Toripalimab combined with targeted therapy and chemotherapy achieves pathologic complete response in gastric carcinoma: A case report.

BACKGROUND: Neoadjuvant or perioperative chemotherapy combined with surgery can reduce postoperative recurrence and improve the long-term survival rate of patients with locally advanced resectable gastric carcinoma. Nivolumab combined with chemotherapy has been recommended by the National Comprehensive Cancer Network guidelines as a first-line therapy for advanced gastric carcinoma/ adenocarcinoma of the gastroesophageal junction and serves as the basis for immunotherapy combined with chemotherapy to become a neoadjuvant therapy. Herein, we report a case in which pathologic complete response was achieved by neoadjuvant administration of toripalimab, Herceptin, and docetaxel, oxaliplatin, calcium folinate, and fluorouracil (FLOT) chemotherapy followed by surgery for human epidermal growth factor receptor 2 (HER2)- and programmed death-ligand 1 (PD-L1)-positive locally advanced gastric carcinoma. We hope that this case will shed some light on neoadjuvant therapy for gastric carcinoma. CASE SUMMARY: The patient was diagnosed with locally advanced adenocarcinoma of the cardia. Immunohistochemistry of the baseline tissues suggested that the tissues were HER2- (fluorescent in situ hybridization) and PD-L1-positive (combined positive score = 1). The patient underwent surgery following a four-cycle neoadjuvant therapy comprising Herceptin, toripalimab, and FLOT chemotherapy. The postoperative pathological findings showed mild atypical hyperplasia of the local glands with chronic mucosal inflammation (proximal stomach), no clear residual tumor (tumor regression grade 0), no regional lymph node metastasis, and negative upper and lower cut ends. The levels of tumor markers were reduced to normal levels after re-examination. With good postoperative recovery, the four-cycle preoperative chemotherapy was continued at the same dosage as that previously administered. After the treatment, the patient was monitored every 3 mo with a follow-up of 12 mo (4 times). As of February 27, 2022, he was in a good condition without disease progression. The clinical trial registration number is E2019401. CONCLUSION: There are many ongoing studies on neoadjuvant immunotherapy combined with chemotherapy or radiotherapy; however, most of these studies are phase II studies with small cohorts. According to the results of some current studies, these combined regimens have shown promising results in terms of efficacy and safety. However, the clinical efficacy and safety of the neoadjuvant therapies used in these combined regimens need to be confirmed by additional prospective phase III clinical trials, and further exploration of molecular markers for effective populations is required.

Fufang Xueshuantong alleviates diabetic retinopathy by activating the PPAR signalling pathway and complement and coagulation cascades.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Xueshuantong (FXST) is a traditional Chinese patent medicine composed of Panax notoginseng (Burkill) F.H.Chen (Araliaceae), Salvia miltiorrhiza Bunge (Lamiaceae), Astragalus propinquus Schischkin (Leguminosae), and Scrophularia ningpoensis Hemsl. (Scrophulariaceae). It has been widely used for the treatment of diabetic retinopathy (DR) and exerts a positive clinical therapeutic effect. AIM OF THE STUDY: The aim of this study was to observe the effect of FXST on diabetic rat retinas and investigate its pharmacological mechanism for improving DR. METHODS: The diabetic rat model was established by intraperitoneal injection of streptozotocin. The rats were divided into a normal group, diabetic group, and FXST group. The rats in the FXST group were treated with FXST by intragastric administration for 12 weeks while other rats were given the same volume of normal saline. The haemodynamic parameters of the central retinal artery in the rats were measured by ultrasound. Haematoxylin-eosin staining was utilised to observe the pathological structural changes in the retina. The apoptosis of retinal nerve cells was detected by terminal deoxynucleotidyl transferase dUTP nick end labelling. RNA sequencing was used to screen the differentially expressed genes (DEGs), and enrichment analyses were performed. The DEGs were validated through real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: The peak systolic velocity, end diastolic velocity, and mean velocity decreased while the resistance index and pulsatility index increased in the diabetic rat retinas. FXST also improved haemodynamics. In contrast with the diabetic group, FXST allayed the disorder and oedema of the retinal structure in addition to reversing the reductions in retinal thickness and retinal ganglion cell number. It also decreased the apoptosis index of retinal cells. A total of 1134 DEGs were identified by RNA sequencing in the FXST group compared to the diabetic group, including 814 upregulated genes and 320 downregulated genes. These genes were enriched in the complement and coagulation cascades as well as the peroxisome proliferator-activated receptor (PPAR) signalling pathway. Several DEGs, including PPAR gamma, perilipin 4, acyl-CoA dehydrogenase long chain, CD55 molecule, and plasminogen activator urokinase, were identified by qRT-PCR, and the results were consistent with the RNA sequencing data. CONCLUSIONS: FXST alleviates DR by improving the haemodynamics and morphological alterations of diabetic rat retinas, which are mediated by complement and coagulation cascades and the PPAR signalling pathway.

