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Background: Immune checkpoint inhibitor rechallenge has emerged as a prominent study area in non-small cell lung cancer (NSCLC). β-glucan was reported to reverse resistance to anti-PD-1/PD-L1 inhibitors by regulating the tumor microenvironment. In this self-initiated clinical trial (ChiCTR2100054796), NSCLC participants who have previously failed anti-PD-1 therapy received β-glucan (500 mg, bid, d1-21), Envafolimab (300 mg, d1) and Endostar (210 mg, civ72h) every 3 weeks until disease progression or unacceptable toxicity. The clinical efficacy and adverse events were observed, while serum samples were collected for proteomic analysis., Results: Twenty Three patients were enrolled from January 2022 to March 2023 (median age, 65 years; male, n = 18 [78.3%]; squamous NSCLC, n = 9 [39.1%]; mutant type, n = 13 [56.5%]). The overall response rate (ORR) was 21.7% and disease control rate (DCR) was 73.9%. Median progression-free survival (mPFS) and median overall survival (mOS) was 4.3 months [95% CI: 2.0-6.6] and 9.8 months [95% CI: 7.2-12.4], respectively. The mPFS between PD-L1 positive and negative subgroup has significant difference (6.3 months vs. 2.3 months, p = 0.002). Treatment-related adverse events (TRAEs) occurred in 52.2% of patients. The most common TRAEs were hypothyroidism (26.1%) and fatigue (26.1%). 2 (8.7%) grade 3 adverse events were reported. No adverse reaction related deaths have been observed. Proteomic analysis revealed that the levels of CASP-8, ARG1, MMP12, CD28 and CXCL5 correlated with resistance to the treatment while the levels of CD40-L and EGF related to the favorable response., Conclusion: β-glucan combined with Envafolimab and Endostar has considerable efficacy and safety for immune rechallenge in metastatic NSCLC patients who failed of anti-PD-1 treatment previously, especially for PD-L1 positive patients., (© 2024. The Author(s).)

Background: It is challenging to improve the effects of chemotherapy and reduce its adverse impact on the ovaries. Our previous study suggested that the combination of galaxamide could enhance the antitumor effect of cisplatin (CIS) in HeLa cell xenograft mice. However, their potential effects on ovarian tissues remain unknown., Methods: The Hela tumor-bearing female BALB/c mice model was established and randomly divided into three groups: control group (PBS group), CIS group (0.3 mg/kg CIS group) and galaxamide group (0.3 mg/kg CIS + 3 mg/kg galaxamide-treated group). The serum sex hormones levels, ovarian morphology, functional and molecular characterisation were determined and compared with those of the control group., Results: The hormonal effects indicated premature ovarian insufficiency (POI) associated with CIS-induced tumor-bearing mice. CIS induces the apoptosis in primordial and developing follicles and subsequently increases follicular atresia, eventually leading to follicle loss. After cotreatment, galaxamide significantly increased anti-Mullerian hormone (AMH) and follicle-stimulating hormone receptor (FSHR) expression and prevented the CIS-induced PI3K pathway, which triggers follicle activation, apoptosis or atresia., Conclusion: These findings demonstrate that galaxamide could attenuate CIS-induced follicle loss by acting on the PI3K signaling pathway by stimulating AMH and/or FSHR and thus provides promising therapeutic options for patients with cervical cancer., (© 2024. The Author(s).)

Introduction: Osteoporosis is one of the important bone abnormalities in chronic kidney disease-mineral and bone disorder (CKD-MBD) and still lacks a sensitive biomarker to diagnose. Fibroblast growth factor 21 (FGF21) can stimulate bone loss in patients with diabetes and increase in CKD patients. In this study, we investigated whether FGF21 could serve as a biomarker to predict osteoporosis in a haemodialysis cohort., Methods: We recorded demographic information, biochemical data, and serum FGF21 and FGF23 levels and measured the CT attenuation values of 339 haemodialysis patients from two large medical centres. We assessed the correlation of CT attenuation values with serum FGF21 and FGF23 levels and tested whether they were independent factors for osteoporosis. ROC curves were constructed to compare the prognostic value of FGF21 and FGF23 for osteoporosis., Results: Based on the CT attenuation value, serum FGF21 levels were higher in our osteoporosis group (median 640.86 pg/ml vs. 245.46 pg/ml, P ˂ 0.01). Meanwhile, FGF21 (r = -0.136, P < 0.05) and FGF23 (r = -0.151, P < 0.05) were both negatively associated with osteoporosis. Moreover, FGF21 (β = -0.067, P < 0.05) was an independent factor for osteoporosis. Furthermore, FGF21 combined with age yielded a marked specificity (90.5 %) and sensitivity (61.8 %) in predicting osteoporosis of haemodialysis patients with less residual renal function., Conclusions: FGF21 has a positive relationship with the incidence of osteoporosis in patients on haemodialysis. FGF21 combined with age is a good predictive biomarker for osteoporosis in patients on haemodialysis, especially those with less residual renal function.

