Comparison of 3 Different Surgical Techniques for Rotator Cuff Repair in a Rabbit Model: Direct Suture, Inlay Suture, and Polyether Ether Ketone (PEEK) Suture Anchor.

BACKGROUND: Rotator cuff tears have been repaired using the transosseous method for decades. The direct suture (DS) technique has been widely used for rotator cuff tears; however, the retear rate is relatively high. Suture anchors are now used frequently for rotator cuff repair (RCR) in accordance with recent developments in materials. However, polyether ether ketone (PEEK) may still cause complications such as the formation of cysts and osteophytes. Some studies have developed the inlay suture (IS) technique for RCR. PURPOSE/HYPOTHESIS: To compare how 3 different surgical techniques-namely, the DS, IS, and PEEK suture anchor (PSA)-affect tendon-bone healing after RCR. We hypothesized that the IS technique would lead to better tendon-to-bone healing and that the repaired structure would be similar to the normal enthesis. STUDY DESIGN: Controlled laboratory study. METHODS: Acute infraspinatus tendon tears were created in 36 six-month-old male rabbits, which were divided into 3 groups based on the technique used for RCR: DS, IS, and PSA. Animals were euthanized at 6 and 12 weeks postoperatively and underwent a histological assessment and imaging. The expression of related proteins was demonstrated by immunohistochemistry and immunofluorescence staining. Mechanical properties were evaluated by biomechanical testing. RESULTS: At 12 weeks, regeneration of the enthesis was observed in the 3 groups. However, the DS group showed a lower type I collagen content than the PSA and IS groups, which was similar to the results for scleraxis. The DS group displayed a significantly inferior type II collagen expression and proteoglycan deposition after safranin O/fast green and sirius red staining. With regard to runt-related transcription factor 2 and alkaline phosphatase, the IS group showed upregulated expression levels compared with the other 2 groups. CONCLUSION: Compared with the DS technique, the PSA and IS techniques contributed to the improved maturation of tendons and fibrocartilage regeneration, while the IS technique particularly promoted osteogenesis at the enthesis. CLINICAL RELEVANCE: The IS and PSA techniques may be more beneficial for tendon-bone healing after RCR.

Inhibition of MFN1 restores tamoxifen-induced apoptosis in resistant cells by disrupting aberrant mitochondrial fusion dynamics.

Tamoxifen (TAM) resistance presents a major clinical obstacle in the management of estrogen-sensitive breast cancer, highlighting the need to understand the underlying mechanisms and potential therapeutic approaches. We showed that dysregulated mitochondrial dynamics were involved in TAM resistance by protecting against mitochondrial apoptosis. The dysregulated mitochondrial dynamics were associated with increased mitochondrial fusion and decreased fission, thus preventing the release of mitochondrial cytochrome c to the cytoplasm following TAM treatment. Dynamin-related GTPase protein mitofusin 1 (MFN1), which promotes fusion, was upregulated in TAM-resistant cells, and high MFN1 expression indicated a poor prognosis in TAM-treated patients. Mitochondrial translocation of MFN1 and interaction between MFN1 and mitofusin 2 (MFN2) were enhanced to promote mitochondrial outer membrane fusion. The interaction of MFN1 and cristae-shaping protein optic atrophy 1 (OPA1) and OPA1 oligomerization were reduced due to augmented OPA1 proteolytic cleavage, and their apoptosis-promoting function was reduced due to cristae remodeling. Furthermore, the interaction of MFN1 and BAK were increased, which restrained BAK activation following TAM treatment. Knockdown or pharmacological inhibition of MFN1 blocked mitochondrial fusion, restored BAK oligomerization and cytochrome c release, and amplified activation of caspase-3/9, thus sensitizing resistant cells to apoptosis and facilitating the therapeutic effects of TAM both in vivo and in vitro. Conversely, overexpression of MFN1 alleviated TAM-induced mitochondrial apoptosis and promoted TAM resistance in sensitive cells. These results revealed that dysregulated mitochondrial dynamics contributes to the development of TAM resistance, suggesting that targeting MFN1-mediated mitochondrial fusion is a promising strategy to circumvent TAM resistance.

Iron-based autotrophic denitrification driven by sponge iron for nitrite removal in an anaerobic bioreactor: Effect of iron and carbon source.

