Predictive value of prognostic nutritional index (PNI) in recurrent or unresectable hepatocellular carcinoma received anti-PD1 therapy.

BACKGROUND: Clinical trials have shown that anti-PD1 therapy, either as a monotherapy or in combination, is effective and well-tolerated in patients with recurrent or unresectable hepatocellular carcinoma (HCC). In this study, we aimed to investigate the prognostic value of immune-nutritional biomarkers in measuring the effects of anti-PD1 therapy in these patients. METHODS: We enrolled and followed up with 85 patients diagnosed with advanced HCC who underwent anti-PD1 therapy at the First Medical Centre of Chinese People's Liberation Army (PLA) General Hospital between January 2016 and January 2021. The retrospective analysis aimed to determine whether immune-nutritional biomarkers could serve as promising prognostic indices in these patients. RESULTS: In this retrospective study, patients in the PNI-high group showed a better progression-free survival (PFS) compared to those in the PNI-low group (9.5 months vs. 4.2 months, P = 0.039). Similarly, the median overall survival (OS) was longer in the PNI-high group (23.9 months, 95%CI 17.45-30.35) than in the PNI-low group (11.7 months, 95%CI 9.27-14.13) (P = 0.002). These results were consistent with sub-analyses of the anti-PD1 therapy. Furthermore, both univariate and multivariate analyses indicated that a higher pre-treatment PNI ( > = 44.91) was a significant predictive factor for favorable outcomes in this patient cohort (HR = 0.411, P = 0.023). CONCLUSION: Our study suggests that pre-treatment PNI is a critical predictive factor in patients with recurrent or unresectable HCC undergoing anti-PD1 therapy.

Grape Seed Proanthocyanidins Exert a Neuroprotective Effect by Regulating Microglial M1/M2 Polarisation in Rats with Spinal Cord Injury.

Spinal cord injury (SCI) is a highly disabling disorder for which few effective treatments are available. Grape seed proanthocyanidins (GSPs) are polyphenolic compounds with various biological activities. In our preliminary experiment, GSP promoted functional recovery in rats with SCI, but the mechanism remains unclear. Therefore, we explored the protective effects of GSP on SCI and its possible underlying mechanisms. We found that GSP promoted locomotor recovery, reduced neuronal apoptosis, increased neuronal preservation, and regulated microglial polarisation in vivo. We also performed in vitro studies to verify the effects of GSP on neuronal protection and microglial polarisation and their potential mechanisms. We found that GSP regulated microglial polarisation and inhibited apoptosis in PC12 cells induced by M1-BV2 cells through the Toll-like receptor 4- (TLR4-) mediated nuclear factor kappa B (NF-κB) and phosphatidylinositol 3-kinase/serine threonine kinase (PI3K/AKT) signaling pathways. This suggests that GSP regulates microglial polarisation and prevents neuronal apoptosis, possibly by the TLR4-mediated NF-κB and PI3K/AKT signaling pathways.

A pectin methyltransferase modulates polysaccharide dynamics and interactions in Arabidopsis primary cell walls: Evidence from solid-state NMR.

Plant cell walls contain cellulose embedded in matrix polysaccharides. Understanding carbohydrate structures and interactions is critical to the production of biofuel and biomaterials using these natural resources. Here we present a solid-state NMR study of cellulose and pectin in 13C-labeled cell walls of Arabidopsis wild-type and mutant plants. Using 1D 13C and 2D 13C-13C correlation experiments, we detected a highly branched arabinan structure in qua2 and tsd2 samples, two allelic mutants for a pectin methyltransferase. Both mutants show close physical association between cellulose and the backbones of pectic homogalacturonan and rhamnogalacturonan-I. Relaxation and dipolar order parameters revealed enhanced microsecond dynamics due to polymer disorder in the mutants, but restricted motional amplitudes due to tighter pectin-cellulose associations. These molecular data shed light on polymer structure and packing in these two pectin mutants, helping to elucidate how pectin could influence cell wall architecture at the nanoscale, cell wall mechanics, and plant growth.

