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In 2011, the FDA approved ipilimumab, the first immune checkpoint inhibitor(ICI), targeting CTLA-4, opening the field of immune checkpoint therapy (ICT). ICIs can induce durable clinical responses and improve survival in selected population. However, significant challenges still remain, including mechanisms of resistance, patient selection, management of serious immune-related adverse events, and rational therapeutic combinations. This review surveys the current understanding of response and resistance to ICIs and proposes a path forward to improving efficacy and minimizing toxicities.
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Objective:To explore the effects of Baduanjin and balancer exercise on motor and non-motor symptoms for patients with mild to moderate Parkinson's disease (PD). Methods:From May, 2017 to September, 2018, 31 patients with PD were collected from the inpatients, outpatients and outside of our hospitals. The patients accepted Baduanjin and balancer exercise successively, three weeks for each exercise, and were assessed with Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part I, II, III and IV, and Non-motor Symptoms Scale (NMSS) before and after each exercise. Results:Four cases dropped out during Baduanjin exercise. The total score, the scores of part I, II and III of MDS-UPDRS, and NMSS score (t > 3.274, P < 0.01) decreased significantly after Baduanjin exercise. Other three cases dropped out during balancer exercise. The total score and the score of part III of MDS-UPDRS decreased significantly after balancer exercise (t > 2.763, P < 0.05). Conclusion:Baduanjin exercise can improve the motor and non-motor symptoms of mild to moderate PD, but not significant for motor complications; while balancer exercise can improve the motor symptoms, but not significant for non-motor symptoms and motor complications.
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Objective:To analyze the target design and dosimetric parameters of patients with recurrent adenoid cystic carcinoma (ACC) in the parotid gland who were treated with 125I interstitial brachytherapy alone. Methods:A retrospective analysis was conducted for 25 patients with recurrent adenoid cystic carcinoma in parotid gland who were histopathologically diagnosed between January 2015 and October 2019. These patients were treated with 125I interstitial brachytherapy alone, with prescribed doses of 100-120 Gy. The target volume was designed according to the pathological characteristics of ACC and recurrence sites. The pre- and post-operation dosimetric parameters (i.e., local control rates) were calculated using the treatment planning system. Results:In this study, the local recurrence sites included the superficial lobe (10/25) and deep lobe (7/25) of the parotid gland primarily and the skull base region (four patients) and mastoid posterior region (four patients) secondarily. The number of 125I seeds ranged from 16 to 111, with a median number of 59. The activity of radioactive particles was 18.5-25.9 MBq. The 3- and 5-year local control rates were 81.5% and 61.5%, respectively. No significant differences were found between pre- and post-operative dosimetric parameters such as D90, V100, and V150. There was no significant difference in local control rates among the four different recurrence sites. Conclusions:125I interstitial brachytherapy is proven to be an effective approach in the treatment of recurrent adenoid cystic carcinoma in the parotid gland. Satisfying local control rates can be achieved through target delineation performed according to recurrence sites and perineural invasion characteristics of ACC.