The study investigated the denitrification effect of the iron autotrophic denitrification process for removing nitrite under anaerobic conditions, utilizing sponge iron as the electron donor. When the C/N ratio equaled 1, defined as the ratio of chemical oxygen demand to total nitrogen (TN), and the influent nitrite nitrogen (NO2--N) was at 80 mg/L, the average steady-state TN effluent concentration of this system was 41.94 mg/L during the 79-day experiment. The TN value exhibited a significant decrease compared to both the sponge iron system (68.69 mg/L) and the carbon source system (56.50 mg/L). Sponge iron is beneficial for providing an electron donor and ensuring an anaerobic system, fostering an environment that promotes microorganism growth while effectively inhibiting the conversion of nitrite to nitrate. In addition, carbon sources play a vital role in ensuring microorganism growth and reproduction, thereby aiding in TN removal. The optimal parameters based on the effectiveness of TN removal in the iron autotrophic denitrification system were determined to be s-Fe0 dosage of 30 g/L and C/N = 1.5. These results suggest that the iron autotrophic denitrification process, driven by sponge iron, can effectively remove nitrite under anaerobic conditions.

An integrated strategy for reducing anastomotic leakage in patients undergoing McKeown esophagectomy.

Objective: To describe our experience of reducing anastomotic leakage, a problem that has not been properly solved. Methods: Starting in January 2020, we began implementing our integrated strategy (application of an esophageal diameter-approximated slender gastric tube, preservation of the fibrous tissue around the residual esophagus and thyroid inferior pole anastomosis) in consecutive patients undergoing esophagectomy without a nasogastric tube or a nasal-jejunum feeding tube. Additionally, the blood supply at the site of the anastomosis was evaluated with a near-infrared fluorescence thoracoscope after the completion of esophagogastric anastomosis in the integrated strategy group. Results: Of 570 patients who were reviewed, 119 (20.9%) underwent the integrated strategy, and 451 (79.1%) underwent the conventional strategy. The rate of anastomotic leakage was 2.5% in the integrated strategy group and 10.2% in the conventional strategy group (p = 0.008). In the integrated strategy group, the site of most of the anastomotic blood supply was the residual esophagus dominant (82.4%), followed by the gastroesophageal dual-dominant (12.6%) and the gastric tube dominant (5.0%). The reconstruction route was more likely to be orthotopic in the integrated strategy group than in the conventional strategy group (89.9% vs. 38.6%, p = 0.004). Gastric dilation was identified in 3.4% of the patients in the integrated strategy group and in 21.1% in the conventional strategy group. Conclusions: Patients who underwent our proposed integrated strategy (Zhengzhou Strategy) during McKeown esophagectomy without a nasogastric tube or a nasal-jejunum feeding tube had a strikingly lower rate of anastomotic leakage and a relatively lower rate of postoperative complications, such as gastric tube dilation and delayed gastric emptying.

A Triply Linked Porphyrin-Norcorrole Hybrid with Singlet Diradical Character.

Norcorrole Ni(II) complexes have recently received considerable attention because they are readily accessible antiaromatic molecules. Their high stability under ambient conditions and ease of synthesis have enabled the exploration of the intrinsic properties of antiaromatic molecules. Here, we report the synthesis and properties of meso-meso singly linked porphyrin-norcorrole hybrids and a triply linked porphyrin-norcorrole hybrid. The singly linked and triply linked porphyrin-norcorrole hybrids were fully characterized, including an X-ray structural analysis. Due to their orthogonal conformation, the singly linked hybrids maintain the individual electronic properties of their porphyrin and norcorrole subunits, while the triply linked hybrid shows a significantly smaller electrochemical HOMO-LUMO gap (0.45 eV) than that of Ni(II) dimesitylnorcorrole (1.08 eV). Furthermore, the triply linked hybrid exhibits singlet diradical characteristics, as confirmed by VT NMR, ESR, and SQUID experiments.

Comparison of Short-term and Three-year Oncological Outcomes Between Robotic and Laparoscopic Gastrectomy for Gastric Cancer: A Large Multicenter Cohort Study.

