[Outcomes and measurements of randomized controlled trial for traditional Chinese medicine in treatment of endometriosis].

This study aims to analyze the outcomes and measurements of randomized controlled trial(RCT) for traditional Chinese medicine(TCM) treatment of endometriosis(EM) and provide a basis for the building of the core outcome set(COS) of EM. The RCT for TCM treatment of EM was retrieved from medical literature databases with the time interval from inception to February 3, 2022. The Cochrane risk of bias assessment tool was employed to evaluate the risk of bias of the included RCT, and descriptive analyses of the extracted information were carried out. A total of 519 RCTs were included, with the sample sizes ranging from 28-582 patients and 239 outcome indicators(8 outcome indicators per RCT on average). According to the functional properties, the reported outcome indicators were classified into 7 indicators: clinical efficacy assessment, indicators of clinical symptoms and signs, TCM symptom efficacy indicators, physical and chemical examinations, quality of life, long-term prognosis, and safety events. All the 519 RCTs had problems, such as the lack of differentiation between primary and secondary outcome indicators(1.73% RCTs reported such differen-tiation), poor quality, confused criteria for composite outcome indicators and arbitrary combination of indicators(45 criteria for the single outcome indicator of efficiency), and messy measurements(as many as 18 measurements for TCM symptom score). In addition, as a chronic disease, EM requires long-term management. The outcome indicators vary for the patients in different disease stages, such as EM pain, EM infertility, and post-operative EM, while the specific outcome indicator sets for different EM populations remain to be developed. In addition, the time point of measurement for EM long-term outcomes remains unclear, and the definition of TCM syndromes lacks standards. The RCT for TCM treatment had a variety of problems, such as the lack of differentiation of outcome indicators, confusion in criteria and measurements, lack of specific outcome indicator sets for different EM populations, and unclear time points for long-term outcomes. Therefore, the studies about COS need to be carried out urgently.

Long noncoding RNA MALAT1 releases epigenetic silencing of HIV-1 replication by displacing the polycomb repressive complex 2 from binding to the LTR promoter.

Long noncoding RNAs (lncRNAs) may either repress or activate HIV-1 replication and latency; however, specific mechanisms for their action are not always clear. In HIV-1 infected CD4+ T cells, we performed RNA-Sequencing (RNA-Seq) analysis and discovered an up-regulation of MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), an lncRNA previously described in cancer cells that associate with cancer pathogenesis. Moreover, we found that MALAT1 promoted HIV-1 transcription and infection, as its knockdown by CRISPR/Cas9 markedly reduced the HIV-1 long terminal repeat (LTR)-driven gene transcription and viral replication. Mechanistically, through an association with chromatin modulator polycomb repressive complex 2 (PRC2), MALAT1 detached the core component enhancer of zeste homolog 2 (EZH2) from binding with HIV-1 LTR promoter, and thus removed PRC2 complex-mediated methylation of histone H3 on lysine 27 (H3K27me3) and relieved epigenetic silencing of HIV-1 transcription. Moreover, the reactivation of HIV-1 stimulated with latency reversal agents (LRAs) induced MALAT1 expression in latently infected cells. Successful combination antiretroviral therapy (cART) was accompanied by significantly diminished MALAT1 expression in patients, suggesting a positive correlation of MALAT1 expression with HIV-1 replication. Our data have identified MALAT1 as a promoter of HIV-1 transcription, and suggested that MALAT1 may be targeted for the development of new therapeutics.

Flavonoids from Podocarpus macrophyllus and their cardioprotective activities.

One new 8-aryl flavone, podocarflavone A (1), together with 15 previously reported flavonoids were isolated from the twigs and leaves of Podocarpus macrophyllus. Their structures were established on the basis of extensive spectroscopic analysis and by the comparison with spectroscopic data reported in the literature. Antioxidant capacities of the isolated substances were determined using the 1,1-diphenyl-2-picrylhydrazyl, ferrous ions, and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical in vitro assays, and their cytoprotective activities were also tested on H2O2-induced apoptosis in H9c2 cardiomyocytes. The results showed that those flavonoids exhibited significant cardioprotective effects by decreasing the H2O2-induced death of H9c2 cell, and the levels of lactate dehydrogenase and creatine kinase, and by inhibiting the elevated intracellular concentration of reactive oxygen species.

