neifenmi (CO18) on the basis of the control group, the auricular points on both sides were used alternatively. The auricular points were replaced every 3 days with 1 day break, totally 3 weeks (20 days) were required. Before treatment and after 10, 20 days of treatment, the percentage of helper T lymphocyte (Th) and inhibitory T lymphocyte (Ts), ratio of Th and Ts and serum level of CA125 were compared in the two groups. The areas of subchorionic hematoma and gestational sac were evaluated by B ultrasound. The therapeutic effect in the two groups were compared. RESULTS: The effective rate in the observation group was 80.0% (32/40), which was superior to 65.0% (26/40) in the control group (P<0.05). After 10, 20 days of treatment, the percentage of Th and ratio of Th and Ts were lower than before treatment, the percentage of Ts were increased in the two groups (P<0.01). After 20 days of treatment, the percentage of Th and ratio of Th and Ts in the observation group were lower than the control group (P<0.01), the percentage of Ts was higher than the control group (P<0.01). After 10, 20 days of treatment, the serum levels of CA125 were reduced compared before treatment in the two groups (P<0.01), and the serum levels of CA125 in the observation group were lower than the control group (P<0.01). After 10, 20 days of treatment, the ratio of subchorionic hematoma area and gestational sac area in the observation group was lower than the control group (P<0.01). CONCLUSION: Auricular acupuncture combined with dextroprogesterone can improve the effective rate of patients with threatened abortion in early pregnancy complicated with subchorionic hematoma, regulate immune factors, promote the hematoma absorption, and has a better synergistic effect with dextroprogesterone.

Identification and functional analysis of an iron-binding protein, ferritin heavy chain subunit, from the swallowtail butterfly, Papilio xuthus.

Ferritin, which is ubiquitous among all living organisms, plays a crucial role in maintaining iron homeostasis, immune response, and detoxification. In the present research, we identified an iron-binding protein, ferritin heavy chain subunit, from Papilio xuthus and named PxFerHCH. The complete complementary DNA of PxFerHCH was 1,252 bp encoding a sequence of 211 amino acids, which includes an iron-responsive element. Phylogenetic analysis showed that PxFerHCH is clustered with Manduca sexta and Galleria mellonella ferritin heavy chain subunits. Expression levels of PxFerHCH in various tissues were analyzed by reverse transcription quantitative polymerase chain reaction, and the results exhibited that PxFerHCH was expressed in all tissues with the highest expression in the fat body. The relative expression level of PxFerHCH in response to bacterial (Escherichia coli and Staphylococcus aureus) challenges sharply increased by about 12 hr postinfection (hpi) and then decreased at 24 hpi. In addition, the iron-binding capacity and antioxidation activity of recombinant PxFerHCH protein were also investigated. These results reveal that PxFerHCH might play an important role in defense against bacterial infection.

[Adjuvant therapy of acupoint catgut embedding for threatened abortion after in vitro fertilization-embryo transfer: a randomized controlled trial].

OBJECTIVE: To observe the effects of acupoint catgut embedding on miscarriage prevention and pregnancy outcome in patients with threatened abortion after in vitro fertilization-embryo transfer (IVF-ET). METHODS: Sixty cases of patients with threatened abortion after IVF-ET were randomly divided into an observation group and a control group, 30 cases in each group. The patients in the control group were treated with intramuscular injection of progesterone (40 mg) once every day, while the patients in the observation group, on the basis of the treatment of control group, were treated with catgut embedding at Geshu (BL 17), Ganshu (BL 18), Shenshu (BL 23), Pishu (BL 20), Weishu (BL 21), Xuehai (SP 10), Diji (SP 8) and Fuliu (KI 7), once every two weeks, six times as a course of treatment. The treatment was given until 12 weeks into pregnancy. The level of serum human chorionic gonadotropin (HCG), estradiol (E2) and progesterone (P) before and after treatment was recorded; the TCM syndrome score before and after treatment was compared; the successful pregnancy rate and spontaneous abortion rate after treatment were observed in the two groups. RESULTS: Compared before treatment, the scores of TCM syndrome in both groups were reduced after treatment (both P<0.01), and score in the observation group was superior to that in the control group (P<0.05). After treatment, the clinical efficacy in the observation group was superior to that in the control group (P<0.05). After treatment, the hormone levels (ß-HCG, E2, P) in both groups were increased steadily; the hormone levels in 6-week pregnancy, 8-week pregnancy and 10-week pregnancy were significantly higher than those in 4-week pregnancy (all P<0.05); except the levels of P and ß-HCG in 10-week pregnancy, the hormone levels in the observation group were superior to those in the control group (all P<0.05). After treatment, the early abortion rate was 16.7% (5/30) in the observation group, which was lower than 33.3% (10/30) in the control group (P<0.01); the pregnancy rate was 96.0% (24/25) in the observation group, which was higher than 80.0% (16/20) in the control group (P<0.01). CONCLUSION: Acupoint catgut embedding is effective for preventing threatened abortion, which could significantly reduce the spontaneous abortion rate, improve the pregnancy success rate, regulate hormone levels in patients after IVF-ET.

