Physiological occlusal force attenuates replacement root resorption of replanted teeth: an experimental animal study.

BACKGROUND: Tooth avulsion represents the most severe form of dental trauma, necessitating tooth replantation as the primary treatment. However, the risk of replacement root resorption (RRR) poses a significant threat to tooth retention following replantation. This study preliminarily aimed to investigate the effect of physiological occlusal force on RRR after the replantation of avulsed teeth and to explore the potential underlying mechanisms. METHODS: Thirty-six 4-week-old male Sprague-Dawley rats underwent extraction and immediate replantation of their left maxillary molars. The rats were randomly divided into two major groups: the occluded (n = 18) group, where the opposite mandibular teeth were preserved; non-occluded (n = 18) group, where the opposite mandibular teeth were extracted. Within each major group, there were three subgroups corresponding to 7 days, 14 days, and 2 months, resulting in a total of six subgroups, (n = 6 per subgroup). The right maxillary first molars served as the normal control. Various periodontal characteristics were assessed using haematoxylin-eosin (H&E), tartrate-resistant acid phosphatase (TRAP) staining, and micro-computed tomography (micro-CT). RESULTS: Histological staining revealed that under occlusal force, the early stage (day 7) after tooth replantation mainly manifested as root surface resorption, especially in the non-occluded group, which gradually diminished over time. Cementum and periodontal ligament (PDL) repair was observed on day 14. Micro-CT analysis indicated a significant decrease in PDL width in the non-occluded group two months after replantation, consistent with the histological findings, signifying severe RRR in the non-occluded group. CONCLUSIONS: This study provides preliminary evidence that physiological occlusal force may attenuate osteoclastogenesis during the early stage of tooth replantation, thereby reducing the occurrence of RRR and promoting periodontal healing.

The efficacy and safety of short-course radiotherapy followed by sequential chemotherapy and Cadonilimab for locally advanced rectal cancer: a protocol of a phase II study.

BACKGROUND: For patients with locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT), namely, intensifying preoperative treatment through the integration of radiotherapy and systemic chemotherapy before surgery, was commonly recommended as the standard treatment. However, the risk of distant metastasis at 3 years remained higher than 20%, and the complete response (CR) rate was less than 30%. Several clinical trials had suggested a higher complete response rate when combining single-agent immunotherapy with short-course radiotherapy (SCRT). The CheckMate 142 study had shown encouraging outcomes of dual immunotherapy and seemingly comparable toxicity for CRC compared with single-agent immunotherapy in historical results. Therefore, dual immunotherapy might be more feasible in conjunction with the TNT paradigm of SCRT. We performed a phase II study to investigate whether the addition of a dual immune checkpoint inhibitor bispecific antibody, Cadonilimab, to SCRT combined with chemotherapy might further increase the clinical benefit and prognosis for LARC patients. METHODS: This single-arm, multicenter, prospective, phase II study included patients with pathologically confirmed cT3-T4N0 or cT2-4N + rectal adenocarcinoma with an ECOG performance score of 0 or 1. Bispecific antibody immunotherapy was added to SCRT combined with chemotherapy. Patients enrolled would be treated with SCRT (25 Gy in five fractions over 1 week) for the pelvic cavity, followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX and Cadonilimab. The primary endpoint was the CR rate, which was the ratio of the pathological CR rate plus the clinical CR rate. The secondary endpoints included local-regional control, distant metastasis, disease-free survival, overall survival, toxicity profile, quality of life and functional outcome of the rectum. To detect an increase in the complete remission rate from 21.8% to 40% with 80% power, 50 patients were needed. DISCUSSION: This study would provide evidence on the efficacy and safety of SCRT plus bispecific antibody immunotherapy combined with chemotherapy as neoadjuvant therapy for patients with LARC, which might be used as a candidate potential therapy in the future. TRIAL REGISTRATION: This phase II trial was prospectively registered at ClinicalTrials.gov, under the identifier NCT05794750.

Perioperative chemotherapy with docetaxel plus oxaliplatin and S-1 (DOS) versus oxaliplatin plus S-1 (SOX) for the treatment of locally advanced gastric or gastro-esophageal junction adenocarcinoma (MATCH): an open-label, randomized, phase 2 clinical trial.