HuoXue JieDu formula improves diabetic retinopathy in rats by regulating microRNAs.

ETHNOPHARMACOLOGICAL RELEVANCE: HuoXue JieDu Formula (HXJDF) originates from classical formulas and was formed based on clinical experience. It is composed of Euonymus alatus (Thunb.) Siebold, Panax notoginseng (Burkill) F.H. Chen, the roots of Anguina kirilowii (Maxim.) Kuntze, and Coptis omeiensis (C. Chen) C.Y.Cheng. HXJDF prevents the deterioration of diabetic retinopathy. AIM OF THE STUDY: To evaluate the effects of HXJDF on diabetic retinopathy in rats and investigate the roles of miRNAs in the effects of HXJDF. MATERIALS AND METHODS: A single intraperitoneal injection of streptozotocin (STZ) (65 mg/kg) was used to induce diabetes in rats. Rats were divided into three groups: normal, diabetic, and diabetic + HXJDF. Rats were treated with HXJDF (15.4 g/kg) or water by oral gavage for twelve weeks. At the end of the treatment, rats were anaesthetized, and retinal haemodynamic changes were measured. Then, the retinas were removed and examined by haematoxylin and eosin (HE) staining and TUNEL assays. In addition, miRNA expression profiling was performed using miRNA microarrays and further validated by quantitative real-time PCR (qRT-PCR). RESULTS: Diabetes reduced peak systolic velocity (PSV), end-diastolic velocity (EDV), mean velocity (MV) and central retinal vein velocity (CRV) but increased the resistance index (RI) and pulsatility index (PI). In addition, in the diabetic group, retinal cell arrangement was disordered and loosely arranged, the retinal thickness and retinal ganglion cell (RGC) number decreased, and retinal cell apoptosis increased. In addition, 11 miRNAs were upregulated and 4 miRNAs were downregulated. After treatment, HXJDF improved retinal haemodynamics and morphologic changes, restored retinal thickness and RGC number and decreased retinal cell apoptosis. Furthermore, the changes in miRNA expression were significantly abolished by HXJDF. CONCLUSION: HXJDF may prevent DR by regulating the expression of miRNAs.

Correlations between genetic, epigenetic and phenotypic variation of an introduced clonal herb.

Heritable epigenetic modifications may occur in response to environmental variation, further altering phenotypes through gene regulation, without genome sequence changes. However, epigenetic variation in wild plant populations and their correlations with genetic and phenotypic variation remain largely unknown, especially for clonal plants. We investigated genetic, epigenetic and phenotypic variation of ten populations of an introduced clonal herb Hydrocotyle vulgaris in China. Populations of H. vulgaris exhibited extremely low genetic diversity with one genotype exclusively dominant, but significantly higher epigenetic diversity. Both intra- and inter-population epigenetic variation were related to genetic variation. But there was no correlation between intra-/inter-population genetic variation and phenotypic variation. When genetic variation was controlled, intra-population epigenetic diversity was related to petiole length, specific leaf area, and leaf area variation, while inter-population epigenetic distance was correlated with leaf area differentiation. Our study provides empirical evidence that even though epigenetic variation is partly under genetic control, it could also independently play a role in shaping plant phenotypes, possibly serving as a pathway to accelerate evolution of clonal plant populations.

