Objective: To determine the clinical efficacy and mechanism of Piwei Peiyuan Pill (PPP) combined with moxibustion for treating patients with chronic atrophic gastritis (CAG) with spleen and stomach weakness syndrome. Methods: Ninety-six CAG patients with spleen and stomach weakness syndrome who met the inclusion and exclusion criteria were enrolled at the Department of Spleen and Stomach Diseases of the Second Affiliated Hospital of Anhui University of Chinese Medicine from June 2022 to December 2023. The patients were randomly divided into a control, a Chinese medicine, and a combined group using a random number table method, with 32 cases in each group (two cases per group were excluded). The control group was treated with rabeprazole combined with folic acid tablets (both thrice daily), the Chinese medicine group was treated with PPP (8 g, thrice daily), and the combined group was treated with moxa stick moxibustion (once daily) on the basis of the Chinese medicine group for 12 consecutive weeks. Gastric mucosa atrophy in the three groups was observed before and after treatment. The gastric mucosal pathological score was evaluated. The Patient Reported Outcome (PRO) scale was used to evaluate the patients′ physical and mental health status and quality of life.An enzyme-linked immunosorbent assay was used to detect serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4, IL-10, IL-37, and transforming growth factor (TGF)-β levels in each group. Real-time fluorescence PCR was used to detect the relative expression levels of signal transducer and activator of transcription 3 (STAT3) and mammalian target of rapamycin (mTOR) mRNA in each group. Western blotting was used to detect the relative expression levels of proteins related to the STAT3/mTOR signaling pathway, and the adverse drug reactions and events were recorded and compared. Results: There was no statistical difference in age, gender, disease duration, family history of gastrointestinal tumors, alcohol consumption history, and body mass index among the three groups of patients.The total therapeutic efficacy rates of the control, Chinese medicine, and combined groups in treating gastric mucosal atrophy were 66.67% (20/30), 86.67% (26/30), and 90.00% (27/30), respectively (P<0.05). Compared to before treatment, the pathological and PRO scale scores of gastric mucosa in each group decreased after treatment, and TNF-α, IL-1β, IL-37, and TGF-β levels decreased. The relative STAT3 and mTOR mRNA expression levels, as well as the relative STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels decreased (P<0.05), whereas the IL-4 and IL-10 levels increased (P<0.05). After treatment, compared to the control group, the pathological score of gastric mucosa, PRO scale score, TNF-α, IL-1β, IL-37, TGF-β content, relative STAT3 and mTOR mRNA expression levels, and relative STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels in the Chinese medicine and combined groups after treatment were reduced (P<0.05), whereas the IL-4 and IL-10 levels increased (P<0.05). After treatment, compared to the Chinese medicine group, the combined group showed a decrease in relative STAT3, mTOR mRNA expression levels, and STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels (P<0.05). Conclusion The combination of PPP and moxibustion may regulate the inflammatory mechanism of the body by inhibiting the abnormal activation of the STAT3/mTOR signaling pathway, upregulating related anti-inflammatory factor levels, downregulating pro-inflammatory factor expression, and increasing related repair factor expression, thereby promoting the recovery of atrophic gastric mucosa, reducing discomfort symptoms, and improving the physical and mental state of CAG patients with spleen and stomach weakness syndrome.

Calcium-based biomaterials have been intensively studied in the field of drug delivery owing to their excellent biocompatibility and biodegradability. Calcium-based materials can also deliver contrast agents, which can enhance real-time imaging and exert a Ca²⁺-interfering therapeutic effect. Based on these characteristics, amorphous calcium carbonate (ACC), as a brunch of calcium-based biomaterials, has the potential to become a widely used biomaterial. Highly functional ACC can be either discovered in natural organisms or obtained by chemical synthesis However, the standalone presence of ACC is unstable in vivo. Additives are required to be used as stabilizers or core-shell structures formed by permeable layers or lipids with modified molecules constructed to maintain the stability of ACC until the ACC carrier reaches its destination. ACC has high chemical instability and can produce biocompatible products when exposed to an acidic condition in vivo, such as Ca²⁺ with an immune-regulating ability and CO₂ with an imaging-enhancing ability. Owing to these characteristics, ACC has been studied for self-sacrificing templates of carrier construction, targeted delivery of oncology drugs, immunomodulation, tumor imaging, tissue engineering, and calcium supplementation. Emphasis in this paper has been placed on the origin, structural features, and multiple applications of ACC. Meanwhile, ACC faces many challenges in clinical translation, and long-term basic research is required to overcome these challenges. We hope that this study will contribute to future innovative research on ACC.