BACKGROUND: It remains unclear whether addition of docetaxel to the combination of a platinum and fluoropyrimidine could provide more clinical benefits than doublet chemotherapies in the perioperative treatment for locally advanced gastric/gastro-esophageal junction (LAG/GEJ) cancer in Asia. In this randomized, phase 2 study, we assessed the efficacy and safety of perioperative docetaxel plus oxaliplatin and S-1 (DOS) versus oxaliplatin plus S-1 (SOX) in LAG/GEJ adenocarcinoma patients. METHODS: Patients with cT3-4 Nany M0 G/GEJ adenocarcinoma were randomized (1:1) to receive 4 cycles of preoperative DOS or SOX followed by D2 gastrectomy and another 4 cycles of postoperative chemotherapy. The primary endpoint was major pathological response (MPR). RESULTS: From Aug, 2015 to Dec, 2019,154 patients were enrolled and 147 patients included in final analysis, with a median age of 60 (26-73) years. DOS resulted in significantly higher MPR (25.4 vs. 11.8%, P = 0.04). R0 resection rate, the 3-year PFS and 3-year OS rates were 78.9 vs. 61.8% (P = 0.02), 52.3 vs. 35% (HR 0.667, 95% CI: 0.432-1.029, Log rank P = 0.07) and 57.5 vs. 49.2% (HR 0.685, 95% CI: 0.429-1.095, Log rank P = 0.11) in the DOS and SOX groups, respectively. Patients who acquired MPR experienced significantly better survival. DOS had similar tolerance to SOX. CONCLUSIONS: Perioperative DOS improved MPR significantly and tended to produce longer PFS compared to SOX in LAG/GEJ cancer in Asia, and might be considered as a preferred option for perioperative chemotherapy and worth further investigation.

A prospective phase II clinical trial of total neoadjuvant therapy for locally advanced gastric cancer and gastroesophageal junction adenocarcinoma.

To investigate the safety and efficacy of the neoadjuvant chemoradiotherapy (NCRT) followed by neoadjuvant consolidation chemotherapy (NCCT) and surgery for locally advanced gastric cancer (GC) or gastroesophageal junction (GEJ) adenocarcinoma. Patients diagnosed as locally advanced GC or Siewert II/III GEJ adenocarcinoma with clinical stage T3-4 and/or N positive were prospectively enrolled. Patients underwent NCRT (45 Gy/25 fractions) with concurrent S-1, followed by NCCT (4 to 6 cycles of the SOX regimen) 2 to 4 weeks after NCRT. Gastric cancer radical resection with D2 lymph node dissection was performed 4 to 6 weeks after the total neoadjuvant therapy. The study was conducted from November 2019 to January 2023, enrolling a total of 46 patients. During the NCRT, all patients completed the treatment without dose reduction or delay. During the NCCT, 32 patients (69.6%) completed at least 4 cycles of chemotherapy. Grade 3 or higher adverse events in NCRT (5 cases) were non-hematological. During the course of NCCT, a notable occurrence of hematological toxicities was observed, with grade 3 or higher leukopenia (9.7%) and thrombocytopenia (12.2%) being experienced. A total of 28 patients (60.9%) underwent surgery, achieving R0 resection in all cases. A significant proportion of cases (71.4%) exhibited pathological downstaging to ypT0-2, while 10 patients (35.7%) demonstrated a pathologic complete response (pCR). The total neoadjuvant therapy comprising NCRT followed by NCCT and surgery demonstrates a low severe adverse reactions and promising efficacy, which could be considered as a viable treatment for locally advanced GC or GEJ adenocarcinoma.Trial registration: Clinicaltrials.gov (registration number: NCT04062058); the full date of first trial registration was 20/08/2019.

Nodal recurrence mapping and clinical target volumes after resection of intrahepatic cholangiocarcinoma or combined hepatocellular-cholangiocarcinoma.