OBJECTIVE: To compare the short-term and long-term outcomes between robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer. BACKGROUND: The clinical outcomes of RG over LG have not yet been effectively demonstrated. METHODS: This retrospective cohort study included 3599 patients with gastric cancer who underwent radical gastrectomy at eight high-volume hospitals in China from January 2015 to June 2019. Propensity score matching was performed between patients who received RG and LG. The primary end point was 3-year disease-free survival (DFS). RESULTS: After 1:1 propensity score matching, 1034 pairs of patients were enrolled in a balanced cohort for further analysis. The 3-year DFS in the RG and LG was 83.7% and 83.1% ( P =0.745), respectively, and the 3-year overall survival was 85.2% and 84.4%, respectively ( P =0.647). During 3 years of follow-up, 154 patients in the RG and LG groups relapsed (cumulative incidence of recurrence: 15.0% vs 15.0%, P =0.988). There was no significant difference in the recurrence sites between the 2 groups (all P >0.05). Sensitivity analysis showed that RG had comparable 3-year DFS (77.4% vs 76.7%, P =0.745) and overall survival (79.7% vs 78.4%, P =0.577) to LG in patients with advanced (pathologic T2-4a) disease, and the recurrence pattern within 3 years was also similar between the 2 groups (all P >0.05). RG had less intraoperative blood loss, lower conversion rate, and shorter hospital stays than LG (all P >0.05). CONCLUSIONS: For resectable gastric cancer, including advanced cases, RG is a safe approach with comparable 3-year oncological outcomes to LG when performed by experienced surgeons.

Fluorescent in situ hybridization has limitations in screening NRG1 gene rearrangements.

BACKGROUND: NRG1 fusion is a promising therapeutic target for various tumors but its prevalence is extremely low, and there are no standardized testing algorithms for genetic assessment. MOTHODS: In this study, we analyzed 3008 tumors using Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) to screen for NRG1 translocation and p-HER3 expression. RESULTS: Our results demonstrated no cases with p-HER3 positivity through IHC. Nonetheless, 29 cases (0.96%) were identified positive for NRG1 translocation through FISH, with three different signal types. FISH-positive cases were subsequently subjected to next-generation sequencing (NGS) testing. However, only eight of these cases were confirmed with NRG1 fusion through NGS. Notably, we divided FISH into three types and FISH type C group was consistent with NGS results. All NGS NRG1 fusion tumors were adenocarcinomas, with a higher prevalence in females. Our findings indicate that although FISH has limitations in screening NRG1 gene rearrangements, NRG1 fusions can be reliably detected with signals exhibiting low copy numbers of the 5'-end of the gene and no fusion signals. CONCLUSION: Considering the high cost of NGS, FISH remains a useful method for screening NRG1 fusions in various types of tumors. This study provides valuable insights into the molecular mechanisms of NRG1 fusion and identifies potential treatment targets for patients suffering from this disease.

Epidemiology of Lateral Patellar Dislocation Including Bone Bruise Incidence: Five Years of Data from a Trauma Center.

OBJECTIVE: Systematic summary of the epidemiology of patellar dislocation is rare. This study aims to investigate sex-, age-, type-, injury causing events-, incidence of bone bruise and time from last injury (TFLI)-specific characteristics, and detail the epidemiological characteristics of patellar dislocation. METHOD: In this descriptive epidemiological study, a total of 743 patients who have a history of lateral patellar dislocation with either first-time patellar dislocation (FPD) or recurrent patellar dislocation (RPD) between August 2017 and June 2022 at our institution met the inclusion criteria and were selected in this study. Patient characteristics including the type, gender, age, events leading to patellar dislocation, incidence of patellar bone bruise, and the time from last injury (TFLI) of patellar dislocation were retrospectively obtained and described. Magnetic resonance imaging scans (MRI) of the knee were reviewed for insuring bone bruise. RESULTS: Among the 743 patients with patellar dislocation who required surgical reconstruction of the medial retinaculum, 418 (56.2%) had RPD and 325 (43.8%) had FPD. There were more females (65.0%) than males (35.0%) in patellar dislocation patients. Among the female patients, those aged <18 years had higher incidence (31.4%) of patellar dislocation. Among the male patients, those aged <18 and 19-28 years had higher incidence (16.8%) of patellar dislocation. Of all age groups, the prevalence rate of patellar dislocation was high in juvenile population and females, but with no statistical significance. The most common patellar dislocation-causing event was sport accidents (40.1%), followed by life accidents (23.2%). The incidence of left-knee patellar dislocation was slightly higher than that of right-knee patellar dislocation. The incidence of patellar bone bruise of RPD (63.2%) was significantly lower (p < 0.05) than that of FPD (82.2%). Patellar dislocation patients with bone bruise had shorter time from last injury (TFLI) than those without patellar bone bruise (p < 0.05). CONCLUSIONS: The incidence of bone bruise of RPD was lower than that of FPD, and patients with patellar bone bruise may have a shorter time from last injury than those without bone bruise.

Does competitive action intensity influence team performance via leader bottom-line mentality? A social information processing perspective.