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OBJECTIVE: To explore the involvement of miR-34a in cerebral cortex mediated anti-hyperalgesic effect of electroacupuncture (EA) in mice with neuropathic pain induced by chronic constriction injury (CCI) of sciatic nerve, so as to reveal its mechanisms underlying improvement of neuropathic pain. METHODS: A total of 75 male C57BL/6 mice were equally randomized into 3 groups: sham, CCI model and CCI+EA (n=25 in each group). Mice of the sham group received simple separation of the right sciatic nerve without ligation. The CCI model was established by liagation of the right sciatic nerve. EA (2 Hz /15 Hz, 1 mA) was applied to bilateral "Zusanli" (ST36) and "Sanyinjiao" (SP9) for 30 min, once every other day. The mechanical and thermal pain threshold of the bilateral hind-paws was detected at the 3rd, 5th and 7th day after modeling, and the expression of miR-34a of bilateral cerebral cortex tissues and that of p53 protein of the left cerebral cortex were determined by using quantitive real time PCR and Western blot, respectively. RESULTS: The mechnical paw withdrawal frequency were significantly higher and the thermal paw withdrawal latencies (PWLs) were significantly shorter at the affected hind-limb (rather than at the healthy hind limb) on day 3, 5 and 7 in the CCI model group than those in the sham group (P<0.05), and considerably reversed at the affected hind-limb (rather than at the healthy hind limb) in the EA group than in the CCI model group (P<0.05), suggesting an analgesic effect of EA intervention. After modeling, the expression levels of miR-34a and p53 on day 3, 5 and 7 were significantly up-regulated in the left cerebral cortex tissue (rather than in the right cerebral cortex) of the CCI model group in comparison with the sham group (P<0.05). After EA intervention, the up-regulated expression levels of miR-34a and p53 in the left cerebral cortex tissue (rather than in the right cerebral cortex) were obviously suppressed in the EA group relevant to the CCI model group (P<0.05). CONCLUSION: EA stimulation of ST36 and SP9 can down-regulate the expression of miR-34a and p53 in the contra-lateral cerebral cortex tissue of the CCI mice, which may contribute to its anti-hyperalgesic effect.
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In the present study,fresh Guangdilong( GD),originating from Pheretima aspergillum,was taken as the object. The total proteins from GD were firstly separated by SDS-PAGE according to their molecular weights and in-gel digestion was then performed.After that,the peptides were analyzed by nano LC/orbitrap fusion lumos high resolution mass spectrometry( nano LC/orbitrap fusion lumos HR-MS). Protein identification was implemented by comparison with Annelida. fasta database using Proteome Discoverer software.As a result,386 proteins were tentatively identified,including chain F,globin B chain,glyceraldehyde-3-phosphate dehydrogenase,fibrinolytic protein,and so on. Most of the proteins took part in cell structure and energy metabolism,and fibrinolytic protein and lombricine kinase might be related to fibrinolytic activity. Protein classification based on gene ontology was carried out using PANTHER and KEGG for metabolic pathway enrichment. The results indicated that these proteins were related to diverse signal transduction pathways,including metabolic pathways,central carbon metabolism,biosynthesis of amino acids,ribosome,glycolysis,citrate cycle( TCA cycle),and so on. This study would lay the foundation for the further research on the proteins in GD and also their functions.
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Animals , Chromatography, Liquid , Electrophoresis, Polyacrylamide Gel , Gene Ontology , Mass Spectrometry , Oligochaeta , Chemistry , Proteome , ProteomicsABSTRACT
Gelatinous Chinese materia medica (GCMM), as a valuable nourishing traditional medicine in China, has been used widely for a long time. The quality control for GCMM has undergone a long development, including physical and chemical tests, thin layer chromatography, electrophoresis, spectroscopy, HPLC, DNA identification techniques, and LC-MS with unique peptide as target. The article summarizes the progress of quality control system of GCMM in recent years, analyzes the remaining problems, puts forward the feasibility protocol to further improve the quality control system, and provides ideas for the comprehensive evaluation of GCMM and its related products.
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A rapid identification of the constituents in Gualoupi injection was developed by HILIC/Orbitrap Fusion Lumos HRMS. ACQUITY XBridge Amide column was used to isolate the constituents with large polarity. ESI with positive ion mode was employed and "Top Speed" DDA was applied in the MS2 scan. Compound identification was carried out by using Compound Discoverer software through comparing the precursor and product ions information with those in ChemSpider and mzCloud database. As a result, 48 compounds was identified, including alkaloids, amino acid, nucleosides, nucleobases, etc., among which 25 was unambiguously identified by comparing the retention time and mass spectra information with those of reference standards. In general, the main constituents from Gualoupi injection were explained in this study. Additionally, full-scan mass spectra of 21 batches of the injection were collected by the established method. Subsequently, principal component analysis (PCA) with the peak area as the observation ID was employed to analyze the discrimination of different bathes of samples. The results indicated that the batch-to-batch difference was generally from the crude drug, and the preparation process of this injection was relatively stable. In conclusion, a rapid and effective method for the identification of compounds in Gualoupi injection was established by using UHPLC-Orbitrap Fusion Lumos HRMS and the inter-bath stability was also investigated, which may make a great contribution to the study of the bioactive ingredients in Gualoupi injection and also provide vital evidence for the standard promotion.
