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AIM: To investigate the implication of respiratory microbiology on the efficacy of PD-1 inhibitors monotherapy for patients with NSCLC. METHODS: This study was designed as a retrospective study, fifty-eight patients with previously-treated advanced NSCLC who were received PD-1 monotherapy from October 2018 to October 2021 were included. The PD-1 inhibitors were consisted of camrelizumab, sintilimab and pembrolizumab. Additionally, the basic demographic data, therapeutic efficacy data, survival prognosis and adverse reactions during the PD-1 inhibitors treatment were collected and analyzed through the patients' medical records of the department and the electronic medical record system of the hospital. Furthermore, deep induced sputum specimens of the patients before treatment with PD-1 inhibitor were collected. And the respiratory microbiology of 58 samples were detected using 16S rRNA gene sequencing method. The index of respiratory microbiology α diversity was analyzed, and the correlation analysis was performed with the efficacy and prognosis of patients. RESULTS: A total of 58 patients with advanced NSCLC met the study's screening criteria and were evaluable for efficacy and safety profile. Efficacy data suggested that the objective response rate (ORR) and disease control rate (DCR) of the patients who received PD-1 inhibitors was 19.0%(95% CI: 9.9%-31.4%) and 55.2% (95% CI: 41.5%-68.3%). Furthermore, prognostic data obtained from follow-up indicated that the median PFS of the 58 patients with advanced NSCLC was 3.2 months (95% CI: 2.29-4.11) and the median OS was 10.5 months (95% CI: 5.58-15.43). Regarding the exploratory analysis between efficacy and respiratory microbiology, the 58 patients with NSCLC were divided into high α diversity group (group H) and low α diversity group (group L) according to Shannon diversity index of respiratory microecology detection. And the association analysis suggested that the ORR of patients with group H and group L was 23.3% and 17.9%(P c 0.380), respectively. Furthermore, prognostic analysis indicated that the median PFS of patients with group H and group L was 3.8 and 2.8 months, respectively, which was statistically significant (P c 0.034). CONCLUSION: PD-1 inhibitors monotherapy demonstrated preliminary efficacy and prognosis as subsequent line treatment for patients with advanced NSCLC. Patients with higher α -diversity of respiratory microbiology might confer a superior prognosis. And the conclusion should be validated in large sample prospective clinical trials subsequently.
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Aim To study the anti-inflammatory activ¬ity of diterpenes from Tripterygium wilfordii on lipopo- lysaccharide ( LPS)-induced macrophage and its mech¬anism. Methods MTT assay was used to detect the cytotoxicity of compounds. The Griess method was used to detect the NO on LPS-induced RAW264. 7 cells. ELISA was applied to determine the contents of inter- leukin 6 (IL-6) , tumor necrosis factor a ( TNF-a ) , interleukin lp (IL-lfj) and interleukin 18 (IL-18) in cell culture supernatant. Western blot was used to de¬tect IkBcx, .INK, ERK, p38, STAT3 and their phos-phorylation in LPS-induced RAW264.7, as well as the effect on COX-2, iNOS, NLRP3, caspase-1 , cleaved- caspase-1. Flow cytometry was employed to detect the effects of compounds on the phagocytosis of RAW 264. 7 cells. Results Hypoglicin II (1) and ent-pimara-8 (14) , 15-diene-19-ol (6) , two diterpenoid compounds from Tripterygium wilfordii could effectively inhibit the expression of inflammatory mediators ( COX-2 and iN- OS) and inflammatory cytokines (IL-6, IL-lp, IL- 18) in LPS-induced RAW264. 7 cells. Further re¬search found that the phosphorylation of IkBcx , JNK, ERK, P38, STAT3 and NLRP3 was all inhibited; however, there was no significant effect on the expres¬sion of IkBcx, JNK, ERK, P38 and STAT3. At the same time, they also inhibited the phagocytosis of mac-rophages. Conclusions The anti-inflammatory mecha¬nism of Tripterygium wilfordii diterpenoids 1 and 6 might be through inhibiting the production of NLRP3 inflammatory bodies, inflammatory mediators (COX-2 and iNOS) and inflammatory cytokines (IL-6, IL-lp and IL-18) , which is closely related to inhibiting the activation of MAPK, NF-kB and STAT3 pathway.
