Acupuncture for postoperative gastrointestinal dysfunction in cancer: a systematic review and meta-analysis.

Background: Postoperative gastrointestinal dysfunction (PGD) in cancer is the commonest and most severe postoperative complication in patients with cancer. Acupuncture has been widely used for PGD in cancer. This study aimed to evaluate the efficacy and safety of acupuncture for PGD in cancer. Methods: We comprehensively searched eight randomised controlled trials (RCTs) of acupuncture for PGD in cancer published until November 2022. Time to first flatus (TFF) and time to first defecation (TFD) were the primary outcomes, and time to bowel sound recovery (TBSR) and the length of hospital stay (LOS) were the secondary outcomes. The Cochrane Collaboration Risk of Bias Tool was used to assess the quality of the RCTs, and the Grading of Recommendations Assessment, Development, and Evaluations (GRADE) system was used to evaluate the certainty of the evidence. The meta-analysis was performed using RevMan 5.4, and a publication bias test was performed using Stata 15.1. Results: Sixteen RCTs involving 877 participants were included in this study. The meta-analysis indicated that acupuncture could effectively reduce the TFF, TFD, and TBSR compared with routine treatment (RT), sham acupuncture, and enhanced recovery after surgery (ERAS). However, acupuncture did not shorten the LOS compared with RT and ERAS. The subgroup analysis revealed that acupuncture could significantly reduce the TFF and TFD. Acupuncture effectively reduced the TFF and TFD in all cancer types included in this review. Besides, local acupoints in combination with distal acupoints could reduce the TFF and TFD, and distal-proximal acupoints could significantly reduce the TFD. No trial reported adverse events of acupuncture. Conclusions: Acupuncture is an effective and relatively safe modality for treating PGD in cancer. We anticipate that there will be more high-quality RCTs involving more acupuncture techniques and cancer types, focusing on combining acupoints for PGD in cancer, further determining the effectiveness and safety of acupuncture for PGD in patients with cancer outside China. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42022371219.

Biomechanical effects of clear aligners with different thicknesses and gingival-margin morphology for appliance design optimization.

INTRODUCTION: The objectives of this study were to investigate the biomechanical effects of clear aligners (CAs) with various thermoplastic material thicknesses and gingival-margin designs for space closure in extraction treatment and to propose a computer-aided procedure to optimize CA design. METHODS: The radiologic and intraoral scanning technology, in vitro mechanical experiment, viscoelastic modeling, and finite element analysis (FEA) were integrated to establish an orthodontic simulation model. Twelve FEA models of CA were created, comprising combinations of 2 kinds of thicknesses (0.75 and 0.50 mm), 2 forms of gingival-margin shape (scalloped and straight), and 3 types of margin height (-2, 0, and 2 mm). In vitro testing was carried out to determine the actual properties of material thickness. RESULTS: A 0.75-mm-thick aligner resulted in greater periodontal ligament (PDL) stress than 0.50 mm, and there was no clear correlation between the control ability of tooth movement and the thickness. For different margin designs, PDL stress at -2 mm height was significantly lower than those with a higher border. Aligners with straight margins had higher stress than the scalloped aligners, whereas the differences were unnoticeable at 2 mm height. The optimized aligner with differential margin designs was recommended on the basis of biomechanical calculations, which facilitated the efficiency and control of tooth movement for multiple teeth. CONCLUSIONS: The effect of material thickness and margin design of CA on the force and movement differed in different teeth. Preferable CA designs of each tooth during different movement stages should be presented personalized under the guidance of precise biomechanics instead of pure morphologic analysis.

Bisphosphonate-Modified Functional Supramolecular Hydrogel Promotes Periodontal Bone Regeneration by Osteoclast Inhibition.

