Predictive Value of Tumor Mutation Burden in Immunotherapy for Lung Cancer / 中国肺癌杂志

The morbidity and mortality of lung cancer is the first in the world, immunotherapy has become a important treatment strategy in addition to chemotherapy, radiotherapy and targeted therapy. In recent years, the US Food and Drug Administration (FDA) has successively approved immunological checkpoint inhibitors as standard programs for non-small cell lung cancer (NSCLC) in second-line or first-line treatment. The National Comprehensive Cancer Network (NCCN) also recommends immunological checkpoint inhibitors as the standard treatment for small cell lung cancer (SCLC). Now, the treatment for lung cancer has entered the era of precision treatment, it is very important to select effective and reliable biomarker for the dominant populations of lung cancer to receive immunotherapy. A large number of researchs indicated that tumor mutation burden (TMB) may be an independent predicted biomarker for immunotherapy, but with limitations. This article reviewed the predictive value of TMB and its limitations in the field of immunotherapy for lung cancer.

Advances on preparation and pharmacological activities of Typhonium giganteum / 中草药

After processing, the tuber of Typhonium giganteum was used as Typhonii Rhizoma in Chinese materia medica. It has effects such as dispelling wind phlegm, detoxifying, removing stasis, and relieving pain. However, due to its toxicity, it needs to be processed before using. In this paper, the toxicity, processing technology, changes of components and efficacy before and after processing, and pharmacological effects are analyzed and summarized, which will provide reference for further study of T. giganteum.

Effects of siRNA interference combined with hyperbaric oxygen treatment on cerebral edema and apoptosis in the brain tissue of rats after hemorrhage / 中华老年医学杂志

Objective To examine the effects and mechanisms of siRNA targeting aquaporin 4 (AQP 4) in combination with hyperbaric oxygen therapy(HBO) on cerebral edema and apoptosis in the brain tissue of rats after hemorrhage.Methods Rats were randomly divided into four groups,the control group,the hyperbaric oxygen group,the AQP-4 siRNA group and the combination therapy group (24 rats).Thrombin Ⅶ was injected into the caudate nucleus to establish the hemorrhage model.Construction of siRNA targeting aquaporin 4 was conducted.The mRNA expression of AQP-4 was detected by RT-PCR at day 3.Changes in brain moisture and blood-brain barrier perme ability were measured by a wet/dry weight method and Evans blue fluorometry.The nerve cell apoptosis rate was analyzed by Annexin V andTdT-mediated dUTP-biotin nick end labeling (TUNEL).The expression of proteins including AQP-4,MMP-2,MMP-9,Bcl-2 and caspase-3 was detected by Western Blotting.All the animals were given a score for their nerve function at day 3.Results AQP-4 siRNA treatment obtained better effects than HBO in decreasing the brain edema leveland silencing AQP-4 mRNA(P＜0.05)while,the combination therapy group achieved the best results(P＜ 0.05).Compared with the control group,the percentage of apoptotic cells decreased in all the three treatment groups,with the most marked decrease observed in the combination treatment group(4.24± 0.04)％(F=13.76,P=0.001).The expression of AQP-4,MMP-2,MMP-9 and caspase-3 was lower (P＜0.05) and the expression of Bcl-2 was higher(P＜0.01)in the combination treatment group than in the other three groups.Compared with the control group,all the other three groups received better scores on nerve function defect evaluation at day 3 after hemorrhage(P＜0.05),with the combination treatment group again achieving the most favorable score (4.7 ± 1.1) (F=7.21,P =0.013).Conclusions Targeted siRNA interference combined with hyperbaric oxygen can effectively reduce cerebral edema after cerebral hemorrhage,inhibit neuronal apoptosis and promote neuron function recovery.The underlying mechanisms may be related to down-regulation of AQP-4,MMP 2,MMP-9 and caspase-3 expression and up-regulation of Bcl-2 expression.

