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Abstract Postpancreatectomy hemorrhage (PPH) is an important risk factor for postoperative complications after laparoscopic pancreaticoduodenectomy (LPD). Recent studies have reported that the use of ligamentum teres hepatis (LTH) in LPD may reduce the risk of PPH. Therefore, this study aims to investigate whether wrapping the hepatic hilar artery with the LTH can reduce PPH after LPD. We reviewed the data of 131 patients who underwent LPD in our team from April 2018 to December 2023. The patients were divided into Groups A (60 patients) and B (71 patients) according to whether the hepatic portal artery was wrapped or not. The perioperative data of the two groups were compared to evaluate the effect of LTH wrapping the hepatic hilar artery on LPD. The platelet count of Group A was (225.25 ± 87.61) × 10^9/L, and that of Group B was (289.38 ± 127.35) × 10^9/L, with a statistically significant difference (p

Background: Vascular invasion (VI) indicates highly invasive tumor biological behavior and is a major determining factor of poor survival and high risk of metastasis in hepatocellular carcinoma (HCC). Epidemiological evidence of the association between pretherapeutic platelet count (PLT) and the risk of VI and extrahepatic metastasis in HCC remains controversial. Methods: A systematic retrieval was executed in databases of PubMed, Embase, and Web of Science until Dec 2022. Effect size and 95% confidence interval (CI) were extracted or estimated to synthetically investigate the effects of pretherapeutic PLT on VI and extrahepatic metastasis. Meta-analyses were performed by using a random or a fixed effects model. Results: Finally, the current meta-analysis included 15 studies with a total of 12,378 HCC patients. It was shown that, patients with a higher pretherapeutic level of PLT had a significantly increased risk of VI (11 studies,8,759 patients; OR = 1.44, 95%CI: 1.02–2.02) and extrahepatic metastasis (6 studies,8, 951 patients; OR = 2.51, 95% CI: 2.19–2.88) in comparison with patients with a lower PLT. Funnel plots and Begg's tests indicated that there were no significant publication biases. Conclusion: This meta-analysis shows that pretherapeutic elevated PLT is associated with an increased risk of VI and extrahepatic metastasis in HCC.

Abstract Background Drug resistance is a main factor affecting the chemotherapy efficacy of gastric cancer (GC), in which meiosis plays an important role. Therefore, it is urgent to explore the effect of meiosis related genes on chemotherapy resistance. Methods The expression of meiotic nuclear divisions 1 (MND1) in GC was detected by using TCGA and clinical specimens. In vitro and in vivo assays were used to investigate the effects of MND1. The molecular mechanism was determined using luciferase reporter assay, CO-IP and mass spectrometry (MS). Results Through bioinformatics, we found that MND1 was highly expressed in platinum-resistant samples. In vitro experiments showed that interference of MND1 significantly inhibited the progression of GC and increased the sensitivity to oxaliplatin. MND1 was significantly higher in 159 GC tissues in comparison with the matched adjacent normal tissues. In addition, overexpression of MND1 was associated with worse survival, advanced TNM stage, and lower pathological grade in patients with GC. Further investigation revealed that forkhead box protein A1 (FOXA1) directly binds to the promoter of MND1 to inhibit its transcription. CO-IP and MS assays showed that MND1 was coexpressed with transketolase (TKT). In addition,TKT activated the PI3K/AKT signaling axis and enhanced the glucose uptake and lactate production in GC cells. Conclusions Our results confirm that FOXA1 inhibits the expression of MND1, which can directly bind to TKT to promote GC progression and reduce oxaliplatin sensitivity through the PI3K/AKT signaling pathway.