Efficacy of Chinese Herbal Medicines on Pregnancy Outcomes in Patients with Endometriosis in Long-Term Management: A Multicenter Retrospective Cohort Study.

OBJECTIVE: To analyze the factors related to pregnancy of endometriosis and whether Chinese herbal medicines (CHMs) can improve pregnancy outcomes in patients with endometriosis in long-term management. METHODS: This multicenter cohort study retrospectively analyzed the clinical data of endometriosis patients with fertility needs from January 2019 to November 2019. A total of 252 patients with endometriosis from 5 level-III Grade A hospitals in Beijing were included in this study. Univariate and multivariate logistic regression analysis were performed for the relevant factors. The propensity score matching (PSM) function of SPSS software was used to match the CHMs group with the non-CHMs group. The pregnancy rate and live birth rate were analyzed. RESULTS: The results of univariate analysis showed that age, disease course, presence of infertility, presence of adenomyosis, time after surgery or use of gonadotropin-releasing hormone agonist (GnRH-a), use of CHMs and follow-up time were influencing factors of pregnancy in endometriosis patients (P<0.05). The results of multivariate analysis showed that age, presence of adenomyosis, time after surgery or use of GnRH-a, use of CHMs and follow-up time were independent factors affecting pregnancy in endometriosis patients, among which, age ⩾35 years old, presence of adenomyosis and follow-up time >6 months were independent risk factors (OR=0.445, 0.348, 0.140, respectively, P<0.05), time after surgery or use of GnRH-a ⩽6 months and use of CHMs were independent protective factors (OR=3.839, 3.842, respectively, P<0.05). After PSM, 99 pairs of two groups were matched successfully. The pregnancy rate of the CHMs group was higher than that of the non-CHMs group [55.56% (55/99) vs. 36.36% (36/99), P<0.05]. The live birth rate of the CHMs group was higher than that of the non-CHMs group [49.49% (49/99) vs. 35.35% (35/99), P<0.05]. CONCLUSION: CHMs can effectively improve clinical pregnancy rate and live birth rate of patients with endometriosis in the chronic disease management.

Upregulated galectin-1 in Angiostrongylus cantonensis L5 reduces body fat and increases oxidative stress tolerance.

BACKGROUND: Angiostrongylus cantonensis L5, parasitizing human cerebrospinal fluid, causes eosinophilic meningitis, which is attributed to tissue inflammatory responses caused primarily by the high percentage of eosinophils. Eosinophils are also involved in killing helminths, using the peroxidative oxidation and hydrogen peroxide (H2O2) generated by dismutation of superoxide produced during respiratory burst. In contrast, helminthic worms have evolved to attenuate eosinophil-mediated tissue inflammatory responses for their survival. In previous study, we demonstrated the extracellular function of Acan-Gal-1 in inducing the apoptosis of macrophages. Here, the intracellular functions of Acan-Gal-1 were investigated, aiming to further reveal the mechanism involved in A. cantonensis L5 worms surviving inflammatory responses in the human central nervous system. METHODS: In this study, a model organism, Caenorhabditis elegans, was used as a surrogate to investigate the intracellular functions of Acan-Gal-1 in protecting the worm from its host's immune attacks. First, structural characterization of Acan-Gal-1 was analyzed using bioinformatics; second, qRT-PCR was used to monitor the stage specificity of Acan-gal-1 expression in A. cantonensis. Microinjections were performed to detect the tissue specificity of lec-1 expression, the homolog of Acan-gal-1 in C. elegans. Third, microinjection was performed to develop Acan-gal-1::rfp transgenic worms. Then, oxidative stress assay and Oil Red O fat staining were used to determine the functions of Acan-Gal-1 in C. elegans. RESULTS: The results of detecting the stage specificity of Acan-gal-1 expression showed that Acan-Gal-1 was upregulated in both L5 and adult worms. Detection of the tissue specificity showed that the homolog of Acan-gal-1 in C. elegans, lec-1 was expressed ubiquitously and mainly localized in cuticle. Investigating the intracellular functions of Acan-Gal-1 in the surrogate C. elegans showed that N2 worms expressing pCe-lec-1::Acan-gal-1::rfp, with lipid deposition reduced, were significantly resistant to oxidative stress; lec-1 mutant worms, where lipid deposition increased, showed susceptible to oxidative stress, and this phenotype could be rescued by expressing pCe-lec-1::Acan-gal-1::rfp. Expressing pCe-lec-1::Acan-gal-1::rfp or lec-1 RNAi in fat-6;fat-7 double-mutant worms, where fat stores were reduced, had no significant effect on the oxidative stress tolerance. CONCLUSION: In C. elegans worms, upregulated Acan-Gal-1 plays a defensive role against damage due to oxidative stress for worm survival by reducing fat deposition. This might indicate the mechanism by which A. cantonensis L5 worms, with upregulated Acan-Gal-1, survive the immune attack of eosinophils in the human central nervous system.