Background: Nitrate plays an important role in grapevines vegetative and reproductive development. However, how grapevines uptake, translocate and utilize nitrate and the molecular mechanism still remains to be investigated., Results: In this study, we report the functional characterization of VvNPF6.5, a member of nitrate transporter 1/peptide transporter family (NRT1/PTR/NPF) in Vitis vinifera. Subcellular localization in Arabidopsis protoplasts indicated that VvNPF6.5 is plasma membrane localized. Quantitative RT-PCR analysis indicated that VvNPF6.5 is expressed predominantly in roots and stems and its expression is rapidly induced by nitrate. Functional characterization using cRNA-injected Xenopus laevis oocytes showed that VvNPF6.5 uptake nitrate in a pH dependent way and function as a dual-affinity nitrate transporter involved in both high- and low-affinity nitrate uptake. Further ectopic expression of VvNPF6.5 in Arabidopsis resulted in more 15 NO 3 - accumulation in shoots and roots and significantly improved nitrogen use efficiency (NUE). Moreover, VvNPF6.5 might participate in the nitrate signaling by positively regulating the expression of primary nitrate response genes., Conclusion: Our results suggested that VvNPF6.5 encodes a pH-dependent, dual-affinity nitrate transporter. VvNPF6.5 regulates nitrate uptake and allocation in grapevines and is involved in primary nitrate response.

Background: Liver cancer is one of the most common cancers in the world. The primary aim of this research was to discover the correlation between single nucleotide polymorphisms (SNPs) of the MIR155HG and liver cancer risk., Methods: The selected SNPs in MIR155HG were genotyped utilizing the Agena MassARRAY platform. We evaluated the correlation between MIR155HG polymorphisms and Liver cancer by genetic model analysis, stratification analysis and haplotype analysis. Relative risk of Liver cancer was shown based on odds ratios (ORs) and 95% confidence intervals (95% CIs)., Results: Our results uncovered that rs12482371 and rs1893650 in the MIR155HG were associated with protection against Liver cancer. And the rs928883 was related to increase risk of Liver cancer. Furthermore, apart from rs77218221, other selected SNPs formed two LD blocks, and haplotype "GATAG" in block 2 elevated individual liver cancer risk., Conclusions: MIR155HG gene polymorphism may be correlated to Liver cancer susceptibility in Han Chinese population, particularly in males and aged ≤55 years.

