Progress in phosphorylation of natural products.

Natural medicines are a valuable resource for the development of new drugs. However, factors such as low solubility and poor bioavailability of certain constituents have hindered their efficacy and potential as pharmaceuticals. Structural modification of natural products has emerged as an important research area for drug development. Phosphorylation groups, as crucial endogenous active groups, have been extensively utilized for structural modification and development of new drugs based on natural molecules. Incorporating phosphate groups into natural molecules not only enhances their stability, bioavailability, and pharmacological properties, but also improves their biological activity by altering their charge, hydrogen bonding, and spatial structure. This review summarizes the phosphorylation mechanism, modification approaches, and biological activity enhancement of natural medicines. Notably, compounds such as polysaccharides, flavonoids, terpenoids, anthraquinones, and coumarins exhibit increased antioxidation, anticancer, antiviral, immune regulatory, Antiaging, enzyme inhibition, bacteriostasis, liver protection, and lipid-lowering effects following phosphorylation modification.

Synthetic lethal combination of CHK1 and WEE1 inhibition for treatment of castration-resistant prostate cancer.

WEE1 and CHEK1 (CHK1) kinases are critical regulators of the G2/M cell cycle checkpoint and DNA damage response pathways. The WEE1 inhibitor AZD1775 and the CHK1 inhibitor SRA737 are in clinical trials for various cancers, but have not been thoroughly examined in prostate cancer, particularly castration-resistant (CRPC) and neuroendocrine prostate cancers (NEPC). Our data demonstrated elevated WEE1 and CHK1 expressions in CRPC and NEPC cell lines and patient samples. AZD1775 resulted in rapid and potent cell killing with comparable IC50s across different prostate cancer cell lines, while SRA737 displayed time-dependent progressive cell killing with 10- to 20-fold differences in IC50s. Notably, their combination synergistically reduced the viability of all CRPC cell lines and tumor spheroids in a concentration- and time-dependent manner. Importantly, in a transgenic mouse model of NEPC, both agents alone or in combination suppressed tumor growth, improved overall survival, and reduced the incidence of distant metastases, with SRA737 exhibiting remarkable single agent anticancer activity. Mechanistically, SRA737 synergized with AZD1775 by blocking AZD1775-induced feedback activation of CHK1 in prostate cancer cells, resulting in increased mitotic entry and accumulation of DNA damage. In summary, this preclinical study shows that CHK1 inhibitor SRA737 alone and its combination with AZD1775 offer potential effective treatments for CRPC and NEPC.

Synthetic lethal combination of CHK1 and WEE1 inhibition for treatment of castration-resistant prostate cancer.

WEE1 and CHEK1 (CHK1) kinases are critical regulators of the G2/M cell cycle checkpoint and DNA damage response pathways. The WEE1 inhibitor AZD1775 and the CHK1 inhibitor SRA737 are in clinical trials for various cancers, but have not been examined in prostate cancer, particularly castration-resistant (CRPC) and neuroendocrine prostate cancers (NEPC). Our data demonstrated elevated WEE1 and CHK1 expressions in CRPC/NEPC cell lines and patient samples. AZD1775 resulted in rapid and potent cell killing with comparable IC50s across different prostate cancer cell lines, while SRA737 displayed time-dependent progressive cell killing with 10- to 20-fold differences in IC50s. Notably, their combination synergistically reduced the viability of all CRPC cell lines and tumor spheroids in a concentration- and time-dependent manner. Importantly, in a transgenic mouse model of NEPC, both agents alone or in combination suppressed tumor growth, improved overall survival, and reduced the incidence of distant metastases, with SRA737 exhibiting remarkable single agent anticancer activity. Mechanistically, SRA737 synergized with AZD1775 by blocking AZD1775-induced feedback activation of CHK1 in prostate cancer cells, resulting in increased mitotic entry and accumulation of DNA damage. In summary, this preclinical study shows that CHK1 inhibitor SRA737 alone and its combination with AZD1775 offer potential effective treatments for CRPC and NEPC.

Comparison of the mid-term clinical efficacy of different fixtaion methods combined with oblique lumbar interbody fusion in treating lumbar degenerative diseases.