[Effects of Radix Hedysari, Radix Astragalus and compatibility of Angelica Sinensis on blood deficiency model mice induced by cyclophosphamide].

OBJECTIVE: To study the intervention effects of Radix Hedysari, Radix Astragalus and compatibility of Angelica Sinensis on blood deficiency model mice induced by cyclophosphamide (CTX). METHODS: The mice were randomly divided into 7 groups, 10 mice each group. The blood deficiency model was established by CTX. The blank group and model group were treated with saline by gavage, while mice in positive group were administered with Lvjiaobuxue granule. Four dosage group were administered with Radix Hedysari, Radix Hedysari-Radix Angelica Sinensis(5:1), Radix Astragalus and Radix Astragalus-Radix Angelica Sinensis(5:1) water decoction. All the drugs were administered to mice for consecutive 7 d. The contents of red blood cell (RBC), lymphocyte(LYM), hematocrit (HCT), white blood cell (WBC), platelet (PLT) were detected by hematology analyzer, while thymus index(TI), spleen index(SI), reticulocyte (RC), marrow karyocyte (MK) were calculated, and the femur by pathological section were observed by microscope. RESULTS: Compared with blank group, the contents of RBC, WBC, HCT, PLT, LYM were decreased in model group (P<0.05). Compared with model group, the contents of RBC, WBC, HCT, PLT, LYM, RC and marrow karyocyte were increased in Hedysari-Angelica Sinensis(5:1) and Astragalus Angelica Sinensis(5:1) (P<0.05), at the same time, the pathological damage of femur could be improved. CONCLUSIONS: The effect of enrichment blood on blood deficiency model mice in Hedysari-Angelica Sinensis (5:1) and Astragalus-Angelica Sinensis(5:1) were superior to Hedysari and Astragalus.

Meta-analysis of traditional Chinese medicine Jianpi therapy in treatment of atopic dermatitis / 中国中药杂志

To evaluate the clinical efficacy of traditional Chinese medicine Jianpi therapy in the treatment of atopic dermatitis. CNKI, Wanfang knowledge service platform, VIP journal database, Chinese biomedical literature database (CBM), PubMed, the Cochrane Library and EMbase database from inception to December 2017 were searched for the randomized controlled trials (RCTs) on traditional Chinese medicine Jianpi therapy in the treatment of atopic dermatitis. Literature selection and information extraction was completed and screened by two independent reviewers, and then the Cochrane recommended bias risk assessment method was used to evaluate the bias risk, and Review Manager 5.3 was used for the data analysis. Totally 37 clinical RCTs were included in this study, involving 2 973 patients. Analysis results showed that as compared with the western medicine, traditional Chinese medicine Jianpi therapy had higher clinical effective rate, with statistically significant difference (OR=4.05,95%CI[3.27, 5.03],<0.000 01); the improvement of score was more evident, including SCORAD score (WMD=-9.82,95%CI[-13.31,-6.33],<0.000 01), EASI score (WMD=-2.80,95%CI[-3.54,-2.07],<0.000 01), and itching VAS score (WMD=-0.79, 95%CI[-1.10,-0.47],<0.000 01)；the improvement of serum biochemical levels was more evident,including interferon-γ (IFN-γ) (WMD=1.75,95%CI[1.14,2.35],<0.000 01), interleukin-4 (IL-4) (WMD=-3.15,95%CI[-4.16,-2.15],<0.000 01), and Eosinophil direct count (EOS) (WMD=-0.11,95%CI[-0.20,-0.02], =0.02)；recurrence rate was significantly reduced (OR=0.36,95%CI[0.21,0.60],<0.000 1); and trial-related adverse events were reported in 11 RCTs. Studies have shown that traditional Chinese medicine Jianpi therapy had significantly higher clinical efficacy than western medicine in the treatment of atopic dermatitis. However, due to the publication bias and low quality bias of included RCTs in this study, more multicenter, high quality, large-sample, randomized double-blind controlled trials are needed to further demonstrate the conclusion.

