Liver transplantation following two conversions in a patient with huge hepatocellular carcinoma and portal vein invasion: A case report.

BACKGROUND: Surgical resection and liver transplantation (LT) are the most effective curative options for hepatocellular carcinoma (HCC). However, few patients with huge HCC (> 10 cm in diameter), especially those with portal vein tumor thrombus (PVTT), can receive these treatments. Selective internal radiation therapy (SIRT) can be used as a conversion therapy for them because it has the dual benefit of shrinking tumors and increasing residual hepatic volume. However, in patients with huge HCC, high lung absorbed dose often prevents them from receiving SIRT. CASE SUMMARY: A 35-year-old man was admitted because of emaciation and pain in the hepatic region for about 1 month. The computed tomography scan showed a 20.2 cm × 19.8 cm tumor located in the right lobe-left medial lobes with right portal vein and right hepatic vein invasion. After the pathological type of HCC was confirmed by biopsy, two conversions were presented. The first one was drug-eluting bead transarterial chemoembolization plus hepatic arterial infusion chemotherapy and lenvatinib and sintilimab, converted to SIRT, and the second one was sequential SIRT with continued systemic treatment. The tumor size significantly decreased from 20.2 cm × 19.8 cm to 16.2 cm × 13.8 cm, then sequentially to 7.8 cm × 6.8 cm. In the meantime, the ratio of spared volume to total liver volume increased gradually from 34.4% to 55.7%, then to 62.9%. Furthermore, there was visualization of the portal vein, indicating regression of the tumor thrombus. Finally, owing to the new tumor in the left lateral lobe, the patient underwent LT instead of resection without major complications. CONCLUSION: Patients with inoperable huge HCC with PVTT could be converted to SIRT first and accept surgery sequentially.

Lignin-polyurea/luffa seed oil microcapsules for anti-mold modification of bamboo.

Bamboo has shown enormous potential across construction, furniture, and other fields as an efficient replacement for wood. However, during its application, bamboo is susceptible to microbial infection and mildew, resulting in damage to the internal structure that adversely affects its mechanical properties. In the present study, lignin-based polyurea resin/luffa seed oil (LSO) microcapsules (LSO@LPMC) were prepared by interfacial polymerization method. These microcapsules were then applied on bamboo for mold-prevention modification through vacuum impregnation and epoxy resin-microcapsule coating, which significantly improved the mold resistance of bamboo. Microcapsules could alleviate the excessive release of carbon and nitrogen sources within the LSO. The prepared LSO@LPMC exhibited a high encapsulation efficiency (90.76 %) and excellent sustained release performance. LSO benefited from active functional groups including aldehyde and carboxyl groups, thus the enzymes and proteins on the cell surface could be easily deactivated, ultimately leading to microbial lysis and death. The bamboo samples modified with microcapsule coating exhibited excellent antifungal activity and mechanical properties. The processing technology of these microcapsules provides a theoretical reference and practical foundation for the promotion and application of LSO in the field of anti-mold modification of bamboo.

Effect of natural astaxanthin on sperm quality and mitochondrial function of breeder rooster semen cryopreservation.

Cryopreservation causes higher reactive oxygen species (ROS) concentrations, leading to oxidative stress and lipid peroxidation damage sperm, and using antioxidants can improve semen quality after freeze-thaw. Natural astaxanthin (ASTA) can be inserted into cell membranes and its antioxidant properties are stronger than other antioxidants. We aimed to investigate the effects of ASTA supplementation in the Beltsville Poultry Semen Extender (BPSE) on post-thaw rooster semen quality and to explore the potential mechanism of rooster semen quality change. The qualifying semen ejaculates collected from 30 adult male Jinghong No.1 laying hen breeder roosters (65wk old) were pooled, divided into four aliquots, and diluted with BPSE having different levels of ASTA (0, 0.5, 1, or 2µg/mL). Treated semen was cryopreserved and kept in liquid nitrogen. The entire experiment was replicated three times independently. Sperm viability, motility, curvilinear velocity, amplitude of lateral head displacement, straightness, plasma membrane integrity, and acrosome integrity were observed highest (P < 0.05) with 1µg/mL ASTA at freeze-thawing. Higher (P < 0.05) antioxidant enzyme (CAT-like, SOD) activities and free radical (·OH, O2.-) scavenging ability, less ROS and malondialdehyde (MDA) concentrations were recorded with the addition of appropriate concentrations of ASTA compared to control. In addition, the levels of mitochondrial membrane potential (MMP), adenosine triphosphate (ATP), and lactate dehydrogenase (LDH) in the 1µg/mL ASTA group improved compared to the control group, and decreased the amount of AIF protein level but increased the Bcl-2 protein level (P < 0:05). Collectively, these results demonstrate that adding ASTA in the BPSE promoted rooster freeze-thaw sperm quality, which may be related to reducing ROS levels, protecting the antioxidant defense system, preventing lipid peroxidation, improving mitochondrial structural and functional integrity, and inhibiting sperm apoptosis.

