Renal cell carcinoma (RCC) is a common lethal urological cancer,the distant metastasis of which is the leading cause of death.Although targeted agents have remarkably improved the overall prognosis of RCC patients,nearly all the patients eventually acquire therapeutic resistance.With the advent of immune checkpoint inhibitors,immunotherapy based on tumor microenvironment (TME) has shown a broad scope in clinical application.The deepening understanding of TME leads to the changes of therapeutic strategies for advanced RCC,and the combination of targeted therapy and immunotherapy is exhibiting a promising prospect.Herein,we reviewed the TME characteristics,candidate predictive biomarkers,and possible targets for future development of drugs against RCC.
Carcinoma, Renal Cell/therapy* ; Female ; Humans ; Immune Checkpoint Inhibitors ; Immunotherapy ; Kidney Neoplasms/therapy* ; Male ; Tumor Microenvironment

Occupational Health Services ; methods ; organization & administration

Objective To explore the reasons why patients with Keshan disesse complicated with hypertension and their interaction in Fuyu County, Heilongjiang Province. Methods Fifty-three patients with Keshan disease were investigated in January, April and July in 2007. Blood pressure was measured and the risk factors of hypertension were investigated. According to the diagnostic criteria of hypertension, patients were divided into hypertension group and non-hypertension group, and then the risk factors of hypertension, as well as the course of Keshan disease, were compared between the two groups. The risk factors include age, gender, family history of hypertension, salt intake in diet, smoking, drinking and obesity. Results The age of hypertension group[(57.83±8.89)years] was significantly higher than that of non-hypertension group [(51.53 ± 9.43)years, t = 2.3630, P < 0.05) ;while the course of Keshan disease in non-hypertension group [(31.63 ± 8.66)years] was notably longer than that in hypertension group [(25.08±11.41)years, t = 2.0224, P < 0.05] ;No statistically significant difference in gender, family history of hypertension, salt intake in diet, smoking, drinking and obesity was observed between the two groups(χ2 = 0.0072,0.1779,0.0029,0.1555,0.119,0.7679, all P > 0.05). Conclusions Age might be an important factor in patients with Keshan disease accompanied by hypertension, and the role of other risk factors of hypertension should not be overlooked;whether Keshan disease and hypertension can affect each other needs further investigation.

A new benzene derivative microintegerrin C (1) and a new norsesquiterpenoid microintegerrin D (2), along with six known compounds (3-8), were isolated and identified from stems and leaves of Micromelum integerrimum by various chromatographies such as silica gel, Sephadex LH-20, RP-18 column chromatography and HPLC. Their structures were mainly identified based on the spectral data analysis such as 1D-, 2D-NMR and HR-EI-MS. All known compounds were isolated from this plant for the first time.
Chromatography, High Pressure Liquid ; Plant Leaves ; chemistry ; Plant Stems ; chemistry ; Rutaceae ; chemistry ; Sesquiterpenes ; isolation & purification

OBJECTIVETo observe the analgesic effect and safety of acupuncture-anesthetic composite anesthesia (AACA) in hysteroscopic surgery.

METHODSTotally 93 patients undergoing hysteroscopic surgery were randomly assigned to the intravenous anesthesia group (A group, 30 cases), the AACA group (B group, 32 cases), and the acupuncture combined with intravenous anesthesia group (C group, 31 cases). Patients in Group A were anesthetized by sufentanil combined propofol. Those in Group B were anesthetized by sufentanil combined acupuncture. Those in Group C were anesthetized by sufentanil, propofol combined acupuncture. Yinlian and Ququan (LR8) were needled for patients in Group B and C. The peri-operative mean arterial pressure (MAP), heart rate (HR), and oxygen saturation (SpO2), the surgical time, the recovery time, the sufentanil and propofol dosages, adverse anesthesia reactions were observed. Meanwhile, the OAA/S score, Ramsay sedation score, and Visual Analogue Score (VAS) were also measured.

RESULTSCompared with Group A and C, patients in Group B were awake, with obvious increased OAA/S score (P < 0.01). Ramsay sedation score was significantly lower (P < 0.01).The MAP and HR were elevated (P < 0.05). The patient case of SpO2 less than 85% during the operation decreased (P < 0.05). The incidence of postoperative dizziness was reduced (P < 0.05). Compared with Group A, the propofol consumption decreased in Group C (P < 0.05). There was no statistical difference in the operation time, the sufentanil dosage, VAS score, the incidence of postoperative nause- a and vomiting among the three groups (P > 0.05).

CONCLUSIONSThe patients were awake in AACA. The intraoperative sedation was better than that obtained by intravenous anesthesia. But the analgesic effect was similar to that obtained by intravenous anesthesia.

