Novel Cocktail Therapy Based on a Nanocarrier with an Efficient Transcytosis Property Reverses the Dynamically Deteriorating Tumor Microenvironment for Enhanced Immunotherapy.

The immune checkpoint blockade (ICB) faces a low response rate in clinical cancer treatment. Chemotherapy could enhance the response rate of the ICB, but patients would suffer from side effects. The off-target toxicity could be reduced by loading the chemotherapeutic agent through nanocarriers. Therefore, we developed a polymeric carrier for doxorubicin (DOX) loading to form DOX nanoparticles (DOX NPs), which were spatiotemporally responsive to the tumor microenvironment (TME). DOX NPs had an efficient transcytosis property for deep tumor infiltration and sustained drug release ability. Unfortunately, a binary therapy of DOX NPs and ICB induces tumor adaptive resistance and causes dynamic deterioration of the TME. We propose for the first time that TGF-ß1 is a major cause of tumor adaptive resistance and developed an immune cocktail therapy containing DOX NPs, ICB, and TGF-ß1 gene silencing nanoparticles. This therapy successfully overcame tumor adaptive resistance by reversing the immunosuppressive TME and achieved enhanced tumor treatment efficiency.

An evaluation of the efficacy of percutaneous reduction and screw fixation without bone grafting in Sanders Type-II and Type-III displaced intra-articular calcaneal fractures.

BACKGROUND: The aim of this retrospective monocentric study was to investigate the clinical efficacy of percutaneous reduction and screw fixation without bone grafting in Sanders Type-II and Type-III displaced intra-articular calcaneal fractures (DIACFs). METHODS: The medical records of calcaneal fractures patients who were admitted to our department from January 2018 to January 2020 were retrospectively reviewed, and those meeting the inclusion criteria were fnally included for analysis. All patients were treated with percutaneous reduction and screw fixation, and no patients received bone grafting. The radiologic parameters evaluated included the BÖhler angle and the calcaneal height. In addition, the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scores, Maryland Foot Score (MFS), and visual analog scale (VAS) score were determined. RESULTS: Thirty-eight patients with Sanders Type-II and Type-III DIACFs were finally included, including 30 males and 8 females aged 21 to 61 years [(42.6 ± 9.6) years]. According to the Essex-Lopresti classification, 27 of the fractures were the tongue type, and 11 were the joint compression type. According to the Sanders classification, 27 of the fractures were type II, and 11 were type III. Immediately postoperatively, the calcaneal height had recovered to 39.8 ± 2.1 mm, the BÖhler angle had recovered from 4.2° ± 13.6° preoperatively to 27.2° ± 3.4° (P = 0.000). All patients were followed up for 18-42 months [(25.2 ± 9.5) months]. All fractures healed. No differences were found in the outcome measures six-months postoperatively (BÖhler angle, p = 0.24; calcaneal height, p = 0.82) or at final follow-up (BÖhler angle, p = 0.33; calcaneal height, p = 0.28) compared to the immediately postoperative values. At the final follow-up, the AOFAS score was 91.7 ± 7.4 points, with an excellent and good rate of 92.1%; the MFS was 90.3 ± 7.8 points, with an excellent and good rate of 92.1%; and the VAS score was 2.2 ± 1.5 points. None of the patients had incision complications, and one patient developed traumatic arthritis. CONCLUSION: Percutaneous reduction and screw fixation without bone grafting in Sanders Type-II and Type-III DIACFs can achieve good recovery and maintenance of the BÖhler angle and calcaneal height. Moreover, it has the advantage of a low complication rate.

A novel minimally invasive percutaneous treatment for Essex-Lopresti joint depression-type DIACFs by ligamentotaxis.