Natural Products of Pharmacology and Mechanisms in Nucleus Pulposus Cells and Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IDD) is one of the main causes of low back pain (LBP), which severely reduces the quality of life and imposes a heavy financial burden on the families of affected individuals. Current research suggests that IDD is a complex cell-mediated process. Inflammation, oxidative stress, mitochondrial dysfunction, abnormal mechanical load, telomere shortening, DNA damage, and nutrient deprivation contribute to intervertebral disc cell senescence and changes in matrix metabolism, ultimately causing IDD. Natural products are widespread, structurally diverse, afford unique advantages, and exhibit great potential in terms of IDD treatment. In recent years, increasing numbers of natural ingredients have been shown to inhibit the degeneration of nucleus pulposus cells through various modes of action. Here, we review the pharmacological effects of natural products on nucleus pulposus cells and the mechanisms involved. An improved understanding of how natural products target signalling pathways will aid the development of anti-IDD drugs. This review focuses on potential IDD drugs.

Clinical features, treatment and prognosis analysis of the asymptomatic patients with retinoblastoma / 中华眼底病杂志

Objective:To analyze the clinical features, treatment and prognosis of asymptomatic patients with retinoblastoma.Methods:A retrospective series of case study. Eight asymptomatic patients (11 eyes) with the diagnosis of retinoblastoma by screening enrolled in Department of Ophthalmology of The Eye-ENT Hospital of Fudan University from January 2006 to March 2019 were included. There were 6 males and 3 females ranging from 2 days to 20 months, with a median age of 6 months. Five patients were unilateral retinoblastoma while 3 patients were bilateral. Based on the International Classification of Intraocular Retinoblastoma, 4 eyes were stage A, 3 eyes were stage B and 4 eyes were stage C. One patient had family history. Four patients were evaluated the Rb1 mutation. Routine ophthalmic examinations and ultra-wide field fundus imaging were performed on the 16 parents and 3 siblings of the 8 patients. Systemic intravenous chemotherapy was performed using the Carboplatin, Vincristine, Etoposide protocol, intra-arterial chemotherapy using Carboplatin and Melphalan, and local treatment involved cryotherapy and transpupillary thermotherapy. The mean follow-up time is 47.25 months.Results:None of the 8 children had any ocular symptoms. Six patients received intravenous chemotherapy (5-6 times), 1 patient received intra-arterial chemotherapy (3 times), and 1 patient just received local treatment. Among the 11 eyes, 9 eyes were treated with local cryotherapy and 8 eyes were treated with transpupillary thermotherapy. During the follow-up period, 2 patients had new tumor, and the average time was 6.3 months after the last chemotherapy. At the last follow-up, the tumor disappeared in 11 eyes, remained stable in 11 eyes. The eye protection rate was 100% (8/8) for patients without eyeball excision. The best corrected visual acuity was 0.1 for 3 eyes and 1.0 for 5 eyes. Three eyes were not found. One heterozygous mutation of Rb1 gene [1c.35_69del (p.T12fs)] was identified in 1 patient, and the other 3 patients were not detected. One had bilateral bulbar tuberculosis of the 16 parents, 1 had bilateral RB of the 3 siblings. They were the mother and brother of a child with bilateral RB.Conclusions:Fundus screening is helpful for the detection of early RB. The eye protection rate is high and the long-term vision prognosis is good after systemic or topical chemical drugs (IVC, IAC) and ocular topical treatment (cryopreservation and transpupillary thermotherapy).

[Preliminary study on response and its mechanism of ginsenoside biosynthesis in Panax ginseng to water regulation].