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Objective:To investigate the incidence, risk factors, and outcomes of acute kidney injury (AKI) in cancer patients receiving immune checkpoint inhibitors (ICIs).Methods:A retrospective analysis was performed on the inpatients who received ICIs therapy in Beijing Shijitan Hospital, Capital Medical University from October 2015 to December 2020. According to the Kidney Disease: Improving Global Outcomes (KDIGO) definition of AKI, patients were divided into AKI group and non-AKI group, and the patients in the AKI group were further divided into ICIs related AKI (ICIs-AKI) and AKI due to other etiologies. The clinical characteristics of the patients were compared. Multivariate logistic regression was used to analyze the influencing factors of AKI, and sensitivity analysis was used to evaluate the influencing factors of ICIs-AKI.Results:A total of 279 cancer patients over 18 years old were included in this study, in which 175(62.7%) were males. There were 41 patients (14.70%) in AKI group, including 25 patients (8.96%) in ICIs-AKI group and 16 patients (5.73%) in AKI due to other etiologies group. Patients in the AKI group were characterized by higher proportions of hypertension, diuretics use and baseline eGFR<60 ml·min -1·(1.73 m 2) -1, extrarenal immune-related adverse events (irAEs) and a lower plasma albumin level (all P<0.05). The patients in the ICIs-AKI group had higher proportions of new aseptic leukocyturia, blood eosinophil count>500/ml, combined extrarenal irAEs, glucocorticoid use and discontinued ICIs treatment (all P<0.05). Multivariate logistic regression results showed that hypertension ( OR=3.424, 95% CI 1.559-7.522, P=0.002), use of diuretics ( OR=4.620, 95% CI 2.111-10.112, P<0.001), baseline eGFR<60 ml·min -1·(1.73 m 2) -1 ( OR=3.668, 95% CI 1.336-10.070, P=0.012) and extrarenal irAEs ( OR=9.909, 95% CI 4.198-23.391, P<0.001) were associated with AKI in cancer patients receiving ICIs therapy. Sensitivity analysis indicated that the risk factors of ICIs-AKI included use of diuretics and baseline eGFR<60 ml·min -1·(1.73 m 2) -1, similar to the results of the above analysis, extrarenal irAEs ( OR=17.572, 95% CI 6.302-48.995, P<0.001) were also associated with ICIs-AKI independently. Conclusions:AKI is not uncommon in patients treated with ICIs. Concomitant hypertension, baseline eGFR<60 ml·min -1·(1.73 m 2) -1 and use of diuretics are independent risk factors for AKI in such patients. Patients should be alert to the risk of ICIs-AKI when appearing extrarenal irAEs. Distinguishing ICIs-AKI from AKI caused by other causes will present a frequent challenge to clinical practitioners.