In order to investigate the potential mechanisms of probiotic-fermented coconut water in treating enteritis, this study conducted a comprehensive analysis of the effects of probiotic intervention on the recovery from Dextran Sodium Sulfate-induced acute enteritis in Wenchang chicks. The analysis encompassed the assessment of growth performance, serum indicators, intestinal tissue structure, and metagenomic and metabolomic profiles of cecal contents in 60 Wenchang chicks subjected to intervention. This approach aimed to elucidate the impact of probiotic intervention on the recovery process from acute enteritis at both the genetic and metabolic levels in the avian model. The results revealed that intervention with Saccharomyces cerevisiae Y301 improved the growth rate of chicks. and intervention with Lactiplantibacillus plantarum MS2c regulated the glycerophospholipid metabolism pathway and reshaped the gut microbiota structure in modeling chicks with acute enteritis, reducing the abundance of potentially pathogenic bacteria from the Alistipes and increasing the abundance of potentially beneficial species from the Christensenellaceae. This intervention resulted in the production of specific gut metabolites, including Gentamicin C and polymyxin B2, recognized for their therapeutic effects on acute enteritis. The combined intervention of S. cerevisiae Y301 and L. plantarum MS2c not only enhanced growth performance but also mitigated intestinal wall damage and increased the abundance of gut metabolites such as gentamicin C and polymyxin B2, thereby mitigating symptoms of enteritis. Furthermore, this combined intervention reduced the levels of serum immune markers, including IL-10, IL-6, TNF-α, IFN-γ, and D-lactic acid, thus mitigating intestinal epithelial cell damage and promoting acute enteritis recovery. This study provides crucial insights into the mechanisms of action of probiotics and probiotic-fermented coconut water in acute enteritis recovery, offering new perspectives for sustainable farming practices for Wenchang chicken.

Abstract Background Cholangiocarcinoma (CCA) is one of the deadliest cancers of the digestive tract. The prognosis of CCA is poor and the 5-year survival rate is low. Bioinformatic analysis showed that early mitotic inhibitor 2 (EMI2) was overexpressed in CCA but the underlying mechanism is not known. Methods The data on bile duct carcinoma from TCGA and GEO databases were used to detect the expression of EMI2. The transcription factors of EMI2 were predicted using JASPAR and PROMO databases. Among the predicted transcription factors, YY1 has been rarely reported in cholangiocarcinoma, and was verified using the luciferase reporter gene assay. RT-PCR was performed to predict the downstream pathway of EMI2, and PI3K/Akt was suspected to be associated with it. Subsequently, in vivo and in vitro experiments were conducted to verify the effects of silencing and overexpressing EMI2 and YY1 on the proliferation, invasion, and metastasis of the bile duct cancer cells. Results EMI2 was highly expressed in CCA. Silencing EMI2 inhibited the proliferation, invasion, and migration of CCA cells, arrested cell cycle in the G1 phase, and promoted of apoptosis. The luciferase reporter gene assay showed that YY1 bound to the promoter region of EMI2, and after silencing YY1, the expression of EMI2 decreased and the progression of CCA was inhibited. Moreover, key proteins in the PI3K/Akt signaling pathway decreased after silencing EMI2. Conclusion EMI2 may be one of the direct targets of YY1 and promotes the progression of CCA through the PI3K/Akt signaling pathway.

DFT calculations are performed to investigate the electronic and optical absorption properties of two-dimensional heterostructures constructed by Janus MoSSe and germanene. It is found that a tiny gap can be opened up at the Dirac point in both Ge/SMoSe and Ge/SeMoS heterostructures, with intrinsic high-speed carrier mobility of the germanene layer being well preserved. An n-type Schottky contact is formed in Ge/SMoSe, while a p-type one is formed in Ge/SeMoS. Compared to corresponding individual layers, germanene-MoSSe heterostructures can exhibit extended optical absorption ability, ranging from ultraviolet to infrared light regions. The position of the Dirac cone, the Dirac gap value as well as the position of the optical absorption peak for both Ge/SMoSe and Ge/SeMoS heterostructures can be tuned by in-plane biaxial strains. It is also predicted that a Schottky–Ohmic transition can occur when suitable in-plane strain is imposed (especially tensile strain) on heterostructures. These results can provide a helpful guide for designing future nanoscale optoelectronic devices based on germanene-MoSSe vdW heterostructures.