Regeneration of periodontal tissue remains a challenge. Under periodontitis, osteoclasts are overactivated and bone loss occurs. We incorporated sodium alendronate (Alen), a medication commonly used to treat osteoporosis, into a supramolecular hydrogel system in order to create a novel biomaterial that would promote periodontal bone regeneration by inhibiting osteoclast overactivation. The Nap-Gly-Phe-Phe (NapGFF) peptide chain was modified to synthesize the functional Nap-Alen gelator. Afterward, the Nap-Alen/HAP supramolecular hydrogel composite with a suitable hydroxyapatite (HAP) ratio was constructed, which has outstanding mechanical properties and 3D structure. In addition to its good biocompatibility, it can inhibit the proliferation of bone marrow-derived macrophages (BMDMs) and differentiation of osteoclasts. Due to the simultaneous introduction of porous HAP, the hydrogel with a nanofiber structure was formed into a 3D mesh-like sparse porous composite hydrogel. While enhancing the mechanical properties of the gel, the porous structure facilitated the attachment and migration of bone regeneration-related cells. Therefore, it can effectively promote the regeneration of periodontal bone. In the future, by modifying the biophysical properties and loading stem cells or cytokines, this supramolecular hydrogel composite constructed in this study may provide a new strategy for tissue regeneration engineering and provide a preliminary experimental basis for relevant clinical translational studies.

Introducing surface-to-surface matching technique to evaluate mandibular symmetry: A retrospective study.

Objectives: This study introduced a three-dimensional (3D) surface-to-surface matching technique to evaluate the mandibular symmetry of teenagers and adults with unilateral second molar scissor bite. Methods: The targets came from 73 cone-beam computed tomography (CBCT) images with unilateral second molar scissor bite, including teenagers (n = 30) and adults (n = 43). 73 images without scissor bite and matched in sex and age were selected as controls. The scans were developed into 3D mandible models and seven mandibular functional unit models, including condylar process (Co), coronoid process (Cr), mandibular ramus (Ra), mandibular angle (Ma), alveolar process (Ap), mandibular body (Mb) and chin process (Ch). The surface-to-surface matching technique was introduced. 3D deviation analysis and matching percentages calculation were performed and compared to evaluate the symmetry of the mandible. Results: Comparisons were made between the study samples and control samples. For teenagers, the matching percentages of the entire mandible (55.31 ± 7.24%), Mb (69.04 ± 9.22%) and Co (65.19 ± 10.67%) in the study group were lower than that of the entire mandible (60.87 ± 6.38%) (P <0.01), Mb (75.0 ± 8.71%) (P <0.05) and Co (70.25 ± 8.20%) (P <0.05) in the control group. While Ap, Ra, Ch, Cr and Ma showed no statistically significant differences (P >0.05). For adults, the matching percentages of the entire mandible (48.88 ± 9.77%), Ap (65.83 ± 11.21%), Mb (64.43 ± 12.03%), Ch (79.17 ± 10.29%), Ra (64.11 ± 9.84%) and Co (61.08 ± 11.64%) in the study group were lower than the entire mandible (59.28 ± 5.49%) (P <0.01), Ap (73.65 ± 9.10%) (P <0.01), Mb (71.66 ± 8.40%) (P <0.01), Ch (83.86 ± 5.59%) (P <0.05), Ra (68.54 ± 7.87%) (P <0.05) and Co (66.20 ± 10.62%) (P <0.05) of the control group. Only Cr and Ma showed no statistically significant differences (P >0.05). Conclusion: Mandibular asymmetry was observed in both teenagers and adults with unilateral second molar scissor bite. Moreover, compared with teenagers, more mandibular units of adult patients were affected. Clinical significance: Based on the surface-to-surface matching technique, the symmetric and morphological information of the mandible can be converted into visual color maps and quantitative descriptions. This method can bring convenience to the study of the growth of mandible, orthodontic treatment and orthognathic surgery design.

Circular RNA circ_0048764 promotes the development of breast cancer by regulating microRNA-1296-5p/tripartite motif containing 14 axis.