Observation on time-effect for the stimulating at Zusanli (ST 36) with minimally invasive embedding with PGLA in the healthy person / 中国针灸

OBJECTIVE@#To explore the objectivity and time-effect of stimulating effect at acupoint with PGLA in the healthy person, and to provide a basis for the rational interval of minimally invasive embedding of PGLA.@*METHODS@#Before embedding, 8 h, 3rd, 7th, 10th, 14th day after embedding, medical imaging magnetic resonance imaging (MRI) scanning technique was used to collect local T2WI pressure-lowering and T2-Mapping 8 echoes sequence image of left Zusanli (ST 36) in 8 cases of healthy person. The T2-Mapping 8 echoes sequence image was generated by the relevant software to the T2-Mapping image and the local T2 value was measured. The characteristics of local T2WI pressure-fat image signal intensity and the change of T2 value at left Zusanli (ST 36) with minimally invasive embedding with PGLA were observed and analyzed.@*RESULTS@#①There was no abnormal signal on the T2WI pressure-fat image on the left Zusanli (ST 36) point before the embedding. The high-signal was seen on the local T2WI pressure-fat image at each time point after embedding, there was no significant difference in local signal intensity between 8 h, 3rd and 7th day after embedding. The local signal intensity decreased on the 10th day after embedding, and the local signal intensity decreased significantly on the 14th day after embedding.②The T2 value at each time point after embedding increased significantly compared with that before embedding (all 0.05); there was no significant difference between the T2 value on the 7th and the 10th day after embedding (>0.05)，the T2 value on the 14th day after embedding was significantly lower than that on the 7th day after embedding (<0.01).@*CONCLUSION@#It has a stimulating effect on the local acupoints with minimally invasive embedding with PGLA in the healthy person, and the stimulating effect has certain time-effect. The effective stimulation time is about 2 weeks. The rational interval period for the minimally invasive embedding with the PGLA of the same specification type should be about 2 weeks.

Constraints on the evolution of phenotypic plasticity in the clonal plant Hydrocotyle vulgaris.

The evolution of phenotypic plasticity of plant traits may be constrained by costs and limits. However, the precise constraints are still unclear for many traits under different ecological contexts. In a glasshouse experiment, we grew ramets of 12 genotypes of a clonal plant Hydrocotyle vulgaris under the control (full light and no flood), shade and flood conditions and tested the potential costs and limits of plasticity in 13 morphological and physiological traits in response to light availability and flood variation. In particular, we used multiple regression and correlation analyses to evaluate potential plasticity costs, developmental instability costs and developmental range limits of each trait. We detected significant costs of plasticity in specific petiole length and specific leaf area in response to shade under the full light condition and developmental range limits in specific internode length and intercellular CO2 concentration in response to light availability variation. However, we did not observe significant costs or limits of plasticity in any of the 13 traits in response to flood variation. Our results suggest that the evolution of phenotypic plasticity in plant traits can be constrained by costs and limits, but such constraints may be infrequent and differ under different environmental contexts.

Nutrient enrichment alters impacts of Hydrocotyle vulgaris invasion on native plant communities.

Nutrients may affect the invasiveness of alien plants and the invasibility of native plant communities. We performed a greenhouse experiment to investigate the interactive effect of invasion by a clonal herb Hydrocotyle vulgaris and nutrient enrichment on biomass and evenness of native plant communities. We established three types of plant communities (H. vulgaris alone, native plant communities without or with H. vulgaris) under low and high levels of nutrients. Native communities consisted of eight native, terrestrial species of three functional groups, i.e. four grasses, two legumes, and two forbs. Invasion of H. vulgaris had no effect on biomass of the native community, the functional groups, or the individual species. High nutrients increased biomass of grasses, but reduced evenness of the community. High nutrients also decreased the competitive effect, and the relative dominance index of H. vulgaris. Therefore, high nutrients reduced the competitive ability of H. vulgaris and enhanced the resistance of the native community to invasion. The results provide a basis for management strategies to control the invasion and spread of H. vulgaris by manipulating resource availability to support native communities.