Leader bottom-line mentality (LBLM) exists when leaders solely focus on securing bottom-line outcomes to the exclusion of alternative considerations. Our research examines why leaders adopt LBLMs and the implications of this focused leadership strategy on team sales performance and pro-environmental behavior. Utilizing social information processing theory, we examine LBLM as a mediator and contend that competitive action intensity in the work environment provokes LBLM, which then signals to teams the importance of raising sales performance and reducing pro-environmental behavior. We also suggest that leader performance reward expectancy (i.e., perceptions that rewards are directly tied to high performance) serves as a first-stage moderator and team performance reward expectancy serves as a second-stage moderator, with higher (vs. lower) levels of each strengthening the indirect effects of competitive action intensity, through LBLM, onto team sales performance and pro-environmental behavior. Utilizing field data from a large pharmaceutical company (Study 1) as well as an experimental causal chain design (Studies 2a and 2b), we found support for our theoretical model. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Development and validation of prognostic nomogram for cirrhotic patients with acute kidney injury upon ICU admission.

This study aims to develop and validate a prognostic nomogram that accurately predicts the short-term survival rate of cirrhotic patients with acute kidney damage (AKI) upon ICU admission. For this purpose, we examined the admission data of 3060 cirrhosis patients with AKI from 2008 to 2019 in the MIMIC-IV database. All included patients were randomly assigned to derivation and validation cohorts in a 7:3 ratio. The derivation cohort used the least absolute shrinkage and selection operator (LASSO) regression model to identify independent predictors of AKI. A prognostic nomogram was constructed via multivariate logistic regression analysis in the derivation cohort and subsequently verified in the validation cohort. Nomogram's discrimination, calibration, and clinical utility were evaluated using the C-index, calibration plot, and decision curve analysis (DCA). A total of 2138 patients were enrolled in the derivation cohort, with a median follow-up period of 15 days, a median survival time of 41 days, and a death rate of 568 patients (26.6%). The cumulative survival rates at 15 and 30 days were 75.8% and 57.5%, respectively. The results of the multivariate analysis indicated that advanced AKI stage, use of vasoactive drugs, advanced age, lower levels of ALB, lower mean sBp, longer INR, and longer PT were all independent risk factors that significantly influenced the all-cause mortality of cirrhosis patients with AKI (all p < 0.01). The C-indices for the derivation and the validation cohorts were 0.821 (95% CI 0.800-0.842) and 0.831 (95% CI 0.810-0.852), respectively. The model's calibration plot demonstrated high consistency between predicted and actual probabilities. Furthermore, the DCA showed that the nomogram was clinically valuable. Therefore, the developed and internally validated prognostic nomogram exhibited favorable discrimination, calibration, and clinical utility in forecasting the 15-day and 30-day survival rates of cirrhosis patients with AKI upon admission to the ICU.

Shikonin reverses cancer-associated fibroblast-induced gemcitabine resistance in pancreatic cancer cells by suppressing monocarboxylate transporter 4-mediated reverse Warburg effect.

BACKGROUND: Gemcitabine is a first-line chemotherapeutic agent for pancreatic cancer (PC); however, most patients who receive adjuvant gemcitabine rapidly develop resistance and recurrence. Cancer-associated fibroblasts (CAFs) are a crucial component of the tumor stroma that contribute to gemcitabine-resistance. There is thus an urgent need to find a novel therapeutic strategy to improve the efficacy of gemcitabine in PC cells under CAF-stimulation. PURPOSE: To investigate if shikonin potentiates the therapeutic effects of gemcitabine in PC cells with CAF-induced drug resistance. METHODS: PC cell-stimulated fibroblasts or primary CAFs derived from PC tissue were co-cultured with PC cells to evaluate the ability of shikonin to improve the chemotherapeutic effects of gemcitabine in vitro and in vivo. Glucose uptake assay, ATP content analysis, lactate measurement, real-time PCR, immunofluorescence staining, western blot, and plasmid transfection were used to investigate the underlying mechanism. RESULTS: CAFs were innately resistant to gemcitabine, but shikonin suppressed the PC cell-induced transactivation and proliferation of CAFs, reversed CAF-induced resistance, and restored the therapeutic efficacy of gemcitabine in the co-culture system. In addition, CAFs underwent a reverse Warburg effect when co-cultured with PC cells, represented by enhanced aerobic glycolytic metabolism, while shikonin reduced aerobic glycolysis in CAFs by reducing their glucose uptake, ATP concentration, lactate production and secretion, and glycolytic protein expression. Regarding the mechanism underlying these sensitizing effects, shikonin suppressed monocarboxylate transporter 4 (MCT4) expression and cellular membrane translocation to inhibit aerobic glycolysis in CAFs. Overexpression of MCT4 accordingly reversed the inhibitory effects of shikonin on PC cell-induced transactivation and aerobic glycolysis in CAFs, and reduced its sensitizing effects. Furthermore, shikonin promoted the effects of gemcitabine in reducing the growth of tumors derived from PC cells and CAF co-inoculation in BALB/C mice, with no significant systemic toxicity. CONCLUSION: These results indicate that shikonin reduced MCT4 expression and activation, resulting in inhibition of aerobic glycolysis in CAFs and overcoming CAF-induced gemcitabine resistance in PC. Shikonin is a promising chemosensitizing phytochemical agent when used in combination with gemcitabine for PC treatment. The results suggest that disrupting the metabolic coupling between cancer cells and stromal cells might provide an attractive strategy for improving gemcitabine efficacy.