Breast cancer (BC) is one of the leading causes of cancer-related deaths in females. Circular RNA (circRNA), as reported, is involved in the progression of BC. This work focuses on clarifying the biological function of circ_0048764 in BC and its hidden mechanism. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expressions of circ_0048764, microRNA-1296-5p (miR-1296-5p), and tripartite motif containing 14 (TRIM14) in BC tissues and cell lines. Besides, the status of proliferation, migration, invasion and apoptosis of BC cells was probed by cell counting kit-8 (CCK-8), EdU, transwell and flow cytometry assays. Western blot was adopted to examine the level of TRIM14 protein in BC cells. In addition, dual-luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay were conducted to corroborate the targeting relationships between miR-1296-5p and circ_0048764 or TRIM14. It was revealed that circ_0048764 expression was remarkably up-regulated in BC tissues and cells, and circ_0048764 expression was associated with TNM stage and tumor size. Functionally, overexpression of circ_0048764 significantly promoted BC cell proliferative, migrative and invasive abilities and inhibited apoptosis, while circ_0048764 knockdown exerted the opposite effects. Mechanistically, circ_0048764 directly targeted miR-1296-5p and could negatively modulate its expression in BC cells. Besides, miR-1296-5p could reverse the influence of circ_0048764 on BC viability, migration, invasion and apoptosis. Moreover, TRIM14 was confirmed to be a downstream target of miR-1296-5p. Circ_0048764 positively regulated TRIM14 expression in BC cells via targeting miR-1296-5p. Collectively, it is concluded that circ_0048764 promotes the development of BC via modulating the miR-1296-5p/TRIM14 axis.

Low torque is a risk factor for non-carious cervical lesions (NCCLs) in maxillary premolars.

PURPOSE: To determine the prevalence of non-carious cervical lesions (NCCLs) in maxillary premolars of different torques and simulated cervical stress profiles of the premolars under coincident loadings using finite element analysis (FEA). METHODS: The CBCT scans of 616 maxillary premolars from 154 subjects were retrospectively evaluated. The premolars were ascribed into low torque group (LTG) <-10.9°, medium torque group (MTG) -10.9° to -3.9°, and high torque group (HTG) >-3.9°, when the torque was referring to the occlusion plane. The prevalence of NCCLs in each group was evaluated. Then finite element models of a maxillary first premolar, its adjacent teeth and alveolar bone were established. The models were prepared with ANSYS software generating the premolars presenting different torques. The mastication scenario for the premolars in maximum intercuspation position was simulated. RESULTS: The prevalence of NCCLs was 15.7% in LTG, 7.9% in MTG and 5.5% in HTG. The prevalence of LTG was significantly higher than that of MTG (P< 0.05) and HTG (P< 0.01). As for FEA, the stresses at the buccal necks of the premolars basically increased with decrease of the torque. The tensile stress peaks were in the cemento-enamel junction in most premolars of the LTG, while in the middle of the crowns in premolars of MTG and HTG. CLINICAL SIGNIFICANCE: Low torque with excessive lingual inclination is a risk factor for NCCLs of maxillary premolars, and excessive tensile stress concentration in buccal necks during mastication may be responsible for that.

Utility of urinary ctDNA to monitoring minimal residual disease in early breast cancer patients.

BACKGROUND: Cancer recurrence for patients with early breast cancer is significant. Patients will benefit from more non-invasive modes of monitoring and we aim to study the feasibility of urinary circulating tumor DNA (ctDNA) to monitor for residual disease (MRD). METHODS: In this longitudinal study, 300 early breast cancer patients were recruited prospectively. Measurements were taken prior to treatment and at different time points thereafter for a total of 8 measurements. Comparisons were made with healthy volunteers and patients without detectable mutations in urine specimens. Disease free relapse were correlated to both urinary DNA quantity and ctDNA concentration. RESULTS: Baseline index measurements showed 38% of patients with detectable mutations. The concordance with biopsy tissues was 97.3%. Overall, breast cancer patients had higher urinary DNA compared with healthy volunteers. Over time, fluctuations in urinary DNA was negligible in healthy volunteers, indicating the stability of the marker. Among the patients with detectable mutations, we observed that higher urinary DNA quantity measurements at 6-month and patients with positive mutations were associated with greater risk of relapse. Hazard ratios for patients in this category was 1.65 (95% CI 1.26-2.16) and 1.98 (95% CI 1.48-2.63) respectively. CONCLUSION: Urinary DNA offers non-invasive probing and real-time monitoring of breast cancer relapse. Our results demonstrated clear clinical relevance in breast cancer and significant risk profiling of early breast cancer patients. This potentially aids to complement current cancer relapse monitoring and may help in early intervention.