Interaction and band structure-determined inhibition of negative Cr (VI) and positive Fe (III) for antibiotic photodegradation by nitrogen-doped dissolved black carbon.

The influences of the positive Fe3+ and the negative Cr2O72- on the tetracycline (TC) photodegradation by N-doped dissolved black carbon (NDBC) have been investigated in this work. A series of samples (NDBC300, NDBC400 and NDBC500) have been extracted from the corresponding biochar. NDBC400 has the best photodegradation performance (79%) for TC under visible light irradiation. Adding Cr2O72- and Fe3+ can reduces TC photodegradation efficiency into 37% and 53%, respectively. This maybe from that Cr2O72- has stronger interaction with NDBC400 than Fe3+ since it can quench more fluorescence intensity of NDBC400 than Fe3+. Furthermore, Cr2O72- can reduce the steady-state concentration of 3NDBC400*, 1O2 and •OH, whereas Fe3+can just reduce the steady-state concentration of 3NDBC400* and increase the concentration of •OH. This may explain why Cr2O72- has stronger inhibit performance of TC photodegradation by NDBC400 than Fe3+. The band structures of NDBC400, NDBC400-Fe3+ and NDBC400-Cr2O72- are constructed. And the VB of NDBC400-Fe3+ has a stronger ability to produce •OH than NDBC400. In summary, coupling interaction and band structure characterization of NDBC400, NDBC400-Fe3+ and NDBC400-Cr2O72- can explain well why Cr2O72 has stronger inhibition effect than Fe3+ and Fe3+ can increase the concentration of •OH. This work provides a deep insight for the photochemical behavior of dissolved black carbon and the transformation behavior of the co-existed metal ions and antibiotics.

Correlation between glymphatic dysfunction and cranial defect in severe traumatic brain injury: a retrospective case-control study based on a diffusion tensor image analysis along the perivascular space (DTI-ALPS) investigation.

Background: To date, limited research has been conducted on the functionality of the glymphatic system during the recovery phase of severe traumatic brain injury (sTBI). This study aimed to use a diffusion tensor image analysis along the perivascular space (DTI-ALPS) to evaluate glymphatic system function in patients recovering from sTBI who underwent unilateral decompressive craniectomy, and to examine the correlation between the ALPS index and the size of the cranial defect. We hypothesized that assessments would reveal ongoing impairments in glymphatic system function among sTBI patients during the recovery phase. Methods: A total of 23 patients with a history of sTBI who had previously undergone unilateral decompressive craniectomy at Xiangya Hospital of Central South University from January 2020 to December 2020 were enrolled in the study, along with 33 healthy control (HC) subjects. All the subjects underwent magnetic resonance imaging (MRI) with DTI scans, and the ALPS index was subsequently calculated to assess glymphatic system functionality. Additionally, the circumference and sectional area of the cranial defect were measured for each patient. An analysis of variance (ANOVA) was used to compare the ALPS index values between the sTBI patients and HC subjects, while a Pearson correlation analysis was used to examine the correlation between the ALPS index and cranial defect characteristics. Results: The ALPS index values of both the craniectomy side (t=-9.08, P<0.001) and non-craniectomy side (t=-5.06, P<0.001) of the sTBI group were significantly lower than those of the HC group. However, no statistically significant differences were observed between the ALPS index values of the craniectomy and non-craniectomy sides. Additionally, no significant differences were observed in the ALPS index values of both the craniectomy and non-craniectomy sides among the early, intermediate, and late recovery phases. In the sTBI patients, a moderately strong negative correlation was found between the circumference of the cranial defect and the ALPS index of the craniectomy side (r=-0.62, P=0.002), and a moderately negative correlation was found between the sectional area of the cranial defect and the ALPS index of the craniectomy side (r=-0.56, P=0.005). Conclusions: The non-invasive DTI-ALPS technique revealed significantly reduced ALPS index values during the recovery phase of sTBI, indicating persistent impairment in glymphatic system function. A significant negative correlation was found between the ALPS index value of the craniectomy side and the size of the cranial defect. These findings suggest that the ALPS index may serve as a valuable prognostic factor in the recovery phase of sTBI.

