OBJECTIVE To analyze the blood components of Suanzaoren Decoction after oral administration using UHPLC-Q Exactive Orbitrap-MS technology.METHODS Female Sprague-Dawley(SD)rats were used as experimental subjects,and Suanza-oren Decoction was administered orally.Serum samples were collected,and the aqueous extract of Suanzaoren Decoction and the serum were analyzed using UHPLC-Q Exactive Orbitrap-MS technology to identify the prototype components and metabolites absorbed into the blood by comparing and analyzing with the LuMet-TCM database.RESULTS It showed that a total of 458 components were iden-tified in the aqueous extract of Suanzaoren Decoction,and 26 chemical components were identified in the blood,including 23 prototype components and 3 metabolites.CONCLUSION The prototype components absorbed into the blood discovered in this study may be the active ingredients of Suanzaoren Decoction,providing a reference for the research on the pharmacodynamic material basis of Suanza-oren Decoction.

The use of immune checkpoint inhibitors(ICIs)has dramatically changed the treatment landscape of advanced non-small cell lung cancer (NSCLC), and have improved the survival outcomes of advanced patients while offering better overall safety compared to chemotherapy.However, due to immune senescence, the efficacy and safety of immunotherapy in elderly patients are different from those in non-elderly patients.Moreover, most clinical trials have limited data on elderly patients, and immunotherapy in the elderly population lacks high-level evidence-based medical support.This article introduces the theoretical basis of immunotherapy in the elderly population, summarizes clinical data on the efficacy and safety of immunotherapy for advanced NSCLC in the elderly, and analyses the immunotherapy for special subgroups of elderly patients, aiming to provide a reference basis for treating this population.The results showed that single-agent immunotherapy had good efficacy and safety in elderly patients with advanced NSCLC in the age group of 65-74 years, obtaining long-term survival benefits, However, the benefits of immunotherapy in the elderly population ≥75 years old remian unclear, and the outcomes of immunotherapy in the elderly ≥80 years old were poor.In addition, the performance status (PS) score of ≥2 was a significant factor in reducing the efficacy of single-agent immunotherapy in elderly patients.In addition, a pre-treatment PS score of ≥2 was an independent risk factor for reducing the efficacy of immunotherapy alone.Immunotherapy in combination with chemotherapy in the elderly has shown efficacy comparable to the overall population.However, there is an increased incidence of treatment-related adverse events(TRAEs)in patients ≥75 years of age.Dual-immunity combination therapies are not currently recommended for the treatment of advanced NSCLC in the elderly.Elderly patients with brain metastases have poor prognosis, and treatment may consider ICIs in combination with local radiotherapy.Basic research on how to improve the benefit of immunotherapy in elderly patients is also ongoing.In conclusion, the therapeutic prospect of immunotherapy in advanced NSCLC in the elderly is promising, and more exploration is needed in the future.

[This corrects the article DOI: 10.1016/j.apsb.2018.08.009.].

OBJECTIVE To analyze the blood components of Suanzaoren Decoction after oral administration using UHPLC-Q Exactive Orbitrap-MS technology.METHODS Female Sprague-Dawley(SD)rats were used as experimental subjects,and Suanza-oren Decoction was administered orally.Serum samples were collected,and the aqueous extract of Suanzaoren Decoction and the serum were analyzed using UHPLC-Q Exactive Orbitrap-MS technology to identify the prototype components and metabolites absorbed into the blood by comparing and analyzing with the LuMet-TCM database.RESULTS It showed that a total of 458 components were iden-tified in the aqueous extract of Suanzaoren Decoction,and 26 chemical components were identified in the blood,including 23 prototype components and 3 metabolites.CONCLUSION The prototype components absorbed into the blood discovered in this study may be the active ingredients of Suanzaoren Decoction,providing a reference for the research on the pharmacodynamic material basis of Suanza-oren Decoction.