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Objective To investigate the protective effects of tribulus terrestris L (TTL) against light-induced photoreceptor degeneration and its underlying mechanisms.Methods BALB/c mice were randomly divided into normal control group,light exposure group and TTL administration group,with 12 mice in each group,and then exposed to light at the intensity of 10,000 lux for 30 min for the establishment of a retinal damage model of BALB/C mice.And 100 μL TTL decoction was intraperitoneally administered into mice of TTL administration group 30 min prior to illumination.Saline vehicle was administrated into the mice of normal control group and light exposure group.Next,intraperitoneal injection of dihydroethidium (DHE) was performed 22 h after illumination,and the eyes were enucleated 2 h later and subjected to cryosectioning for microscopic detection of the in situ retinal oxidative stress.Then,retinas were dissected 6 and 24 h after illumination,which was followed by total RNA extraction,reverse transcription and RT-PCR to assess the expression level of proinflammatory cytokines.Meanwhile,the expression levels of interleukin-β (IL-1 β),chemokine (Ccl2),cyclooxygenase-2 (COX-2),tumor necrosis factor-α (TNF-α),cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) mRNA were determined.Results Prominent oxidative stress was observed in retinal pigment epithelial cells and photoreceptor cells in the light exposure group when compared with the normal control group and TTL administration group,with significant difference (both P ＜ 0.001).Moreover,results of RT-PCR revealed that the expression of IL-1β,Ccl2,COX-2,TNF-α,ICAM-1 and VCAM-1 mRNA was significantly elevated as a result of light exposure compared to those from vehicle-treated normal controls with a significant difference (all P ＜ 0.01).TTL treatment resulted in significantly decreased expression of IL-1β,Ccl2,COX-2,TNF-α,ICAM-1 and VCAM-1 mRNA compared to those from light-exposed vehicle-treated controls with significant differences (all P ＜0.01).Conclusion In the retinal degeneration model,TTL protects the photoreceptor cells against fight-induced degeneration in part through suppressing light-induced retinal oxidative stress and inflammatory responses.
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Objective:To investigate the differences in the curative effects of neoadjuvant chemotherapy(NAC) for different subtypes of Luminal B breast cancer and its prognosis,and to discuss the clinical treatment characteristics of different subgroups.Methods:A total of 246 cases of Luminal B like breast cancer patients who completed the projected NAC courses and surgical treatment were selected.All the biopsy specimens before treatment were positive for estrogen receptot(ER).According to the expressions of progesterone receptor(PR), human epidermal growth factor-2(Her-2)and cell proliferation nuclear antigen Ki-67,246 cases of Luminal B breast cancer patients were divided into 3 subgroups.A subgroup(PR low expression group),Her-2 negative and PR< 20% or negative,Ki-67 any levels;B subgroup(PR high expression group),Her-2 negative,PR≥20% and Ki-67 ≥14%;C subgroup(Her-2 positive group),Her-2 positive,Ki-67 and PR any levels.The clinical pathological materials and follow-up recurrence events of the patients were collected.Results:Among the three subtypes of Luminal B breast cancer,there were no significant differences in the age,the size of primary tumor and the stage of TNM(P>0.05).There were significant differences in the lymph node metastasis rate among three subgroups(P=0.018),and the lymph node metastasis rate was the highest in A subgroup among three subgroups. There were no significant differences in the clinical response and pathological response among three subgroups(P=0.123,P=0.06).8.5%(21/246)patients achieved the pathological complete response(pCR);the rates of pCR in three subgroups had statistically significant difference(P=0.009);the rate of pCR in C subgroup was the highest, and the rate of pCR in B subgroup was the lowest.The Log-Rank test of the survival curves of three subgroups had not statistically significant difference(P=0.216),but the 3-year disease-free survival(DFS)and 5-year DFS of the patients in B subgroup were slightly higher than those in other two groups.The DFS of the patients in C subgroup was longer than that of the patients with Her-2 overexpression breast cancer at the same period,and the difference was statistically significant(P=0.047).Conclusion:Her-2 positive Luminal B breast cancer is more likely to achieve pCR in NAC and the prognosis is better than Her-2 overexpressing breast cancer.The patients with high expression of PR in Luminal B breast cancer patients have a tend of overall survival advantage compared with the patients with PR low expression and Her-2 positive expression.