Background: Leflunomide (LEF) is a first-line disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA). However, there are still a few nonresponders. It is logical to suggest that employing combinations including LEF that produce synergistic effects in terms of pharmacological activity is a promising strategy to improve clinical outcomes., Methods: We propose a novel approach for predicting LEF combinations through investigating the potential effects of drug targets on the disease signaling network. We first constructed an RA signaling network with disease-associated driver genes. Thousands of available FDA-approved and investigational compounds were then selected based on a drug-RA network, which was generated using an algorithm model named synergistic score that combines chemical structure, functional prediction and target pathway. We then validated our predicted combination in a prospective clinical trial., Results: Ligustrazine (LIG), a key component of the Chinese herb Chuanxiong and an approved drug in China, ranked first according to synergistic score. In the clinical trial, after 48 weeks, the American College of Rheumatology (ACR) 20 response rate was significantly lower ( P  < 0.05) in the LEF group [58.8% (45.4%, 72.3%)] than in the LEF + LIG group [78.7% (68.5%, 89.0%)]. Consistently, the erosion score was lower in patients treated with LEF + LIG than in those treated with LEF (0.34 ± 0.20 vs 1.12 ± 0.30, P  < 0.05)., Conclusions: Our algorithm combines structure and target pathways into one model that predicted that the combination of LEF and LIG can reduce joint inflammation and attenuate bone erosion in RA patients. To our knowledge, this study is the first to apply this paradigm to evaluate drug combination hypotheses., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Background: Clinical practice guidelines (CPGs) for Chinese medicine (CM) are being developed to assist doctors with appropriate decisions concerning CM care. To date, there has been little investigation on the perspectives of those to whom the guidelines are directed., Methods: A self-administered questionnaire was sent to 4503 doctors in 28 provinces of China in the latter half of 2012. Questions were organized around the topics of knowledge, application, practice changes, beliefs and outcomes of implementation. Basic classificatory data on specialties and years of qualification were also collected., Results: Replies were received from 4495 CM doctors (99.82%). Of these, 85.56% of CM doctors reported being familiar with CPG recommendations, but the overall adherence rate was only 50.39%. The length of time practicing CM may influence the rate of adherence, since 709 doctors (51.90%) with less than 5 years of experience reported never having followed CPGs. Doctors in nine specialties showed a modest degree of homogeneity in their attitudes towards CM diagnosis and treatment, which were generally positive. Most doctors regarded CPG-recommended therapies as safe (92%), economic (84%), and effective (76%). Approximately four-fifths of those questioned selected 'acceptable' (60.84%) and 'acceptable after revision' (19.23%) regarding their comprehensive assessment of the CPGs., Conclusions: An encouraging result from this survey is that the majority of CM doctors support the concept of CPGs for the practice of CM. However, the results of this survey also suggest that improving the adherence of CM doctors to the guidelines remains a major challenge to improving the practice standards for CM.

Background: Citrus fruits are widely used as food and or for medicinal purposes, and they contain a host of active substances that contribute to health. The immature fruits of Citrus sinensis Osbeck and its cultivars (CS), C. junos Sieb. ex Tanaka (CJ), C. aurantium L. and its cultivars (CA) and Poncirus trifoliate Raf. (PT) are the most commonly used medicinal herbs in Traditional Chinese Medicine, called Zhishi. And their mature fruits can be used as food., Results: In this study, the essential oils of four different Zhishi species were extracted by steam distillation and detected using gas chromatography- mass spectrometry (GC-MS). A total of 39 volatiles from the four species were tentatively identified. The limonene was the most abundant amongst the four species. Principal component analysis (PCA) of essential oils showed a clear separation of volatiles among CS, CJ and PT. However, CA could not be separated from these three species. Additionally, the volatiles accounting for the variations among the widely separated species were characterized through their corresponding loading weight., Conclusion: Sesquiterpenes were identified as characteristic markers for PT. The content of some monoterpenes could be as taxonomic markers between CS and CJ. This work is of great importance for the evaluation and authentication of Zhishi samples through essential oils.

Background: Rhodiola plants are used as a natural remedy in the western world and as a traditional herbal medicine in China, and are valued for their ability to enhance human resistance to stress or fatigue and to promote longevity. Due to the morphological similarities among different species, the identification of the genus remains somewhat controversial, which may affect their safety and effectiveness in clinical use., Results: In this paper, 47 Rhodiola samples of seven species were collected from thirteen local provinces of China. They were identified by their morphological characteristics and genetic and phytochemical taxonomies. Eight bioactive chemotaxonomic markers from four chemical classes (phenylpropanoids, phenylethanol derivatives, flavonoids and phenolic acids) were determined to evaluate and distinguish the chemotaxonomy of Rhodiola samples using an HPLC-DAD/UV method. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) were applied to compare the two classification methods between genetic and phytochemical taxonomy., Conclusions: The established chemotaxonomic classification could be effectively used for Rhodiola species identification.