MicroRNAs: emerging biomarkers and therapeutic targets in pancreatic cancer.

Pancreatic cancer (PC) is a highly malignant disease with high aggressiveness and a dismal prognosis, which is challenging to diagnose clinically early and gains low benefit from standard therapies. MicroRNAs (miRNAs) have become a hot topic in oncology research. Current evidence indicates that miRNAs are regulators involved in the entire process of PC, providing new diagnostic and therapeutic strategies for this fatal disease. Related research has been rapidly updated, making it necessary to review it to propose new directions and ideas and provide guidance for the development of precision medicine for PC. We reviewed the relevant literature through Pubmed, Embase, Web of Science and Medline, showing that abnormally expressed miRNAs in PC patients have the potential to be used as biomarkers for diagnosis and prognosis, highlighting the excellent prospect of combining miRNAs with traditional therapies, and the effective application of these factors for PC, especially miRNA mimics and inhibitors. MiRNAs participate in the entire process of PC and play important roles in diagnosis, treatment and prognosis. They are potential factors in conquering PC in the future.

Imatinib dose reduction after major molecular response in chronic-phase chronic myeloid leukemia.

BACKGROUND: In people with chronic-phase chronic myeloid leukemia (CML) receiving imatinib and achieving major molecular response (MMR), dose reduction may decrease adverse events but may be associated with a loss of molecular response. Whether digital droplet polymerase chain reaction (ddPCR) can identify persons in whom dose reduction might be unsuccessful is unknown. METHODS: Data from 716 consecutive subjects who achieved MMR after initial imatinib therapy (400 mg/day) were obtained. A total of 486 subjects remained on full-dose imatinib, whereas 230 subjects had their dose reduced to 300 or 200 mg/day. The outcomes of these cohorts were compared via landmark and propensity score matching analyses. RESULTS: Imatinib dose reduction showed no significant effect on the subsequent achievement of deeper molecular responses (4- and 4.5-log reductions in BCR::ABL1 transcripts; MR4 and MR4.5), maintenance of MMR, or attainment of therapy-free remission when compared with subjects without dose reduction. In subjects achieving MR4, however, the probability of maintaining MR4 (p = .002) was lower in the reduced-dose group. In multivariable analyses, failure to achieve MR4.5 as determined by ddPCR at the time of dose reduction was significantly associated with briefer MMR failure-free survival (FFS; hazard ratio [HR], 10.3; 95% confidence interval [CI], 1.3-82.9; p = .03) and MR4 FFS (HR, 6.8; 95% CI, 2.6-18.0; p < .001). CONCLUSIONS: Imatinib dose reduction after achieving MMR does not adversely affect response deepening or MMR maintenance in chronic-phase CML but compromises MR4 maintenance. The results of ddPCR may identify people who benefit from imatinib dose reduction.

Laparoscopic Surgery for Superior Mesenteric Artery Syndrome.

BACKGROUND: Superior mesenteric artery syndrome (SMAS) is a rare condition, for which laparoscopic surgery was successfully performed safely and with long-term efficacy. METHODS: This single center retrospective clinical study comprised 66 patients with SMAS, surgically treated between January 2010 and January 2020, who were allocated to three different surgical groups according to their medical history and symptoms (Laparoscopic duodenojejunostomy, n = 35; Gastrojejunostomy, n = 16; Duodenojejunostomy plus gastrojejunostomy, n = 15). Patient demographics, surgical data and postoperative outcomes were retrieved from the medical records. RESULTS: All operations were successfully completed laparoscopically, and with a median follow-up of 65 months, the overall symptom score was significantly reduced from 32 to 8 (p < 0.0001) and the BMI was increased from 17.2 kg/m2 to 21.8 kg/m2 (p < 0.0001). CONCLUSIONS: When conservative measures failed in the treatment of SMAS, laparoscopic surgery proved to be a safe and effective method. The specific surgical technique was selected according to the history and symptoms of each individual patient. To our knowledge, this study represents the largest number of laparoscopic procedures at a single center for the treatment of superior mesenteric artery syndrome.