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Objective To investigate the optimum target plasma concentration of propofol in preventing the adverse effects of carboprost tromethamine in the patients undergoing caesarean section.Methods One hundred and twenty-eight nulliparous parturients who were at full term with a singleton fetus,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,aged 24-37 yr,weighing 54-78kg,scheduled for elective caesarean section under combined spinal-epidural anesthesia,were randomly divided into 4 groups (n =32 each) using a random number table:control group (group C),and different concentrations of propofol groups (P1-3 groups).Carboprost tromethamine 250 μg was injected into the body of the uterus,and propofol with the target plasma concentrations of 0.8,1.2 and 1.6 μg/ml was simultaneously given by target-controlled infusion in P1,P2 and P3 groups,respectively,and normal saline was infused at a rate of 0.5 ml · kg-1 · h-1 in group C.The occurrence of cardiovascular events was recorded from the end of carboprost tromethamine administration until the end of surgery.The relatedadverse effects after carboprost tromethamine administration,and Ramsay sedation score at 15 mm after carboprost tromethamine administration were recorded,and satisfactory sedation was defined as Ramsay sedation score of 2.The occurrence of complications associated with combined spinal-epidural anesthesia was recorded during the postoperative follow-up.Results Compared with group C,the incidence of carboprost tromethamine-related adverse effects was significantly decreased in P2 and P3 groups,the rate of satisfactory sedation was significantly increased in P1 and P2 groups,the incidence of hypotension and tachycardia was significantly decreased in group P1 (P＜0.05),and no significant change was found in the incidence of carboprost tromethamine-related adv erse effects in group P1,and in the rate of satisfactory sedation in group P3 (P＞ 0.05).Compared with group P1,the incidence of carboprost tromethaminerelated adverse effects was significantly decreased in P2 and P3 groups,the rate of satisfactory sedation was significantly increased in group P2,and the rate of satisfactory sedation was significantly decreased in group P3 (P＜0.05).Compared with group P2,the rate of satisfactory sedation was significantly decreased (P＜0.05),and no significant change was found in the incidence of carboprost tromethamine-related adverse effects in group P3 (P＞0.05).No cardiovascular events were found in group P2,and the incidence of hypotension was 9％ in group P3.Conclusion The optimum target plasma concentration of propofol in preventing the adverse effects of carboprost tromethamine is 1.2 μg/ml in the patients undergoing caesarean section.
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Objective To investigate the relationships between axillary lymph node metastasis and clinicopathologic features in the patients with cT1-2 N0 breast cancer and clarify the law of axillary lymph node metastasis,and to find the risk factor,and provide the theoretical basis for individuation therapy.Methods 687 patients with cT1-2 N0 breast cancer were divided into negative group and positive group according to the pathological results of axillary lymph node,and the clinicopathologic features were layered.The risk factors of axillary lymph node metastasis were screened out by Chi-square test and Logistic regression analysis.Results In 687 cases of cT1-2 N0 breast cancer,156 (22.7%)cases were observed with axillary lymph node metastasis. The age,cT stage,pT stage, pathological type,vascular invasion,perineural invasion estrogen receptor (ER),progesterone receptor (PR), and molecular subtyping were the factors that influenced axillary lymph node metastasis in univariate analyses.The age < 35 years, cT2 , invasive ductal carcinoma, vascular invasion positive and Luminal subtyping were the independent risk factors of axillary lymph nodes metastasis in multivariate analyses (r = 3.440,P = 0.010;r =1.770,P =0.007;r = 3.397,P = 0.001;r = 7.434,P = 0.000;r = 2.212,P = 0.015).Conclusion In the patients with cT1-2 N0 breast cancer,the age,cT,pathological type,vascular invasion and molecular subtyping are important predictors of axillary lymph node metastasis and vascular invasion was the most important predictor.The preoperative comprehensive analysis and evaluation of clinical data and preoperative pathological results obtained will help to select the right surgical operation.