Characteristics of Sports Injuries in Athletes During the Winter Olympics: A Systematic Review and Meta-analysis.

Background: Athletes in the Winter Olympic Games are subject to high injury rates given the physical demands of sports. Comprehensive data regarding injury characteristics in these athletes are limited. Purpose: To summarize and analyze data regarding the incidence and characteristics of sports injuries occurring in the Winter Olympic Games. Study Design: Scoping review; Level of evidence, 4. Methods: A systematic review of the PubMed, EMBASE, Web of Science, and China National Knowledge Infrastructure databases was conducted. Included were studies reporting the incidence of sports injuries during the Winter Olympics Games from 1995 through 2021. From 168 studies initially retrieved, 4 studies (8824 athletes, 1057 injured athletes) were included. A single-group meta-analysis of sports injury characteristics was performed, with subgroup analysis performed according to the different sports, injury locations, and injury types. Injury severity (time lost from sport) and mechanism were also assessed. Result: The overall injury incidence rate (IIR) during the Winter Olympic Games was 9.6% (95% CI, 4.1%-19.8%). Snow sports were associated with the highest IIR (11.3%), with the top 3 events being the snowboard cross event in snowboarding (31.4%), the aerials event in freestyle skiing (28.6%), and the slopestyle event in snowboarding (27.7%). The most common injury locations were the knee (IIR = 20.0%; 95% CI 17.9%-22.0%), head (IIR = 10.6%; 95% CI, 9.4%-11.9%), and ankle (IIR = 8.2%; 95% CI 7.8%-8.7%). The most common injury types were contusion/hematoma/bruise (IIR = 29.9%; 95% CI 29.7%-30.0%), sprain (dislocation, subluxation, instability, ligamentous, rupture) (IIR = 21.9%; 95% CI 21.4%-22.3%), and strain (muscle rupture, tear, tendon rupture) (IIR = 11.3%; 95% CI 11.0%-11.6%). Regarding injury severity, most athletes had no time lost from sport (64.5%); 24.0% lost fewer than 7 days, and 11.5% lost more than 7 days. The most common injury mechanism was noncontact-related injury (63.3%). Conclusion: In Winter Olympics sports, snow-sport injuries were more common than those associated with other sports, and the most common injury location was the knee. Most injuries did not require time loss, and the most were noncontact-related injuries.

Comparison of Bone Bruise Pattern Epidemiology between Anterior Cruciate Ligament Rupture and Patellar Dislocation Patients-Implications of Injury Mechanism.