Effect of compounds on the purification and antibody preparation of the extracellular domain fragment of the receptor CD163.

BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) has been acknowledged as one of the most important agents affecting swine. The scavenger receptor CD163 is one of the important entry mediators for PRRSV. RESULTS: The tD4 and tD5 CD163 genes were amplified, and the PCR products were cloned into pET-28a(+) (designated pET-28a-tD4 and pET-28a-tD5, respectively). The plasmids pET-28a-tD4 and pET-28a-tD5 were then transformed into the E. coli BL21 (DE3) strain and expressed by adding 1 mmol/L of isopropyl-beta-D-thiogalactopyranoside. The proteins were highly expressed in the supernatant from the tD4- and tD5-producing cells that were incubated with a binding buffer containing the following compounds: ß-mercaptoethanol, urea, Tween 20, glycerol, and SDS, while they were rarely expressed in the supernatant from the tD4- and tD5-producing cells that were incubated with binding buffer without the compounds. The tD4 and tD5 proteins were purified, and BALB/c mice were immunized with the purified proteins. Western blotting analysis showed that the tD4 and tD5 proteins were capable of reacting with tD5 antibodies; the titer of both the tD4 and tD5 antiserums was 1:160 against the tD5 protein, as shown by ELISA. CONCLUSIONS: These studies provide a new way for the purification of proteins expressed in inclusion bodies and the preparation of the corresponding antibodies.

[Mutation analysis of the pathogenic gene in a Chinese family with Brachydactyly type B1].

We identified and characterized a Chinese family with autosomal dominant Brachydactyly type B1 (BDB1). Linkage analysis revealed that the disease gene of the Chinese BDB1 family was linked to ROR2 locus. Mutational hot spot of ROR2 gene was amplified by polymerase chain reaction (PCR) and sequenced directly. A c.2265C>A heterozygous mutation was detected in all of the patients. This mutation led to the change of p.Y755X in protein level and a truncated ROR2 protein losing integrant domains was generated. The mutation was detected in all the patients, but not in all the normal individuals of this family and 50 normal controls. This paper for the first time reported a c.2265C>A mutation in ROR2 gene of a family with BDB1 in China, which enriches ROR2 gene mutation spectrum in Chinese with BDB1.

[Anaphylactoid reactions inducing effect of polysorbate 80 and polysorbate 80 contained Houttuynia cordata injection on beagle].

