Integrative evaluation of primary and metastatic lesion spectrum to guide anti-PD-L1 therapy of non-small cell lung cancer: results from two randomized studies.

Objectives: Clinical benefits of immune-checkpoint blockade (ICB) versus standard chemotherapy have been established in unselected non-small cell lung cancer (NSCLC). However, the response to ICB therapy among patients is heterogeneous in clinical practice. Materials and Methods: We retrospectively assessed the predicitive effect of the primary and metastatic lesion spectrum (baseline sum of the longest diameters [SLD], number of metastatic sites and specific organ metastases) on the efficacy of atezolizumab over docetaxel in OAK and POPLAR trial cohorts. A decision model, termed DSO (Diameter-Site-Organ), based on the spectrum was developed and validated for guiding ICB. Results: Higher SLD (>38 mm) and more metastatic sites (≥2) were characterized with pronounced overall survival (OS) benefits from atezolizumab versus docetaxel. Specifically, adrenal gland and brain metastases were identified as favorable predictors of atezolizumab treatment. The DSO model was developed in the discovery cohort to integrate the directive effect of the primary and metastatic lesion spectrum. Remarkably, a general pattern of enhanced efficacy of atezolizumab versus docetaxel was observed along with the increase of the DSO score. For patients with DSO score > 0, atezolizumab yielded a significantly prolonged OS than docetaxel, whereas OS was generally similar between two treatments in patients with DSO score ≤ 0. Equivalent findings were also seen in the internal and external validation cohorts. Conclusions: The response to anti-PD-L1 therapy among patients varied with the primary and metastatic lesion spectrum. The DSO-based system might provide promising medication guidance for ICB treatment in NSCLC patients.

[Efficacy observation on acupuncture prescription of regulating yin-yang and five viscera for intractable insomnia].

OBJECTIVE: To explore a more optimal therapy for intractable insomnia. METHODS: Seven hundred cases of intractable insomnia that were in accordance with the criteria were randomly divided into an observation group (368 cases) and a control group (332 cases). The acupuncture prescription of regulating yin-yang and five viscera was applied in the observation group, where Dazhui (GV 14), Shenmai (BL 62), Guanyuan (CV 4), Zhaohai (KI 6), Geshu (BL 17), etc. were selected. The acupuncture prescription of tranquilizing mind was applied in the control group, where Baihui (GV 20), Sishencong (EX-HN 1), Anmian (Extra), Shenmen (HT 7), Sanyin jiao (SP 6) were selected. The treatment was given once a day, ten times of which made a session. After the treatment for 4 sessions, the clinical efficacy and Pittsburgh sleep quality index (PSQI) were compared between two groups. RESULTS: The total effective rate was 92.6% (338/365) in the observation group, which was superior to 73.1% (242/331) in the control group (P < 0.05). The PSQI score was obviously decreased in two groups after the treatment (both P < 0.05), in which the decreasing in the observation group was superior to that in the control group (P < 0.05). CONCLUSION: The acupuncture prescription of regulating yin-yang and five viscera has better effect for intractable insomnia, which could be considered as a more optimal therapy.

Effect of Bu-Zhong-Yi-Qi-Tang on deficiency of N-glycan/nitric oxide and islet damage induced by streptozotocin in diabetic rats.

AIM: To investigate the effect of Bu-Zhong-Yi-Qi-Tang (Decoction for Reinforcing Middle Jiao and Replenishing Qi) on deficiency of N-glycan/nitric oxide (NO) and islet damage induced by injecting two medium doses of streptozotocin (STZ). METHODS: Diabetes was induced by intraperitoneal injection of STZ at 55 mg/kg on day 1 and day 8. Islet damage was evaluated using a scoring system. Nitrite, nitrate, alpha-mannosidase and amylase activities were measured by colorimetry. N-glycan patterns of amylase were determined with lectin [ConA, pisum sativum agglutinin (PSA), peanut agglutinin (PNA), and lens culinaris agglutinin (LCA)] affinity precipitation method. RESULTS: Severe islet necrosis and mild islet atrophy were observed in diabetic rats. The number and size of islets, the activities of alpha-mannosidase, amylase and nitrite were decreased, while the binding of PNA and LCA to amylase was increased. All of which were improved after treatment with Bu-Zhong-Yi-Qi-Tang. Islet damage was significantly correlated with nitrite, nitrate, alpha-mannosidase, amylase and the binding of LCA, PNA, and PSA to amylase. CONCLUSION: STZ-induced islet damage is related to N-glycan deficiency in proteins by blocking alpha-mannosidase activity and no deficiency, accumulation of unfolded proteins, and endoplasmic reticulum stress and activation of cellular signals, all of which are improved after treatment with Bu-Zhong-Yi-Qi-Tang.