Different bone bruise patterns observed using magnetic resonance imaging (MRI) after non-contact anterior cruciate ligament (ACL) rupture and lateral patellar dislocation may indicate different knee injury mechanisms. In this study, 77 ACL ruptures and 77 patellar dislocations in knee MR images taken from patients with bone bruises at our institution between August 2020 and March 2022 were selected and analyzed. In order to determine typical bone bruising patterns following by ACL rupture and patellar dislocation, sagittal- and transverse-plane images were used to determine bone bruise locations in the directions of medial-lateral and superior-inferior with MR images. The presence, intensity, and location of the bone bruises in specific areas of the femur and tibial after ACL rupture and patellar dislocation were recorded. Relative bone bruise patterns after ACL rupture and patellar dislocation were classified. The results showed that there were four kinds of bone bruise patterns (1-, 2-, 3-, and 4- bone bruises) after ACL rupture. The most common two patterns after ACL rupture were 3- bone bruises (including the lateral femoral condyle and both the lateral-medial tibial plateau, LF + BT; both the lateral-medial femoral condyle and the lateral tibial plateau, BF + LT; and the medial femoral condyle and both the medial and lateral tibial plateau, MF + BT) followed by 4- bone bruises (both the lateral-medial femoral condyle and the tibial plateau, BF + BT), 2- bone bruises (the lateral femoral condyle and tibial plateau, LF + LT; the medial femoral condyle and the lateral tibial plateau, MF + LT; the lateral femoral condyle and the medial tibial plateau, LF + MT; the medial femoral condyle and the tibial plateau, MF + MT; both the lateral-medial tibial plateau, 0 + BT), and 1- bone bruise (only the lateral tibial plateau, 0 + LT). There was only a 1- bone bruise (the latera femoral condyle and medial patella bone bruise) for patellar dislocation, and the most common pattern of patellar dislocation was in the inferior medial patella and the lateral anterior inferior femur. The results suggested that bone bruise patterns after ACL rupture and patellar dislocation are completely different. There were four kinds of bone bruise patterns after non-contact ACL rupture, while there was only one kind of bone bruise pattern after patellar dislocation in patients, which was in the inferior medial patella and lateral anterior inferior femur.

Licochalcone A Induces Ferroptosis in Hepatocellular Carcinoma via Reactive Oxygen Species Activated by the SLC7A11/GPX4 Pathway.

Liver cancer is a common malignant tumor, and its incidence is increasing yearly. Millions of people suffer from liver cancer annually, which has a serious impact on global public health security. Licochalcone A (Lico A), an important component of the traditional Chinese herb licorice, is a natural small molecule drug with multiple pharmacological activities. In this study, we evaluated the inhibitory effects of Lico A on hepatocellular carcinoma cell lines (HepG2 and Huh-7), and explored the inhibitory mechanism of Lico A on hepatocellular carcinoma. First, we evaluated the inhibitory effects of Lico A on hepatocellular carcinoma, and showed that Lico A significantly inhibited and killed HepG2 and Huh-7 cells in vivo and in vitro. Transcriptomic analysis showed that Lico A inhibited the expression of solute carrier family 7 member 11 (SLC7A11), which induced ferroptosis. We confirmed through in vivo and in vitro experiments that Lico A promoted ferroptosis in hepatocellular carcinoma cells by downregulating SLC7A11 expression, thereby inhibiting the glutathione (GSH)-glutathione peroxidase 4 (GPX4) pathway and inducing activation of reactive oxygen species (ROS). In this study, we suggest that Lico A is a potential SLC7A11 inhibitor that induces ferroptotic death in hepatocellular carcinoma cells, thereby providing a theoretical basis for the development of natural small molecule drugs against hepatocellular carcinoma.

Muscle dynamics analysis by clustered categories during jogging in patients with anterior cruciate ligament deficiency.

BACKGROUND: Patients with anterior cruciate ligament (ACL) deficiency (ACLD) tend to have altered lower extremity dynamics. Little is known about the changes in dynamic function and activation during jogging in patients with ACLD. METHODS: Twenty patients with an injured ACL before ACL reconstruction (ACLD group) and nine healthy male volunteers (control group) were recruited. Each volunteer repeated the jogging experiment five times. Based on the experimental data measured, a musculoskeletal multibody dynamics model was employed to simulate the tibiofemoral joint dynamics during jogging. Eighteen muscles were used for analysis. The obtained dynamics data were used for clustering and curve difference analysis. RESULTS: The 18 muscles studied were divided into 3 categories. All the quadriceps, the soleus, the gastrocnemius, and the popliteus were classified as label 1. All the hamstrings were classified as label 2, and the sartorius muscles were classified as label 3. Among them, the classification of the short head of the biceps femoris was significantly different between the two groups (P < 0.001). The force curves of all 18 muscles and the between-group differences were studied according to clustered categories. Most muscle force in label 1 was approaching zero in the terminal stance phase, which was significantly lower than that in the control group (P < 0.05). The muscle force in label 2 had areas with significant differences in the stance phase. Muscle force in label 3 was significantly lower than that in the control group in the pre-swing phase. CONCLUSIONS: This study showed that there are various changes of muscle function and activation in patients with ACLD. Through clustering and curve analysis, the joint reactions and changes of different muscle forces in the gait cycle between the ACLD and control groups could be further clarified.

Meniscal fibrocartilage regeneration inspired by meniscal maturational and regenerative process.