Background: Scarce evidence exists for clinical target volume (CTV) definitions of regional lymph nodes (LNs) in intrahepatic cholangiocarcinoma (iCCA) or combined hepatocellular-cholangiocarcinoma (cHCC-CCA). We investigated the mapping pattern of nodal recurrence after surgery for iCCA and cHCC-CCA and provided evidence for the nodal CTV definition. Methods: We retrospectively reviewed the medical records of patients with iCCA or cHCC-CCA who underwent surgery between 2010 and 2020. Eligibility criteria included patients pathologically diagnosed with iCCA or cHCC-CCA after surgery and a first recurrent event in regional LNs during follow-up. All recurrent LNs were registered onto reference computed tomography images based on the vascular structures to reconstruct the node mapping. Fifty-three patients were eligible. LN regions were classified into four risk groups. Results: Hepatic hilar and portal vein-vena cava were the most common recurrent regions, with recurrence rates of 62.3 % and 39.6 % (high-risk regions), respectively. Recurrence rates in the left gastric, diaphragmatic, common hepatic, superior mesenteric vessels, celiac trunk, and paracardial regions ranged from 15.1 % to 30.2 % (intermediate-risk regions). There were fewer recurrences in the para-aortic (16a1, a2, b1) and splenic artery and hilum regions, with rates <10 % (low-risk regions). No LN recurrence was observed in the para-oesophageal or para-aortic region (16b2) (very low-risk regions). Based on node mapping, the CTV should include high- and intermediate-risk regions for pathologically negative LN patients during postoperative radiotherapy. Low-risk regions should be included for pathologically positive LN patients. Conclusion: We provide evidence for CTV delineation in patients with iCCA and cHCC-CCA based on recurrent LN mapping.

Characterization of a Straboviridae phage vB_AbaM-SHI and its inhibition effect on biofilms of Acinetobacter baumannii.

Acinetobacter baumannii (A. baumannii) is a popular clinical pathogen worldwide. Biofilm-associated antibiotic-resistant A. baumannii infection poses a great threat to human health. Bacteria in biofilms are highly resistant to antibiotics and disinfectants. Furthermore, inhibition or eradication of biofilms in husbandry, the food industry and clinics are almost impossible. Phages can move across the biofilm matrix and promote antibiotic penetration. In the present study, a lytic A. baumannii phage vB_AbaM-SHI, belonging to family Straboviridae, was isolated from sauce chop factory drain outlet in Wuxi, China. The DNA genome consists of 44,180 bp which contain 93 open reading frames, and genes encoding products morphogenesis are located at the end of the genome. The amino acid sequence of vB_AbaM-SHI endolysin is different from those of previously reported A. baumannii phages in NCBI. Phage vB_AbaM-SHI endolysin has two additional ß strands due to the replacement of a lysine (K) (in KU510289.1, NC_041857.1, JX976549.1 and MH853786.1) with an arginine (R) (SHI) at position 21 of A. baumannii phage endolysin. Spot test showed that phage vB_AbaM-SHI is able to lyse some antibiotic-resistant bacteria, such as A. baumannii (SL, SL1, and SG strains) and E. coli BL21 strain. Additionally, phage vB_AbaM-SHI independently killed bacteria and inhibited bacterial biofilm formation, and synergistically exerted strong antibacterial effects with antibiotics. This study provided a new perspective into the potential application value of phage vB_AbaM-SHI as an antimicrobial agent.

Early Weight-bearing Rehabilitation Protocol After Anterior Cruciate Ligament Reconstruction.

Anterior cruciate ligament (ACL) injury is one of the common sports injuries. Anterior cruciate ligament reconstruction (ACLR) is the mainstream treatment for ACL injury, aiming to regain normal anatomical structure and stability of the knee joint and promote the patient's return to sports. Under the guidance of the concept of enhanced recovery after surgery, early weight-bearing rehabilitation (EWB) is an important factor affecting patient function and quality of life. However, there is no consensus on whether EWB rehabilitation can be performed after ACL surgery. This study aims to explore the safety and feasibility of EWB after ACL surgery. The study implemented a gradual EWB rehabilitation program in the experimental group, including weight-shifting training, balance training, and gait training on the affected lower limb, and assessed wound healing and stability of the knee joint. The study found that EWB after ACLR is safe and feasible. EWB rehabilitation not only does not pose a negative effect on the patient's knee pain, swelling, wound healing, and stability, but also helps to improve knee active flexion and quality of life faster and better. The EWB program in this study is simple, safe, and effective, and it provides strong theoretical guidance and practical demonstration for accelerated rehabilitation after ACLR.

Anlotinib plus Sintilimab achieved in an antitumor effect of complete remission in a patient with advanced hepatocellular carcinoma: a case report.