Objective:To observe the functional differences in the key brain areas in patients with different levels of consciousness after severe brain injury, and provide reference for confirming the objective diagnosis indicators for prolonged disorders of consciousness.Methods:Thirty right handedness patients with different levels of consciousness after severe brain injury (initial post-traumatic Glasgow coma scale scores<9), admitted to our hospital from January 2016 to December 2020, were chosen in our study. The levels of consciousness of these patients were assessed by revised Coma Recovery Scale (CRS-R); according to the diagnostic criteria of prolonged disorders of consciousness, 8 patients were into group of unresponsive wakefulness syndrome/vegetative state (UWS/VS), 8 patients were into group of micro-conscious state (MCS), 6 patients were into group of emergence from MCS (eMCS), and 8 were into group of locked-in syndrome (LIS). The regional homogeneity (ReHo) was used to analyze resting-state functional MRI (rs-fMRI) data to explore the differences of brain functional activity in patients with different levels of consciousness.Results:Strong resting-state activities were noted in the right middle temporal gyrus of the UWS/VS patients, the left culmen and inferior parietal lobule of the MCS patients, the left superior occipital gyrus and inferior frontal gyrus of eMCS patients, and the left inferior temporal gyrus and cingulate gyrus of the LIS patients. As compared with that in the UWS/VS patients, the ReHo value of the left insula in the MCS patients was significantly enhanced (voxel=1 341, t=-5.380, P<0.05); as compared with the those in the eMCS patients, the peak brain area with reduced ReHo value in the MCS patients was the left culmen (voxel=549, t=-5.377, P<0.05), while the peak brain area with enhanced ReHo value was the left insula (voxel=438, t=3.751, P<0.05); as compared with that in the LIS patients, the peak brain areas of enhanced ReHo in the MCS patients were the left medial frontal gyrus (voxel=1 014, t=5.406, P< 0.05) and left extra-nuclear (voxel=229, t=4.115, P<0.05), while the peak brain areas of enhanced ReHo in the eMCS patients was the left medial frontal gyrus (voxel=421, t=3.397, P<0.05). Conclusion:In the resting state, there are functional differences in the key brain regions of patients with different levels of consciousness, mainly in the predominant hemisphere, left insula and cerebellum; these regions may be the target regions for objective evaluation of prolonged disorders of consciousness.

AIM: To optimize an orthopedic non-muscle invasive bladder cancer (NMIBC) model in nude mouse by comparing four different ways of cellular transplantation, and to evaluate the efficacy of drug by bladder instillation, so as to provide a stable and efficient animal model for the treatment of bladder cancer. METHODS: After disruption of bladder mucosa by dilute acid-alkali or silver nitrate, T24 cells were instilled into the nude mouse bladder. T24 cells were injected directly into the bladder with mechanical injury of bladder mucosa. T24 cells were injected into the bladder wall. On the 14th day after making models, the nude mice were sacrificed. And the bladder mass and histopathological changes of tumor (including bladder) was observe to confirm the formation of orthopedic bladder cancer. The dynamic changes of orthopedic bladder cancer were observed after injecting T24 cells into the bladder wall. Gemcitabine was used to verify the applicability of the model of injecting T24 cells into the bladder wall in vivo. RESULTS: No tumor was found in the bladder after intravesical instillation of T24 cells with dilute acid-alkali or silver nitrate treatment. With mechanical injury of bladder mucosa, all nude mice had tumors after injection T24 cells. But the number of tumors varied and often occurred at multiple sites. The tumor was found in the bladder of all nude mice by injecting T24 cells into bladder wall, and there was only one tumor. The tumor showed slow linear growth within 15 days and rapid linear growth from day 18 to 31. In vivo efficacy evaluation, gemcitabine 150 mg/kg intravesical perfusion could significantly inhibit the growth of NMIBC in nude mice replicated by direct injection of T24 cells into the bladder wall, and the tumor inhibition rate was 97.1%. CONCLUSION: The orthotopic NMIBC model can not be established with the bladder mucosa injuried by dilute acid-alkali or silver nitrate treatment. The number and size of orthotopic bladder cancer are different by mechanical injury of bladder mucosa. Injection of T24 cells into the bladder wall of nude mouse can successfully establish the orthotopic NMIBC model, which can be used for the evaluation of NMIBC therapeutic drugs.