Autophagy-related polymorphisms predict hypertension in patients with metastatic colorectal cancer treated with FOLFIRI and bevacizumab: Results from TRIBE and FIRE-3 trials.

PURPOSE: The most frequent bevacizumab-related side-effects are hypertension, proteinuria, bleeding and thromboembolism. To date, there is no biomarker that predicts anti-VEGF-associated toxicity. As autophagy inhibits angiogenesis, we hypothesised that single-nucleotide polymorphisms (SNPs) within autophagy-related genes may predict bevacizumab-mediated toxicity in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients with mCRC treated with first-line FOLFIRI and bevacizumab in two phase III randomised trials, namely the TRIBE trial (n = 219, discovery cohort) and the FIRE-3 trial (n = 234, validation cohort) were included in this study. Patients receiving treatment with FOLFIRI and cetuximab (FIRE-3, n = 204) served as a negative control. 12 SNPs in eight autophagy-related genes (ATG3/5/8/13, beclin 1, FIP200, unc-51-like kinase 1, UVRAG) were analysed by PCR-based direct sequencing. RESULTS: The FIP200 rs1129660 variant showed significant associations with hypertension in the TRIBE cohort. Patients harbouring any G allele of the FIP200 rs1129660 SNP showed a significantly lower rate of grade 2-3 hypertension compared with the A/A genotype (3% versus 15%, odds ratio [OR] 0.17; 95% confidence interval [CI], 0.02-0.73; P = 0.009). Similarly, G allele carriers of the FIP200 rs1129660 SNP were less likely to develop grade 2-3 hypertension than patients with an A/A genotype in the FIRE-3 validation cohort (9% versus 20%, OR 0.43; 95% CI, 0.14-1.11; P = 0.077), whereas this association could not be observed in the control cohort (12% versus 9%, OR 1.40; 95% CI, 0.45-4.04; P = 0.60). CONCLUSION: This is the first report demonstrating that polymorphisms in the autophagy-related FIP200 gene may predict hypertension in patients with mCRC treated with FOLFIRI and bevacizumab.

A case study of Ramsay Hunt Syndrome in conjunction with cranial polyneuritis.

RATIONALE: Ramsay Hunt syndrome in conjunction with cranial polyneuritis is not extensively documented, and is very easily misdiagnosed. PATIENT CONCERNS: A case of a 53-year-old male with Ramsay Hunt syndrome in conjunction with cranial polyneuritis is presented with early symptoms of vertigo, cephalalgia, and facial palsy, followed by zoster oticus 10 days later. DIAGNOSES: Diagnosis was challenging as this condition presents with multiple neuropathies, and attempting to diagnose based on clinical symptoms was often misleading. Polymerase chain reaction can be used to test for presence of the virus in the cerebrospinal fluid, followed by targeted drug therapy. INTERVENTIONS: Acupuncture, in conjunction with fire cupping, bloodletting around the afflicted region on the face, as well as oral consumption of herbal medicine and vitamins for nerve nourishment was given to treat this disease. OUTCOMES: Due to misdiagnosis resulting in delayed treatment, peripheral facial paralysis was left as the main sequelae, while other symptoms responded quickly to treatment. After a 6-month follow-up, facial palsy was still present. LESSONS: Considering that targeted antiviral therapy can be used to increase the effectiveness of treatment, early diagnosis, and timely use of medication is critical.

Altered effective connectivity of resting state networks by acupuncture stimulation in stroke patients with left hemiplegia: A multivariate granger analysis.