The use of immune checkpoint inhibitors(ICIs)has dramatically changed the treatment landscape of advanced non-small cell lung cancer (NSCLC), and have improved the survival outcomes of advanced patients while offering better overall safety compared to chemotherapy.However, due to immune senescence, the efficacy and safety of immunotherapy in elderly patients are different from those in non-elderly patients.Moreover, most clinical trials have limited data on elderly patients, and immunotherapy in the elderly population lacks high-level evidence-based medical support.This article introduces the theoretical basis of immunotherapy in the elderly population, summarizes clinical data on the efficacy and safety of immunotherapy for advanced NSCLC in the elderly, and analyses the immunotherapy for special subgroups of elderly patients, aiming to provide a reference basis for treating this population.The results showed that single-agent immunotherapy had good efficacy and safety in elderly patients with advanced NSCLC in the age group of 65-74 years, obtaining long-term survival benefits, However, the benefits of immunotherapy in the elderly population ≥75 years old remian unclear, and the outcomes of immunotherapy in the elderly ≥80 years old were poor.In addition, the performance status (PS) score of ≥2 was a significant factor in reducing the efficacy of single-agent immunotherapy in elderly patients.In addition, a pre-treatment PS score of ≥2 was an independent risk factor for reducing the efficacy of immunotherapy alone.Immunotherapy in combination with chemotherapy in the elderly has shown efficacy comparable to the overall population.However, there is an increased incidence of treatment-related adverse events(TRAEs)in patients ≥75 years of age.Dual-immunity combination therapies are not currently recommended for the treatment of advanced NSCLC in the elderly.Elderly patients with brain metastases have poor prognosis, and treatment may consider ICIs in combination with local radiotherapy.Basic research on how to improve the benefit of immunotherapy in elderly patients is also ongoing.In conclusion, the therapeutic prospect of immunotherapy in advanced NSCLC in the elderly is promising, and more exploration is needed in the future.

The stimulator of interferon genes(STING),an integral adaptor protein in the DNA-sensing pathway,plays a pivotal role in the innate immune response against infections.Additionally,it presents a valuable therapeutic target for infectious diseases and cancer.We observed that fangchinoline(Fan),a bis-benzylisoquinoline alkaloid(BBA),effectively impedes the replication of vesicular stomatitis virus(VSV),encephalomyocarditis virus(EMCV),influenza A virus(H1 N1),and herpes simplex virus-1(HSV-1)in vitro.Fan treatment significantly reduced the viral load,attenuated tissue inflammation,and improved survival in a viral sepsis mouse model.Mechanistically,Fan activates the antiviral response in a STING-dependent manner,leading to increased expression of interferon(1FN)and interferon-stimulated genes(ISGs)for potent antiviral effects in vivo and in vitro.Notably,Fan interacts with STING,preventing its degradation and thereby extending the activation of IFN-based antiviral responses.Collectively,our findings highlight the potential of Fan,which elicits antiviral immunity by suppressing STING degra-dation,as a promising candidate for antiviral therapy.

Neurogenesis decline in hippocampal dentate gyrus (DG) participates in stress-induced depressive-like behaviors, but the underlying mechanism remains poorly understood. Here, we observed low-expression of NOD-like receptor family pyrin domain containing 6 (NLRP6) in hippocampus of stress-stimulated mice, being consistent with high corticosterone level. NLRP6 was found to be abundantly expressed in neural stem cells (NSCs) of DG. Both Nlrp6 knockout (Nlrp6^-/-) and NSC-conditional Nlrp6 knockout (Nlrp6CKO) mice were susceptible to stress, being more likely to develop depressive-like behaviors. Interestingly, NLRP6 was required for NSC proliferation in sustaining hippocampal neurogenesis and reinforcing stress resilience during growing up. Nlrp6 deficiency promoted esophageal cancer-related gene 4 (ECRG4) expression and caused mitochondrial dysfunction. Corticosterone as a stress factor significantly down-regulated NLRP6 expression, damaged mitochondrial function and suppressed cell proliferation in NSCs, which were blocked by Nlrp6 overexpression. ECRG4 knockdown reversed corticosterone-induced NSC mitochondrial function and cell proliferation disorders. Pioglitazone, a well-known clinical drug, up-regulated NLRP6 expression to inhibit ECRG4 expression in its protection against corticosterone-induced NSC mitochondrial dysfunction and proliferation restriction. In conclusion, this study demonstrates that NLRP6 is essential to maintain mitochondrial homeostasis and proliferation in NSCs, and identifies NLRP6 as a promising therapeutic target for hippocampal neurogenesis decline linked to depression.

Natural products, and especially the active ingredients found in traditional Chinese medicine (TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such, traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and single-cell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization.