Abstract We aimed to compare the efficacy of percutaneous transhepatic biliary stenting (PTBS) and PTBS combined with 125I particles implantation in the treatment of advanced extrahepatic cholangiocarcinoma (EHC). A total of 184 advanced EHC patients, who received PTBS (PTBS group) or PTBS combined with 125I particles implantation (PTBS + 125I group) from January 2012 to April 2017 in our department, were retrospectively reviewed. The improvement of jaundice and liver function was observed in both groups. The postoperative complications, risk of biliary re-obstruction, and overall survival (OS) were compared between the two groups. Amongst, 71 cases received PTBS and 113 had the additional implantation of 125I particles. The jaundice and liver function were significantly improved in all patients, especially in PTBS + 125I group. There was no significant difference in the risk of postoperative complications between the two groups. However, the risk of biliary re-obstruction significantly reduced in PTBS + 125I group (19.5% vs. 35.2%, p = 0.017). Kaplan Meier analysis showed that patients in PTBS + 125I group had a significantly better OS, both for hilar and distal cholangiocarcinoma. Univariate analysis demonstrated that preoperative levels of carbohydrate antigen 19-9 (CA19-9), total bilirubin, neutrophil count, lymphocyte count, and different therapeutic method were significant factors affecting OS. Multivariate analysis further identified the treatment of PTBS combined with 125I particles implantation as an independent protective prognostic factor (HR = 0.26, 95% CI: 0.17–0.39, p

As highly conserved non-coding RNAs of approximately 18–24 nucleotides, microRNAs (miRNAs) regulate the expression of target genes. Multiple studies have demonstrated that miRNAs participate in the regulation of human cancer. MircoRNA-217 (miR-217) participates in the regulation of various tumors by specifically binding target genes and post-transcriptional regulation. In recent years, there have been numerous reports about miR-217 in tumor progression. MiR-217 is known mainly as a tumor suppressor, although some studies have shown that it functions as an oncomiR. Here, we review the current research related to miR-217, including its role in tumor progression and the molecular mechanisms.

Background. Banxia Xiexin Decoction (BXXD) reportedly regulates glycolipid metabolism and inhibits pancreatic β-cell apoptosis. This study is aimed at investigating the protective effect of BXXD on tert-butyl hydroperoxide- (t-BHP-) induced apoptosis in MIN6 cells and the underlying mechanisms. Methods. MIN6 cells were preincubated with BXXD or liraglutide (Li) with or without PI3K inhibitor LY294002 (LY) for 12 h, following which t-BHP was added to induce MIN6 cell apoptosis. The protective effects of BXXD on MIN6 cells were evaluated by detecting cell viability and proliferation and glucose-stimulated insulin secretion (GSIS). The antiapoptotic effects were evaluated by Hoechst 33342 staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay (TUNEL). Malondialdehyde and glutathione peroxidase content and superoxide dismutase activity were measured using commercial kits. The expression of PI3K/AKT/FOXO1 signaling pathway-related signal molecules, and that of apoptotic indicators Bax, P27, and Caspase-3, was quantified using western blotting. Results. Preincubation with BXXD significantly improved t-BHP-induced proliferation inhibition and apoptosis and enhanced GSIS. t-BHP induced the generation of reactive oxygen species and inhibited the activities of antioxidant enzymes, which could be neutralized by pretreatment with BXXD. BXXD promoted the phosphorylation of AKT and FOXO1 in t-BHP-induced MIN6 cells. Moreover, BXXD attenuated the expression of related apoptotic indicators Bax, P27, and Caspase-3. LY abolished these effects of BXXD. Conclusion. BXXD protected MIN6 cells against t-BHP-induced apoptosis and improved insulin secretory function through modulation of the PI3K/AKT pathway and the downstream FOXO1, thus suggesting a novel therapeutic approach for type 2 diabetes mellitus (T2DM).

Aim. Child-Pugh (CP) grade has been used to assess liver function and postoperative outcomes in biliary tract neoplasms. The aim of this study was to preliminarily explore the prognostic significance of an alternative model of liver function, called albumin-bilirubin (ALBI) grade, in patients with extrahepatic cholangiocarcinoma (EHC). Methods. A total of 109 advanced EHC patients, who received percutaneous transhepatic biliary stenting combined with iodine-125 seed implantation from January 2012 to April 2017 in our department, were enrolled. Preoperative clinical data were collected to calculate the CP and ALBI grades. The performance of ALBI score in predicting postoperative death was compared with that of CP score by using the receiver operating characteristic (ROC) curve. Kaplan-Meier analysis and Cox regression model were performed for overall survival (OS) analysis. Results. The median survival time of our cohort was 12 months, and the 1-year and 2-year survival rates were 56.9% and 12.8%, respectively. The area under the ROC curve of ALBI score for predicting death was significantly greater than the CP score (0.751, 95% CI: 0.641–0.861, P