OBJECTIVE: To compare the clinical efficacy of minimally invasive percutaneous treatment by ligamentotaxis with traditional open reduction and internal fixation in the treatment of Essex-Lopresti joint depression-type displaced intra-articular calcaneal fractures (DIACFs). METHODS: The medical records of patients with calcaneal fractures admitted to our department from January 2016 to December 2020 were retrospectively analyzed, and patients who met the inclusion criteria were finally included for analysis. Twenty-one patients underwent minimally invasive percutaneous treatment by ligamentotaxis (Group A), while eighteen patients were treated by traditional open reduction and internal fixation through an extended lateral approach (Group B). The preoperative waiting time, operative time, hospital stay, radiologic parameters (calcaneal height, width, length, Böhler angle and Gissane angle), American Foot and Ankle Surgery Association (AOFAS) hindfoot scores, Maryland Foot Score (MFS), visual analogue scale (VAS), and incidence of complications of the included patients were all recorded and analysed. RESULTS: Thirty-nine patients with Essex-Lopresti joint depression type DIACFs were finally included. According to the Sanders classification, 22 were type II, 12 were type III and 5 were type IV. The preoperative waiting time and the hospital stay of Group A were 3.7 ± 1.6 d and 7.2 ± 1.7 d, respectively, which were significantly shorter than those of Group B (6.9 ± 2.0 d and 12.4 ± 1.5 d) (P < 0.05). There was no significant difference in the operative time between the two groups (88.8 ± 9.8 min vs. 91.3 ± 12.1 min; P > 0.05). No significant differences were shown in the radiological parameters (calcaneal height, width, length, Böhler angle and Gissane angle) or the satisfactory rate of joint surface reduction (SRJSR) of the two groups immediately postoperatively. All patients were followed up for 14 to 56 months [(30.2 ± 10.4) months]. All fractures healed. At the final follow-up, there were no significant differences in the radiological parameters or the SRJSR between the two groups (P > 0.05). No significant differences were shown in the AOFAS scores, MFS or VAS scores between the two groups [(89.5 ± 8.2) vs. (89.4 ± 9.0), P > 0.05; (87.5 ± 8.3) vs. (86.3 ± 8.9), P > 0.05; and (2.1 ± 1.2) vs. (2.2 ± 1.2), P > 0.05]. The excellent and good rates of the AOFAS scores and MFS were 90.5% and 85.7%, respectively, in Group A and 88.9% and 88.9%, respectively, in Group B (P > 0.05). Four patients experienced wound complications, including 1 superficial incision infection, 2 skin necrosis around the incision edge and 1 deep infection in Group B, while there were no wound complications in Group A (P < 0.05). One patient in each group suffered traumatic arthritis (P > 0.05). CONCLUSIONS: In the assessment of Essex-Lopresti joint depression type DIACFs, minimally invasive percutaneous treatment by ligamentotaxis has similar clinical outcomes to traditional open reduction and internal fixation through an extended lateral approach. However, the former has the advantages of shorter preoperative waiting time and hospital stay, and lower incidence of incision complications.

Photothermal-Chemotherapy Enhancing Tumor Immunotherapy by Multifunctional Metal-Organic Framework Based Drug Delivery System.

Immunotherapy holds great promise for patients undergoing tumor treatment. However, the clinical effect of immunotherapy is limited because of tumor immunogenicity and its immunosuppressive microenvironment. Herein, the metal-organic framework (MIL-100) loaded with chemotherapeutic agent mitoxantrone (MTO) was combined with photothermal-chemotherapy for enhancing immunogenic cell death. MIL-100 loaded with MTO and hyaluronic acid as nanoparticles (MMH NPs) yielded an NP with two therapeutic properties (photothermal and chemotherapy) with dual imaging modes (photoacoustic and thermal). When MMH NPs were coinjected with an anti-OX40 antibody in colorectal cancer, the highest antitumor efficacy and a robust immune effect were achieved. This work provides a novel combined therapeutic strategy, which will hold great promise in future tumor therapy.

Comparative Effect of Liuzijue Qigong and Conventional Respiratory Training on Trunk Control Ability and Respiratory Muscle Function in Patients at an Early Recovery Stage From Stroke: A Randomized Controlled Trial.

OBJECTIVES: To compare the effects of Liuzijue Qigong and conventional respiratory training on trunk control ability and respiratory muscle functions in patients at an early recovery stage from stroke. DESIGN: A single-blind, randomized controlled trial. SETTING: A hospital. PARTICIPANTS: Patients (N=60) within 2 months poststroke. INTERVENTIONS: The experimental group (n=30) received conventional rehabilitation training combined with Liuzijue exercise, and the control group (n=30) received conventional rehabilitation training combined with conventional respiration training. The training in the 2 groups was conducted 5 times per week for 3 weeks. MAIN OUTCOME MEASURES: Trunk Impairment Scale (TIS), maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), maximum expiratory mid-flow (MMEF), diaphragmatic movement, the change of intra-abdominal pressure (IAP), Berg Balance Scale (BBS), and Modified Barthel Index (MBI). All outcome measures were assessed twice (at baseline and 3 weeks). RESULTS: Both groups significantly improved in TIS, MIP, FVC, PEF, and the change of IAP, BBS, and MBI when pre- and postassessments (P<.05) were compared. Compared with the control group, there was a significant difference in the experimental group in the static sitting balance subscale (P=.014), dynamic balance subscale (P=.001), coordination subscale (P<.001), TIS total scores (P<.001; effect size [ES]=0.9), MIP (P=.012; 95% confidence interval [CI], 2.23-17.69; ES=0.67), MEP (P=.015; 95% CI, 1.85-16.57; ES=0.65), change of IAP (P=.001), and MBI (P=.016; 95% CI, 1.51-14.16; ES=0.64). No significant differences were found between the 2 groups in FEV1 (P=.24), FVC (P=.43), PEF (P=.202), MMEF (P=.277), the diaphragmatic movement of quiet breathing (P=.146), deep breathing (P=.102), and BBS (P=.124). CONCLUSIONS: Liuzijue exercise showed more changes than conventional respiratory training in improving trunk control ability, respiratory muscle functions, and activities of daily living ability in patients at an early recovery stage from stroke.

Liuzijue qigong versus traditional breathing training for patients with post-stroke dysarthria complicated by abnormal respiratory control: Results of a single-center randomized controlled trial.