OBJECTIVE: To evaluate the sensitization effect of polysorbate 80 and polysorbate 80 contained Houttuynia cordata Injection in different concentrations on Beagle. METHODS: Beagles, a kind of animal highly sensitive to sensitizing agents, were randomly divided into 18 groups, 3 in each group. They received respectively the intravenous infusion of polysorbate 80 made by different factories in different concentrations (0.25%, 0.10%, 0.05%), and Houttuynia cordata Injection containing polysorbate 80 in concentration of 0.25% or 0.30%, with the constant infusing speed of 5 mL/min and volume of 10 mL/kg. Changes of animals' condition were observed before infusion and in the 24 h after infusion, time of symptom appearance and disappearance was recorded, and the grade of response was determined. Moreover, blood samples of animals were collected before infusion and 10 min after ending infusion for measuring histamine content in plasma using ELISA. Then the sensitization effect was comprehensively estimated by combined consideration of the responding grade and histamine level. RESULTS: No typical symptom of anaphylactoid reaction and over 1-fold increase of histamine level was found in all groups that received intravenous infusion of polysorbate 80 or polysorbate 80 contained Houttuynia cordata Injection in different concentrations. Estimation showed that all test solutions didn't induce typical anaphylactoid reaction on Beagle. CONCLUSIONS: Considering both the appearance of symptoms and the elevation of blood content of histamine could be taken as the criteria for comprehensive diagnosis of anaphylactoid reactions. The solubilization effect and safety (for foreclose anaphylactoid reaction) of polysorbate 80 could be ensured by controlling its quality and concentration below 0.25% or 0.30%.

[Fluorescence spectra analysis of whey protein isolate-dextran conjugate].

The mixed whey protein isolate (WPI)-dextran was treated by dry-heating to prepare Maillard reaction products (MRPs), which was characterized by the browning. The free amino groups content significantly decreased by 35.77% and 30.53% in glycated protein samples, as the molecular weight of dextran increased from 67 to 150 kD, respectively. This suggested that it was more difficult to be linked with WPI molecule when the chain length of dextran was increased. The characteristic of WPI-dextran conjugate was studied by fluorescence spectra in the paper. The maximum fluorescence intensity at 405 nm was obviously enhanced and G67 showed high fluorescence intensity than G150 over the wavelength range form 350 to 500 nm. This result revealed that the flourescent substance, a feature in Maillard reaction model system, was generated. As showed in the fluorescence spectra, the maximum fluorescence intensity at 470 nm was significantly decreased and the fluorescence intensity in each solution was in the order as follows: WPI>G150>G67. Moreover, the measurement of surface hydrophobicity index further showed that the hydrophobicity of WPI could be suppressed due to these two kinds of different molecular weight dextran.

Observation and measurement of applied anatomical features for thoracic intervertebral foramen puncture on computed tomography images.

BACKGROUND: Thoracic intervertebral foramen puncture is the key step for interventional therapy on the thoracic nerve roots or dorsal root ganglia. The anatomical features of the thoracic spine are complex, and puncture injury to the pleura, blood vessels, spinal cord, and other tissues may cause serious complications. The spatial anatomical characteristics and related parameters for thoracic intervertebral foramen puncture remain poorly understood. AIM: To observe and summarize the spatially applied anatomical characteristics for intervertebral foramen puncture on different vertebral segments. METHODS: A total of 88 patients (41 males and 47 females) who underwent thoracic minimally invasive interventional treatment at Nanjing Drum Tower Hospital from January 2019 to June 2020 were included. Computed tomography images of 167 thoracic vertebral segments scanned in the prone position were collected. The width of the intertransverse space (DP), the height of the rib neck/head above the lower transverse process (DR), the width of the lateral border of the articular process/lamina (WP), and the width of the posterior border of the vertebral body (WV) were measured. At the upper 1/3 of the intervertebral foramina, the horizontal inclination angle (α) from the lateral border of the articular process/lamina to the posterolateral border of the vertebral body was measured. The ratios DR/DP and WP/WV were calculated. The intervertebral foramen parameters were compared between segments. RESULTS: No rib head/neck occlusion (DR/DP > 0) was found in the intertransverse spaces of T1-2 and T12-L1. The incidence of occlusion for the upper thoracic segments (T1-5, n = 138), middle thoracic segments (T5-9, n = 116), and lower thoracic segments (T9-L1, n = 80) were 76.81%, 100%, and 82.50%, respectively. The incidence of occlusion for the middle thoracic segments was significantly higher than that for the upper and lower thoracic segments (P < 0.05). The incidence of > 1/2 occlusion (DR/DP > 1/2) for the upper, middle, and lower thoracic segments was 7.97%, 74.14%, and 32.50%, respectively. The incidence of > 1/2 occlusion for the middle thoracic segments was significantly higher than that for the upper and lower thoracic segments (P < 0.05). WP was longer than WV on T1-2 to T9-10 and shorter than WV on T10-11 to T12-L1. The horizontal puncture angle (α) into the external opening of the intervertebral foramina was positively correlated with the segments of the thoracic vertebrae from the cephalic to caudal portion (left: r = 0.772, P < 0.01; right: r = 0.771, P < 0.01), and the horizontal inclination angle for T11-12 and T12-L1 was 90°. CONCLUSION: It is necessary to identify the spatial impact of the rib head/neck on the puncture path of the intervertebral foramina and design appropriate puncture angles for different segments.