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<p><b>OBJECTIVE</b>To determine the independent prognostic factors of primary synovial sarcoma.</p><p><b>METHODS</b>The clinical data of 52 patients followed up from 66 patients with synovial sarcoma treated between September 1997 and September 2008 was analyzed retrospectively. There were 28 male and 24 female patients aged from 11 to 71 years old. Three and five-year overall survival (OS), recurrence rate and 9 prognostic factors were analyzed in this study. Univariate and multivariate analysis were performed to determine the prognostic factors of OS.</p><p><b>RESULTS</b>Fifty-two patients were followed up with the follow-up time ranged from 6 to 88 months (median 32 months). The 3-, 5-year overall survival rate and local recurrence rate were 52.8%, 30.3% and 32.7% respectively. Univariate showed tumor size < 5 cm, tumor located at extremities, adequate surgical margin and radical resection combined with radiotherapy had better survival rate (P < 0.05). Multivariate analysis demonstrated that tumor size, primary site and adequate surgical margin were independent prognostic factors for OS. Patients received radical resection combined with radiotherapy have longer median relapse time (25 months) compared with marginal resection combined with radiotherapy (18 months) and single radical resection (12 months). Thirty-five (67%) patients were treated with chemotherapy and seventeen (33%) patients received no chemotherapy for the primary tumor. Treatment with chemotherapy was not associated with an improved OS (P = 0.52).</p><p><b>CONCLUSIONS</b>The independent prognostic factors of synovial sarcoma are tumor size, primary site and adequate surgical margin. Doxorubicin and ifosfamide based chemotherapy was not associated with an improved OS in patients with synovial sarcoma. Radical resection combined with radiotherapy can best control local condition.</p>
Subject(s)
Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Young Adult , Antineoplastic Agents , Therapeutic Uses , Follow-Up Studies , Kaplan-Meier Estimate , Multivariate Analysis , Neoplasm Recurrence, Local , Prognosis , Regression Analysis , Retrospective Studies , Sarcoma, Synovial , Diagnosis , Drug Therapy , Radiotherapy , General SurgeryABSTRACT
Objective To investigate whether the activation of secretory prophospholipase A2 (sPLA2) plays the role in the pathophysiological mechanism of acute aristolochic acid nephropathy (AAN) in rats. Methods Wistar rats were randomly divided into two groups. Model group received decocted Aristolochia Manshuriensis Kom 30 g·kg-1d-1 by gavage for 7 days following tap water in same way for additional 7 days. Control group received only tap water by garage at parallel time. The renal pathological changes were observed at the 4th, 8th and 14th day. The injury of renal tubules and interstitium was observed under light microscope following a semi-quantity grade. The level of Scr was measured to evaluate glomerular function. Urinary N-acetyl-beta-glucosaminidase (NAG) was tested as renal tubular injury marker. The activity of sPLA2 in serum was detected by manifesting the color of thiols in the substrate. The protein expression of renal cortex and medulla COX-2 was analyzed by Western blot. The metabolic products of pretaglandins (PC, s) including 6-kcto-PGF1α and TXB2 in the plasma and urine were assayed by radioimmunoassay. The ratio of 6-keto-PGF1α/TXB2 was calculated. Results After Aristolochia administration, the tubulointerstitial injury and Scr increased in AA rats and reached the peak at the 8th day, the tubulointerstitial injury index(8.14±2.55 vs 1.50±0.71, P<0.05) and Scr[(0.24±0.10) vs (0.19±0.02) μmol/g, P<0.05] increased significantly in AA rats compared with control group. The activity of sPLA2 (μmol ·min-1·mg-1) in AA group elevated by 1.3-fold compared to control group at 8th day (133.15±17.05 vs 101.3±16.07, P<0.05), while theexpression of COX-2 in renal cortex increased (1.16±0.36 vs 0.69±0.28, P<0.05) with no change in renal medulla. Even though the levels of serum 6-keto-PGF1α and TXB2 did not change obviously in both AA and control group, but urinary levels of 6-keto-PGF1α and TXB2 increased by 2-fold and 3-fold in AA group compared to control group, respectively (all P<0.05), while the ratio of 6-keto-PGF1α/TXB2 decreased significantly (207.53±17.52 vs 296.64±51.31, P<0.05). All of above changes recovered to the control level at the 14th day except the tubulointerstitial injury index. Conclusion Serum sPLA2 is activated in the rots with acute kidney injury induced by aristolochic acid, which accompanied by up-regulated expression of COX-2 in renal cotex and increased the metabolic products of vasoconstrictive PG s in urine. These changes may participate the mechanism of renal peritubular ischemia in AAN.