OBJECTIVE: The aim of the study was to investigate whether liuzijue qigong could improve the ability of respiratory control and comprehensive speech in patients with stroke dysarthria. DESIGN: A randomized controlled trial. SETTING: The research was carried out in the department of rehabilitation. PARTICIPANTS: Altogether, a total of 98 stroke patients with dysarthria participated in the study. INTERVENTIONS: Patients were randomly divided into two groups (the experimental group: basic articulation + liuzijue qigong, 48 patients or the control group: basic articulation + traditional breathing training, 50 patients). All therapies were conducted once a day, five times a week for three weeks. MAIN MEASURES: Primary outcome measure: Speech breathing level of the modified Frenchay Dysarthria Assessment. Secondary outcome measures: the modified Frenchay Dysarthria Assessment, maximum phonation time, maximal counting ability, /s/, /z/, s/z ratio, and the loudness level. All outcome measures were assessed twice (at baseline and after three weeks). RESULTS: At three weeks, There were significant difference between the two groups in the change of speech breathing level (81% vs 66%, P = 0.011), the modified Frenchay Dysarthria Assessment (5.54 (4.68-6.40) vs 3.66 (2.92-4.40), P = 0.001), maximum phonation time (5.55 (4.92-6.18) vs 3.01(2.31-3.71), P < 0.01), maximal counting ability (3.08(2.45-3.71) vs 2.10 (1.53-2.67), P = 0.018), and /s/ (3.08 (2.39-3.78) vs 1.87 (1.23-2.51), P = 0.004), while no significant differences were found in the change of /z/ (3.08 (2.31-3.86) vs 2.10 (1.5-2.64), P = 0.08), s/z ratio (1.26 (0.96-1.55) vs 1.03 (0.97-1.09), P = 0.714), and the change of loudness level (69% vs 60%, P = 0.562). CONCLUSIONS: Liuzijue qigong, combined with basic articulation training, could improve the respiratory control ability, as well as the comprehensive speech ability of stroke patients with dysarthria. TRIAL REGISTRATION: ChiCTR-INR-16010215.

A novel closed reduction technique for treating femoral shaft fractures with intramedullary nails, haemostatic forceps and the lever principle.

BACKGROUND: Faster, easier, more economical and more effective versions of the minimally invasive reduction procedure for femoral shaft fractures need to be developed for use by orthopaedic surgeons. In this study, a fracture table was used to restore limb length, and long, curved haemostatic forceps and the lever principle were utilized to achieve minimally invasive reduction and intramedullary nail fixation of femoral shaft fractures. METHODS: A retrospective analysis involving 20 patients with femoral shaft fractures reduced with a fracture table; long, curved haemostatic forceps; and the lever principle was conducted. The operative effect was evaluated on the basis of the operative time, reduction time, fluoroscopy time, and intraoperative blood loss. RESULTS: All 20 cases were reduced in a closed fashion, and no conversions to open reduction were needed. The average operative time and fracture reduction time for all patients were 69.1 ± 13.5 min (range, 50-100 min) and 6.7 ± 1.9 min (range, 3-10 min), respectively. The fluoroscopy exposure time during the reduction process was 5-15 s, with an average time of 8.7 ± 2.7 s. The average intraoperative blood loss was 73.5 ± 22.5 mL (range, 50-150 mL). The patients exhibited excellent alignment in the injured limb after intramedullary nailing. Seventeen patients successfully completed a follow-up after fracture healing. The healing time ranged from 4 to 6 months. CONCLUSIONS: Displaced femoral shaft fractures in adults can be treated by a labour-saving lever technique involving fragments, 2 haemostatic forceps and soft tissue envelope-assisted closed reduction and intramedullary nail fixation. This technique is easy to perform; reduces blood loss, the fluoroscopy time and the surgical time for intraoperative reduction; and leads to excellent fracture healing.

ADAMTS-6 is a predictor of poor prognosis in patients with esophageal squamous cell carcinoma.

BACKGROUND: A disintegrin and metalloprotease with thrombospondin motif (ADAMTS) enzymes play important roles in cell functions including adhesion, invasion, migration, and proliferation. ADAMTS-6 is a member of the ADAMTS family; reports of its relationship with esophageal squamous cell carcinoma (ESCC) progression are rare. It is unclear whether ADAMTS-6 could be an independent ESCC biomarker. METHODS: ADAMTS-6 expression was detected by immunohistochemistry (IHC) in 171 paraffin-embedded ESCC specimens; relationships with patients' clinicopathological features and Twist-1 expression were analyzed by the Pearson Chi-square method, respectively. Overall survival (OS) and disease-free survival (DFS) were determined using the Kaplan-Meier method and compared using the long-rank test. RESULTS: ADAMTS-6 was expressed mainly in the cytoplasm and nucleus; the expression was significantly higher in tumor tissues. Increased expression of ADAMTS-6 correlated with clinical stage (P = 0.009), pT stage (P = 0.042), lymph node metastasis (P = 0.014) and recurrence (P = 0.033). There were no significant correlations between ADAMTS-6 expression and other clinicopathological parameters including age, sex, tumor size, distant metastasis, differentiation, …chemotherapy, radiotherapy, CD68 expression and epithelial mesenchymal transition (EMT) status. Kaplan-Meier survival curves revealed that upregulated expression of ADAMTS-6 indicated short OS (P = 0.001) and DFS (P = 0.002). Multivariate analysis confirmed that high ADAMTS-6 expression was an independent factor for ESCC prognosis. ADAMTS-6 expression was significantly correlated with Twist-1 expression in ESCC cancer cells (P = 0.007) and stromal cells (P < 0.001). Patients with ESCC revealing expression of both ADAMTS-6 and Twist-1 exhibited significantly reduced OS and DFS rates than other patients. CONCLUSIONS: High ADAMTS-6 expression is a useful marker of poor prognosis in patients with ESCC.