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Objective To study the safety of transfusion of itraconazole through PICC and to evaluate the effect of different amount of blood transfusion before and after the infusion. Methods Patients were recruited from January 1, 2014, until December 31, 2015, in the Hematology hematopoietic stem cell transplantation ward. Thiry-two patients were recruited in the control group. Ninety patients wererecruited in the experience group. They were randomly assigned to three groups with 30 cases each, extracting different amounts of itraconazole before infusion, back phlebotomize in group A, B, C respectively was 10.0, 0.5, 1.0 ml. Comparing the phlebitis and obstruction after ten days from the transfusion day on. Results Catheter obstruction was not observed in any case. There was a significant difference between control group (21.9%,7/32) and observation group (0) regarding the incidence of phlebitis (χ2=21.157,P 0.05). Conclusions Drawing a small amount of blood volume before itraconazole injection through PICC can effectively avoid the drug-induced catheterobstruction. What′s more, transfusion through PICC can significantly reduce the incidence of phlebitis compared with peripheral infusion.
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Objective To identify the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) gargle in patients who had oral mucositis after allogeneic hematopoietic stem cell transplantation. Methods A total of 134 patients were enrolled in this study from 2014 to 2015. They were randomly divided into two groups:the experimental group (n=65) and the control group (n=69). Both groups received preventive measures for oral mucositis. But once oral mucositis occurred, the control group continued with the routine nursing measure, while the experimental group added GM-CSF gargle based on previous routine nursing measure. The effective rate and healing time were compared between two groups. Results The effective rate of the experimental group (81.54%, 53/65) was significantly higher than that of the control group (24.64%,17/69) (χ2=43.434, P=0.000). The median healing time in the experimental group was 4.5 days, shorter than 9.0 days in the control group (Z=-5.379, P< 0.01). Conclusions GM-CSF gargle can control the oral mucositis after allogeneic hematopoietic stem cell transplantation.
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Objective To investigate the comprehensive prevention strategy in the prevention of oral mucositis (OM) during allogeneic hematopoietic stem cell transplantation (HSCT). Methods A total of 721 patients who received HSCT from January 2010 to December 2011 at the Institute of Hematology, Peking University were enrolled. All the patients received the comprehensive prevention strategy of OM. Results A total of 315 patients (43.7 percents) suffered from OM during HSCT, the median time from HSCT to OM occurrence was 5 days. There were 173 (54.9 percents), 91(28.9 percents), 37(11.7 percents), and 14(4.4 percents) patients suffered from gradeⅠ,Ⅱ,Ⅲ, and IV OM, respectively. Tongue OM was most common. A total of 111 patients suffered from multiple OM (≥2 locations). Multiplicity showed that duration of agranulocytosis≥15 days was the only independent risk factor of OM in HSCT [ hazard ratio (HR) value 1.5, P<0.05 ]. Neutrophil engraftment time≥12 days was significantly associated with prolonged OM (≥8 days) (HR=2.1, P<0.05). Patient age ≥20 was independent risk factor for occurrance of grade Ⅲ-Ⅳ OM (HR=2.7, P<0.05). Conclusions Comprehensive prevention strategy can overcome the risk factors of OM and prevent the occurrence of OM during HSCT.