Background: To compare the clinicopathological features and prognosis between younger and aged patients with hepatocellular carcinoma (HCC). Methods: We analyzed the outcome of 451 HCC patients underwent liver resection, transcatheter arterial chemoembolization and radiofrequency ablation, respectively. Then risk factors for aged and younger patients′ survival were evaluated by multivariate analysis, respectively. Results: The patients who were older than 55 years old were defined as the older group. The overall survival for aged patients was significantly worse than those younger patients. The younger patients had similar liver functional reserve but more aggressive tumor factors than aged patients. Cox regression analysis showed that the elevated levels of aspartate aminotransferase (AST) (Wald χ2 = 3.963, P = 0.047, hazard ratio [HR] =1.453, 95% confidence interval [CI]: 1.006-2.098), lower albumin (Wald χ2 = 12.213, P < 0.001, HR = 1.982, 95% CI: 1.351-2.910), tumor size (Wald χ2 = 8.179, P = 0.004, HR = 1.841, 95% CI: 1.212-2.797), and higher alpha-fetoprotein level (Wald χ2 = 4.044, P = 0.044, HR = 1.465, 95% CI: 1.010-2.126) were independent prognostic factors for aged patients, while only elevated levels of AST (Wald χ2 = 14.491, P < 0.001, HR = 2.285, 95% CI: 1.493-3.496) and tumor size (Wald χ2 = 21.662, P < 0.001, HR = 2.928, 95% CI: 1.863-4.604) were independent prognostic factors for younger patients. Conclusions: Age is a risk factor to determine the prognosis of patients with HCC. Aged patients who have good liver functional reserve are still encouraged to receive curative therapy.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection with a high mortality. 5-Hydroxytryptamine (5-HT) is an important regulatory factor in inflammation. The aim of this study is to investigate the role of 5-HT on cecal ligation and puncture- (CLP-) induced sepsis in the mouse model. CLP was performed on C57B/6 wild-type (WT) mice and tryptophan hydroxylase 1 (TPH1) knockout (KO) mice. The results showed that the 5-HT-sufficient group mice had a significantly lower survival rate than the 5-HT-deficient group in CLP-induced sepsis and septic shock. The KO-CLP sepsis group received a lower clinical score than the WT-CLP sepsis group. Meanwhile, the body temperature of mice in the KO-CLP sepsis group was higher than that in the WT-CLP sepsis group and was much closer to the normal body temperature 24 hours after CLP. The tissue histopathology analysis revealed that 5-HT markedly exacerbated histological damages in the peritoneum, lung, liver, kidney, intestinal tissue, and heart in sepsis. Moreover, significant lower levels of TNF-α, IL-6, bacterial loads, MPO, and ROS were discovered in the KO-CLP sepsis group in contrast to the WT-CLP sepsis group. In conclusion, 5-HT drives mortality and exacerbates organ dysfunction by promoting serum cytokines and bacterial loads as well as facilitating oxidative stress in the process of sepsis.

Nanosized Al2O3 powder is synthesized by thermal Metal Organic Chemical Vapor Deposition (MOCVD)combined withplasma. The effects of reaction temperature, pressure, Al(CH3)3 (TMA) concentration and reactant gases (CO2 and O2) on the characteristics of the synthesized Al2O3 powders are investigated. The experimental results demonstrate that very fineAl2O3 powders with mean particle size of about 2.5 nm can be obtained at 5.3kPareactor pressure and 1000 oCby the thermal MOCVD. As the pressure is increased from 5.3kPa to 100 kPa, the mean diameter of Al2O3 powders also reaches to 10 nm. In other words, the increase in pressure has a negative effect on the synthesis of nanosized Al2O3. Meanwhile, it is also observed that the increment of temperature can promote the synthesis of fine Al2O3 powder.