Tenascin-C is a potential cancer-associated fibroblasts marker and predicts poor prognosis in prostate cancer.

Tenascin-C (TNC), as a member of the extracellular matrix (ECM), plays an important role in cancer cell proliferation and migration and tumor invasion in various types of cancer. Here, we attempted to investigate the role of TNC as a prognostic factor in prostate cancer. We studied TNC expression via immunohistochemistry in 145 prostate cancer tissue samples. The clinicopathological relevance of TNC expression was examined, as well as other cancer-associated fibroblasts (CAFs)-related factors. Our results showed that the high levels of TNC expression in prostate cancer stroma was significantly associated with lymph node metastasis (P = 0.024) and clinical stage (P = 0.032). Furthermore, TNC was positively correlated with increased micro-vessel density (MVD) (P = 0.017) and tumor associated macrophage (TAM) population (P = 0.025). In both univariate and multivariate Cox regression analyses, TNC (P < 0.001) was an independent poor prognostic factor for overall survival in prostate cancer patients. Moreover, over-expression of TNC (P < 0.001), SMA (P = 0.042) and vimentin (P = 0.010) were significantly correlated with the lower overall survival. In addition, TNC expression in prostate cancer stroma was significantly associated with FSP1 (P = 0.011), SMA (P = 0.021), and vimentin (P = 0.002). In conclusion, our study revealed that high level of TNC as a potential biomarker of CAFs was significantly correlated with the poor prognosis for prostate cancer patients.

Tenascin C is a prognostic determinant and potential cancer-associated fibroblasts marker for breast ductal carcinoma.

Tenascin C (TNC) is a key of extracellular matrix glycoprotein and highly express in numerous human malignancies. Herein, we attempted to clarify the clinicopathological significance of TNC as a prognostic determinant of breast ductal carcinoma. Then, we investigated TNC immunohistochemical expression in 150 breast ductal carcinomas and 27 normal breast tissue samples. Clinical relevance of TNC expression and the association TNC expression with other factors related to cancer-associated fibroblasts were also examined. In results, TNC expression was significantly higher in breast ductal carcinoma (56.0%) than normal breast tissues (25.9%). The upregulation TNC in cancer stromal were associated with pT stage (P=0.003), lymph node metastasis (P=0.002) and tumor node metastasis stage (P=0.001), also was correlated with an increase in tumor-associated macrophage population (P<0.001). The microvessel density (MVD) was significantly higher in TNC positive group than in negative group (P<0.001). In both univariate and multivariate Cox regression analyses, TNC was an independent poor prognostic factor for overall survival (OS) in breast ductal carcinoma patients. Importantly, over-expression TNC (P<0.001), FSP1 (P<0.001), SMA (P=0.002) and Vimentin (P=0.049) were significantly correlation with the lower OS (P<0.005). In addition, TNC expression in breast ductal carcinoma stromal was positively correlated with FSP1 (P<0.001), SMA (P=0.001) and Vimentin (P<0.001). In conclusion, the high expression of TNC could be a useful cancer-associated fibroblasts marker for the prediction of prognosis of breast ductal carcinoma patients.

Gli1 expression in cancer stem-like cells predicts poor prognosis in patients with lung squamous cell carcinoma.

PURPOSE: Glioma-associated oncogene homolog 1 (Gli1) is involved in cancer stem cell (CSC) maintenance in various tumors; however, its expression and clinical significance in lung squamous cell carcinoma (LSCC) has not been reported. In this study, we aimed to reveal the clinical significance of Gli1 in LSCC and investigate the potential of Gli1 as a CSC marker by comparing its expression with that of other stemness-related genes in LSCC. METHODS: We assessed the expressions of Gli1, LSD1, CD44, Sox9 and Sox2 by immunohistochemistry in the tissue specimens obtained from 101 patients with LSCC. The relationship of Gli1 expression with clinicopathological parameters and cell-cycle regulating genes was investigated. RESULTS: Gli1 expression was significantly correlated with T stage (P<0.001), lymph node metastasis (P=0.002), and clinical stage (P=0.005) of LSCC. The Kaplan-Meier survival analysis revealed that the expression of Gli1 in LSCC was all significantly associated with poor overall survival (OS: P=0.005). Cox regression analysis further confirmed that Gli1 is a prognostic marker of unfavorable clinical outcome of LSCC. Gli1 expression was significantly correlated with the expression of stemness-related genes such as LSD1 (P=0.009) and CD44 (P<0.001), but not with those of Sox2 and Sox9. However, Gli1 expression was associated with the expression of hypoxia-inducible factors1α (HIF1α; P<0.001) and Cyclin D1 (P=0.002), respectively. In additionally, microvessel density (MVD) was significantly higher in Gli1-positive LSCC than in the negative LSCC (P=0.026). CONCLUSIONS: Our results suggest that Gli1 may be a potential LSCC stem cell marker and an independent indicator of poor prognosis for patients with LSCC.