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<p><b>OBJECTIVE</b>To observe whether adenosine Al receptor (Al R) mediated neuroprotection of Shenmai Injection (SI) on rat cerebral ischemia/reperfusion (I/R) injury.</p><p><b>METHODS</b>The focal cerebral I/R model was established by middle cerebral artery occlusion (MCAO). Totally 60 successfully modeled rats was divided into 5 groups according to randomized block principle, i.e., the model group, the SI group, the SI + AlR antagonist (1,3-dipropyl-8-cyclopentylxanthine, DPCPX) group, the AlR antagonist control group, and the dimethyl sulfoxide (DMSO) control group, 12 in each group. Besides, a sham-operation group was set up (n =12). SI at 15 mL/kg was peritoneally injected to mice in the SI group immediately after cerebral I/R. Equal volume of normal saline was injected to mice in the model group and the sham-operation group. DPCPX at 1 mg/mL was peritoneally injected to mice in the Al R antagonist control group 30 min before peritoneal injecting SI. DPCPX at 1 mg/kg and DMSO at 1 mL/kg were peritoneally injected to mice in the AlR antagonist control group and the DMSO control group 30 min immediately before cerebral I/R. Rats' neurobehavioral scores were assessed after 24 h reperfusion. The volume of cerebral infarction and Bcl-2 protein expression of cerebral infarction penumbra were also detected. Results Compared with the sham-operation group, neurobehavioral scores, the volume of cerebral infarction, and Bcl-2 protein expression increased (all P <0. 05). Compared with the model group, neurobehavioral scores and the volume of cerebral infarction obviously decreased, but Bcl-2 protein expression increased in the SI group (all P <0. 05). Compared with the SI group, neurobehavioral scores increased, the volume of cerebral infarction was obviously enlarged, and Bcl-2 protein expression was obviously reduced in the A1R antagonist control group (all P <0. 05).</p><p><b>CONCLUSIONS</b>SI's neurobehavioral scores could be partially reversed in the Al R antagonist control group, the volume of cerebral infarction and Bcl-2 protein expression improved. AlR might possibly meditate neuroprotection of SI on MACO mire</p>
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Animals , Mice , Rats , Adenosine , Brain Ischemia , Drug Therapy , Drug Combinations , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Infarction, Middle Cerebral Artery , Neuroprotection , Physiology , Neuroprotective Agents , Pharmacology , Therapeutic Uses , Rats, Sprague-Dawley , Receptor, Adenosine A1 , Metabolism , Reperfusion Injury , Drug Therapy , XanthinesABSTRACT
<p><b>OBJECTIVE</b>To observe the clinical efficacy of transcutaneous acupoint electrical stimulation (TAES) combined intravenous injection and/or Neiguan (P6) injection with droperidol in preventing and treating post-operative nausea and vomiting (PONV) after thyroid tumor surgery.</p><p><b>METHODS</b>Recruited were 120 female patients who underwent selective thyroid tumor surgery were randomly assigned to the control group, the TAES group, the IV group (intravenous injection of droperidol), and the P6 group [Neiguan point (P6) injection of droperidol], respectively, 30 cases in each group. Thirty min before anesthesia induction, 2 mL 0.9% normal saline injection was intravenously injected to those in the control group. Patients in the TAES group received TEAS at bilateral P6 points. 2.5 mg (1 mL) droperidol added in 1 mL 0.9 normal saline was intravenously injected to those in the IV group and injected at bilateral P6 points of those in the P6 group. The occurrence and severity of PONV were observed within 0 - 6 h and within 6 - 24 h after operation in each group.</p><p><b>RESULTS</b>Compared with the control group, the incidence and the severity of PONV within 0 - 6 h and within 6 - 24 h after thyroid surgery were significantly reduced in the three treatment groups (P < 0.05). There was no statistical difference in the incidence or the severity of PONV among the TAES, IV and P6 groups (P > 0.05).</p><p><b>CONCLUSIONS</b>TEAS at P6 could dramatically reduce the occurrence and the severity of PONV after thyroid tumor surgery. Besides, it got equivalent effect to that by intravenous injecting droperidol or by injecting droperidol at P6.</p>
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Adult , Female , Humans , Middle Aged , Acupuncture Points , Postoperative Nausea and Vomiting , Prospective Studies , Single-Blind Method , Thyroid Neoplasms , General Surgery , Transcutaneous Electric Nerve StimulationABSTRACT