The aim of this study was to explore the response feature of resting-state networks (RSNs) of stroke patients with left hemiplegia by acupuncture stimulation.Nineteen stroke patients with left hemiplegia and 17 controls were recruited in this study. Resting-state functional magnetic resonance imaging data before and after acupuncture were acquired using magnetic scanning. The independent component analysis (ICA) was employed to extract RSNs related to motion, sensation, cognition, and execution, including sensorimotor network (SMN), left and right frontoparietal network (LFPN and RFPN), anterior and posterior default mode network (aDMN, pDMN), visual network (VN), and salience network (SN). Granger causality method was used to explore how acupuncture stimulation affects the causality between intrinsic RSNs in stroke patients. Compared with healthy subjects, stroke patients presented the more complex effective connectivity. Before acupuncture stimulation, LFPN inputted most information from other networks while DMN outputted most information to other networks; however, the above results were reversal by acupuncture. In addition, we found aDMN reside in between SMN and LFPN after acupuncture.The finding suggested that acupuncture probably integrated the effective connectivity internetwork by modulating multiple networks and transferring information between LFPN and SMN by DMN as the relay station.

[Prophylactic administration of all-trans retinoic acid alleviates inflammation in rats with collagen-induced arthritis].

OBJECTIVE: To investigate the effects of prophylactic administration of all-trans retinoic acid (ATRA) in relieving inflammation in a rat model of collagen-induced arthritis (CIA). METHODS: Female Wistar rats (6 to 8 weeks old) were randomly divided into normal control group, solvent control group, and prophylactic ATRA treatment (0.05, 0.5, and 5 mg/kg) groups. All the rats except for those in normal control group were subjected to subcutaneous injection of type II collagen and incomplete Freund adjuvant in the tails to induce CIA, followed by injection on the following day with saline, corn oil or different doses of ATRA 3 times a week. The arthritis index (AI) scores, histological scores, serum levels of TNF-α, IL-17A, and IL-10, and expressions of proteases related with cartilage damage were evaluated. RESULTS: On the 15th day after the primary immunization, the AI scores increased significantly in all but the normal control groups; the scores increased progressively in all the 3 ATRA groups but remained lower than that in the solvent control group, which was stable over time. The rats in the 3 ATRA groups showed obvious pathologies in the knee and ankle joints, but the semi-quantitative scores of pathology damage showed no significance among them. Compared with those in solvent control group, the serum IL-17A and TNF-α levels decreased, serum IL-10 level increased, and the expressions of ADAMT-4 and MMP-3 proteins decreased significantly in the knees in the 3 ATRA groups. CONCLUSION: ATRA can reduce the production of TNF-α and IL-17A and increase the production of IL-10 to alleviate the inflammation in rats with CIA. ATRA may delay the progression of RA by correcting the imbalance of Th1/Th2 and Th17/Treg.

[The Effects of All-trans Retinoic Acid on the Expression of Inflammatory Cytokines and Cartilage Damage Related Protease in Rats with Collagen Induced Arthritis].

OBJECTIVES: To investigate the effects of all-trans retinoic acid (ATRA) on arthritis and the expressions of inflammatory cytokines and cartilage damage related proteases of the collagen-induced arthritis model (CIA) rats in vivo. METHODS: The CIA model of rheumatoid arthritis was induced with C2 and incomplete Freund's adjuvant. The rats were randomly divided into control group, CIA model group and two ATRA dose groups (ATRA 0.50 mg/kg group and ATRA 1.00 mg/kg group). ATRA were given three times per week for six weeks in ATRA groups. Morphological changes, arthritis index (AI) scores, the semi-quantitative scores of pathology damage, the protein expressions of cartilage damage related proteases and the serum levels of TNF-α, IL-17A, IFN-γ, IL-4, IL-10 were observed. RESULTS: The AI scores of ATRA groups were similar to CIA model group ( P<0.05). Apparent morphological disorders in knee and ankle joints were observed in the CIA model group and ATRA 1.00 mg/kg group. The structure of knee joint was improved slightly in ATRA 0.50 mg/kg group. The serum levels of TNF-α, IFN-γ and IL-17A were decreased in both ATRA groups; ATRA also can increase the serum level of IL-4. Compared to CIA model group, the protein expressions of ADAMTS-4, MMP3, MMP1 were decreased in both ATRA groups ( P<0.05). CONCLUSIONS: ATRA, which was able to inhibit pro-inflammatory cytokines secretion, could correct the imbalance of Th1/Th2 and Th17/Treg. ATRA also can reduce the expressions of cartilage damage related proteases, which proved that ATRA may have a beneficial effect on rheumatoid arthritis.