Microsurgery or open cervical foraminotomy for cervical radiculopathy? A systematic review.

OBJECTIVE: The purpose of this article was to systematically review the clinical outcomes of microendoscopic foraminotomy compared with the traditional open cervical foraminotomy. METHODS: A literature search of two databases was performed to identify investigations performed in the treatment of cervical foraminotomy with microsurgery or an open approach. Data including blood loss, surgical time, hospital stay, complications, clinical success rate, reduction of arm and neck pain, improvement of neurological function, and repeated surgery rate were summarized, calculated and compared. Results of clinical success were performed by calculattng effect indicators and standard errors based on a single rate to assess heterogeneity in the two groups. RESULTS: The initial literature search resulted in 713 articles, of which, 26 were determined as relevant on abstract review. An open foraminotomy approach was performed in 16 and a microsurgery approach in ten studies. The open group demonstrated minimal to moderate heterogeneity, with I (2) value of 27 %; and microsurgery group demonstrated minimal heterogeneity, with I (2) value of 1 %. Aggregated data found that patients treated by microsurgery foraminotomy have lower blood loss by 100.1 ml (open: 149.5 ml, microsurgery: 49.4 ml, n = 1257), shorter surgical time by 24.9 minutes (open 88.7 minutes, microsurgery 63.8 minutes, n = 1423),and shorter hospital stay by 3.0 days (open 4.1 days, microsurgery 1.1 days, n = 1350), compared with patients treated by open cervical foraminotomy. The pooled clinical success rate was 89.7 % [confidence interval (CI) 87.7-91.6) in the open group versus 92.5 % (CI 89.9-95.1) in the microsurgery group, with no statistical difference (p = 0.095). Overall complication rates were not statistically significant between groups (p = 0.757). The incidence of dural tears was 1.07 %( 12/1121) in patients undergoing microsurgery versus 0.27 % (2/745) for open surgery (p = 0.091). The incidence of infection was 0.54 % (6/1121) in patients undergoing microsurgery versus 0.40 % (3/745) for open surgery (p = 0.949). The incidence of root injury was 0.80 % (9/1121) in patients undergoing microsurgery versus 1.48 % (11/745) for open surgery (p = 0.166). Revision surgery occurred in 2.32 % (27/1163) in the microsurgery group versus 3.35 % (28/835) for traditional surgery, with no statistical difference (p = 0.164). Pooled reduction in visual analogue scale for the arm (VASA) was 75.0 % (CI 66.0-84.0) in the open group and 87.1 % (CI:76.7, 97.5) in the microsurgery group, with no statistical difference (p = 0.065). Pooled reduction in VAS of the neck (VASN) was 66.2 % (CI:52.2, 80.2) in the open group and 68.1 % (CI:36.4, 99.8) in the microsurgery group, with no statistical difference(p = 0.894). Pooled improvement in neurological function was 55.3 % (CI:18.6, 91.9) in the open group and 64.9 % (CI:34.6, 95.2) in the microsurgery group, with no statistical difference (p = 0.576). CONCLUSIONS: Although advantages of cervical microsurgery are less blood loss and shorter surgical time and hospital stay over the standard open technique, there is no significant difference in clinical success rate, complication rate, reduction of arm and neck pain and improvement of neurological function between microsurgery and open cervical foraminotomy.

Early Posttraumatic Antifibrinolysis Reduces Perioperative Hidden Blood Loss in Elderly Patients with an Intertrochanteric Fracture: A Randomized Controlled Trial.