Objective: The objective of this study was to decipher chemical interactions between Danshen and Danggui using liquid chromatography–mass spectrometry (LC-MS) and explore the mechanisms of Danshen–Danggui against stroke using network pharmacology and molecular docking. Materials and Methods: First, the chemical compounds of Danshen–Danggui were profiled using ultra-high-performance liquid chromatography (HPLC)-quadrupole time-of-flight MS. Accurately characterized compounds in various proportions of Danshen–Danggui were quantified using HPLC combined with triple quadrupole electrospray tandem MS. Network pharmacology was used to uncover the essential mechanisms of action of Danshen–Danggui against stroke. Discovery Studio Software was used for the molecular docking verification of key active chemicals and stroke-related targets. Results: A total of 53 compounds were characterized, and 22 accurately identified constituents (10 phenolic acids, 8 phthalides, and 4 tanshinones) were quantified in 15 proportions of Danshen–Danggui. The quantification results showed that Danggui significantly increased the dissolution of most phenolic acids (compounds from Danshen), whereas Danshen promoted the dissolution of most phthalides (compounds from Danggui). Overall, the combination of Danshen and Danggui at a 1:1 ratio resulted in the maximum total dissolution rate. Further network pharmacology and molecular docking results indicated that Danshen–Danggui exerted anti-stroke effects mainly by regulating inflammation-related (tumor necrosis factor, hypoxia-inducible factor, and toll-like receptor) signaling pathways, which ranked among the top three pathways based on Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Conclusion: The chemical compounds in Danshen–Danggui could interact with each other to increase the dissolution of the most active compounds, which could provide a solid basis for uncovering the compatibility mechanisms of Danshen–Danggui and Danshen–Danggui-based formulae.

Abstract The effects of evodiamine (EVO) on oral squamous cell carcinoma (OSCC) are not yet understood. Based on our earlier findings, we hypothesized that evodiamine may affect OSCC cell proliferation and glutamate metabolism by modulating the expression of EPRS (glutamyl‐prolyl‐tRNA synthetase 1). From GEPIA, we obtained EPRS expression data in patients with OSCC as well as survival prognosis data. An animal model using Cal27 cells in BALB/c nude mice was established. The expression of EPRS was assessed by immunofluorescence, Western blotting, and quantitative PCR. Glutamate measurements were performed to evaluate the impact of evodiamine on glutamate metabolism of Cal27 and SAS tumor cells. transient transfection techniques were used to knock down and modulate EPRS in these cells. EPRS is expressed at higher levels in OSCC than in normal tissues, and it predicts poor prognosis in patients. In a nude mouse xenograft model, evodiamine inhibited tumor growth and the expression of EPRS. Evodiamine impacted cell proliferation, glutamine metabolism, and EPRS expression on Cal27 and SAS cell lines. In EPRS knockdown cell lines, both cell proliferation and glutamine metabolism are suppressed. EPRS's overexpression partially restores evodiamine's inhibitory effects on cell proliferation and glutamine metabolism. This study provides crucial experimental evidence supporting the potential therapeutic application of evodiamine in treating OSCC. Evodiamine exhibits promising anti‐tumor effects by targeting EPRS to regulate glutamate metabolism.

Abstract Background The tumorigenesis of infused umbilical cord mesenchymal stem cells (UC-MSCs) is being preclinically evaluated. Methods We observed tumor formation in NOD SCID mice after a single subcutaneous injection of hUC-MSCs and the effect of these cells on tumor growth in tumor-bearing mice. Three generations (P5, P7, and P10) of hUC-MSCs (1 × 107) from two donors (hUC-MSC1 and hUC-MSC2) were inoculated subcutaneously into NOD SCID mice. Subcutaneous transplantation models were established in NOD SCID mice with human cervical cancer HeLa cells (solid tumor) and human B cell lymphoma Raji cells (hematological tumor). Then, the animals were euthanized, gross dissection was performed, and tissues were collected. Various organs were observed microscopically to identify pathological changes and tumor metastasis. Results In the tumorigenesis experiment, no general anatomical abnormalities were observed. In the tumor promotion experiment, some animals in the HeLa groups experienced tumor rupture, and one animal died in each of the low- and medium-dose hUC-MSC groups. The results may have occurred due to the longer feeding time, and the tumor may have caused spontaneous infection and death. Pathological examination revealed no metastasis to distant organs in any group. In the Raji tumor model, some animals in each group experienced tumor rupture, and one animal in the medium-dose hUC-MSC group died, perhaps due to increased tumor malignancy. Thus, hUC-MSCs neither promoted nor inhibited tumor growth. No cancer cell metastasis was observed in the heart, liver, spleen, lungs, kidneys or other important organs, except that pulmonary venule metastasis was observed in 1 animal in the model group. Conclusions Injected hUC-MSCs were not tumorigenic and did not significantly promote or inhibit solid or hematological tumor growth or metastasis in NOD SCID mice.