Effects of Saikokaryukotsuboreito on Spermatogenesis and Fertility in Aging Male Mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Aspermia caused by exogenous testosterone limit its usage in late-onset hypogonadism (LOH) patients desiring fertility. Saikokaryukotsuboreito (SKRBT) is reported to improve serum testosterone and relieve LOH-related symptoms. However, it is unclear whether SKRBT affects fertility. We aimed to examine the effects of SKRBT on spermatogenesis and fertility in aging male mice.</p><p><b>METHODS</b>Thirty aging male mice were randomly assigned to three groups. Mice were orally administered with phosphate-buffer solution or SKRBT (300 mg/kg, daily) or received testosterone by subcutaneous injections (10 mg/kg, every 3 days). Thirty days later, each male mouse was mated with two female mice. All animals were sacrificed at the end of 90 days. Intratesticular testosterone (ITT) levels, quality of sperm, expression of synaptonemal complex protein 3 (SYCP3), and fertility were assayed.</p><p><b>RESULTS</b>In the SKRBT-treated group, ITT, quality of sperm, and expression of SYCP3 were all improved compared with the control group (ITT: 85.50 ± 12.31 ng/g vs. 74.10 ± 11.45 ng/g, P = 0.027; sperm number: [14.94 ± 4.63] × 106 cells/ml vs. [8.79 ± 4.38] × 106 cells/ml, P = 0.002; sperm motility: 43.16 ± 9.93% vs. 33.51 ± 6.98%, P = 0.015; the number of SYCP3-positive cells/tubule: 77.50 ± 11.01 ng/ml vs. 49.30 ± 8.73 ng/ml, P < 0.001; the expression of SYCP3 protein: 1.23 ± 0.09 vs. 0.84 ± 0.10, P < 0.001), but fertility was not significantly changed (P > 0.05, respectively). In the testosterone-treated group, ITT, quality of sperm, and expression of SYCP3 were markedly lower than the control group (ITT: 59.00 ± 8.67, P = 0.005; sperm number: [4.34 ± 2.45] × 106 cells/ml, P = 0.018; sperm motility: 19.53 ± 7.69%, P = 0.001; the number of SYCP3-positive cells/tubule: 30.00 ± 11.28, P < 0.001; the percentage of SYCP3-positive tubules/section 71.98 ± 8.88%, P = 0.001; the expression of SYCP3 protein: 0.71 ± 0.09, P < 0.001), and fertility was also suppressed (P < 0.05, respectively).</p><p><b>CONCLUSION</b>SKRBT had no adverse effect on fertility potential in aging male mice.</p>

Electro-acupuncture combined with surface gastric pacing in the treatment of gastrointestinal dysfunction after spinal cord injury / 中华物理医学与康复杂志

Objective To explore the effects of electro-acupuncture combined with surface gastric pacing on gastrointestinal dysfunction for patients with spinal cord injury (SCI).Methods Seventy-five SCI patients with gastrointestinal dysfunction were divided randomly into an electro-acupuncture group (group A),a gastric pacing treatment group (group B) and a group for which electro-acupuncture was combined with gastric pacing (group C).There were 25 cases in each group.Members of group A were given 30 minutes of electro-acupuncture per day ; those of group B had 30 minutes of gastric pacing treatment twice per day ; group C was provided with both 30 minutes of electro-acupuncture and one 30-minute gastric pacing treatment per day.All of the interventions lasted ten days.Before and after the treatment,all patients were assessed using a clinical symptoms score and with electrogastrograms,and any adverse effects were observed.Results There was a significant improvement in upper abdominal pain and epigastric discomfort,bloating and early satiety,nausea,vomiting,as well as belching and loss of appetite in each group after treatment.Before treatment there was no significant difference in the average clinical symptom scores of the three groups.After treatment the values had decreased,and those of group C were significantly lower than group A or B.The average scores of groups B and A were not significantly different.The electrogastrogram results showed than after treatment there was significant improvement in N％ and T％ in groups A and B,and also significant improvement in N％,B％ and T％ in group C compared to before treatment.Group C's improvements were all significantly greater than those observed in groups A and B.Conclusion Electro-acupuncture or gastric pacing alone can give some improvement in gastrointestinal function and its electrophysiological indicators,but their combined effects are better than when either is used alone.