Retraction notice to "Role of hepatic neuropeptide Y-Y1 receptors in a methionine- cholinedeficient model of non-alcoholic steatohepatitis" [Life Sci. 245 (2020) 117356].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. Concern has been raised by a reader about both the inappropriateness of certain methods used to prepare Figures 1A and 3A; as well as the lack of important information including the exact age of the mice and details of the ELISA used. These issues could undermine the scientific grounds of the article. Apologies are offered to readers of the journal that this was not detected during the submission process.

Establishment and Validation of an Integrated Model to Predict Postoperative Recurrence in Patients With Atypical Meningioma.

BACKGROUND: This study aims to establish an integrated model based on clinical, laboratory, radiological, and pathological factors to predict the postoperative recurrence of atypical meningioma (AM). MATERIALS AND METHODS: A retrospective study of 183 patients with AM was conducted. Patients were randomly divided into a training cohort (n = 128) and an external validation cohort (n = 55). Univariable and multivariable Cox regression analyses, the least absolute shrinkage and selection operator (LASSO) regression analysis, time-dependent receiver operating characteristic (ROC) curve analysis, and evaluation of clinical usage were used to select variables for the final nomogram model. RESULTS: After multivariable Cox analysis, serum fibrinogen >2.95 g/L (hazard ratio (HR), 2.43; 95% confidence interval (CI), 1.05-5.63; p = 0.039), tumor located in skull base (HR, 6.59; 95% CI, 2.46-17.68; p < 0.001), Simpson grades III-IV (HR, 2.73; 95% CI, 1.01-7.34; p = 0.047), tumor diameter >4.91 cm (HR, 7.10; 95% CI, 2.52-19.95; p < 0.001), and mitotic level ≥4/high power field (HR, 2.80; 95% CI, 1.16-6.74; p = 0.021) were independently associated with AM recurrence. Mitotic level was excluded after LASSO analysis, and it did not improve the predictive performance and clinical usage of the model. Therefore, the other four factors were integrated into the nomogram model, which showed good discrimination abilities in training cohort (C-index, 0.822; 95% CI, 0.759-0.885) and validation cohort (C-index, 0.817; 95% CI, 0.716-0.918) and good match between the predicted and observed probability of recurrence-free survival. CONCLUSION: Our study established an integrated model to predict the postoperative recurrence of AM.

Chinese Medicine in Management of Chronic Disease Endometriosis.

Endometriosis (EM), a refractory, highly recurrent and life-threatening chronic disease, requires long-term management and long-term drug treatment. Our previous studies showed that Chinese medicine (CM) can inhibit the postoperative recurrence of EM, improve quality of life, shorten the time to conception and increase pregnancy rates. CM produces few adverse reactions with high safety. These characteristics might be associated with the mechanism of CM's inhibition of recurrence. Therefore, we believe that CM may represent a good choice for long-term drug treatment and is worthy of clinical application.

Role of hepatic neuropeptide Y-Y1 receptors in a methionine-choline-deficient model of non-alcoholic steatohepatitis.