Systemic therapies-based combination treatments have been developed rapidly in patients with advanced hepatocellular carcinoma (HCC). However, there are still a few patients not applicable to any recommended therapies, making it considerable to try new therapeutic options. Among them, anlotinib, a new oral tyrosine kinase inhibitor, is being widely used for many advanced malignancies. We present the first case of the antitumor effect of complete remission by anlotinib combined with an anti-programmed cell death protein 1 antibody, sintilimab, in a patient with advanced HCC. In April 2020, a 51-year-old male patient was diagnosed with large HCC and underwent hepatectomy with R0 resection. Two months later, he was admitted to our hospital because of a tumor relapse with multiple liver and lung metastases. After the failure of comprehensive treatment containing sorafenib, camrelizumab and transhepatic arterial chemotherapy and embolization, 2 months after tumor relapse, the patient started to receive anlotinib and sintilimab. The multiple tumor nodules were remarkable repressed both in the liver and lung. Six months after anlotinib plus sintilimab treatment, there were no residual tumors, and the alpha-fetoprotein level was decreased from 2310.9 mg/L to normal. Also, the patient continued to receive anlotinib to date. In subsequent follow-up visits until now, there was no sign of recurrence found on imaging. Anlotinib is a promising alternative for patients insensitive to the first-line targeted drugs. More clinical studies should be conducted to further broaden the clinical indications of anlotinib and immunotherapy in patients with HCC.

A dynamic visualization clinical tool constructed and validated based on the SEER database for screening the optimal surgical candidates for bone metastasis in primary kidney cancer.

The implementation of primary tumor resection (PTR) in the treatment of kidney cancer patients (KC) with bone metastases (BM) has been controversial. This study aims to construct the first tool that can accurately predict the likelihood of PTR benefit in KC patients with BM (KCBM) and select the optimal surgical candidates. This study acquired data on all patients diagnosed with KCBM during 2010-2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was utilized to achieve balanced matching of PTR and non-PTR groups to eliminate selection bias and confounding factors. The median overall survival (OS) of the non-PTR group was used as the threshold to categorize the PTR group into PTR-beneficial and PTR-Nonbeneficial subgroups. Kaplan-Meier (K-M) survival analysis was used for comparison of survival differences and median OS between groups. Risk factors associated with PTR-beneficial were identified using univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC), area under the curve (AUC), calibration curves, and decision curve analysis (DCA) were used to validate the predictive performance and clinical utility of the nomogram. Ultimately, 1963 KCBM patients meeting screening criteria were recruited. Of these, 962 patients received PTR and the remaining 1061 patients did not receive PTR. After 1:1 PSM, there were 308 patients in both PTR and non-PTR groups. The K-M survival analysis results showed noteworthy survival disparities between PTR and non-PTR groups, both before and after PSM (p < 0.001). In the logistic regression results of the PTR group, histological type, T/N stage and lung metastasis were shown to be independent risk factors associated with PTR-beneficial. The web-based nomogram allows clinicians to enter risk variables directly and quickly obtain PTR beneficial probabilities. The validation results showed the excellent predictive performance and clinical utility of the nomograms for accurate screening of optimal surgical candidates for KCBM. This study constructed an easy-to-use nomogram based on conventional clinicopathologic variables to accurately select the optimal surgical candidates for KCBM patients.

Construction of 2D/3D g-C3N4/BiOI Photocatalysts with p-n Heterojunction and Their Performance in Photocatalytic Degradation of Amaranth Dye.

The g-C3N4 (graphitic carbon nitride)/BiOI (bismuth oxyiodide) photocatalysts, boasting a unique nanomicrosphere architecture, were synthesized through a tripartite process involving heat polycondensation, hydrothermal treatment, and hybrid methods, using melamine, bismuth nitrate, and potassium iodide as starting materials. The photocatalyst was comprehensively characterized and analyzed while its efficacy in photocatalytic degradation of amaranth (AR) under various lighting conditions was investigated, and the catalytic mechanism was determined by kinetic analysis and free radical scavenging experiments. The results showed that g-C3N4 formed a strong bond with BiOI. The resulting composite catalyst retains the inherent 2D lamellar structure of g-C3N4, as well as the 3D microsphere structure of BiOI, thereby creating heterojunctions via p-n interactions. Under visible light exposure, g-C3N4/BiOI-15% demonstrated optimal catalytic performance, achieving a degradation rate of 74.64% for AR and exhibiting the highest rate constant. Radical tests confirmed that -O2- (superoxide anion) plays a crucial role as active species in the photocatalytic reaction.

Effectiveness and mechanism of action of rTMS combined with quadriceps strength training in individuals with knee osteoarthritis: study protocol for a randomized controlled trial.