Triptolide synergistically enhances temozolomide-induced apoptosis and potentiates inhibition of NF-κB signaling in glioma initiating cells.

Glioblastoma multiforme (GBM) is a lethal solid cancer in adults. Temozolomide (TMZ) is a first-line chemotherapeutic agent but the efficacy is limited by intrinsic and acquired resistance in GBM. Triptolide (TPL), a derivative from traditional Chinese medicine, demonstrated anti-tumor activity. In this study, we explored the interaction of TPL and TMZ in glioma-initiating cells (GICs) and the potential mechanism. A GIC line (GIC-1) was successfully established. Cell viability of GIC-1 after treatment was measured using a CCK-8 assay. The interaction between TPL and TMZ was calculated from Chou-Talalay equations and isobologram. Self-renewal was evaluated with tumor sphere formation assay. Apoptosis was assessed with flow cytometry and western blot. Luciferase assay was employed to measure NF-κB transcriptional activity. The expression of NF-κB downstream genes, NF-κB nuclear translocalization and phoshorylation of IκBα and p65 were evaluated using western blot. We found that GIC-1 cells were resistant to TMZ, with the expected IC50 of 705.7 µmol/L. Co-treatment with TPL yielded a more than three-fold dose reduction of TMZ. TPL significantly increased the percentage of apoptotic cells and suppressed the tumor sphere formation when combined with TMZ. Phosphorylation of IκBα and p65 coupled with NF-κB nuclear translocalization were notably inhibited after a combined treatment. Co-incubation synergistically repressed NF-κB transcriptional activity and downstream gene expression. TPL sensitizes GICs to TMZ by synergistically enhancing apoptosis, which is likely resulting from the augmented repression of NF-κB signaling. TPL is therefore a potential chemosensitizer in the treatment of GBM.

Experimental study on the osseointegration of foam TiC/Ti composites.

Macroporous ceramics have demonstrated osteoconductive properties because of their biocompatibility and 3D macroporous structure, and these materials have recently been widely studied as bone replacement materials. The foam TiC/Ti composites discussed in this study have good mechanical properties, balancing out metallic toughness and ceramic strength. Furthermore, because of the high porosity and pore connectivity of these TiC/Ti composites, they have the potential to be a new bone replacement material. The purpose of this study was to evaluate the osseointegration of foam TiC/Ti composites, preliminarily discuss the TiC/Ti ossification mechanism, and to obtain reliable data on the use of foam TiC/Ti composites as bone replacement materials. The foam TiC/Ti composites were sited in 40 Japanese white rabbits for 4, 8, 12 and 24 weeks. The foam TiC/Ti composites were compared to foam SiC. M-CT (micro-computed tomography) analysis, histological analysis, SEM (scanning electron microscopy) observation and EDS (energy-dispersive x-ray spectrometer) analysis were conducted to estimate the osseointegration of the materials. The histological observations and quantitative analysis exhibited significantly more ossification area (volume), trabeculae maturity, and calcium and phosphorus content in the foam TiC/Ti composites compared to the foam SiC (p < 0.05). The results from this study suggest that the foam TiC/Ti composites possess good osseointegration capacity and have the potential to be a new bone replacement material.