Efficacy and safety of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer: a systematic review and meta-analysis.

Background: Various trials have demonstrated the clinical benefits of lenvatinib plus pembrolizumab in patients with advanced or recurrent endometrial cancer, regardless of mismatch repair (MMR) status or histologic subtype. The majority of the previously published trials had small sample sizes. Here, we aimed to assess the reported efficacy and safety profile of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer. Methods: We utilized the Cochrane Library, PubMed, Web of Science and Embase databases to identify clinical trials evaluating the efficacy and safety of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer. The outcomes analyzed were progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the disease control rate (DCR) and the incidence of adverse events (AEs). Subgroup analysis was conducted on the basis of MMR status (deficient, dMMR or proficient, pMMR). Results: Four trials (582 patients) were included. The pooled ORR was 32.7% [95% confidence interval (CI): 28.9-36.5]. Subgroup analysis revealed an ORR of 48.1% (95% CI: 26.1-70.2) for dMMR group and 33.1% (95% CI: 25.7-40.6) for pMMR group. The pooled DCR was 74.9% (95% CI: 71.3-78.4%). Subgroup analysis revealed a DCR of 81.0% (95% CI: 64.5-97.6) for the dMMR group and 76.3% (95% CI: 66.3-86.3) for the pMMR group. Follow-up was reported in all included studies. The median range time of PFS and OS was 5.3 months-258 days and 17.2 months-not reached, respectively. Regarding safety, the overall pooled proportions of any-grade AE and AEs ≥ grade 3 were 95.8% (95% CI: 89.5-100.0) and 80.2% (95% CI: 59.9-100.0), respectively. Conclusion: Lenvatinib plus pembrolizumab showed a relevant clinical benefit and significant toxicity in patients with advanced and recurrent endometrial cancer. Further studies encompassing long-term outcomes are warranted. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=522160/, identifier CRD42024522160.

The role of ZEB1 in mediating the protective effects of metformin on skeletal muscle atrophy.

Metformin is an important antidiabetic drug that has the potential to reduce skeletal muscle atrophy and promote the differentiation of muscle cells. However, the exact molecular mechanism underlying these functions remains unclear. Previous studies revealed that the transcription factor zinc finger E-box-binding homeobox 1 (ZEB1), which participates in tumor progression, inhibits muscle atrophy. Therefore, we hypothesized that the protective effect of metformin might be related to ZEB1. We investigated the positive effect of metformin on IL-1ß-induced skeletal muscle atrophy by regulating ZEB1 in vitro and in vivo. Compared with the normal cell differentiation group, the metformin-treated group presented increased myotube diameters and reduced expression levels of atrophy-marker proteins. Moreover, muscle cell differentiation was hindered, when we artificially interfered with ZEB1 expression in mouse skeletal myoblast (C2C12) cells via ZEB1-specific small interfering RNA (si-ZEB1). In response to inflammatory stimulation, metformin treatment increased the expression levels of ZEB1 and three differentiation proteins, MHC, MyoD, and myogenin, whereas si-ZEB1 partially counteracted these effects. Moreover, marked atrophy was induced in a mouse model via the administration of lipopolysaccharide (LPS) to the skeletal muscles of the lower limbs. Over a 4-week period of intragastric administration, metformin treatment ameliorated muscle atrophy and increased the expression levels of ZEB1. Metformin treatment partially alleviated muscle atrophy and stimulated differentiation. Overall, our findings may provide a better understanding of the mechanism underlying the effects of metformin treatment on skeletal muscle atrophy and suggest the potential of metformin as a therapeutic drug.

Advances in Subcellular Accumulation Design for Recombinant Protein Production in Tobacco.

Plants and their use as bioreactors for the generation of recombinant proteins have become one of the hottest topics in the field of Plant Biotechnology and Plant Synthetic Biology. Plant bioreactors offer superior engineering potential compared to other types, particularly in the realm of subcellular accumulation strategies for increasing production yield and quality. This review explores established and emerging strategies for subcellular accumulation of recombinant proteins in tobacco bioreactors, highlighting recent advancements in the field. Additionally, the review provides reference to the crucial initial step of selecting an optimal subcellular localization for the target protein, a design that substantially impacts production outcomes.