BACKGROUND: To compare the mid-term follow-up clinical efficacy among three treatment approaches for lumbar degenerative diseases (LDD): standalone oblique lumbar interbody fusion (SF), oblique lumbar interbody fusion combined with lateral screw fixation (LF), and oblique lumbar interbody fusion combined with posterior screw fixation (PF). METHOD: This retrospective study included a total of 71 cases of single level LDD that underwent OLIF in Hospital of Chengdu University of Traditional Chinese Medicine were retrospectively collected between March 2016 and September 2017. Patients were divided into three groups: 24 cases in the SF group, 24 cases in the LF group and 23 cases in the PF group. Various parameters, such as operation time, hospitalization time, and complications, were recorded. The fusion condition was assessed at last follow up. Clinical outcomes were evaluated using the Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) from pre-operation to 5 years post-surgery. RESULTS: Significantly lower mean operation time and hospitalization time were observed in the SF and LF groups compared to the PF group (p < .05). However, no significant difference in fusion rate was found among the three groups. Regarding clinical outcomes, there was no statistically significant difference in VAS scores between the three groups during all follow-up periods. At the 6th month and 1st year after surgery, the SF and LF groups had significantly lower Oswestry Disability Index (ODI) scores compared to the PF group (p < .05). There was no significant difference in perioperative complication rates among the three groups (p > .05). In the LF group, one case of instrument displacement and urethra injury were reported, while in the SF, LF, and PF groups, 10, 9, and 3 cases of cage subsidence were reported, respectively. CONCLUSION: The study findings suggest that oblique lumbar interbody fusion (OLIF) is a safe and effective treatment for mid-term management of lumbar degenerative diseases (LDD). Compared to the posterior screw fixation (PF) group, both the standalone OLIF (SF) and OLIF combined with lateral screw fixation (LF) groups showed advantages in terms of reduced operation time, shorter hospitalization, and faster symptom alleviation in the short-term. However, OLIF combined with PF demonstrated comparable symptom relief in the mid-term and had the additional benefit of lower cage subsidence rates while improving fusion rates as well.

Liquid-crystal-based fiber laser sensor for non-invasive gas detection.

This Letter reports a new optical fiber gas sensor for measuring breath acetone. The sensor is based on photonic bandgap (PBG) mode laser emission sensing technology using liquid crystal (LC), which is combined with silica fiber and chiral nematic liquid crystal (CNLC), thus providing an ultra-compact, fast-response and simple-to-produce sensing system with a fast response that can accurately and quantitatively determine the concentration of respiratory acetone within the normal oral temperature range (35-38°C). Since LCs are affected by temperature, we propose a method that eliminates the influence of the temperature to solve the problem of the temperature influence when measuring gas. The detection of acetone leads to splitting of the dual laser peaks, with a linear correlation of 0.99. The sensor has a limit of detection of 65 ppm for acetone vapor and thus is suitable for breath acetone detection in diabetic patients.

Protein kinase D2 confers neuroprotection by promoting AKT and CREB activation in ischemic stroke.

Ischemic stroke, constituting 80-90% of all strokes, is a leading cause of death and long-term disability in adults. There is an urgent need to discover new targets and therapies for this devastating condition. Protein kinase D (PKD), as a key target of diacylglycerol involved in ischemic responses, has not been well studied in ischemic stroke, particularly PKD2. In this study, we found that PKD2 expression and activity were significantly upregulated in the ipsilateral side of the brain after transient focal cerebral ischemia, which coincides with the upregulation of PKD2 in primary neurons in response to in vitro ischemia, implying a potential role of PKD2 in neuronal survival in ischemic stroke. Using kinase-dead PKD2 knock-in (PKD2-KI) mice, we examined whether loss of PKD2 activity affected stroke outcomes in mice subjected to 1 h of transient middle cerebral artery occlusion (tMCAO) and 24 h of reperfusion. Our data demonstrated that PKD2-KI mice exhibited larger infarction volumes and worsened neurological scores, indicative of increased brain injury, as compared to the wild-type (WT) mice, confirming a neuroprotective role of PKD2 in ischemia/reperfusion (I/R) injury. Mouse primary neurons obtained from PKD2-KI mice also exhibited increased cell death as compared to the WT neurons when subjected to in vitro ischemia. We have further identified AKT and CREB as two main signaling nodes through which PKD2 regulates neuronal survival during I/R injury. In summary, PKD2 confers neuroprotection in ischemic stroke by promoting AKT and CREB activation and targeted activation of PKD2 may benefit neuronal survival in ischemic stroke.

A systematic review and meta-analysis of risk factors for reoperation after degenerative lumbar spondylolisthesis surgery.