Qilin pills combined with levofloxacin for asthenospermia accompanied with accessory sex gland infection: a clinical observation / 中华男科学杂志

<p><b>OBJECTIVE</b>To observe the efficacy of the combination of Qilin Pills and levofloxacin in the treatment of asthenospermia accompanied with accessory sex gland infection.</p><p><b>METHODS</b>We randomly assigned 80 asthenospermia patients with accessory sex gland infection to groups 1 and 2 of equal number, the former treated with Qilin Pills + levofloxacin, and the latter with levofloxacin only. Qilin Pills were administered at the dose of 6 g tid for 30 days, and levofloxacin at the dose of 0.5 g qd for 20 days. We obtained semen parameters, including the percentage of progressively motile sperm and peroxidase-positive white blood cell (WBC) count, before and after medication, and compared the clinical effects between the two groups.</p><p><b>RESULTS</b>All the patients accomplished the clinical trial. The therapeutic effectiveness rates in improving progressive sperm motility were 60% in group 1 and 17.5% in group 2, with statistically significant differences between the two groups (P < 0.05). As for the peroxidase-positive WBC count in semen, the effectiveness rates were 87.5% and 82.5%, respectively, with no significant differences between the two groups (P > 0.05).</p><p><b>CONCLUSION</b>For the treatment of asthenospermia accompanied with accessory sex gland infection, Qilin Pills combined with levofloxacin is evidently better than levofloxacin alone in improving sperm motility, and it has no obvious adverse effects.</p>

Effect of major components of maijunan tablets on the transport of hydrochlorothiazide in Caco-2 cell monolayer model / 药学学报

To study the effects of major components of Maijunan tablets, puerarin (Pue) and rhynchophylline (Rhy) on the transport of hydrochlorothiazide (Hct) Caco-2 cell monolayer model, the transport parameters of Hct, such as apparent permeability coefficient (P(app) (B --> A) and P(app) (A --> B)) and the ratio of P(app) (B --> A) versus P(app) (A --> B), were studied and compared when Hct was used solely and co-used with Pue and/or Rhy. The effects of drug concentrations, conveying times, P-glyprotein (P-gp) inhibitor verapamil and conveying Liq pH values on the transport of Hct in the above conditions were also investigated. The results indicated that the absorption of Hct in Caco-2 cell monolayer model could be a carrier-mediated active transport, along with the excretion action mediated by P-gp. Pue can decrease the excretion action of Hct mediated by P-gp, and Rhy had no significant effect on the transport of Hct. The co-use of Hct, Pue and Rhy enhanced the absorption of Hct. Meanwhile, conveying Liq pH value had significant influence on the transport of Hct. The absorption of Hct at pH 6.0 was higher than that at pH 7.4.

Study on the effects of two kinds of cactus polysaccharide on erythrocyte immune function of S180 mice / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effects of two kinds of cactus polysaccharide on erythrocyte immune function in S180 mice.</p><p><b>METHOD</b>Classical pharmaceutical method and test kit.</p><p><b>RESULT</b>The cactus polysaccharide increased the content of RBC-CaR, RFER, decreased the content of RFIR, raised the content of sialic acid. And the effect of median dose group of medical cactus polysaccharide and high dose group of edible cactus polysaccharide is very remarkable (P < 0.01) compared with model group.</p><p><b>CONCLUSION</b>The cactus polysaccharide improved the erythrocyte function of tumor-mice, which may be one of anti-tumor mechanisms.</p>

Study on the effects of two kinds of cactus polysaccharide on erythrocyte membrane protein and fluidity of the lipid in S180 mice / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effects of two kinds of cactus polysaccharide on Band 3 protein, cross-linking protein and lipid fluidity of erythrocyte membrane in S180 mice.</p><p><b>METHOD</b>The membrane protein content was analysed by SDS-PAGE. Lipid fluidity was measured by Skinitzky method.</p><p><b>RESULT</b>The two kinds of cactus polysaccharide increased the content of Band 3 protein and decreased the content of cross-linking protein, raised the lipid fluidity. While the effect of median dose group of medical cactus polysaccharide is very remarkable (P < 0.01), the effect of high dose group of edible cactus polysaccharide is very remarkable (P < 0.01).</p><p><b>CONCLUSION</b>By improving the erythrocyte membrane function of tumor-mice, they enhanced the immune function, which may be one of anti-tumor mechanisms.</p>