Objective To synthesize and fusion express the predicted T-cell epitopes of Schistosoma japonicum, and analyze their immunogenicities. Methods The plus and minus oligo-nucleic acid strands of epitopes P7, P17, P18 were synthesized following their DNA sequence, respectively. The Nco I restriction enzyme sites were added to the 5′ end of epitope gene and the Xho I restriction enzyme sites were added to the 3′ end of epitope gene. The plus and minus strand of each epitope gene was annealed to form double strand DNA fragments. Then the double strand DNA fragments encoding epitope peptide were cloned into the site between Nco I and Xho I of plasmid pET32c(+) to construct recombinant plasmid which was transformed into E.coli DH5?. The recombinant plasmid containing P7, P17, P18 genes respectively was identified by PCR, restriction digestion and DNA sequencing, and then transformed into E.coli BL21 (DE3) for expressing the fusion protein. The fusion protein of peptide-thioredoxin(Trx) was expressed by inducing with IPTG and analyzed with SDS-PAGE. The fusion proteins were purified with Ni2+ column affinity chromatography. Meanwhile, the peptides P7, P17, P18 were synthesized artificially following their amino acid se-quence. By using the purified epitope peptide fusion proteins and synthesized epitope peptides, the splenic cells of C57BL/6J mice immunized with ultraviolet-attenuated cercaria of Schistosoma japonicum were stimulated respectively. The stimulation activity of fusion proteins and synthesized peptides were assayed by detecting the incorporation rate of 3 H-thymidine. Results The double strand DNA fragments of epitopes P7, P17, P18 were successfully cloned to form recombinant plasmids, all of which could express a 20 kDa fusion protein. Both the fusion protein and synthesized epitope peptides of P7 and P17 were able to stimulate the lymphocyte cells to proliferation effectively. Conclusion The peptide P7 and peptide P17 are testified as T-cell epitopes of Schistosoma japonicum.

Objective To explore the protective effect of recombinant superoxide dismutase(SOD)fusion protein against the infection of Schistosoma japonicum Chinese strain.Methods The recombinant SOD fusion protein was expressed and purified with Glutathione sepharose 4B.C57BL/6J mice were immunized with the recombinant SOD fusion protein mixed with Freund adjuvant.Four weeks after the final immunization,the mice of the experiment and control groups were challenged with(45?2)S.japonicum cercariae.All the mice were sacrificed on the forty-fifth day after the challenge to calculate the worm reduction rate and egg reduction rate,and to observe the pathologic changes of liver tissue of the mice.Results The worm reduction rate was 35.63% and the egg reduction rate was 31.17% in the experiment group.The number of granuloma in the live tissue of the experiment group was less than that of the control group,and the mean diameter of single granuloma in the experiment group reduced by 22.32% compared with that of the control group.The IgG subclass levels of IgG1,IgG2a,IgG2b were higher than those of the control group.Conclusion The recombinant SOD fusion protein has a protective effect against Schistosoma japonicum infection.

As an important part of Chinese medicinal materials, uncommon-territorial herbs are also the most complex parts in the herbal medicine markets. Through years of investigation on the key markets of Chinese herbal medicine, the meaning of uncommon-territorial herbs, their historical evolution, origin and characteristics were clarified in this paper, and some countermeasures were put forward for its development.
Biological Evolution ; China ; Drugs, Chinese Herbal ; chemistry ; history ; Herbal Medicine ; history ; History, 20th Century ; History, 21st Century ; History, Ancient ; Medicine, Chinese Traditional ; history ; Plants, Medicinal ; chemistry ; growth & development

Objective To investigate the efficacy and safety of domestic oseltamivir in patients with influenza. Methods A randomized, single-blinded, controlled clinical trial was performed.Patients in the study group received domestic oseltamivir, while the patients in control group received foreign oseltamivir. The doses were both 75 mg every time, twice a day. The treatment durations in both groups were 5 days. Chi square test was performed to compare baseline characteristics and the difference of side effects. Paired t test was used to compare the efficacy. Results Two hundred and nine patients were enrolled in this study (98 cases in study group. 111 cases in control group). The trend in body temperature change was similar in the two groups (t = 0. 061, P>0. 05). The score of symptom severity decreased more quickly in patients treated with foreign oseltamivir compared to those treated with domestic oseltamivir during the period from 24 h to 48 h. However, the difference between the two groups diminished gradually and was not statistically significant at 72 h (t=0. 875,P>0. 05). The safety of the domestic and foreign oseltamivir were comparable(X2 = 0. 197,P>0. 05). Conclusion The domestic oseltamivir is as effective and safe as the foreign oseltamivir.

Objective　To study the relationship between atherosclerotic plaques in carotid artery and ischemic cerebrovascular diseases. Methods　The extracranial carotid arteries (ECA) and middle cerebral artery (MCA) of 54 patients with transient ischemic attack (TIA) or cerebral infarction (CI) were examined with doppler ultrasound. The distribution of atherosclerotic plaque, degree of stenosis and ultrasounic classification of ECA and the mean velocity of blood flow in MCA were examined. Results　①Stenosis over middle-grade on asymptomatic side in extracranial internal carotid artery (EICA) in group of patients with TIA was significantly higher than symptomatic side(P<0.01). Stenosis over high-grade on asymptomatic side in ELCA in group of patients with CI was significantly higher than symptomatic side (P<0.01). ②Flat and soft plaque are most common in group of patients with TIA or CI, then are hard and ulcerative plaques. Incidence of soft plaques on asymptomatic side in group of patients with TIA or CI are significantly higher than symptomatic side (P<0.01); ③Among the group of patients with CI, mean velocity of MCA decreased on asymptomatic side in 31 cases (68.9%), and significantly higher than symptomatic side (P<0.01). Conclusion　Atheroclerotic plaques in carotid artery and intracranial hemodynamic characteristics are the important risk factors for ischemic cerebrovascular diseases. These findings have important values in predicting subsequent TIA or CI in asymptomatic subjects.