Meniscus is a complex and crucial fibrocartilaginous tissue within the knee joint. Meniscal regeneration remains to be a scientific and translational challenge. We clarified that mesenchymal stem cells (MSCs) participated in meniscal maturation and regeneration using MSC-tracing transgenic mice model. Here, inspired by meniscal natural maturational and regenerative process, we developed an effective and translational strategy to facilitate meniscal regeneration by three-dimensionally printing biomimetic meniscal scaffold combining autologous synovium transplant, which contained abundant intrinsic MSCs. We verified that this facilitated anisotropic meniscus-like tissue regeneration and protected cartilage from degeneration in large animal model. Mechanistically, the biomechanics and matrix stiffness up-regulated Piezo1 expression, facilitating concerted activation of calcineurin and NFATc1, further activated YAP-pSmad2/3-SOX9 axis, and consequently facilitated fibrochondrogenesis of MSCs during meniscal regeneration. In addition, Piezo1 induced by biomechanics and matrix stiffness up-regulated collagen cross-link enzyme expression, which catalyzed collagen cross-link and thereby enhanced mechanical properties of regenerated tissue.

Multifactor analysis of the technique in total laparoscopic gastric cancer.

BACKGROUND: Esophageal gastric anastomosis is a common surgical technique used to treat patients with gastric cancer who undergo total gastrectomy. However, using simple anastomosis techniques alone may not meet the needs of patients in some cases and can lead to complications such as anastomotic stenosis and ulceration. In order to overcome these issues and improve patient prognosis, muscle flap reconstruction technique has emerged. Muscle flap reconstruction is a method of improving gastric-esophageal anastomosis by transplanting muscle tissue. By covering the anastomotic site with muscle tissue, it not only enhances the stability of the anastomosis site but also increases blood supply, promoting healing and recovery of the anastomosis. Therefore, the use of muscle flap reconstruction technique in esophageal gastric anastomosis during total gastrectomy for gastric cancer is increasingly widely applied. AIM: To determine the effectiveness of esophagogastric anastomosis using the muscle flap reconstruction technology in total abdominal gastrectomy for gastric cancer and perform follow-up experiments to understand the factors affecting patients' prognosis. METHODS: The study subjects were 60 patients with gastric cancer who were admitted to our hospital between October 2018 and January 2022. All patients underwent esophagogastric anastomosis using the double muscle flap reconstruction technology in total abdominal gastrectomy. Perioperative indicators were determined, and patients were followed up for 1 year. Furthermore, patient outcomes were observed within 1 year, followed by patient classification based on different outcomes. Moreover, clinicopathological parameters were observed and relevant factors affecting patient prognosis were analyzed. RESULTS: The operation time was 318 ± 43 min, the formation time of esophageal double muscle flap anastomosis was 110 ± 13 min, the number of lymph node dissections was 26 ± 6, the incision length was 3 ± 0.6 cm, intraoperative bleeding volume was 48 ± 15 mL, first anal exhaust time was 5.3 ± 1.8 d, first meal time was 6.0 ± 1.6 d, length of hospital stay was 11.8 ± 2.5, and treatment cost was 5.8 ± 0.7 thousand yuan. The patient experienced three postoperative complications: 2 cases of pulmonary infection and 1 case of respiratory discomfort. During 1-year follow-up, 50 patients survived and 10 died. Univariate analysis revealed that histological types, tumor size, tumor-node-metastasis staging, vascular invasion, and postoperative adjuvant radiotherapy and chemotherapy were the main factors affecting the prognosis of surviving patients. Furthermore, Cox regression analysis revealed that postoperative adjuvant radiotherapy and chemotherapy were the main factors affecting patient prognosis. The survival time of the survival group was significantly higher than that of the death group (P < 0.05). CONCLUSION: Esophagogastric anastomotic using muscle flap reconstruction exhibits good effects on patients who undergo total abdominal gastrectomy for cancer. Postoperative adjuvant radiotherapy and chemotherapy are the main factors affecting patient prognosis.

The impact of the chalcogen-substitution element and initial spectroscopic state on excited-state relaxation pathways in nucleobase photosensitizers: a combination of static and dynamic studies.