BACKGROUND: Quadriceps training is necessary in function and activity of daily living for patients with knee osteoarthritis (KOA). However, it did not reduce the rate of surgical treatment for end-stage KOA in the long term. This may be related to brain structure changes and maladaptive plasticity in KOA patients. Transcranial Magnetic Stimulation (TMS) could enhance the functional connectivity of brain regions and improves maladaptive plasticity. However, the synergistic effect of the combination of the two for treat KOA is still unclear. Therefore, the purpose of this study is to investigate whether the High-Frequency rTMS combined with quadriceps strength training can improve the pain and function in KOA more effectively than quadriceps training alone and explore the mechanism of action. METHODS: This study is an assessor-blind, sham-controlled, randomized controlled trial involving 12 weeks of intervention and 6 months follow-up. 148 participants with KOA will receive usual care management and be randomized into four subgroups equally, including quadriceps strength training, high-frequency rTMS training, sham rTMS and quadriceps strength training, high-frequency rTMS and quadriceps strength training. The rehabilitation interventions will be carried out 5 days per week for a total of 12 weeks. All outcomes will be measured at baseline, 4 weeks, 8 weeks, and 12 weeks during the intervention and 1 month, 3 months and 6 months during the follow-up period. The effectiveness outcomes will be included visual analog scale, isokinetic knee muscle strength, Knee Injury and Osteoarthritis Outcome score and 36-Item Short-Form Health Survey score; The act mechanism outcomes will be included motor evoked potential, grey matter density, white matter, subcortical nuclei volumes, cortical thickness and functional connectivity by MRI. Two-way of variance with repeated measures will be used to test the group and time effect for outcome measures. DISCUSSION: The study will be the first protocol to examine whether there are synergistic effects following high-frequency rTMS combined with quadriceps strength training for treat KOA and clarify the mechanism of action. High-frequency rTMS can be added into the training program for KOA patients if it is proven effective. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300067617. Registered on Jan.13,2023.

Correlation analysis of hypertension, traditional Chinese medicine constitution, and LPL gene polymorphism in the elderly in communities in Shanghai.

BACKGROUND: Research on the genetic mechanisms of hypertension has been a hot topic in the cardiovascular field. OBJECTIVE: To study the correlation between senile hypertension and traditional Chinese medicine (TCM) constitution and lipoprotein lipase (LPL) gene polymorphism and to provide the theoretical basis for TCM prevention and treatment of hypertension. METHODS: The elderly population in communities in Shanghai (hypertensive: 264 cases; non-hypertensive: 159 cases) was taken as the research object. Essential data and information on TCM constitution were collected. The LPL gene mutation was detected using the second-generation sequencing method. Statistical analysis was performed to clarify the relationship between hypertension and senile hypertension. The correlation of TCM constitution with risk factors and LPL gene polymorphisms was studied. RESULTS: The primary TCM constitutions in the hypertension group were phlegm-dampness constitution (51.52%), yin-deficiency constitution (17.42%), balanced constitution (15.53%), and yin-deficiency (9.43%). Logistic regression analysis showed that the phlegm-dampness constitution (P< 0.05, OR = 2.587) and yin-deficiency constitution (P< 0.01, OR = 2.693) were the risk constitutions of hypertension in the elderly. A total of 37 LPL gene mutation loci (SNP: 22; new discovery: 15) were detected in the LPL gene, and the mutation rates of rs254, rs255, rs3208305, rs316, rs11570891, rs328, rs11570893, and rs13702 were relatively high, which were 26.24%, 26.24%, 16.08%, 14.66%, 13.24%, 12.06%, and 10.64%. In the phlegm-dampness group, the proportion of rs254 CC type, rs255 TT type, and rs13702 TT type in the hypertensive group (77.21%, 77.21%, and 93.38%) was higher than that in the non-hypertensive group (56.41%, 56.41%, and 82.05%), The difference was statistically significant (P< 0.05). CONCLUSION: The phlegm-dampness constitution and yin-deficiency constitution are the risk factors of hypertension in the elderly; in the phlegm-dampness population, rs254 CC type, rs255 TT type, and rs13702 TT type are the risk factors for elderly hypertension.

Analysis of survival benefit from primary tumor resection and individualized prediction of overall survival for lung cancer patients with bone metastasis: Worth it or not?