For determining the corrosion behavior of L320 steel at different flow rates in CO2/O2 environments, the flow state of the target pipeline was simulated through the multiphase flow transient simulation software, and the flow velocity range of the indoor simulation experiment was determined. The L320 steel was selected for the high temperature and high pressure dynamic reactor experiment with different flow rates under the CO2/O2 coexistence systems, and the corrosion products were studied by scanning electron microscope and X - ray diffractometer for the microscopic morphology observation and composition analysis. Results showed that the temperature and pressure showed a downward trend with increasing mileage, and the gas flow rate and wall shear force of the pipeline exhibited a gradually increasing trend with the increase of the mileage. Based on the Pearson correlation coefficient method, it was determined that the flow velocity was the main controlling factor affecting the corrosion rate. With the increase of flow rate, the uniform corrosion rate of L320 under the condition of CO2/O2 coexistence gradually increased. The corrosion products of the CO2/O2 coexistence systems were Fe2O3, FeOOH, Fe(OH)3, Fe3O4, FeCO3, etc. The research conclusions could provide reference for the protection of L320 steel in CO2/O2 coexistence environment at different flow rates.

Abstract Background The ovaries are the core reproductive organs in women and are critical for maintaining normal reproductive function and endocrine system stability. An ageing C57 mouse model was used to evaluate the efficacy and mechanism of mouse umbilical cord mesenchymal stem cells (mUCMSCs) and to explore the mechanism by which mUCMSCs promote the antioxidant repair of mouse granulosa cells (mGCs). Results Eighteen-month-old C57 mice were randomly divided into a model group and a treatment group. At the same time, 2-month-old C57 mice were established as a young group (15 mice per group). The mice in the treatment group were injected via the tail vein with GFP-labelled mUCMSCs. The ovarian volume in ageing C57 mice was decreased, and there were no follicles at any stage. After mUCMSC transplantation, the mouse ovaries increased in size, follicles at various stages were observed in the cortex, and the antral follicle counts increased. The serum E2, AMH, and INH-B levels of mice in the treatment group were significantly higher than those of mice in the model control group (P

Zanthoxylum nitidum (Roxb.) DC. (ZN), with strong effects of anti-inflammation and antioxidant activities is treated as a core herb in traditional Chinese medicine (TCM) preparation for treating stomachache, toothache, and rheumatoid arthritis. However, the active ingredients of ZN are not fully clarified due to its chemical complexity. In the present study, a double spectrum–effect analysis strategy was developed and applied to explore the bioactive components in herbs, and ZN was used as an example. Here, the chemical components in ZN were rapidly and comprehensively profiled based on the mass defect filtering-based structure classification (MDFSC) and diagnostic fragment-ion-based extension approaches. Furthermore, the fingerprints of 20 batches of ZN samples were analyzed by high-performance liquid chromatography, and the anti-inflammatory and antioxidant activities of the 20 batches of ZN samples were studied. Finally, the partial least squares regression (PLSR), gray relational analysis models, and Spearman’s rank correlation coefficient (SRCC) were applied to discover the bioactive compounds in ZN. As a result, a total of 48 compounds were identified or tentatively characterized in ZN, including 35 alkaloids, seven coumarins, three phenolic acids, two flavonoids, and one lignan. The results achieved by three prediction models indicated that peaks 4, 12, and 17 were the potential anti-inflammatory compounds in ZN, whereas peaks 3, 5, 7, 12, and 13 were involved in the antioxidant activity. Among them, peaks 4, 5, 7, and 12 were identified as nitidine, chelerythrine, hesperidin, and oxynitidine by comparison with the standards and other references. The data in the current study achieved by double spectrum–effect analysis strategy had great importance to improve the quality standardization of ZN, and the method might be an efficiency tool for the discovery of active components in a complex system, such as TCMs.