The study is aimed to explore the effect of soil moisture content on ginsenoside biosynthesis and explain its mechanism from the perspectives of antioxidant enzyme system and gene expression of key enzymes in the pathway of ginsenoside synthesis. In the study,two years old Panax ginseng was used as the experimental material and three moisture gradient,40% of saturated water content( W1),60%( W2),80%( W3) were set up. The content of 11 monomeric saponins were determined by HPLC. With GAPDH as a reference gene,six key enzymes( HMGR,SS,ß-AS,CYP716 A47,CYP716 A52 v2,CYP716 A53 v2) in ginseng saponin synthesis pathway expression were analyzed by fluorescent quantitative PCR and the activities of superoxide dismutase( SOD),peroxidase( POD),catalase( CAT) activity and MDA content were also determined. With the increase of soil water,the content of ginseng saponin and biomass showed an increasing trend. PPD( Rb1,Rc,Rb2,Rd,Rh2,Rb3,Rg3),PPT( Rg1,Re,Rf) ginsenoside,Ro and total ginsenoside reached the maximum value on August 30,were 9.92,5.48,0.63 mg·g-1,respectively. During the whole regulation period,the antioxidant activity of W3 was greater than that of W1,and the MDA content was less than that of W1. At W3,expression levels of ß-AS,CYP716 A47 and CYP716 A53 v2 showed an increasing trend,while HMGR and SS genes showed relatively stable expression levels under various water conditions. According to the correlation analysis,HMGR and SS genes in the W3 treatment group were significantly positively correlated with PPD,PPT ginsenoside and Ro,CYP716 A52 v2 gene was significantly positively correlated with Ro,and CYP716 A47 gene was significantly positively correlated with PPD ginsenoside. There was a significant positive correlation between ß-AS gene and PPD ginsenoside in W1 and W2 treatment. Therefore,W3 is the optimum moisture content,ginseng total saponins and monomer saponin content is the highest,the gene closely correlation with content of saponins and more conducive to the accumulation of ginsenosides.

Effects of the combined extracts of Herba Epimedii and Fructus Ligustri Lucidi on bone mineral content and bone turnover in osteoporotic rats.

BACKGROUND: The decoction combination of Herba Epimedii and Fructus Ligustri Lucidi has been used to treat osteoporosis for almost 50 years by practitioners of traditional Chinese medicine. However, it is unclear what specific effects this combination of herbs has on the skeleton. The aim of this study was to assess the effects of the combined extracts from Herba Epimedii and Fructus Ligustri Lucidi on the bone turnover and bone mineral content in a rat model of osteoporosis induced by retinoic acid. METHODS: Fifty male Wistar rats were randomly assigned to the normal control group, osteoporosis model group, or treatment groups in which osteoporosis was induced and then the combined extracts of Herba Epimedii and Fructus Ligustri Lucidi were administered at 50, 100, or 200 mg/kg/day for 3 weeks via oral gavage. The rat osteoporosis model was induced by intragastric administration of 70 mg/kg/day of retinoic acid for 2 weeks. Bone turnover markers, bone biomechanical properties, and the calcium and phosphorus content of the right tibia and serum were measured. RESULTS: The retinoic acid administration decreased the bone mass and the contents of calcium and phosphorus in the bone mineral, weakened the biomechanical properties, and increased bone turnover by stimulating bone resorption and collagen metabolism. Treatment with the combined extracts of Herba Epimedii and Fructus Ligustri Lucidi significantly mitigated the effects of osteoporosis on the rats by decreasing bone metabolism, improving the bone mineral content, and increasing the biomechanical properties. CONCLUSIONS: The results of this study highlight the anti-osteoporosis effects of the combined extracts of Herba Epimedii and Fructus Ligustri Lucidi. These findings may contribute to the development of natural anti-osteoporosis herbal medicines.

Effect of the combined extracts of herba epimedii and fructus ligustri lucidi on sex hormone functional levels in osteoporosis rats.

The combination of Herba Epimedii and Fructus Ligustri Lucidi has been used to treat osteoporosis for almost 50 years by Professor Shizeng Li, a famous doctor of traditional Chinese medicine (TCM). However, it is unclear whether the combination of the effective constituents of the two herbs may have a protective influence on the skeleton. In the present study, we investigated the effects of the combination extracts of Herba Epimedii and Fructus Ligustri Lucidi on rat model of osteoporosis induced by retinoic acid by gavage. With administrations of the combination extracts of the two herbs (50, 100, and 200 mg/kg/day) via oral gavage for 3 weeks, bone mineral density (BMD), femur histomorphometry, some sex hormones, and sex hormone receptors were measured. Results showed that the combined extracts could increase BMD, affect bone histomorphometry, coordinate the sex hormones at the level of hypothalamus-pituitary-gonad axis, and increase the protein and mRNA expressions of sex hormone receptors. The findings suggested that the combination extracts of Herba Epimedii and Fructus Ligustri Lucidi might be beneficial as an alternative medicine for the prevention and treatment of osteoporosis.