BACKGROUND: This study aimed to determine the efficacy and safety of posttraumatic antifibrinolysis with multidose tranexamic acid (TXA) in reducing perioperative hidden blood loss (HBL) in elderly intertrochanteric fracture patients. METHOD: Ninety-six elderly intertrochanteric fracture patients admitted to our department from June 2021 to September 2022 were randomized into two groups. The control group (Group A) received 100 mL of normal saline, while the experimental group (Group B) received 1.5 g of TXA intravenously q12 h from postadmission Day 1 (PAD1) to the day before surgery, and both groups received 1.5 g of TXA q12 h from postoperative Day 1 (POD1) to POD3. Haemoglobin (Hb), haematocrit (Hct), coagulation parameters, fibrinogen degradation product (FDP), and D-dimer (D-D) were recorded from PAD1 to POD3. HBL was calculated using the gross formula and recorded as the primary outcome. RESULT: In all-over analyses, the patients in Group B had lower perioperative HBL (on PAD3, POD1, and POD3), preoperative HBL (HBLpre), decline of haemoglobin (ΔHb-on PAD3), allogeneic blood transfusion (ABT) rate, FDP (on PAD3), and D-D (on PAD3) compared with Group A. No significant differences were exhibited in postoperative HBL (HBLpost) between the 2 groups. In subgroup analyses, for patients who received intervention within 24 h, the result is consistent with the whole. For patients who received intervention over 72 h of injury, there were no significant differences in perioperative HBL, ΔHb, ABT rate, FDP, and D-D between the 2 groups. There were no significant differences in APTT, PT, the rate of venous thromboembolism, wound complications, or 90-day mortality between the 2 groups. CONCLUSION: For elderly intertrochanteric fracture patients, early posttraumatic antifibrinolysis with multidose TXA is effective in reducing perioperative HBL, which mainly manifests as the reduction of preoperative HBL, especially for patients injured within 24 h. Application of TXA beyond 72 h of injury was ineffective.

Protamine 1 as a secreted colorectal cancer-specific antigen facilitating G1/S phase transition under nutrient stress conditions.

PURPOSE: Cancer testis antigens (CTAs) are optimal tumor diagnostic markers and involved in carcinogenesis. However, colorectal cancer (CRC) related CTAs are less reported with impressive diagnostic capability or relevance with tumor metabolism rewiring. Herein, we demonstrated CRC-related CTA, Protamine 1 (PRM1), as a promising diagnostic marker and involved in regulation of cellular growth under nutrient deficiency. METHODS: Transcriptomics of five paired CRC tissues was used to screen CRC-related CTAs. Capability of PRM1 to distinguish CRC was studied by detection of clinical samples through enzyme linked immunosorbent assay (ELISA). Cellular functions were investigated in CRC cell lines through in vivo and in vitro assays. RESULTS: By RNA-seq and detection in 824 clinical samples from two centers, PRM1 expression were upregulated in CRC tissues and patients` serum. Serum PRM1 showed impressive accuracy to diagnose CRC from healthy controls and benign gastrointestinal disease patients, particularly more sensitive for early-staged CRC. Furthermore, we reported that when cells were cultured in serum-reduced medium, PRM1 secretion was upregulated, and secreted PRM1 promoted CRC growth in culture and in mice. Additionally, G1/S phase transition of CRC cells was facilitated by PRM1 protein supplementation and overexpression via activation of PI3K/AKT/mTOR pathway in serum deficient medium. CONCLUSIONS: In general, our research presented PRM1 as a specific CRC antigen and illustrated the importance of PRM1 in CRC metabolism rewiring. The new vulnerability of CRC cells was also provided with the potential to be targeted in future. Diagnostic value and grow factor-like biofunction of PRM1 A represents the secretion process of PRM1 regulated by nutrient deficiency. B represents activation of PI3K/AKT/mTOR pathway of secreted PRM1.

Comparison of Interobserver Agreement of Four Classification Systems for Lateral Clavicle Fractures between Two Groups of Surgeons: A Multicenter Study.

OBJECTIVE: Distal clavicle fracture classification directly affects the treatment decisions. It is unclear whether the classification systems implemented differ depending on surgeons' backgrounds. This study aimed to compare the interobserver agreement of four classification systems used for lateral clavicle fractures by shoulder specialists and general trauma surgeons. METHODS: Radiographs of 20 lateral clavicle fractures representing a full spectrum of adult fracture patterns were analyzed by eight experienced shoulder specialists and eight general trauma surgeons from 10 different hospitals. All cases were graded according to the Orthopedic Trauma Association (OTA), Neer, Jäger/Breitner, and Gongji classification systems. To measure observer agreement, Fleiss' kappa coefficient (κ) was applied and assessed. RESULTS: When only X-ray films were presented, both groups achieved fair agreement. However, when the 3D-CT scan images were provided, improved interobserver agreement was found in the specialist group when the OTA, Jäger/Breitner, and Gongji classification systems were used. In the generalist groups, improved agreement was found when using the Gongji classification system. In terms of interobserver reliability, the OTA, Neer, and Jäger/Breitner classification systems showed better agreement among shoulder specialists, while a slightly lower level of agreement was found using the Gongji classification system. For the OTA classification system, interobserver agreement had a mean kappa value of 0.418, ranging from 0.446 (specialist group) to 0.402 (generalist group). For the Neer classification system, interobserver agreement had a mean kappa value of 0.368, ranging from 0.402 (specialist group) to 0.390 (generalist group). For the Jäger/Breitner classification system, the inter-observer agreement had a mean kappa value of 0.380, ranging from 0.413 (specialist group) to 0.404 (generalist group). For the Gongji classification system, interobserver agreement had a mean kappa value of 0.455, ranging from 0.480 (specialist group) to 0.485 (generalist group). CONCLUSION: Generally speaking, 3D-CT scans provide a richer experience that can lead to better results in most classification systems of lateral clavicle fractures, highlighting the value of digitization and specialization in diagnosis and treatment. Competitive interobserver agreement was exhibited in the generalist group using the Gongji classification system, suggesting that the Gongji classification is suitable for general trauma surgeons who are not highly experienced in the shoulder field.