ABSTRACTThe ongoing COVID-19 pandemic is causing huge impact on health, life, and global economy, which is characterized by rapid spreading of SARS-CoV-2, high number of confirmed cases and a fatality/case rate worldwide reported by WHO. The most effective intervention measure will be to develop safe and effective vaccines to protect the population from the disease and limit the spread of the virus. An inactivated, whole virus vaccine candidate of SARS-CoV-2 has been developed by Wuhan Institute of Biological Products and Wuhan Institute of Virology. The low toxicity, immunogenicity, and immune persistence were investigated in preclinical studies using seven different species of animals. The results showed that the vaccine candidate was well tolerated and stimulated high levels of specific IgG and neutralizing antibodies. Low or no toxicity in three species of animals was also demonstrated in preclinical study of the vaccine candidate. Biochemical analysis of structural proteins and purity analysis were performed. The inactivated, whole virion vaccine was characterized with safe double-inactivation, no use of DNases and high purity. Dosages, boosting times, adjuvants, and immunization schedules were shown to be important for stimulating a strong humoral immune response in animals tested. Preliminary observation in ongoing phase I and II clinical trials of the vaccine candidate in Wuzhi County, Henan Province, showed that the vaccine is well tolerant. The results were characterized by very low proportion and low degree of side effects, high levels of neutralizing antibodies, and seroconversion. These results consistent with the results obtained from preclinical data on the safety.

Ischemia-reperfusion injury is an important contributor to acute kidney injury and a major factor affecting early functional recovery after kidney transplantation. We conducted this experiment to investigate the protective effect of induced multipotent stem cell transplantation on renal ischemia-reperfusion injury. Forty rabbits were divided into four groups of 10 rabbits each. Thirty rabbits were used to establish the renal ischemia-reperfusion injury model, and ten rabbits served as the model group and were not treated. Among the 30 rabbits with renal ischemia-reperfusion injury, 10 rabbits were treated with induced peripheral blood mononuclear cells (PBMCs), and 10 other rabbits were treated with noninduced PBMCs. After three weekly treatments, the serum creatinine levels, urea nitrogen levels and urine protein concentrations were quantified. The kidneys were stained with hematoxylin-eosin (HE), periodic acid-Schiff (PAS) and Masson's trichrome and then sent for commercial metabolomic testing. The kidneys of the rabbits in the model group showed different degrees of pathological changes, and the recovery of renal function was observed in the group treated with induced cells. The results indicate that PBMCs differentiate into multipotent stem cells after induction and exert a therapeutic effect on renal ischemia-reperfusion injury.

Background/Aims: Stem cell-based therapy is attractive in many clinical studies, but current data on the safety of stem cell applications remains inadequate. This study observed the safety, immunological effect of cynomolgus monkey umbilical cord mesenchymal stem cells (mUC-MSCs) injected into cynomolgus monkeys, in order to evaluate the safety of human umbilical cord mesenchymal stem cells (hUC-MSCs) prepared for human clinical application. Methods: Eighteen cynomolgus monkeys were divided into three groups. Group 1 is control group, Group 2 is low-dose group, Group 3 is high-dose group. After repeated administrations of mUC-MSCs, cynomolgus monkeys were observed for possible toxic reactions. Results: During the experiment, no animal died. There were no toxicological abnormalities in body weight, body temperature, electrocardiogram, coagulation and pathology. In the groups 2 and 3, AST and CK transiently increased, and serum inorganic P slightly decreased. All animals were able to recover at 28 days after the infusion was stopped. In the groups 2 and 3, CD3+ and IL-6 levels significantly increased, and recovery was after 28 days of infusion. There were no obvious pathological changes associated with the infusion of cells in the general and microscopic examinations. Conclusions: The safe dosage of repeated intravenous infusion of mUC-MSCs in cynomolgus monkeys is 1.0 × 107/kg, which is 10 times of that in clinical human use.

As a well-known traditional Chinese medicine (TCM) prescription, Xin-Sheng-Hua Granule (XSHG) has been applied in China for more than 30 years to treat postpartum diseases, especially anemia. However, underlying therapeutic mechanisms of XSHG for anemia were still unclear. In this study, plasma metabolomics profiling with UHPLC-QTOF/MS and multivariate data method was firstly analyzed to discover the potential regulation mechanisms of XSHG on anemia rats induced by bleeding from the orbit. Afterward, the compound-target-pathway network of XSHG was constructed by the use of network pharmacology, thus anemia-relevant signaling pathways were dissected. Finally, the crucial targets in the shared pathways of metabolomics and network pharmacology were experimentally validated by ELISA and Western Blot analysis. The results showed that XSHG could exert excellent effects on anemia probably through regulating coenzyme A biosynthesis, sphingolipids metabolism and HIF-1α pathways, which was reflected by the increased levels of EPOR, F2, COASY, as well as the reduced protein expression of HIF-1α, SPHK1, and S1PR1. Our work successfully explained the polypharmcological mechanisms underlying the efficiency of XSHG on treating anemia, and meanwhile, it probed into the potential treatment strategies for anemia from TCM prescription.