[Study on effect of combination of Epimedii Folium and Ligustri Lucidi Fructus on osteoporosis rats induced by retinoic acid].

OBJECTIVE: To explore the effect of combination of Epimedii Folium and Ligustri Lucidi Fructus on osteoporosis rats induced by retinoic acid. METHOD: Sixty three-month-old male Wistar rats were randomly divided into the normal control group, the model group, the Epimedii Folium group, the Ligustri Lucidi Fructus group, the combination group of Epimedii Folium and Ligustri Lucidi Fructus and the raloxifene group. The osteoporosis model was established through oral administration with retinoic acid for two weeks. Meanwhile, all of treatment groups were administered with corresponding drugs for three weeks. The contents of serum calcium (Ca), phosphorus (P), alkaline phosphatase (AKP) and tartrate-resistant acid phosphatase (StrACP) were detected, and the pathomorphological changes of femurs were observed. RESULT: The model control group showed much lower contents of serum Ca and P than the normal control group, but with significantly higher AKP and StrACP activity than the normal control group. The femoral head area showed reduced, narrow and sparse trabecular bones, with typical osteoporosis-like changes. Compared with the model control group, all of treated groups showed significant increase in Ca and P contents in serum, and down-regulate AKP and StrACP levels, while trabecular bones became more and wider, and densely interweaved as a reticular formation. Among them, the combination group showed the most significant effect. CONCLUSION: Epimedii Folium and Ligustri Lucidi Fructus could effectively correct the abnormal bone metabolism and improve pathological conditions of bone tissues, so as to show the anti-osteoporosis effect. The combined application of the two drugs showed a better efficacy.

[Study on establishment of kidney deficient aging model and comparison with D-galactose induced aging model].

OBJECTIVE: To establish a kidney deficient aging model (KDAM), assess it in antioxidant capacity, HPAT axis function and bone metabolism, and compare with D-galactose aging model. METHOD: Aging rat model was established by injecting D-galactose solution, meanwhile dexamethasone solution was injected to establish kidney deficient aging model. Then these models were evaluated by serum MDA (malondialdehyde) and GSH-Px (glutathione peroxidase), liver SOD (superoxide dismutase), adrenal, thymus and spleen index, CD4(+), CD8(+), and serum COR (cortisol), BGP (bone Gla-protein), plasma ACTH (adrenocorticotropic hormone) and CRH (corticotropin-releasing hormone). RESULT: Compared with the normal group, the aging model group and the kidney deficient aging group showed significant decrease in liver SOD activity (P < 0.01 on average) and significant increase in serum MDA content (P < 0.01 on average) , and the kidney deficient aging group revealed remarkable decline in plasma ACTH content (P < 0.05). Compared with the normal group and the aging model group, the kidney deficient aging model group's weight, serum GSH-Px decreased (P < 0.01, P < 0.05), adrenal index decreased (P < 0.05, P < 0.01), serum COR decreased (P < 0.05 on average), plasma CRH increased (P < 0.05, P < 0.01), serum BGP content significantly decreased (P < 0.01 on average), value of CD4(+), CD8(+) decreased (P < 0.05, P < 0.01), CD4(+)/CD8(+) increased, but without significant difference. CONCLUSION: The kidney deficient aging model shows significant decrease in antioxidant capacity, dysfunction of HPAT axis disorder and abnormal bone metabolism. However, D-galactose aging model only shows a significant difference in antioxidant capacity.

Simultaneous determination of three Aconitum alkaloids in six herbal medicines by high-performance liquid chromatography.