BACKGROUND: The clinical management of lung cancer (LC) patients with bone metastasis (BM) is still a significant challenge. This study aimed to explore the role of primary tumor resection (PTR) on survival outcome of LC patients with BM and to develop two web-based nomograms for predicting the overall survival (OS) of LC patients with BM who received PTR and those who did not. METHODS: We enrolled LC patients with BM from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. Propensity score matching (PSM) was then conducted to balance the baseline characteristics of covariates between patients in surgery and non-surgery groups. Next, Kaplan-Meier analysis with log-rank test was performed to evaluate the survival benefit of PTR before and after PSM methods and to explore the impact of surgical resection extent on the prognosis of LC patients with BM and clinical outcomes in patients with different metastatic patterns. Cox proportional hazard regression analysis was then applied to determine the independent prognostic factors for OS of patients receiving PTR and did not receiving PTR, respectively. Subsequently, we constructed two individualized nomograms for predicting the 12-, 18- and 24-months OS. Finally, receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were generated to evaluate discrimination, accuracy and clinical utility of the nomograms. RESULTS: A total of 7747 eligible patients were included in this analysis. The survival analysis revealed that PTR was closely associated with better survival outcome among LC patients with BM(P < 0.05), while the survival benefit of PTR was suboptimal in patients presented with multiple metastases(P > 0.05). Besides, lobectomy shows best survival benefit. Two nomograms were then constructed based on independent prognostic factors of patients in the surgery group and the non-surgery group. The ROC curves showed good discrimination of the two nomograms, with the area under curve (AUC) of each time point being higher than 0.7 in both the training set and testing set. The calibration curves also demonstrated satisfactory consistency between actual survival and nomogram-predicted OS of both nomograms. The DCA showed high benefit of nomogram in a clinical context. Moreover, the study population was stratified into three groups based on the scores of the nomogram, and the survival analysis showed that this prognostic stratification was statistically significant (p < 0.05). CONCLUSIONS: This study showed that surgical resection of the primary site strategy can prolong survival of LC patients with BM to some extent, depending on different sites of metastasis and highly selected patients. Furthermore, the web-based nomograms showed significant accuracy in predicting OS for patients with or without surgery, which may provide valuable insights for patients' counseling and individualized decision-making for clinicians.

Pan-Cancer Single-Nucleus Total RNA Sequencing Using snHH-Seq.

Tumor heterogeneity and its drivers impair tumor progression and cancer therapy. Single-cell RNA sequencing is used to investigate the heterogeneity of tumor ecosystems. However, most methods of scRNA-seq amplify the termini of polyadenylated transcripts, making it challenging to perform total RNA analysis and somatic mutation analysis.Therefore, a high-throughput and high-sensitivity method called snHH-seq is developed, which combines random primers and a preindex strategy in the droplet microfluidic platform. This innovative method allows for the detection of total RNA in single nuclei from clinically frozen samples. A robust pipeline to facilitate the analysis of full-length RNA-seq data is also established. snHH-seq is applied to more than 730 000 single nuclei from 32 patients with various tumor types. The pan-cancer study enables it to comprehensively profile data on the tumor transcriptome, including expression levels, mutations, splicing patterns, clone dynamics, etc. New malignant cell subclusters and exploring their specific function across cancers are identified. Furthermore, the malignant status of epithelial cells is investigated among different cancer types with respect to mutation and splicing patterns. The ability to detect full-length RNA at the single-nucleus level provides a powerful tool for studying complex biological systems and has broad implications for understanding tumor pathology.

Efficacy and safety of platelet-rich plasma combined with Tai Chi for knee osteoarthritis: study protocol for a placebo-controlled randomized trial.