Outcomes of surgical resection and vagus nerve stimulation in patients with medically refractory epilepsy and glutamic acid decarboxylase 65 antibody positivity.

Epilepsy associated with high-titer glutamic acid decarboxylase 65 (GAD65) IgG is often refractory to immunotherapies and antiseizure medication. This study sought to determine the efficacy of vagus nerve stimulation (VNS) and surgical resection in patients with drug-resistant epilepsy associated with GAD65-IgG. We retrospectively identified 15 patients with drug-resistant epilepsy and high serum GAD65 antibody titers (>20 nmol·L-1) who underwent VNS implantation (n = 6), surgical resection (n = 7), or both (n = 2). A responder to VNS was defined as someone with a ≥50% reduction in seizure frequency, and a favorable surgical outcome was defined as Engel I-II. Of the eight patients who underwent VNS implantation, three (37.5%) were initially responders, but this was not sustained in two. Of the nine patients who underwent surgical resection, three (33.3%) had a favorable outcome; however, only one patient was seizure-free at last follow-up. Pathology was available in six patients, and only one had evidence of inflammation; this patient had seizure onset 1 year prior to surgery. Favorable seizure outcome correlated with older age at time of resective surgery, with a trend favoring later age of seizure onset. Taken together, surgical resection and VNS implantation may have limited efficacy in this patient population but can be considered in carefully selected cases.

Diagnosis, treatment, and prognosis of adult pancreatoblastoma.

BACKGROUND: Pancreatoblastoma (PB) is one of the rare malignant tumors that typically occurs in children. Cases of PB in adults are highly unusual. This disease often presents with subtle symptoms and lacks characteristic clinical manifestations, leading to diagnostic challenges. OBJECTIVE: This study integrates the relevant literature on adult PB, conducting data analysis on clinical features, laboratory and imaging results, pathological characteristics, and treatments according to inclusion and exclusion criteria. Kaplan-Meier univariate analysis and Log-rank tests are employed to analyze survival data from adult PB follow-up, exploring factors influencing prognosis. RESULTS: A total of 65 articles were included, encompassing 103 cases of adult PB. The average age of PB patients was 41.78 years (range 19-81 years), and the male-to-female ratio was 1.06:1. Patients frequently presented with abdominal pain as the initial symptom. Laboratory results lacked specificity and imaging findings often presented as large, well-defined masses. PB exhibited distinctive pathological features, including squamous corpuscles (n = 76, 89.41%) and acinar differentiation (n = 34, 40%), with frequent positive expression of Trypsin, Chymotrypsin, and AACT (Alpha-1-Antichymotrypsin). APC (Adenomatous Polyposis Coli) gene mutation was the most common molecular alteration in adult PB. During the follow-up period, 43.59% of patients died (range 3 days to 348 months). The primary factors affecting prognosis were the presence of metastasis (χ2 = 3.996, p = 0.046) and incomplete surgical resection (χ2 = 5.586, p = 0.018), with mean survival times of 48 months and 27 months, respectively. CONCLUSIONS: PB in adults is an invasive tumor. The key to distinguishing PB from other pancreatic tumors lies in recognizing its unique pathological feature, the squamous corpuscles. Timely and complete surgical resection is the preferred treatment following diagnosis. Patients with incomplete resection or the presence of lymph nodes or (and) distant metastases have a poor prognosis.

NIR-triggered and Thermoresponsive Core-shell nanoparticles for synergistic anticancer therapy.