Lipid nanoemulsions are promising nanodrug delivery carriers that can improve the efficacy and safety of paclitaxel(PTX).However,no intravenous lipid emulsion of PTX has been approved for clinical treatment,and systemic safety profiles have not yet been reported.Here we outline the development of a PTX-loaded tumor-targeting intravenous lipid emulsion(PTX Emul)and describe its characteristics,colloidal stability,and systemic safety profiles in terms of acute toxicity,long-term toxicity,and tox-icokinetics.We also compare PTX Emul with conventional PTX injection.Results showed that PTX Emul exhibited an ideal average particle size(approximately 160 nm)with narrow size distribution and robust colloidal stability under different conditions.Hypersensitivity reaction and hemolysis tests revealed that PTX Emul did not induce hypersensitivity reactions and had no hemolytic potential.In addition,where the alleviated systemic toxicity of PTX Emul may be attributed to the altered toxicokinetic characteristics in beagle dogs,including the decreased AUC and increased plasma clearance and volume of distribution,PTX Emul alleviated acute and long-term toxicity as evidenced by the enhanced the median lethal dose and approximate lethal dose,moderate body weight change,decreased bone marrow suppression and organ toxicity compared with those under PTX injection at the same dose.A fundamental understanding of the systemic safety profiles,high tumor-targeting efficiency,and superior antitumor activity in vivo of PTX Emul can provide powerful evidence of its therapeutic potential as a future treatment for breast cancer.

Objective:To investigate the relationship between transcription factors (TFs) and the prognosis of colon cancer, and to construct a prognosis model through TCGA and GEO dual databases, so as to quantify the risk of patients and guide clinical treatment decisions.Methods:The transcriptome and clinical data of colon cancer in TCGA and GEO databases were used in this study. The transcriptome data were annotated and the gene expression was calculated. The difference analysis of TFs in TCGA and GEO (log2FC > 1, P-value (Fdr) < 0.05) was performed. The difference TFs of double data intersection were used for correlation prognosis analysis ( P<0.01). The risk coefficient and risk value of prognosis-related TFs were calculated by COX multivariate analysis, and the prognosis model of TFs was constructed by COX model with "survival" and "glmnet" package. The survival curve ( P<0.001) and ROC curve (AUC>0.75) of the sequence set and verification set were drawn, and the distribution of risk value was visualized. After grouping according to risk value, GSEA enrichment analysis was calculated, gene set grid was constructed, target genes were predicted, and finally, pathway enrichment analysis of GO and KEGG was carried out. Results:387 TFs with different expressions in TCGA and GEO databases were used to draw heat map, volcanic map and TFs-related forest map, and the prognosis model of colon cancer was constructed according to COX multivariate analysis=0.310×HSF4+0.137×IRX3-0.127×ATOH1+0.290×OVOL3+0.137×HOXC6+0.155×SIX2+0.092×ZNF556-0.444×CXXC5+0.429×TIGD1+0.413×TCF7L1. Through enrichment analysis, our results showed that these prognostic factors may directly or indirectly act on cancer pathways, such as basic cell carcinoma and cancer signaling pathway, local tissue-cell adhesion, and extracellular matrix.Conclusions:The constructed TFs prognosis model of colon cancer can quantify the prognostic risk of colon cancer, and its high-risk group is an independent risk factor of colon cancer prognosis. This model is a new way to evaluate the prognosis of colon cancer.

Long noncoding RNA (lncRNA) are defined as noncoding RNA with a length of more than 200 nucleotides, which can regulate a variety of cellular processes. LncRNA H19 is widely involved in the pathophysiological process of intestinal inflammation and intestinal cancer by regulating the function of intestinal mucosal barrier. This article reviewed the effect of lncRNA H19 on intestinal mucosal barrier under different intestinal states and inflammation-cancer related signaling pathway.