AIMS: NPY-Y1R plays an important role in dietary regulation. Although germline knockdown of NPY-Y1R in mice alleviates high-fat-diet-induced obesity and increases CPT1α levels in the liver, the role of the Y1 receptor in specific tissues has not been studied. MAIN METHODS: MCD diet is the most widely used method to establish a model of lean NASH in a short time. We therefore evaluated the role of liver NPY-Y1R in NASH progression. KEY FINDINGS: In mice with liver-specific knockout of NPY-Y1R (LivKO) and wild-type control littermates fed MCD diet for 4 weeks, NPY-Y1R deficiency significantly decreased body and liver weight. Moreover, NPY-Y1R deletion protected mice against hepatic steatosis and injury. LivKO decreased TG, TC, and FFA levels in the liver and alanine aminotransferase activity in plasma. To clarify the mechanism, we evaluated the key enzymes involved in triglyceride hydrolase and fatty-acid oxidase. Expression of ATGL, CPT1α, and ACO was significantly increased in LivKO mice, whereas expression of fatty-acid synthase was significantly decreased. mRNA expression analysis revealed a marked reduction of genes involved in de-novo lipogenesis and monosaturated fatty-acid synthesis, including sterol-regulatory element-binding protein 1c and fatty-acid synthase. Moreover, liver injury-related factors were significantly decreased in LivKO mice, such as TNF-α, inducible nitric oxide synthase, and MCP-1. Thus, NPY-Y1R deficiency in the liver alleviates lipid deposition and injury. However, NPY-Y1R did not affect inflammation and fibrosis. SIGNIFICANCE: NPY-Y1R deficiency in the liver directly suppresses not only hepatic steatosis, but also liver injury, and thus provides a treatment option for NASH.

The Establishment of an In Vivo HIV-1 Infection Model in Humanized B-NSG Mice.

Suitable animal models for human immunodeficiency virus type 1 (HIV-1) infection are important for elucidating viral pathogenesis and evaluating antiviral strategies in vivo. The B-NSG (NOD-PrkdcscidIl2rgtm1/Bcge) mice that have severe immune defect phenotype are examined for the suitability of such a model in this study. Human peripheral blood mononuclear cells (PBMCs) were engrafted into B-NSG mice via mouse tail vein injection, and the repopulated human T-lymphocytes were observed at as early as 3-weeks post-transplantation in mouse peripheral blood and several tissues. The humanized mice could be infected by HIV-1, and the infection recapitulated features of T-lymphocyte dynamic observed in HIV-1 infected humans, meanwhile the administration of combination antiretroviral therapy (cART) suppressed viral replication and restored T lymphocyte abnormalities. The establishment of HIV-1 infected humanized B-NSG mice not only provides a model to study virus and T cell interplays, but also can be a useful tool to evaluate antiviral strategies.

Accuracy study of a binocular-stereo-vision-based navigation robot for minimally invasive interventional procedures.

BACKGROUND: Medical robot is a promising surgical tool, but no specific one has been designed for interventional treatment of chronic pain. We developed a computed tomography-image based navigation robot using a new registration method with binocular vision. This kind of robot is appropriate for minimal invasive interventional procedures and easy to operate. The feasibility, accuracy and stability of this new robot need to be tested. AIM: To assess quantitatively the feasibility, accuracy and stability of the binocular-stereo-vision-based navigation robot for minimally invasive interventional procedures. METHODS: A box model was designed for assessing the accuracy for targets at different distances. Nine (three sets) lead spheres were embedded in the model as puncture goals. The entry-to-target distances were set 50 mm (short-distance), 100 mm (medium-distance) and 150 mm (long-distance). Puncture procedure was repeated three times for each goal. The Euclidian error of each puncture was calculated and statistically analyzed. Three head phantoms were used to explore the clinical feasibility and stability. Three independent operators conducted foramen ovale placement on head phantoms (both sides) by freehand or under the guidance of robot (18 punctures with each method). The operation time, adjustment time and one-time success rate were recorded, and the two guidance methods were compared. RESULTS: On the box model, the mean puncture errors of navigation robot were 1.7 ± 0.9 mm for the short-distance target, 2.4 ± 1.0 mm for the moderate target and 4.4 ± 1.4 mm for the long-distance target. On the head phantom, no obvious differences in operation time and adjustment time were found among the three performers (P > 0.05). The median adjustment time was significantly less under the guidance of the robot than under free hand. The one-time success rate was significantly higher with the robot (P < 0.05). There was no obvious difference in operation time between the two methods (P > 0.05). CONCLUSION: In the laboratory environment, accuracy of binocular-stereo-vision-based navigation robot is acceptable for target at 100 mm depth or less. Compared with freehand, foramen ovale placement accuracy can be improved with robot guidance.