Recent advancements in cancer treatment have underscored the inadequacy of conventional monotherapies in addressing complex malignant tumors. Consequently, there is a growing interest in synergistic therapies capable of overcoming the limitations of monotherapies, leading to more personalized and effective approaches. Among these, the combination of photothermal therapy (PTT) and chemotherapy has emerged as a promising avenue for tumor management. In this study, we present a novel approach utilizing thermoresponsive mesoporous silica nanoparticles (MSN) as a delivery system for the chemotherapeutic drug doxorubicin. By incorporating photothermal agent copper sulfide (CuS) nanoparticles into the MSN, the resulting composite material exhibits potent photothermal properties. Furthermore, the integration of an upper critical solution temperature (UCST) polymer within the silica outer layer serves as a "gatekeeper", enabling precise control over drug release kinetics. This innovative nanomaterial effectively merges thermoresponsive behavior with PTT, thereby minimizing the collateral damage associated with traditional chemotherapy on healthy tissues. Moreover, in both in vitro studies using mouse breast carcinoma cells (4 T1) and in vivo experiments utilizing a 4 T1 tumor-bearing mouse model, our nanomaterials demonstrated synergistic effects, enhancing the anti-tumor efficacy of combined PTT and chemotherapy. With its remarkable photothermal conversion efficiency, robust stability, and biocompatibility, the UCST-responsive nanoplatform holds immense potential for clinical applications.

Chidamide represses MYC expression and might improve survival for patients with double expressor lymphoma.

Double expressor lymphoma (DEL), characterized by high expressions of both MYC and BCL-2, displays poor prognosis after current therapies. The HDAC inhibitor chidamide has been approved for treatment of T cell lymphoma, but its efficacy on B cell lymphoma is unclear. Here, by combining inhibition screening and transcriptomic analyses, we found that the sensitivity of B lymphoma cells to chidamide was positively correlated with the expression levels of MYC. Chidamide treatment reduced MYC protein levels and repressed MYC pathway in B lymphoma cells with high MYC expressions. Ectopic expression of MYC in chidamide-insensitive B lymphoma cells increased their response to chidamide. Thus, we proposed that adding chidamide into R-CHOP (CR-CHOP) might be effective for DEL, and retrospectively analyzed 185 DEL patients treated in West China Hospital. 80% of patients showed response to CR-CHOP treatment. In the median follow-up of 42 months, CR-CHOP significantly improve the survival for DEL patients with R-IPI ≤2. Totally 35 patients underwent autologous stem cell transplantation (ASCT) in remission and demonstrated a trend for better survival. Combining CR-CHOP with ASCT resulted in the most superior PFS and OS above all. For response patients, CR-CHOP reduced relapse with better PFS than R-CHOP-like regimens with or without ASCT. Taken together, our data indicated that chidamide repressed the MYC pathway in B lymphoma and is potentially efficacious to treat DEL.

Acceleration of bone repairation by BMSCs overexpressing NGF combined with NSA and allograft bone scaffolds.

BACKGROUND: Repairation of bone defects remains a major clinical problem. Constructing bone tissue engineering containing growth factors, stem cells, and material scaffolds to repair bone defects has recently become a hot research topic. Nerve growth factor (NGF) can promote osteogenesis of bone marrow mesenchymal stem cells (BMSCs), but the low survival rate of the BMSCs during transplantation remains an unresolved issue. In this study, we investigated the therapeutic effect of BMSCs overexpression of NGF on bone defect by inhibiting pyroptosis. METHODS: The relationship between the low survival rate and pyroptosis of BMSCs overexpressing NGF in localized inflammation of fractures was explored by detecting pyroptosis protein levels. Then, the NGF+/BMSCs-NSA-Sca bone tissue engineering was constructed by seeding BMSCs overexpressing NGF on the allograft bone scaffold and adding the pyroptosis inhibitor necrosulfonamide(NSA). The femoral condylar defect model in the Sprague-Dawley (SD) rat was studied by micro-CT, histological, WB and PCR analyses in vitro and in vivo to evaluate the regenerative effect of bone repair. RESULTS: The pyroptosis that occurs in BMSCs overexpressing NGF is associated with the nerve growth factor receptor (P75NTR) during osteogenic differentiation. Furthermore, NSA can block pyroptosis in BMSCs overexpression NGF. Notably, the analyses using the critical-size femoral condylar defect model indicated that the NGF+/BMSCs-NSA-Sca group inhibited pyroptosis significantly and had higher osteogenesis in defects. CONCLUSION: NGF+/BMSCs-NSA had strong osteogenic properties in repairing bone defects. Moreover, NGF+/BMSCs-NSA-Sca mixture developed in this study opens new horizons for developing novel tissue engineering constructs.

The mechanical regulatory role of ATP13a3 in osteogenic differentiation of pre-osteoblasts.