Discovering a new cell transplantation approach for treating chronic renal insufficiency is a goal of many nephrologists. In vitro-cultured peripheral blood mononuclear cells (PBMCs) were reprogrammed into induced mesenchymal stem cells (iMSCs) by using natural inducing agents made in our laboratory. The stem cell phenotype of the iMSCs was then identified. Unilateral ureteral obstruction (UUO) was used to create an animal model of chronic renal insufficiency characterized by renal interstitial fibrosis. The induced and non-induced PBMCs were transplanted, and the efficacy of iMSCs in treating chronic renal insufficiency was evaluated using a variety of methods. The ultimate goal was to explore the effects of iMSC transplantation on the treatment of chronic renal insufficiency, with the aim of providing a new therapeutic modality for this disease.

The compatibility between Danggui (Angelicae Sinensis Radix) and Honghua (Carthami Flos) is a known herb pair, which could activate blood circulation and dissipate blood stasis effects. In this paper, we quantified seven main bio-active components (hydroxysafflor yellow A, caffeic acid, p-coumaric acid, kaempferol-3-O-rutinoside, ferulic acid, 3-n-butylphthalide, and ligustilide) in plasma samples in vivo by UPLC-TQ/MS method and investigatedwhether the pharmacokinetic (PK) behaviors of the seven components could be altered in blood stasis rats after oral administration of the Gui-Hong extracts. It was found that the Cmax and AUC0-t of these components in blood stasis rats had increasing tendency compared with normal rats. Most components in model and normal rats had significant difference in some pharmacokinetic parameters, which indicated that the metabolism enzymes and transporters involved in the metabolism and disposition of these bio-active componentsmay bealtered in blood stasis rats. This study was the first report about the pharmacokinetic investigation between normal and blood stasis rats after oral administrationof Gui-Hong extracts, and these results are important and valuable for better clinical applications of Gui-Hong herb pair and relatedTCM formulae.

Background. Systemic lupus erythematosus (SLE) is a multisystem disease that is characterized by the appearance of serum autoantibodies. No effective treatment for SLE currently exists. Methods. We used human umbilical cord mesenchymal stem cell (H-UC-MSC) transplantation to treat B6.Fas mice. Results. After four rounds of cell transplantation, we observed a statistically significant decrease in the levels of mouse anti-nuclear, anti-histone, and anti-double-stranded DNA antibodies in transplanted mice compared with controls. The percentage of CD4+CD25+Foxp3+ T cells in mouse peripheral blood significantly increased after H-UC-MSC transplantation. Conclusions. The results showed that H-UC-MSCs could repair lesions in B6.Fas mice such that all of the relevant disease indicators in B6.Fas mice were restored to the levels observed in normal C57BL/6 mice.

INTRODUCTION: Renal interstitial fibrosis (RIF) is a significant cause of end-stage renal failure. The goal of this study was to characterize the distribution of transplanted induced autologous stem cells in a rabbit model of renal interstitial fibrosis and evaluate its therapeutic efficacy for treatment of renal interstitial fibrosis. METHODS: A rabbit model of renal interstitial fibrosis was established. Autologous fibroblasts were cultured, induced and labeled with green fluorescent protein (GFP). These labeled stem cells were transplanted into the renal artery of model animals at 8 weeks. RESULTS: Eight weeks following transplantation of induced autologous stem cells, significant reductions (P < 0.05) were observed in serum creatinine (SCr) (14.8 ± 1.9 mmol/L to 10.1 ± 2.1 mmol/L) and blood urea nitrogen (BUN) (119 ± 22 µmol/L to 97 ± 13 µmol/L), indicating improvement in renal function. CONCLUSIONS: We successfully established a rabbit model of renal interstitial fibrosis and demonstrated that transplantation of induced autologous stem cells can repair kidney damage within 8 weeks. The repair occurred by both inhibition of further development of renal interstitial fibrosis and partial reversal of pre-existing renal interstitial fibrosis. These beneficial effects lead to the development of normal tissue structure and improved renal function.