【Objective】 To investigate the removal efficacy of inflammatory cytokines and blood compatibility of modified PBTNF. 【Methods】 Acrylic acid (AA) was firstly UV-grafted onto the surface of PBTNF to negatively charge the surface of the material. Subsequently, the three positively charged polyelectrolytes, DA, PEI, and CS were respectively electrostatic self-assembled with GO on the surface of PBTNF, forming two layers of film with GO as the outer layer: PBTNF-(DA/GO)2, PBTNF-(PEI/GO)2, PBTNF-(CS/GO)2. 【Results】 Scanning electron microscopy results showed that compared with the PBTNF grafted with AA, the adhesion of particles was observed on the surface of the three modified materials, and the photo shows that the color of the material surface was deepened after electrostatic self-assembly. The results of wettability showed that the surface hydrophilicity was significantly improved, indicating that the electrostatic self-assembled membrane was successfully immobilized on the surface of PBTNF. The removal efficiency (%) of IL-1β for PBTNF-(DA/GO)2, PBTNF-(PEI/GO)2 and PBTNF-(CS/GO)2 were 69.00±7.36 vs -2.35±2.69 vs -1.59±3.26 (P<0.05). The removal efficiency of IL-6 (%) were 40.15±1.86 vs -13.46±5.72 vs -1.21±3.41 (P<0.05). The removal efficiency of IL-8 (%) were 96.90±0.97 vs 17.84±11.74 vs 43.68±17.38 (P<0.05). The removal efficiency of TNF-α (%) was 44.46±2.50 vs 14.90±7.12 vs 20.64±1.22 (P<0.05). Plasma protein adsorption results (total protein, immunoglobulin G, albumin) and red blood cell deformability index showed that there was no statistical difference among the three modified PBTNFs and the control group (P>0.05). Although the red blood cell osmotic fragility (g/L) of the three modified PBTNFs is higher than that of the former: control group vs PBTNF-(DA/GO)2 vs PBTNF-(PEI/GO)2 vs PBTNF-(CS/GO)2: 4.39±0.05 vs 4.62±0.02 vs 4.48±0.03 vs 4.90±0.03 (P<0.05), the hemolysis rate (%) of them were all less than 5%, and PBTNF-(DA/GO)2 performed the lowest hemolysis rate which was (0.03±0.01)% (compared with PBTNF-(PEI/GO)2, P<0.05). The coagulation function test results showed that compared with the control group, the fibrinogen (g/L) of the three modified PBTNFs had no statistical difference (P>0.05); the activated partial thrombo plastin time (S) slightly extended, but all within the normal range of clinical standard; and the prothrombin time (S) of PBTNF-(CS/GO)2 was prolonged(P<0.05). 【Conclusion】 Among the three positively charged polyelectrolytes, including DA, PEI, and CS, PBTNF-(DA/GO)2 performed the best removal rate of inflammatory cytokines, and the blood compatibility evaluation results showed that PBTNF-(DA/GO)2 had no significant effect on red blood cells and coagulation function. Consequently, in the study of inflammatory cytokines adsorption, DA is expected to be the optimal polyelectrolyte assembling with GO for further research.

【Objective】 To investigate the blood compatibility of transfusion sets for single use, the loss, damage and activation of blood components after passage through the transfusion sets. 【Methods】 Transfusion sets (sample A and B) were assessed by comparing samples of blood component taken prior to and after passage through. The following makers of damage/activation were evaluated: Red blood cells (RBCs)-supernatant free hemoglobin (FHb) and potassium(K⁺ ) amount; platelet concentrates (PCs)-pH, hypotonic shock response (HSR), supernatant lactate dehydrogenase(LDH), CD62P; fresh frozen plasma(FFP) – prothrombin fragments 1 and 2 (F1+ 2), fibrinopeptide A (FPA), coagulation factor Ⅻa (FⅫa), Thrombin-antithrombin complex (TAT). 【Results】 After passing through two types of transfusion sets, the loss of RBCs, PCs and FFP were less than 5%. There is no statistic difference for the change of FHb and K⁺ of RBCs(P>0.05). There were no statistics for pH, LDH(U/L) and CD62P(%) after platelet concentrates passing through both transfusion sets. There was no statistics for the HSR after passing through the sample A, while there was a small but statistically significant increase in the HSR of sample B (37.17±6.49 vs 40.75±6.24, P<0.05). After FFP passing through the transfusion giving sets, there were no statistical difference for F1+ 2, FPA, FⅫa and TAT (P>0.05). 【Conclusion】 Two types of transfusion sets caused negligible effects on RBCs, platelet concentrates and FFP.

Efficient mucosal delivery remains a major challenge for the reason of the respiratory tract mucus act as a formidable barrier to nanocarriers by trapping and clearing foreign particulates. The surface property of nanoparticles determines their retention and penetration ability within the respiratory tract mucus. However, the interaction between nanoparticles and mucus, and how these interactions impact distribution has not been extensively investigated. In this study, polymeric nanoparticles loaded with a baicalein-phospholipid complex were modified with two kinds of polymers, mucoadhesive and mucus-penetrative polymer. Systematic investigations on the physicochemical property, mucus penetration, transepithelial transport, and tissue distribution were performed to evaluate the interaction of nanoparticles with the respiratory tract. Both nanoparticles had a similar particle size and good biocompatibility, exhibited a sustained-release profile, but showed a considerable difference in zeta potential. Interestingly, mucus-penetrative nanoparticles exhibited a higher diffusion rate in mucus, deeper penetration across the mucus layer, enhanced cellular uptake, increased drug distribution in airways, and superior local distribution and bioavailability as compared to mucoadhesive nanoparticles. These results indicate the potential of mucus-penetrative nanoparticles in design of a rational delivery system to improve the efficiency of inhaled therapy by promoting mucus penetration and increasing local distribution and bioavailability.