PURPOSE: The process of osteogenic differentiation hinges upon the pivotal role of mechanical signals. Previous studies found that mechanical tensile strain of 2500 microstrain (µÎµ) at a frequency of 0.5 â€‹Hz promoted osteogenesis in vitro. However, the mechanism of the mechanical strain influencing osteogenesis at the cellular and molecular levels are not yet fully understood. This study aimed to explore the mechanism of mechanical strain on osteogenic differentiation of MC3T3-E1 cells. MATERIALS AND METHODS: Proteomics analysis was conducted to explore the mechanical strain that significantly impacted the protein expression. Bioinformatics identified important mechanosensitive proteins and the expression of genes was investigated using real-time PCR. The dual-luciferase assay revealed the relationship between the miRNA and its target gene. Overexpression and downexpression of the gene, to explore its role in mechanically induced osteogenic differentiation and transcriptomics, revealed further mechanisms in this process. RESULTS: Proteomics and bioinformatics identified an important mechanosensitive lowexpression protein ATP13A3, and the expression of Atp13a3 gene was also reduced. The dual-luciferase assay revealed that microRNA-3070-3p (miR-3070-3p) targeted the Atp13a3 gene. Furthermore, the downexpression of Atp13a3 promoted the expression levels of osteogenic differentiation-related genes and proteins, and this process was probably mediated by the tumor necrosis factor (TNF) signaling pathway. CONCLUSION: Atp13a3 responded to mechanical tensile strain to regulate osteogenic differentiation, and the TNF signaling pathway regulated by Atp13a3 was probably involved in this process. These novel insights suggested that Atp13a3 was probably a potential osteogenesis and bone formation regulator.

Effectiveness of acupuncture on urinary retention after radical hysterectomy for cervical cancer in China: a systematic review and meta-analysis.

Background: Cervical cancer is one of the most common malignant tumors worldwide. Radical hysterectomy is the first choice for patients with early-stage cervical cancer. Studies have suggested that acupuncture may be a more effective therapy for the prevention and treatment of urinary retention after radical hysterectomy. Objective: To systematically evaluate the clinical efficacy of acupuncture in the prevention and treatment of urinary retention after radical hysterectomy. Methods: We searched the Cochrane library, Web of science, PubMed, Embase, Chinese Biomedical Literature Database, Wanfang database, Wipu database, China National Knowledge Infrastructure Database and ClinicalTrials.gov with the time from inception until December 2023, to collect randomized controlled studies on the clinical efficacy of acupuncture for prevention and treatment of urinary retention after radical hysterectomy. Literature meeting criteria was screened for data extraction. Quality evaluation was performed according to the Cochrane Handbook for Systematic Reviews of Interventions. And meta-analysis was performed using RevMan5.3 and stata14.0 software. Results: 22 Randomized controlled trials with 1,563 patients, 854 in treatment group and 709 in control group, were included totally. Meta-analysis results showed that: the total effective rate in acupuncture group was higher than that in control group, with a statistically significant difference [relative risk (RR)] = 1.43, 95% confidence interval (CI 1.22, 1.68), p < 0.0001; the rate of urinary tract infection in acupuncture group was lower than that in control group, with a statistically significant difference [RR] = 0.23, 95% CI (0.07, 0.78), p < 0.05; the time of indwelling urinary catheter was reduced in acupuncture group compared with control group, with a statistically significant mean difference = -3.45, 95% CI (-4.30, -2.59), p < 0.00001; the incidence of urinary retention was lower in acupuncture group than in control group, and the difference was statistically significant [RR = 0.37, 95% CI (0.27, 0.50), p < 0.00001]; the residual urine volume was reduced in acupuncture group compared with control group, with a statistically significant mean difference = -50.73, 95% CI (-63.61, -7.85), p < 0.00001. Conclusion: Acupuncture treatment based on conventional therapy can better prevent and improve urinary retention after radical hysterectomy for cervical cancer, could be a better option for them. Systematic review registration: Registered by PROSPERO and the registration number is CRD42023452387.