The substitution of oxygen with chalcogen in carbonyl group(s) of canonical nucleobases gives an impressive triplet generation, enabling their promising applications in medicine and other emerging techniques. The excited-state relaxation S2(ππ*) → S1(nπ*) → T1(ππ*) has been considered the preferred path for triplet generation in these nucleobase derivatives. Here, we demonstrate enhanced quantum efficiency of direct intersystem crossing from S2 to triplet manifold upon substitution with heavier chalcogen elements. The excited-state relaxation dynamics of sulfur/selenium substituted guanines in a vacuum is investigated using a combination of static quantum chemical calculations and on-the-fly excited-state molecular dynamics simulations. We find that in sulfur-substitution the S2 state predominantly decays to the S1 state, while upon selenium-substitution the S2 state deactivation leads to simultaneous population of the S1 and T2,3 states in the same time scale and multi-state quasi-degeneracy region S2/S1/T2,3. Interestingly, the ultrafast deactivation of the spectroscopic S3 state of both studied molecules to the S1 state occurs through a successive S3 → S2 → S1 path involving a multi-state quasi-degeneracy S3/S2/S1. The populated S1 and T2 states will cross the lowest triplet state, and the S1 → T intersystem crossing happens in a multi-state quasi-degeneracy region S1/T2,3/T1 and is accelerated by selenium-substitution. The present study reveals the influence of both the chalcogen substitution element and initial spectroscopic state on the excited-state relaxation mechanism of nucleobase photosensitizers and also highlights the important role of multi-state quasi-degeneracy in mediating the complex relaxation process. These theoretical results provide additional insights into the intrinsic photophysics of nucleobase-based photosensitizers and are helpful for designing novel photo-sensitizers for real applications.

High expression of NOLC1 as an independent prognostic factor for survival in patients with colorectal cancer.

BACKGROUND: As a phosphorylated protein, NOLC1 is mainly located in the nucleus and is highly expressed in a variety of tumors, participating in the regulation of cell proliferation and aging. This study further investigated the role of NOLC1 in colorectal cancer tumors, aiming to provide sufficient scientific evidence for the clinical treatment of colorectal cancer. METHODS: We used TCGA, GEO, TNMplot, GEPIA, and other databases to explore the expression level of NOLC1 in colorectal cancer patients, as well as the correlation between the clinical characteristics of colorectal cancer patients and their expression, and conducted the prognostic analysis. Immunohistofluorescence (IHF) staining verified the analytical results. Subsequently, KEGG and GO enrichment analysis was used to identify the potential molecular mechanism of NOLC1 promoting the occurrence and development of colorectal cancer. The influence of NOLC1 expression on the immune microenvironment of colorectal cancer patients was further investigated using the TIMER database. GDSC database analysis was used to screen out possible anti-colorectal cancer drugs against NOLC1. Finally, we demonstrated the effect of NOLC1 on the activity and migration of colorectal cancer cells by Edu Cell proliferation assay and Wound Healing assay in vitro. RESULTS: Our results suggest that NOLC1 is overexpressed in colorectal cancer, and that overexpression of NOLC1 is associated with relevant clinical features. NOLC1, as an independent risk factor affecting the prognosis of colorectal cancer patients, can lead to a poor prognosis of colorectal cancer. In addition, NOLC1 may be associated with MCM10, HELLS, NOC3L, and other genes through participating in Wnt signaling pathways and jointly regulate the occurrence and development of colorectal cancer under the influence of the tumor microenvironment and many other influencing factors. Related to NOLC1: Selumetinib, Imatinib, and targeted drugs such as Lapatinib have potential value in the clinical application of colorectal cancer. NOLC1 enhances the proliferation and migration of colorectal cancer cells. CONCLUSIONS: High expression of NOLC1 as an independent prognostic factor for survival in patients with colorectal cancer. NOLC1 enhances the proliferation and migration of colorectal cancer cells. Further studies and clinical trials are needed to confirm the role of NOLC1 in the development and progression of colorectal cancer.

A Magnetic Field Sensor Based on Directional Coupling in a Magnetic Fluid-Filled Photonic Crystal Fiber.

In this paper, a dual-core photonic crystal fiber (DC-PCF) sensitivity sensor filled with magnetic liquid is introduced and investigated with the finite element method (FEM). To regulate the energy coupling involving the two cores, the magnetic fluid is filled into the pore between the two cores. To adjust the coupling between the supermodes in the DC-PCF, the refractive index (RI) of the air hole filled magnetic fluid may change due to the external magnetic field. This specifically created a magnetic fluid-filled DC-PCF; the magnetic fluid-filled hole is not used as the core for energy transmission, thus avoiding transmission loss. The dip wavelength and the magnetic field displayed an excellent linear connection between 80 and 260 Oe, depending on the numerical data. The detection sensitivity of the magnetic field reached 515.75 pm/Oe at a short fiber length of 482 µm. The designed magnetic fluid-filled DC-PCF has high sensitivity and small volume and has great application prospects in magnetic field detection in the medical and industrial fields.