Downregulated RPS-30 in Angiostrongylus cantonensis L5 plays a defensive role against damage due to oxidative stress.

BACKGROUND: Eosinophilic meningitis, caused by fifth-stage larvae of the nematode (roundworm) Angiostrongylus cantonensis, is mainly attributed to the contribution of eosinophils to tissue inflammatory responses in helminthic infections. Eosinophils are associated with the killing of helminths via peroxidative oxidation and hydrogen peroxide generated by the dismutation of superoxide produced during respiratory bursts. In contrast, when residing in the host with high level of eosinophils, helminthic worms have evolved to attenuate eosinophil-mediated tissue inflammatory responses for their survival in the hosts. In a previous study we demonstrated that the expression of the A. cantonensis RPS 30 gene (Acan-rps-30) was significantly downregulated in A. cantonensis L5 roundworms residing in cerebrospinal fluid with a high level of eosinophils. Acan-RPS-30 is a protein homologous to the human Fau protein that plays a pro-apoptotic regulatory role and may function in protecting worms from oxidative stress. METHODS: The isolation and structural characterization of Acan-RPS-30 were performed using rapid amplification of cDNA ends (RACE), genome walking and bioinformatics. Quantitative real-time-PCR and microinjection were used to detect the expression patterns of Acan-rps-30. Feeding RNA interference (RNAi) was used to knockdown the apoptosis gene ced-3. Microinjection was performed to construct transgenic worms. An oxidative stress assay was used to determine the functions of Acan-RPS-30. RESULTS: Our results showed that Acan-RPS-30 consisted of 130 amino acids. It was grouped into clade V with C. elegans in the phylogenetic analysis. It was expressed ubiquitously in worms and was downregulated in both L5 larvae and adult A. cantonensis. Worms expressing pCe-rps30::Acan-rps-30::rfp, with the refractile "button-like" apoptotic corpses, were susceptible to oxidative stress. Apoptosis genes ced-3 and ced-4 were both upregulated in the transgenic worms. The phenotype susceptible to oxidative stress could be converted with a ced-3 defective mutation and RNAi. rps-30-/- mutant worms were resistant to oxidative stress, with ced-3 and ced-4 both downregulated. The oxidative stress-resistant phenotype could be rescued and inhibited by through the expression of pCe-rps30::Acan-rps-30::rfp in rps-3-/- mutant worms. CONCLUSION: In C. elegans worms, downregulated RPS-30 plays a defensive role against damage due to oxidative stress, facilitating worm survival by regulating downregulated ced-3. This observation may indicate the mechanism by which A. cantonensis L5 worms, with downregulated Acan-RPS-30, survive in the central nervous system of humans from the immune response of eosinophils.

Chinese Medicine Sequential Therapy Improves Pregnancy Outcomes after Surgery for Endometriosis-Associated Infertility: A Multicenter Randomized Double-blind Placebo Parallel Controlled Clinical Trial.