[Inhibitory effects of vina-ginsenoside R7 on activation of rat C6 astrocytes induced by LPS and TNF-α combination].

To investigate the inhibitory effect and mechanism of vina-ginsenoside R7 (R7) on the activation of rat C6 astrocytes cells induced by LPS/TNF-α, cells in logarithmic growth phase were cultured in DMEM medium without FBS for 24 h. After dissociated using 0.25% EDTA-trypsin, the cells were seeded into respective plates at the density of 1.5×106 cells per mL and cultured overnight. The cells were divided into the following groups： control group (no treatment), model group (treated with LPS 1 µg•mL⁻¹ and TNF-α 10 µg•L⁻¹ treated for 24 h), R7 groups (pre-treated with 6.25, 12.5, 25, 50, and 75 µmol•L⁻¹ R7, 4 µmol•L⁻¹ L-NMMA for 2 h and then stimulated with LPS 1 mg•L⁻¹ and TNF-α 10 µg•L⁻¹ for 24 h). Cell viability was analyzed by CCK-8 kit. Secretion of nitric oxide (NO) in the medium was measured by Greiss method. Concentrations of interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) were assayed by ELISA kits. Gene expressions of inflammatory factors were examined by quantitative-PCR analysis. Activation of NF-κB was detected by dual luciferase reporter gene assay kit. The results showed that R7 could significantly inhibit the secretion of NO from C6 cells in a dose-effect manner, with an IC50 of 34 µmol•L⁻¹. And it could reduce cell proliferation induced by LPS/TNF-α stimulation. Furthermore, R7 at 50 µmol•L⁻¹ significantly down-regulated gene expressions of iNOS (P<0.001), TNF-α (P<0.001), IL-1ß(P<0.05), and COX-2 (P<0.001), but could not change gene expression of IL-6. However, R7 reduced the secretion of TNF-α (P<0.001) and IL-6 (P<0.001). Further studies disclosed that, different concentrations of R7 (25, 50, 100 µmol•L⁻¹) could significantly inhibit the transcription activity of NF-κB(P<0.05, P<0.01, and P<0.001). In conclusion, R7 could inhibit inflammatory responses in C6 cells induced by LPS/TNF-α probably by inhibiting the transcription activity of NF-κB, which indicates its possible therapeutic effect in neurological diseases related to neuroinflammation.

Coumarins of Anemone raddeana Regel and their biological activity / 药学学报

To study the coumarins of Anemone raddeana Regel, the compounds were separated by silica gel column chromatography and HPLC. Their structures were identified by their physicochemical property and spectral analysis. Two new compounds were isolated and identified as 4, 7-dimethoxyl-5-methyl-6-hydroxy coumarin (1) and 4, 7-dimethoxyl-5-formyl-6-hydroxycoumarin (2). The bioassays indicated that compounds 1 and 2 could significantly inhibit the proliferation of cancer cell, and showed the agonist effect on the transactivity of retinoic acid receptor-alpha (RARalpha). In addition, the two compounds had inhibitory effect against human leukocyte elastase (HLE).

[Effects of integrated disease management program on the outcome of patients with heart failure].

OBJECTIVE: To investigate the feasibility and efficacy on the outcome of patients with heart failure of integrated disease management program with heart failure clinic, patient education and telephone follow-up. METHODS: A total of 145 hospitalized patients with chronic heart failure and LVEF ≤ 45% or patients with LVEF > 45% and NT-proBNP > 1500 ng/L were divided into conventional group (n = 71) and interventional group (n = 74). Patients were followed for 10 to 12 months. RESULTS: Baseline clinical characteristics, LVEF and dose of evidence-based medicine were similar between the 2 groups. During follow-up, the NYHA functional class was higher in conventional group than interventional group (3.2 ± 0.5 vs 1.4 ± 0.5, P < 0.05), and the LVEF deteriorated in the conventional group and improved from 34% to 40%in the interventional group. The proportions of self-monitoring of weight, blood pressure and pulse rate in the interventional group were significantly higher than those of conventional group (P < 0.05). Among patients with systolic heart failure, 40% patients in the interventional group and 11% patients in the conventional group achieved the target doses of ß-blockers (P < 0.05). Cardiovascular event rate of conventional group and interventional group is 91.5% and 27.0% respectively (P < 0.05). CONCLUSION: Integrated disease management program with heart failure clinic, patient education and telephone follow-up can improve patient compliance to heart failure treatment, improve cardiac function and reduce cardiovascular event rate.