Background: Growing evidence shows that herb medicines have some anti-osteoporotic effects, the mechanism underlying is unknown. This study aims to investigate the therapeutic effect of Chinese herb supplements on rats that had osteoporosis-like symptom induced by ovariectomy (OVX)., Methods: OVX or sham operations were performed on virgin Wistar rats at three-month old, which were randomly divided into eight groups: sham (sham); OVX control group (OVX); OVX rats with treatments [either diethylstilbestrol (DES) or Semen Astragali Complanati decoction (SACD) or Rhizoma Cibotii decoction (RCD) or Herba Cistanches decoction (HCD) or Semen Allii Tuberosi decoction (SATD)]. Non-surgical rats were served as a normal control (NC). The treatments began 4 weeks after surgery, and lasted for 12 weeks. Bone mass and its turnover were analyzed by histomorphometry. Levels of protein and mRNA of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in osteoblasts (OB) and bone marrow stromal cells (bMSC) were evaluated by immunohistochemistry and in situ hybridization., Results: Compared to OVX control, TBV% in both SACD and RCD groups was increased significantly, while TRS%, TFS%, MAR, and mAR were decreased remarkably in the SACD group, only TRS% decreased dramatically in the RCD group. No significant changes in bone formation were observed in either HCD or SATD groups. OPG levels in both protein and mRNA were reduced consistantly in OB and bMSC from OVX control rats, in contrast, RANKL levels in both protein and mRNA were increased significantly. These effects were substantially reversed by treatments with either DES or SACD or RCD. No significant changes in both OPG and RANKL expression were observed in OB and bMSC from OVX rats treated with SATD and HCD., Conclusions: Our study showed that SACD and RCD increased bone formation by stimulating OPG expression and downregulating RANKL expression in OB and bMSC. This suggests that SACD and RCD may be developed as alternative anti-osteoporotic agents for therapy of postmenopausal osteoporosis.

Background: The objective of this study was to evaluate the effects of herbal medicines, such as Radix Dipsaci (RDD), Pyrola Herb (PHD), and Cynomorium songaricum decoction (CSD), on osteoporotic rats induced by ovariectomy (OVX)., Methods: OVX or sham operations were performed on 69 virgin Wistar rats that were divided into six groups: sham (sham, n = 12), OVX control group (OVX, n = 12), and OVX rats with treatments (diethylstilbestrol, E2, n = 12; RDD, n = 11, PHD, n = 11, and CSD, n = 11). Non-surgical rats served as normal control (NC, n = 12). The treatments began four weeks after surgery and lasted for 12 weeks. Bone mass and bone turnover were analyzed by histomorphometry. Levels of protein expression and mRNA of OPG and RANKL in osteoblasts (OB) and bone marrow stromal cells (bMSC) were evaluated by immunohistochemistry and in situ hybridization., Results: Compared to NC and sham rats, trabecular bone formation was significantly reduced in OVX rats, but restored in E2-treated rats. Treatment with either RDD or PHD enhanced trabecular bone formation remarkably. No significant change of bone formation was observed in CSD-treated rats. OPG expression of protein and mRNA was reduced significantly in OB and bMSC of OVX control rats. RANKL expression of protein and mRNA was increased significantly in OB and bMSC of OVX control rats. These effects were substantially reversed (increased in OPG and decreased in RANKL) by treatment with E2, RDD, or PHD in OB and bMSC of OVX rats. No significant changes in either OPG or RANKL expression were observed in OB and bMSC of OVX rats treated with CSD., Conclusions: Our study showed that RDD and PHD increased bone formation by stimulating overexpression of OPG and downregulation of RANKL in OB and bMSC. This suggests that RDD and PHD may be used as alternative therapeutic agents for postmenopausal osteoporosis.

Background: One important concept in traditional Chinese medicine (TCM) is "treating different diseases with the same therapy". In TCM practice, some patients with Rheumatoid Arthritis (RA) and some other patients with Coronary Heart Disease (CHD) can be treated with similar therapies. This suggests that there might be something commonly existed between RA and CHD, for example, biological networks or biological basis. As the amount of biomedical data in leading databases (i.e., PubMed, SinoMed, etc.) is growing at an exponential rate, it might be possible to get something interesting and meaningful through the techniques developed in data mining., Results: Based on the large data sets of Western medicine literature (PubMed) and traditional Chinese medicine literature (SinoMed), by applying data slicing algorithm in text mining, we retrieved some simple and meaningful networks. The Chinese herbs used in treatment of both RA and CHD, might affect the commonly existed networks between RA and CHD. This might support the TCM concept of treating different diseases with the same therapy., Conclusions: First, the data mining results might show the positive answer that there are biological basis/networks commonly existed in both RA and CHD. Second, there are basic Chinese herbs used in the treatment of both RA and CHD. Third, these commonly existed networks might be affected by the basic Chinese herbs. Forth, discrete derivative, the data slicing algorithm is feasible in mining out useful data from literature of PubMed and SinoMed.