<p><b>OBJECTIVE</b>To investigate the therapeutic effect of digital dorsal flap based on vascular network for skin defects at fingers.</p><p><b>METHODS</b>From August 2005 to August 2010, 49 cases with 61 skin defects at fingers were treated with the digital dorsal flaps, including 19 at the index fingers, 19 at the middle fingers, 16 at the ring fingers and 3 at the little fingers. The defects were 42 at the distal end, 12 at the middle segment and 7 at the proximal segment. The flaps size ranged from 27 mm x 20 mm to 10 mm x 8 mm.</p><p><b>RESULTS</b>61 flaps in 49 cases survived completely. 52 fingers were followed up for 6-22 months. The aesthetic and functional results were both satisfactory. The flaps sensation was graded as S3, with a discrimination distance of 6-9 mm (median, 7.6 mm). No complication happened in donor sites.</p><p><b>CONCLUSIONS</b>The digital dorsal flap based on vascular network has reliable blood supply with less morbidity to the main artery. It is safe and easily performed with good effect for skin defect at finger.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Finger Injuries , General Surgery , Skin , Wounds and Injuries , Skin Transplantation , Methods , Soft Tissue Injuries , General Surgery , Surgical Flaps , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To investigate the therapeutic effect of free tissue flap anastomosed with reverse descendant branch of lateral femoral circumflex artery for severe soft tissue defect at leg.</p><p><b>METHODS</b>The severe soft tissue defect at leg, without any vessels for anastomosis of free tissue flap, was reconstructed with free tissue flap, which was anastomosed with proximal end of descendant branch of lateral femoral circumflex artery and great saphenous vein. From Oct. 2004 to Dec. 2009, 36 cases were treated with 15 cases of latissimus dorsi musculocutaneous flaps, 12 cases of anterolateral femoral flaps, and 9 cases of thoracoumbilicus flaps.</p><p><b>RESULTS</b>All the 36 free flaps survived completely. The patients were followed up for 6 months to 2.5 years with good cosmetic results.</p><p><b>CONCLUSIONS</b>It is effective and practical to repair the severe soft tissue defects at legs with the reverse descendant branch of lateral femoral circumflex artery to carry the free flaps.</p>
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Adult , Female , Humans , Male , Middle Aged , Young Adult , Femoral Artery , General Surgery , Follow-Up Studies , Free Tissue Flaps , Leg Injuries , General Surgery , Skin Transplantation , Methods , Soft Tissue Injuries , General Surgery , Thigh , General Surgery , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To discuss the application of reverse flap based on two dorsal metacarpal artery for reconstruction of degloved fingertip avulsion.</p><p><b>METHODS</b>From Jan. 2005 to Mar. 2008, 28 cases with degloved fingertip avulsion were treated with reverse flaps based on two dorsal metacarpal artery. The defects were located distal to the distant interphalangeal joints and were 0.8-2.2 cm in length. 10 defects was in the index fingers, 13 in the middle fingers and 5 in the ring fingers. 24 fingers were treated in an emergency surgery. 4 fingers were treated due to skin necrosis.</p><p><b>RESULTS</b>Epidermal necrosis happened at the distal end of flaps in 3 cases. All the other flaps survived completely. 25 cases were followed up for 4-27 months with satisfactory cosmetic and functional results. The 2-points discrimination distance was 6.0-9.0 mm (average, 7.6 mm).</p><p><b>CONCLUSIONS</b>The reverse flap based on two dorsal metacarpal artery is easily performed and reliable for degloved fingertip avulsion with satisfactory results.</p>
Subject(s)
Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Young Adult , Finger Injuries , General Surgery , Follow-Up Studies , Surgical Flaps , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To investigate the therapeutic effect of island flaps pedicled with digital artery for the defects at the end of fingers.</p><p><b>METHODS</b>63 cases with 72 soft tissue defects at the end of fingers were treated with the island flaps. The flap size ranged from 8 mm x 11 mm to 21 mm x 27 mm.</p><p><b>RESULTS</b>All the flaps survived completely. The follow-up period ranged from 4 to 19 months. The functional and cosmetic results were satisfactory. The two-point discrimination was 7 to approximately 9 mm. The TAM functional examination showed excellent in 59 fingers, good in 11 fingers and common in 2 fingers.</p><p><b>CONCLUSIONS</b>The technique with island flap is simple and reliable for the defects at the end of fingers.</p>