Traditional medicine Xianglian pill suppresses high-fat diet-related colorectal cancer via inactivating TLR4/MyD88 by remodeling gut microbiota composition and bile acid metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Previous studies have revealed that a high-fat diet (HFD) promotes the progression of colorectal cancer (CRC) in close association with disturbances in the intestinal flora and metabolic disorders. Xianglian pill (XLP) is a well-established traditional prescription with unique advantages in controlling intestinal flora imbalance and inflammation. However, its therapeutic effects on HFD-related CRC remain largely unknown. AIM OF THE STUDY: The primary objective of this research was to investigate the anticancer mechanism of XLP in countering HFD-related CRC. MATERIALS AND METHODS: The protective effect of XLP was evaluated using azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced CRC model of mice exposed to a HFD. The degree of colorectal carcinogenesis, including body weight, colon length, and histopathology, was measured in mice treated with XLP and untreated mice. The effect of XLP on gut microbiota and its metabolites was detected using 16S rDNA and liquid chromatography/mass spectrometry analysis. Furthermore, a "pseudo-sterile" mouse model was constructed using antibiotics (Abx) to verify whether the gut microbiota and metabolites play a role in the pathogenesis of CRC. RESULTS: XLP inhibited colorectal tumorigenesis in a dose-dependent fashion. Our findings also highlighted that XLP protected the integrity of the intestinal barrier by reducing the expression of pro-inflammatory cytokines, such as IL-6 and TNF-α, as well as the infiltration of pro-inflammatory macrophages. Mechanistically, XLP inhibited the TLR4/MyD88 pathway. Notably, the XLP treatment increased the proportion of probiotics (particularly Akkermansia) and significantly reduced fecal deoxycholic acid (DCA), a microbiota-derived metabolite of bile acids (BA) closely related to Muribaculaceae. Furthermore, after Abx treatment, XLP showed no clear antitumor effects on CRC. Simultaneously, DCA-supplemented feedings promoted colorectal tumorigenesis and provoked obvious colonic inflammation, M1 macrophage infiltration, and colonic injury. In vitro, the results of RAW-264.7 macrophages and normal intestinal epithelial cells treated with DCA corroborated our in vivo findings, demonstrating consistent patterns in inflammatory responses and intestinal barrier protein expression. CONCLUSION: Our findings suggest that XLP inhibits colorectal cancer associated with HFD via inactivating TLR4/MyD88 by remodeling gut microbiota composition and BA metabolism.

Jianpi-Tiaoqi decoction inhibits tumour proliferation and lung metastasis in tumour-bearing mice with triple-negative breast cancer.

Traditional Chinese medicine, specifically the Jianpi Tiaoqi (JPTQ) decoction, has been explored for its role in treating breast cancer, particularly in inhibiting lung metastasis in affected mice. Our study evaluated the effects of JPTQ on several factors, including tumour growth, apoptosis, angiogenesis, epithelial-to-mesenchymal transition (EMT) and immune microenvironment regulation. We used bioluminescence imaging to observe in situ tumour growth and potential lung metastasis. Transcriptomic analysis provided insights into gene expression, whereas flow cytometry was used to examine changes in specific immune cells, such as CD4+ T cells and myeloid-derived suppressor cells. Several essential proteins and genes, including vascular endothelial growth factor (VEGF), matrix metalloprotein-9 (MMP-9) and B-cell lymphoma 2 (Bcl-2), were assessed through quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry. Our findings showed that JPTQ treatment inhibited tumour proliferation in cancer-bearing mice. Bioluminescence imaging and pathological analysis indicated a reduction in lung metastasis. Transcriptome analysis of lung and tumour tissues indicated that the genes associated with EMT, angiogenesis, proliferation and apoptosis were regulated in the JPTQ-treated group. Kyoto Encyclopedia of Genes and Genomes analysis suggested enrichment of immune-related pathways. Flow cytometry indicated that JPTQ treatment reduced the proportion of monocyte-myeloid-derived suppressor cells in the lung and increased the number of CD4+ T cells in the peripheral blood and the number of T helper 1 (Th1) cells in the spleen (P < 0.05). E-cadherin and cleaved caspase 3 were upregulated, whereas Snail, Bcl-2, Ki67 and VEGF were downregulated in the lung and tumour tissues; moreover, the expression of MMP-9 was downregulated in the lung tissue (P < 0.05). In essence, JPTQ not only inhibits tumour growth in affected mice, but also promotes positive immune responses, reduces angiogenesis, boosts tumour cell apoptosis, reverses EMT and decreases breast cancer lung metastasis.