BACKGROUND: No definitive treatment methods of curative for knee osteoarthritis (KOA). The combined therapies that into account both the biochemical and biomechanical may provide potential opportunities for treat KOA, and previous studies have demonstrated that the platelet-rich plasma of intra-articular injection (IAI-PRP) and exercise treatments afford more benefits than do their corresponding monotherapies. The absence of a specific exercise plan and detailed explanation renders the aforementioned study results questionable. Furthermore, Tai Chi (TC) with moderate-intensity, whole body movements and good adherence may prove to be more effective for treating KOA. However, few studies examined the effectiveness and safety of combined IAI-PRP and TC for KOA. METHODS: This study protocol will be a placebo-controlled, assessor-blinded randomized trial involving 12-week intervention and 1-year follow-up. The stratified randomization will be used to randomly assign the 212 participants to four groups: group A (placebo IAI); group B (PRP IAI); group C (TC and placebo IAI); group D (TC and PRP IAI). Injection will be performed once a week, three consecutive times as a course, after a week of rest to continue the next course, a total of 3 courses (12 week). Additionally, the TC interventions will be carried out 3 days per week for a total of 12 weeks. The primary outcome measures will include the efficacy (Western Ontario and McMaster Universities Osteoarthritis Index), acceptability and safety of these interventions. The secondary outcome measures will include physical function (Timed Up and Go test), walking function (Gait Analysis), inflammatory factor levels (e.g., Interleukin-1 ß, interleukin-6, vascular endothelial growth factor), quality of life (36-Item Short Form Health Survey), volume of patellofemoral cartilage and effusion-synovitis (MRI). Two-way of variance with repeated measures will be applied to examine the main effects of the group and the time factor and group-time interaction effects for all outcome measures. DISCUSSION: This trial will be first one to propose an integrated scheme combing IAI-PRP and TC for treatment of KOA, based on the consideration of the biochemical and biomechanical pathogenesis of KOA. These results of the study will provide evidence with high quality for integrated IAI-PRP and TC to treatment KOA. Trial Registration Chinese Clinical Trial Registry ChiCTR2300067559. Registered on 11 January 2023.

A visualized model for identifying optimal candidates for aggressive locoregional surgical treatment in patients with bone metastases from breast cancer.

Background: The impact of surgical resection of primary (PTR) on the survival of breast cancer (BC) patients with bone metastasis (BM) has been preliminarily investigated, but it remains unclear which patients are suitable for this procedure. Finally, this study aims to develop a predictive model to screen BC patients with BM who would benefit from local surgery. Methods: BC patients with BM were identified using the Surveillance, Epidemiology, and End Results (SEER) database (2010 and 2015), and 39 patients were obtained for external validation from an Asian medical center. According to the status of local surgery, patients were divided into Surgery and Non-surgery groups. Propensity score matching (PSM) analysis was performed to reduce selection bias. Kaplan-Meier (K-M) survival and Cox regression analyses were conducted before and after PSM to study the survival difference between the two groups. The survival outcome and treatment modality were also investigated in patients with different metastatic patterns. The logistic regression analyses were utilized to determine significant surgery-benefit-related predictors, develop a screening nomogram and its online version, and quantify the beneficial probability of local surgery for BC patients with BM. Receiver operating characteristic (ROC) curves, the area under the curves (AUC), and calibration curves were plotted to evaluate the predictive performance and calibration of this model, whereas decision curve analysis (DCA) was used to assess its clinical usefulness. Results: This study included 5,625 eligible patients, of whom 2,133 (37.92%) received surgical resection of primary lesions. K-M survival analysis and Cox regression analysis demonstrated that local surgery was independently associated with better survival. Surgery provided significant survival benefits in most subgroups and metastatic patterns. After PSM, patients who received surgery had a longer survival time (OS: 46 months vs. 32 months, p < 0.001; CSS: 50 months vs. 34 months, p < 0.001). Logistic regression analysis determined six significant surgery-benefit-related variables: T stage, radiotherapy, race, liver metastasis, brain metastasis, and breast subtype. These factors were combined to establish the nomogram and a web probability calculator (https://sunshine1.shinyapps.io/DynNomapp/), with an AUC of 0.673 in the training cohort and an AUC of 0.640 in the validation cohort. The calibration curves exhibited excellent agreement. DCA indicated that the nomogram was clinically useful. Based on this model, surgery patients were assigned into two subsets: estimated sur-non-benefit and estimated sur-benefit. Patients in the estimated sur-benefit subset were associated with longer survival (median OS: 64 months vs. 33 months, P < 0.001). Besides, there was no difference in survival between the estimated sur-non-benefit subset and the non-surgery group. Conclusion: Our study further confirmed the significance of local surgery in BC patients with BM and proposed a novel tool to identify optimal surgical candidates.

Isolation, characterization and application of a lytic phage vB_VspM_VS1 against Vibrio splendidus biofilm.