Effects of "Taking the Waist as the Axis" Therapy on trunk postural control disorder after stroke: A randomized controlled trial.

Background: Sufficient attention to trunk rehabilitation after stroke is still lacking. Loss of trunk selective activity is considered to be the leading cause of trunk postural control disorder after stroke. "Taking the Waist as the Axis" Therapy (WAT) was developed as a combination of the concept of "Taking the Waist as the Axis" from Tai Chi and the rehabilitation of trunk dysfunction after stroke. The present clinical trial examined and assessed the effects of WAT on stroke patients. Methods: A total of 43 stroke hemiplegic patients with trunk postural control disorder, whose Trunk Impairment Scale (TIS) scoring between 8 and 18, participated in the present study and were allocated randomly to the experimental (n = 23) or control groups (n = 20). The experimental group received WAT plus conventional therapy, and the control group received "Trunk Selective Activity" Therapy (TSAT) plus conventional therapy. Both groups received treatment once daily and 5 times per week for 3 weeks. The Trunk Impairment Scale (TIS), Fugl-Meyer Assessment (FMA), Berg Balance Scale (BBS), change of Intra-abdominal Pressure (IAP), static balance ability assessment, rapid ventilation lung function test and the Modified Barthel Index (MBI) were evaluated before and after intervention for both groups. Results: The experimental group was superior to the control group in TIS [4 (2, 5) vs. 3 (1.25, 4), p = 0.030], change of IAP [-3 (-8, -1.33) vs. -0.02 (-3.08, 6), p = 0.011], FMA-upper extremity [10 (6, 18) vs. 1 (0, 3), p = 0.002], FMA-lower extremity [2 (1, 4) vs. 1 (0, 2), p = 0.009] and FMA [14 (7, 21) vs. 2 (0.25, 3.75), p = 0.001]. Within experimental group, forced vital capacity (FVC) [81.35 (63.30, 94.88) vs. 91.75 (79.40, 97.90), p = 0.02] was significantly improved. Conclusion: WAT was an effective trunk treatment after stroke, which significantly improved the patients' trunk posture control ability, motor function and forced vital capacity. However, the results still need to be interpreted with caution for the intervention only lasted for 3 weeks.

A retrospective study of deltoid ligament repair versus syndesmotic fixation in lateral malleolus fracture combined with both deltoid ligament injury and inferior tibiofibular syndesmotic disruption.

Background: To compare clinical outcomes of deltoid ligament repair versus syndesmotic fixation in lateral malleolus fracture combined with both deltoid ligament injury and inferior tibiofibular syndesmotic disruption. Methods: Patients diagnosed with lateral malleolus fracture combined with both deltoid ligament injury and inferior tibiofibular syndesmotic disruption who received open reduction and internal fixation (ORIF) were retrospectively reviewed. Seventy-eight patients were enrolled into the study, including 40 patients treated with lateral malleolus fracture ORIF and trans-syndesmotic fixation, and 38 patients treated with lateral malleolus fracture ORIF and deltoid ligament repair. Basic information and pre- and postoperative radiological materials were reviewed. Visual analog pain scale (VAS) score, Olerud-Molander score, and the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale were used for evaluating pain control and functional recovery postoperatively at different time points. Results: No complication was reported in both groups. In the trans-syndesmotic fixation group, all patients received syndesmotic screw removal 6-8 weeks postoperatively. The Olerud-Molander score and AOFAS Ankle-Hindfoot Scale in the deltoid ligament repair group were higher than the trans-syndesmotic fixation group 3 months after operation. No statistical difference was found between the two groups in VAS score from 1 to 12 months postoperatively. Conclusions: Lateral malleolus fracture ORIF and deltoid ligament repair is an effective method for lateral malleolus fracture combined with both deltoid ligament injury and inferior tibiofibular syndesmotic disruption. Compared with trans-syndesmotic fixation, deltoid ligament repair holds the advantage of not needing surgical removal of inferior tibiofibular screws postoperatively.

Metformin reprograms tumor microenvironment and boosts chemoimmunotherapy in colorectal cancer.

Tumor stroma plays an important role in the occurrence, development, and metastasis of colorectal cancer (CRC). The dense collagenous stroma forms a physical barrier for antitumor drugs and sustains a highly tumor immunosuppressive microenvironment. To address this issue, a spatiotemporal combination of antitumor stroma and nanoscale functional materials was used as an antitumor strategy for reprogramming the tumor immune microenvironment. In this combination, metformin hydrochloride (MET) was intraperitoneally injected to disrupt the dense tumor stroma for promoting drug delivery and remodeling the tumor immune microenvironment. Subsequently, intravenously injected multifunctional drug-delivery materials (MIL-100/mitoxantrone/hyaluronic acid nanoparticles, MMH NPs) were visualized by double imaging (photoacoustic (PA) and fluorescence imaging) and generated a robust immune response via immunogenic cell death (ICD). More importantly, the combination treatment also acted synergistically with the anti-OX40 agonist antibody (αOX40), which enhanced the treatment of orthotopic CRC. In summary, the combination strategy of MET/MMH NPs/αOX40 provides a novel and effective clinical option for CRC therapy.