Objective:To understand the clinical characteristics of serotonin syndrome (SS) induced by combined use of linezolid and serotonergic drugs.Methods:Relevant databases at home and abroad as of February 2021 were searched and case reports of SS induced by linezolid combined with serotonergic drugs were collected. Clinical information including patients′ basic characteristics (gender, age, underlying disease, etc.), linezolid and serotonergic drugs application (medication reasons, usage and dosage, drug elution period, etc.), and the occurrence time, clinical manifestations, intervention measures, and outcomes of SS were extracted and analyzed by descriptive statistical method.Results:A total of 50 patients derived from 46 literature were enrolled in the study, including 23 males and 27 females. Of them, 49 patients were aged from 23 to 98 years, and one patient was 4 years old. The reasons for using serotonergic drugs were mental illness (36 patients), pain (8 patients), and Parkinson′s disease (2 patients), etc.; the reasons for using linezolid were staphylococcal infection (24 patients), enterococcal infection (13 patients), and empirical anti-infection treatments (11 patients), etc. Among the 50 patients, 48 were treated with serotonergic drugs and then with linezolid, and 2 were treated with linezolid and then with serotonergic drugs; the drug washout period was not recorded in 44 patients and not long enough in the other 6 patients; the serotonergic drugs were given orally in 40 patients and by intravenous infusion in 10 patients; 35 patients had usage and dosage records, which were all in line with the requirements of drug labels; 27, 16, 5, and 2 patients were treated with 1, 2, 3, and 4 kinds of serotonergic drugs respectively, and the drugs used mainly were selective serotonin reuptake inhibitors, serotonergic drugs and norepinephrine reuptake inhibitors, tricyclic antidepressants, and opioids, etc. Except the administration route of linezolid was not mentioned in 12 patients, it was given by intravenous infusion in 27 patients and orally in 11 patients. The frequency of medication met the requirements of drug labels in 49 patients, and the medication frequency of one child was lower than that specified in the drug labels. SS occurred 3 hours to 20 days after combined use of drugs, mostly 1 to 5 days. The clinical manifestations were mental state change, autonomic nerve dysfunction, and neuromuscular dysfunction in 45, 47, and 45 patients, respectively. After discontinuation of linezolid and/or serotonergic drugs and receiving symptomatic treatments for 2 hours to 9 days, 43 patients were improved, 1 patient died of cardiac arrest after SS occurrence, and 6 patients died of the primary diseases after the symptoms of SS were controlled.Conclusions:SS due to linezolid combined with serotonergic drugs mostly occurred 1 to 5 days after combined use of above 2 drugs, and the clinical manifestations were similar to SS induced by other reasons. After discontinuation of linezolid and serotonergic drugs and symptomatic and supportive treatments, the overall prognosis is acceptable, but serious SS can lead to death.

Objective:To understand the clinical characteristics of serotonin syndrome (SS) induced by combined use of linezolid and serotonergic drugs.Methods:Relevant databases at home and abroad as of February 2021 were searched and case reports of SS induced by linezolid combined with serotonergic drugs were collected. Clinical information including patients′ basic characteristics (gender, age, underlying disease, etc.), linezolid and serotonergic drugs application (medication reasons, usage and dosage, drug elution period, etc.), and the occurrence time, clinical manifestations, intervention measures, and outcomes of SS were extracted and analyzed by descriptive statistical method.Results:A total of 50 patients derived from 46 literature were enrolled in the study, including 23 males and 27 females. Of them, 49 patients were aged from 23 to 98 years, and one patient was 4 years old. The reasons for using serotonergic drugs were mental illness (36 patients), pain (8 patients), and Parkinson′s disease (2 patients), etc.; the reasons for using linezolid were staphylococcal infection (24 patients), enterococcal infection (13 patients), and empirical anti-infection treatments (11 patients), etc. Among the 50 patients, 48 were treated with serotonergic drugs and then with linezolid, and 2 were treated with linezolid and then with serotonergic drugs; the drug washout period was not recorded in 44 patients and not long enough in the other 6 patients; the serotonergic drugs were given orally in 40 patients and by intravenous infusion in 10 patients; 35 patients had usage and dosage records, which were all in line with the requirements of drug labels; 27, 16, 5, and 2 patients were treated with 1, 2, 3, and 4 kinds of serotonergic drugs respectively, and the drugs used mainly were selective serotonin reuptake inhibitors, serotonergic drugs and norepinephrine reuptake inhibitors, tricyclic antidepressants, and opioids, etc. Except the administration route of linezolid was not mentioned in 12 patients, it was given by intravenous infusion in 27 patients and orally in 11 patients. The frequency of medication met the requirements of drug labels in 49 patients, and the medication frequency of one child was lower than that specified in the drug labels. SS occurred 3 hours to 20 days after combined use of drugs, mostly 1 to 5 days. The clinical manifestations were mental state change, autonomic nerve dysfunction, and neuromuscular dysfunction in 45, 47, and 45 patients, respectively. After discontinuation of linezolid and/or serotonergic drugs and receiving symptomatic treatments for 2 hours to 9 days, 43 patients were improved, 1 patient died of cardiac arrest after SS occurrence, and 6 patients died of the primary diseases after the symptoms of SS were controlled.Conclusions:SS due to linezolid combined with serotonergic drugs mostly occurred 1 to 5 days after combined use of above 2 drugs, and the clinical manifestations were similar to SS induced by other reasons. After discontinuation of linezolid and serotonergic drugs and symptomatic and supportive treatments, the overall prognosis is acceptable, but serious SS can lead to death.