Time-dependent differential expression of long non-coding RNAs following peripheral nerve injury.

Long non-coding RNAs (lncRNAs) are widely accepted as key players in various biological processes. However, the roles of lncRNA in peripheral nerve regeneration remain completely unknown. Thus, in this study, we performed microarray analysis to measure lncRNA expression in the distal segment of the sciatic nerve at 0, 3, 7 and 14 days following injury. We identified 5,354 lncRNAs that were differentially expressed: 3,788 lncRNAs were differentially expressed between days 0 and 3; 3,314 lncRNAs were differentially expressed between days 0 and 7; and 2,400 lncRNAs were differentially expressed between days 0 and 14. The results of RT-qPCR of two dysregulated lncRNAs were consistent with those of microarray analysis. Bioinformatics approaches, including lncRNA classification, gene ontology (GO) analysis and target prediction, were utilized to investigate the functions of these dysregulated lncRNAs in peripheral nerve damage. Importantly, we predicted that several lncRNA-mRNA pairs may participate in biological processes related to peripheral nerve injury. RT-qPCR was performed for the preliminary verification of three lncRNA­mRNA pairs. The overexpression of NONMMUG014387 promoted the proliferation of mouse Schwann cells. Thus, the findings of our study may enhance our knowledge of the role of lncRNAs in nerve injury.

Gene expression analysis at multiple time-points identifies key genes for nerve regeneration.

INTRODUCTION: The purpose of this study was to provide a comprehensive understanding of gene expression during Wallerian degeneration and axon regeneration after peripheral nerve injury. METHODS: A microarray was used to detect gene expression in the distal nerve 0, 3, 7, and 14 days after sciatic nerve crush. Bioinformatic analysis was used to predict function of the differentially expressed mRNAs. Microarray results and the key pathways were validated by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Differentially expressed mRNAs at different time-points (3, 7, and 14 days) after injury were identified and compared with a control group (0 day). Nine general trends of changes in gene expression were identified. Key signal pathways and 9 biological processes closely associated with nerve regeneration were identified and verified. CONCLUSIONS: Differentially expressed genes and biological processes and pathways associated with axonal regeneration may elucidate the molecular-biological mechanisms underlying peripheral nerve regeneration. Muscle Nerve 55: 373-383, 2017.

Long non-coding RNA NONMMUG014387 promotes Schwann cell proliferation after peripheral nerve injury.