Metal-organic framework-mediated multifunctional nanoparticles for combined chemo-photothermal therapy and enhanced immunotherapy against colorectal cancer.

Because of molecular heterogeneity in tumors, clinical outcomes of tumor treatment are not very satisfactory, and novel strategies are therefore needed to address this challenge. Combination therapy could efficiently enhance tumor treatment by stimulating multiple pathways, reducing the systemic toxicity of monotherapy, and regulating the tumor immune microenvironments. Herein, metal-organic framework MIL-100 (Fe) nanoparticles (NPs) were synthesized by a microwave-assisted method, and oxaliplatin (OXA) and indocyanine green (ICG) were then loaded into hyaluronic acid (HA)-modified MIL-100 NPs to obtain multifunctional nanoparticles (OIMH NPs). The OIMH NPs exhibited sensitive photoacoustic imaging (PAI) for imaging-guided therapy and showed a good synergistic effect by combining chemotherapy with photothermal therapy (PTT) to kill tumor cells. Immunogenic cell death (ICD) and activation of T cells induced by the chemo-photothermal therapy could sensitize for immune checkpoint blockade (aPD-L1) response, thus eliciting systemic antitumor immunity. Finally, tumor inhibition was observed, which could be attributed to the combination of chemotherapy, PTT, and aPD-L1. On the basis of the study findings, an innovative imaging-mediated combined therapeutic strategy involving multifunctional NPs was proposed, which might potentially offer a new clinical treatment for colorectal cancer. STATEMENT OF SIGNIFICANCE: The metal-organic framework-mediated chemo-photothermal therapy guided by photoacoustic imaging (PAI) is an accurate and effective approach for tumor inhibition, which can synergistically achieve immunogenic cell death and lead to an increasing infiltration of immune cells in the tumor microenvironment, thereby enhancing the sensitivity for immune checkpoint blockade (aPD-L1) therapy. This type of therapy can not only reduce the systemic toxicity caused by traditional treatment methods, but it can also solve the issue of low response of immune checkpoint blockade in colorectal cancer (CRC). Our study provides experimental evidence for using the combination of immunotherapy and chemo-photothermal therapy against CRC.

Comparing the Effects of Short-Term Liuzijue Exercise and Core Stability Training on Balance Function in Patients Recovering From Stroke: A Pilot Randomized Controlled Trial.

AIMS: Liuzijue Qigong (LQG) exercise is a traditional Chinese exercise method in which breathing and pronunciation are combined with movement guidance. Breathing is closely related to balance, and LQG, as a special breathing exercise, can be applied to balance dysfunction after stroke. The purpose of this study was to observe the clinical effects of short-term LQG exercise on balance function in patients recovering from stroke. METHODS: Stroke patients were randomly divided into an Intervention Group (IG) (n = 80) and a Control Group (CG) (n = 80). The IG received conventional rehabilitation training plus LQG and the CG received conventional rehabilitation training plus Core Stability Training (CST). All patients received treatment once a day, 5 times a week for 2 weeks. The primary outcome was Berg Balance Scale (BBS). Secondary outcome measures were static standing and sitting balance with eyes open and closed, Fugl-Meyer Assessment (FMA), Maximum Phonation Time (MPT), Modified Barthel Index (MBI) and diaphragm thickness and mobility during quiet breath (QB) and deep breath (DB). RESULTS: Compared with the CG, the IG showed significant improvement in the BBS (10.55 ± 3.78 vs. 9.06 ± 4.50, P = 0.039), MPT (5.41 ± 4.70 vs. 5.89 ± 5.24, P = 0.001), MBI (12.88 ± 6.45 vs. 10.00 ± 4.84, P = 0.003), diaphragmatic mobility during QB (0.54 ± 0.73 vs. 0.33 ± 0.40, P = 0.01) and diaphragmatic mobility during DB (0.99 ± 1.32 vs. 0.52 ± 0.77, P = 0.003), Cop trajectory in the standing position with eyes open (-108.34 ± 108.60 vs. -89.00 ± 140.11, P = 0.034) and Cop area in the standing positions with eyes open (-143.79 ± 431.55 vs. -93.29 ± 223.15, P = 0.015), Cop trajectory in the seating position with eyes open (-19.95 ± 23.35 vs. -12.83 ± 26.64, P = 0.001) and Cop area in the seating position with eyes open (-15.83 ± 9.61 vs. -11.29 ± 9.17, P = 0.002). CONCLUSIONS: The short-term LQG combined with conventional rehabilitation training significantly improved the balance functions of stroke patients. It also improved static standing and sitting balance with the eyes open, diaphragm functions, maximum phonation time and the quality of daily life for stroke patients. CLINICAL TRIAL REGISTRATION: http://www.chictr.org.cn/edit.aspx?pid=25313&htm=4, Identifier: ChiCTR1800014864.