Antibacteral effect of six Chinese traditional medicines on Yersinia pestis / 中国地方病学杂志

Objective To screen the antibacterial activity of Chinese traditional medicines against Yersinia pestis.Methods Six Chinese traditional medicines(Coptis Chinesis etc)were selected and extracted with pure water to make a concentration of 1 mg/L.Yersinia pestis strain 201 and EV 76 were used to determine the minimal inhibitory concentrations(MIC)of these selected medicines in vitro with liquid dilution method.Results Three herbs had inhibition effects on the strain 201 and EV76 in different extents,among which Rheum palmatum had the strongest effect and MIC was 0.025 00 mg/L.Furthermore,the Chinese traditional medicine had the same MIC on both strain 201 and EV76.Conclusions Chinese traditional medicines commonly used have inhibiting effect on Yersinia pesti.

Effects of moxibustion and Chinese herbs on contents of mitochondrial DNA, serum IL-2 and IL-6 in the aging model rat / 中国针灸

<p><b>OBJECTIVE</b>To probe into the mechanisms of moxibustion and Chinese herbs in delaying aging.</p><p><b>METHODS</b>Sixty SD rats were randomly divided into a young control group, an aging group, a moxibustion group, a Chinese herb group and a moxibustion plus Chinese herb group. In the latter 4 groups, aging rat model was established by hypodermic injection of D-galactose. In the course of modeling, the 3 treatment group were treated by mild-warm moxibustion at "Zusanli (ST 36)", "Shenshu (BL 23)" and "Guanyuan (CV 4)" with reinforcing method, stomach perfusion of decoction of Liuwei Dihuang plus Danggui (Angelica) and Danshen (Salvia Miltiorrhiza Bge), and the moxibustion plus the Chinese herbs, respectively. After treatment for 40 days, liver mitochondrial DNA, serum IL-2 and IL-6 contents were detected.</p><p><b>RESULTS</b>(1) The mitochondrial DNA content of liver cells and serum IL-6 level significantly increased (P < 0.05, P < 0.01) and serum IL-2 level significantly decreased (P < 0.05) in the aging model group as compared with those in the young control group. (2) The mitochondrial DNA content of liver cells and serum IL-6 level significantly decreased (P < 0.05, P < 0.01) and serum IL-2 level significantly increased (P < 0.05) in all the treatment group as compared with those in the aging model group.</p><p><b>CONCLUSION</b>Moxibustion and Chinese herbs function delaying aging though decreasing mitochondrial DNA content of liver cells and serum IL-6 level and increasing serum IL-2 level.</p>

Study on flavonoids in leaves of Apocynum ventum / 中国中药杂志

<p><b>OBJECTIVE</b>To study the flavonoids in the leaves of Apocynum ventum.</p><p><b>METHOD</b>Compounds were separated by repeated polyacrylamide column chromatgraphy combined with Sephadex LH-20 column chromatgraphy, their structures were confirmed by the analysis of spectral data and physicochemical properties.</p><p><b>RESULT</b>Six compounds were isolated from A. ventum. They were elucidated as quercetin (1), kaempferol (2), kaempferol-3-O-(6"-O-acetyl)-beta-D-glucopyranoside (3), quercetin-3-O-(6"-O-acetyl )-beta-D-glucopyranoside (4), quercetin-3-O-(6"-O-acetyl)-beta-D-galactopyranoside (5), kaempferol-7-O-alpha-L-rhamnopyranoside (6).</p><p><b>CONCLUSION</b>Compound 5 and 6 were isolated from the genus Apocynum for the first time.</p>