Schwann cells play a critical role in peripheral nerve regeneration through dedifferentiation and proliferation. In a previous study, we performed microarray analysis of the sciatic nerve after injury. Accordingly, we predicted that long non-coding RNA NONMMUG014387 may promote Schwann cell proliferation after peripheral nerve injury, as bioinformatic analysis revealed that the target gene of NONMMUG014387 was collagen triple helix repeat containing 1 (Cthrc1). Cthrc1 may promote cell proliferation in a variety of cells by activating Wnt/PCP signaling. Nonetheless, bioinformatic analysis still needs to be verified by biological experiment. In this study, the candidate long non-coding RNA, NONMMUG014387, was overexpressed in mouse Schwann cells by recombinant adenovirus transfection. Plasmid pHBAd-MCMV-GFP-NONMMUG014387 and pHBAd-MCMV-GFP were transfected into Schwann cells. Schwann cells were divided into three groups: control (Schwann cells without intervention), Ad-GFP (Schwann cells with GFP overexpression), and Ad-NONMMUGO148387 (Schwann cells with GFP and NONMMUGO148387 overexpression). Cell Counting Kit-8 assay was used to evaluate proliferative capability of mouse Schwann cells after NONMMUG014387 overexpression. Polymerase chain reaction and western blot assay were performed to investigate target genes and downstream pathways of NONMMUG014387. Cell proliferation was significantly increased in Schwann cells overexpressing lncRNA NONMMUG014387 compared with the other two groups. Further, compared with the control group, mRNA and protein levels of Cthrc1, Wnt5a, ROR2, RhoA, Rac1, JNK, and ROCK were visibly up-regulated in the Ad-NONMMUGO148387 group. Our findings confirm that long non-coding RNA NONMMUG014387 can promote proliferation of Schwann cells surrounding the injury site through targeting Cthrc1 and activating the Wnt/PCP pathway.

Investigations of the total flavonoids extracted from flowers of Abelmoschus manihot (L.) Medic against α-naphthylisothiocyanate-induced cholestatic liver injury in rats.

ETHNOPHARMACOLOGY RELEVANCE: The decoction of the flowers of Abelmoschus manihot (L.) Medic was traditionally used for the treatment of jaundice and various types of chronic and acute hepatitis in Anhui and Jiangsu Provinces of China for hundreds of years. Phytochemical studies have indicated that total flavonoids extracted from flowers of A. manihot (L.) Medic (TFA) were the major constituents of the flowers. Our previous studies have investigated the hepatoprotective effects of the TFA against carbon tetrachloride (CCl4) induced hepatocyte damage in vitro and liver injury in vivo. This study aimed to investigate the protective effects and mechanisms of TFA on α-naphthylisothiocyanate (ANIT)-induced cholestatic liver injury in rats. MATERIAL AND METHODS: The hepatoprotective activities of TFA (125, 250 and 500mg/kg) were investigated on ANIT-induced cholestatic liver injury in rats. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were used as indices of hepatic cell damage and measured. Meanwhile, the serum levels of alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), total bilirubin (TBIL), direct bilirubin (DBIL), and total bile acid (TBA) were used as indices of biliary cell damage and cholestasis and evaluated. Hepatic malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione transferase (GST), tumor necrosis factor-α (TNF-α) and nitric oxide (NO) were measured in the liver homogenates. The bile flow in 4h was estimated and the histopathology of the liver tissue was evaluated. Furthermore, the expression of transporters, bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2), and Na(+)-taurocholate cotransporting polypeptide (NTCP) were studied by western blot and reverse transcription-quantitative real-time polymerase chain reaction (RT-PCR) to elucidate the protective mechanisms of TFA against ANIT-induced cholestasis. RESULTS: The oral administration of TFA to ANIT-treated rats could reduce the increases in serum levels of ALT, AST, LDH, ALP, GGT, TBIL, DBIL and TBA. Decreased bile flow by ANIT was restored with TFA treatment. Concurrent administration of TFA reduced the severity of polymorphonuclear neutrophil infiltration and other histological damages, which were consistent with the serological tests. Hepatic MDA and GSH contents in liver tissue were reduced, while SOD and GST activities, which had been suppressed by ANIT, were elevated in the groups pretreated with TFA. With TFA intervention, levels of TNF-α and NO in liver were decreased. Additionally, TFA was found to increase the expression of liver BSEP, MRP2, and NTCP in both protein and mRNA levels in ANIT-induced liver injury with cholestasis. CONCLUSION: TFA exerted protective effects against ANIT-induced liver injury. The possible mechanisms could be related to anti-oxidative damage, anti-inflammation and regulating the expression of hepatic transporters. It layed the foundation for the further research on the mechanisms of cholestasis as well as the therapeutic effects of A. manihot (L.) Medic for the treatment of jaundice.