OBJECTIVE: To evaluate the efficacy and safety of Chinese medicine (CM) improving pregnancy outcomes after surgery for endometriosis-associated infertility. METHODS: A multicenter, randomized, double-blind placebo parallel controlled clinical trial was designed. A total of 202 patients who had laparoscopy for endometriosis-associated infertility with qi stagnation and blood stasis syndrome were included and randomly divided into the CM treatment group and placebo control group at a ratio of 1:1 using a central block randomization from May 2014 to September 2017, 101 patients in each group. The two groups received continuous intervention at 1-5 days after surgery, for 6 menstrual cycles. Before ovulation, the CM group was treated Huoxue Xiaoyi Granule (); after ovulation, Bushen Zhuyun Granule ( was involved. The control group was treated with placebo. Transvaginal ultrasonography was performed every menstrual cycle during the treatment, and female hormone levels in the follicular and luteal phases were measured during the 1st, 3rd and 6th menstrual cycles. The analysis was continued until pregnancy. The primary outcomes were clinical pregnancy rate and pregnancy outcome, and the secondary outcomes were follicular development and endometrial receptivity. Safety evaluations were performed before and after treatment. RESULTS: (1) Clinical pregnancy and live birth rates: the clinical pregnancy and live birth rates of the CM group were significantly higher than those of the placebo group [44.6% (45/101) vs. 29.7% (30/101), 34.7% (35/101) vs. 20.8% (21/101), both P<0.05]. (2) Follicle development: the incidence of dominant follicles, rate of cumulative cycle ovulation, and rate of cumulative cycle mature follicle ovulation were significantly higher in the CM group than those in the placebo group [93.8% (350/373) vs. 89.5% (341/381), 80.4% (275/342) vs. 69.1% (253/366), 65.8% (181/275) vs 56.1% (142/253), P<0.05 or P<0.01]). The incidence of cumulative cycle luteinized unruptured follicle syndrome was significantly lower in the CM group than in the placebo group [11.7% (40/342) vs. 17.8% (65/366), P<0.05). (3) Endometrial receptivity: after treatment, both endometrial types and endometrial blood flow types in the CM group were mainly types A and B, while those in the placebo group were mainly types B and C, with a significant difference between the two groups (both P<0.05). (4) Adverse events: the incidence of adverse events between the two groups was not significantly different (P>0.05). CONCLUSION: Strategies for activating blood circulation-regulating Gan (Liver)-tonifying Shen (Kidney) sequential therapy can effectively improve the clinical pregnancy rate and live birth rate of endometriosis-associated infertility with qi stagnation and blood stasis after laparoscopy, improve follicular development, promote ovulation, improve endometrial receptivity, while being a safe treatment option. (Trial registration No. NCT02676713).

Effects of electro-acupuncture on IGF-I expression in spared dorsal root ganglia and associated spinal dorsal horn in cats subjected to adjacent dorsal root ganglionectomies.

The effects of electro-acupuncture (EA) on insulin-like growth factor-I (IGF-I) expression in the spared dorsal root ganglia (DRG) and associated spinal dorsal horns were explored in cats subjected to unilateral removal of L(1)-L(5) and L(7)-S(2) DRG, sparing the L(6) DRG. Immunohistochemistry revealed the presence of IGF-I immunoreactive products in the L(6) DRG neurons and some neurons and glial cells in the spinal cord. Western blot demonstrated that the level of IGF-I was significantly up-regulated both in the spared DRG and the dorsal horns of L(3) and L(6) cord segments at both 7 and 14 days post operation following EA. The present findings demonstrated the association between neuroplasticity and IGF-I expression, suggesting the possible role of IGF-I in EA promoted spinal cord plasticity.

Effects of electro-acupuncture on NT-4 expression in spinal dorsal root ganglion and associated segments of the spinal dorsal horn in cats subjected to adjacent dorsal root ganglionectomy.

It is well known that neuroplasticity occurs in the central nervous system in response to injury. Electro-acupuncture (EA) may also promote neuroplasticity. But little is known about the underlying molecular mechanisms for the beneficial effects of EA. This study investigated the effects of EA on neurotrophin-4 (NT-4) expression in L(6) spinal dorsal root ganglion (DRG) and associated segments of the spinal dorsal horn in cats subjected to unilateral removal of L(1)-L(5) and L(7)-S(2) DRG. NT-4 protein was normally present in the cytoplasm of the L(6) DRG neurons and L(3) and L(6) spinal dorsal horn neurons and glia. Adjacent ganglionectomy leads to a significant decrease in NT-4 expression in the L(6) DRG, but no change in the spinal dorsal horn. Following EA treatment a significant increase occurred in the L(6) DRG at 14 days post-operation (dpo) as well as the L(6) cord segment at 7 and 14 dpo. These findings pointed to a possible association between NT-4 expression and EA promoted spinal cord plasticity in adult cats subjected to partial ganglionectomy.