Vibrio splendidus is a common pathogen in the ocean that infects Apostichopus japonicus, Atlantic salmon and Crassostrea gigas, leading to a variety of diseases. In this study, a virulent phage vB_VspM_VS1, which infects V. splendidus, was isolated from aquaculture ponds in Dalian, China, and it belongs to the family Straboviridae in the order Caudoviricetes. vB_VspM_VS1 had an adsorption rate of 96% in 15 min, a latent period of 65 min, and a burst size of 140 ± 6 PFU/cell. The complete genome of phage vB_VspM_VS1 consists of a linear double-stranded DNA that is 248,270 bp in length with an average G + C content of 42.5% and 389 putative protein-coding genes; 116 genes have known functions. There are 4 tail fiber genes in the positive and negative strands of the phage vB_VspM_VS1 genome. The protein domain of the phage vB_VspM_VS1 tail fibers was obtained from the Protein Data Bank and the SMART (http://smart.embl.de) database. Bacterial challenge tests revealed that the growth of V. splendidus HS0 was apparently inhibited (OD600 < 0.01) in 12 h at an MOI of 10. In against biofilms, we also showed that the OD570 value of the vB_VspM_VS1-treated group (MOI = 1) decreased significantly to 0.04 ± 0.01 compared with that of the control group (0.48 ± 0.08) at 24 h. This study characterizes the genome of the phage vB_VspM_VS1 that infects the pathogenic bacterium V. splendidus of A. japonicus.

Recent advances in natural gums as additives to help the construction and application of edible biopolymer gels: the example of hydrogels and oleogels.

Novel, innovative approaches like edible gels (hydrogels and oleogels) are important food materials with great scientific interest due to their positive impacts on structural and functional foods and other unique properties. Biopolymers (protein, starch and other polysaccharides) can be excellent and cost-effective materials for the formed edible gels. Recently, natural gums, although also as biopolymers, are preferred as additives to further improve the textural and functional properties of edible gels, which have received extensive attention. However, these studies have not been outlined in previous reviews. In this review, we highlighted the advantages of gums as additives to construct edible gels. Moreover, the various roles (including electrostatic or covalent interactions) for natural gums in regulation of food gel properties (solvent-holding and rheological properties) are highlighted. Finally, the use of natural gums as additives to improve the stability and targeted delivery of phytochemicals in food gels and their application in food systems are summarized. The information covered in this article may be useful for the design of functional foods that can better meet personalized needs of people.

Dual-layer spectral-detector CT for predicting microsatellite instability status and prognosis in locally advanced gastric cancer.

OBJECTIVE: To construct and validate a prediction model based on dual-layer detector spectral CT (DLCT) and clinico-radiologic features to predict the microsatellite instability (MSI) status of gastric cancer (GC) and to explore the relationship between the prediction results and patient prognosis. METHODS: A total of 264 GC patients who underwent preoperative DLCT examination were randomly allocated into the training set (n = 187) and validation set (n = 80). Clinico-radiologic features and DLCT parameters were used to build the clinical and DLCT model through multivariate logistic regression analysis. A combined DLCT parameter (CDLCT) was constructed to predict MSI. A combined prediction model was constructed using multivariate logistic regression analysis by integrating the significant clinico-radiologic features and CDLCT. The Kaplan-Meier survival analysis was used to explore the prognostic significant of the prediction results of the combined model. RESULTS: In this study, there were 70 (26.52%) MSI-high (MSI-H) GC patients. Tumor location and CT_N staging were independent risk factors for MSI-H. In the validation set, the area under the curve (AUC) of the clinical model and DLCT model for predicting MSI status was 0.721 and 0.837, respectively. The combined model achieved a high prediction efficacy in the validation set, with AUC, sensitivity, and specificity of 0.879, 78.95%, and 75.4%, respectively. Survival analysis demonstrated that the combined model could stratify GC patients according to recurrence-free survival (p = 0.010). CONCLUSION: The combined model provides an efficient tool for predicting the MSI status of GC noninvasively and tumor recurrence risk stratification after surgery. CRITICAL RELEVANCE STATEMENT: MSI is an important molecular subtype in gastric cancer (GC). But MSI can only be evaluated using biopsy or postoperative tumor tissues. Our study developed a combined model based on DLCT which could effectively predict MSI preoperatively. Our result also showed that the combined model could stratify patients according to recurrence-free survival. It may be valuable for clinicians in choosing appropriate treatment strategies to avoid tumor recurrence and predicting clinical prognosis in GC. KEY POINTS: • Tumor location and CT_N staging were independent predictors for MSI-H in GC. • Quantitative DLCT parameters showed potential in predicting MSI status in GC. • The combined model integrating clinico-radiologic features and CDLCT could improve the predictive performance. • The prediction results could stratify the risk of tumor recurrence after surgery.