To simultaneously determine three components of aconitine, mesaconitine, and hypaconitine in six species of Aconitum genus, an extraction condition for the total alkaloids was specifically optimized and a simple analytical method of reversed-phased highperformance liquid chromatography (HPLC) was developed. The extraction rate of total alkaloids in A. szechenyianum Gay was 98.3% for repeated extracting three times with an acidic alcohol solution (alcohol: pH 3.0 HAc = 85:15, v/v). The chromatography was carried out on a Phenomenex Luna C(18) column by gradient elution with a mobile phase of 0.03 mol/mL ammonium bicarbonate (pH = 9.50) -acetonitrile at a flow rate of 1.0 mL/min. The method for all three alkaloids had good linear relationships (r > 0.999) in the concentration range of 1.0-200.0 µg/mL. The average recoveries were 96.6-103.1%, and the LOQ and LOD were in the range of 25-37 ng/mL and 9-12 ng/mL, respectively. The quantitative results indicated that contents of the three alkaloids varied significantly among crude aconite roots, so quality control of traditional Chinese medicines containing aconite roots should be taken into account.

LC-MS analysis for the components captured by ECV304 cell from extract of Aconitum szechenyianum Gay.

A novel method of cell affinity screening (CAS), cell affinity capture coupled with LC-MS analysis, was developed for screening the bioactive compounds related to cardiovascular diseases from the natural product libraries. One of the major characteristics lies in its function in affinity-capturing and separating the bioactive components from the natural product libraries in vitro. Another characteristic is its use in analyzing and identifying the target compounds, by employing high-performance liquid chromatography and mass spectrometry. CAS was used for screening the bioactive components from the alkaloid extract derived from Aconitum szechenyianum Gay. Of the five components found to be bound to the oxidative-damaged endothelial cells, the two compounds identified, mesaconitine and aconitine, were recognized in the literature as being related to cardiovascular diseases.

[Acupuncture therapy for arrhythmia and other cardiac disorders: clinical and laboratory investigation].

Clinical studies have shown that acupuncture therapy is effective for certain cardiovascular diseases, especially cardiac arrhythmia resulting from neural dysfunction. The therapeutic efficacy varies depending on types of diseases, acupoints stimulated and acupuncture manipulation (or electroacupuncture parameters). The mechanistic research shows that acupuncture signal initiated at the acupoints is transferred to the brain through afferent nervous pathway and thus modulates the function of neurotransmitter systems. Then, the output signaling cascades relieve the cardiovascular dysfunction through efferent neural regulation. There are also several lines of evidence suggesting that the acupuncture effects involve complex mechanisms at multiple levels, including intracellular signal transduction, gene expression, endocrine secretion, humoral and dielectric regulation. Therefore, the acupuncture effects on cardiovascular disorders are dependent on an integrated mechanism mediated by multiple factors at central and peripheral levels. However, the detail of the mechanism is largely unclear yet. The potential problems in the literature are briefly discussed in this review.

[Study on the optimum extracting conditions of total alkaloids and aconitine in Aconitum szechenyianum Gay].

OBJECTIVE: To optimize the conditions for extractions of total alkaloids and aconitine from Aconitum szechenyianum Gay. METHODS: Using L16 (4(5)) orthogonal test and univariant methods, the exrtaction conditions of total alkaloids aconitine in Aconitum szechenyianum Gay. were optimized under the guidance of the content determination of total alkaloids with bromophemol blue colorimetry and aconitine with HPLC method, respectively. RESULTS: The obtained optimum condition of total alkaloids was that the material was refluxed in 6 times (m/v) acidic alcohol solution( alcohol: pH 3.0 HAc = 85:15, v/v) for 1 h with 3 times. The condition of aconitine was that the material was refluxed in 4 times (m/v) acidic alcohol solution (alcohol: pH 3. p HAc = 15:85, v/v) for 0.5 h with 3 times. Contents of total alkaloids and aconitine in Aconitum szechenyianum Gay. were 0.980% and 0.109%, respectively. CONCLUSION: Through the test and verify, the optimum extraction methods of total alkaloids and aconitine are rational.