BACKGROUND: Considering the high reoperation rate in degenerative lumbar spondylolisthesis (DLS) patients undergoing lumbar surgeries and controversial results on the risk factors for the reoperation, we performed a systematic review and meta-analysis to explore the reoperation rate and risk factors for the reoperation in DLS patients undergoing lumbar surgeries. METHODS: Literature search was conducted from inception to October 28, 2022 in Pubmed, Embase, Cochrane Library, and Web of Science. Odds ratio (OR) was used as the effect index for the categorical data, and effect size was expressed as 95% confidence interval (CI). Heterogeneity test was performed for each outcome effect size, and subgroup analysis was performed based on study design, patients, surgery types, follow-up time, and quality of studies to explore the source of heterogeneity. Results of all outcomes were examined by sensitivity analysis. Publication bias was assessed using Begg test, and adjusted using trim-and-fill analysis. RESULTS: A total of 39 cohort studies (27 retrospective cohort studies and 12 prospective cohort studies) were finally included in this systematic review and meta-analysis. The overall results showed a 10% (95%CI: 8%-12%) of reoperation rate in DLS patients undergoing lumbar surgeries. In surgery types subgroup, the reoperation rate was 11% (95%CI: 9%-13%) for decompression, 10% (95%CI: 7%-12%) for fusion, and 9% (95%CI: 5%-13%) for decompression and fusion. An increased risk of reoperation was found in patients with obesity (OR = 1.91, 95%CI: 1.04-3.51), diabetes (OR = 2.01, 95%CI: 1.43-2.82), and smoking (OR = 1.51, 95%CI: 1.23-1.84). CONCLUSIONS: We found a 10% of reoperation rate in DLS patients after lumbar surgeries. Obesity, diabetes, and smoking were risk factors for the reoperation.

Functional and Structural Outcomes After Arthroscopic Rotator Cuff Repair With or Without Preoperative Corticosteroid Injections.

BACKGROUND: Corticosteroid injections (CSIs) are effective in alleviating pain in patients with rotator cuff tears, but controversy still exists regarding their potential adverse effects on clinical outcomes after rotator cuff repair. PURPOSE: To compare both the functional and the structural outcomes in patients who underwent arthroscopic rotator cuff repair with or without preoperative CSIs. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A retrospective cohort study was carried out among patients who underwent arthroscopic rotator cuff repair for partial- and full-thickness tears between 2015 and 2019. The patients who received preoperative CSIs were included in the CSI group and compared with a group without preoperative CSIs (non-CSI group), matched at a ratio of 1:2 based on tear size, age, and follow-up time. Both functional evaluation and structural assessments using magnetic resonance imaging (MRI) were performed at the final follow-up. Clinical outcomes-including retear rate as the primary outcome; pain; functional scores including the Constant-Murley score, American Shoulder and Elbow Surgeons score, and Fudan University Shoulder Score; range of motion (ROM); tendon integrity; tendon healing type; and cartilage thickness-were compared between the 2 groups with a statistical significance of P < .05 and power of 0.9. RESULTS: Thirty-one patients were included in the CSI group, and 62 were included in the non-CSI group. After a mean 3-year follow-up, the 2 groups demonstrated no significant differences in retear rate; visual analog scale for pain; shoulder functional scores; and active ROM including forward flexion, abduction, external rotation, and internal rotation. No significant differences were observed on postoperative MRI scans of the rotator cuff tendon (tendon integrity, healing type, residual tendon attachment area, etc), cartilage thickness, and muscle atrophy. CONCLUSION: No significant differences were found at a mean 3-year follow-up in the retear rates, pain, ROM, and glenohumeral structure on postoperative MRI scans after arthroscopic rotator cuff repair with or without preoperative CSIs.

Protein Kinase D2 and D3 Promote Prostate Cancer Cell Bone Metastasis by Positively Regulating Runx2 in a MEK/ERK1/2-Dependent Manner.

Advanced-stage prostate tumors metastasize to the bone, often causing death. The protein kinase D (PKD) family has been implicated in prostate cancer development; however, its role in prostate cancer metastasis remains elusive. This study examined the contribution of PKD, particularly PKD2 and PKD3 (PKD2/3), to the metastatic potential of prostate cancer cells and the effect of PKD inhibition on prostate cancer bone metastasis in vivo. Depletion of PKD2/3 by siRNAs or inhibition by the PKD inhibitor CRT0066101 in AR-positive and AR-negative castration-resistant prostate cancer cells potently inhibited colony formation and cell migration. Depletion or inhibition of PKD2/3 significantly blocked tumor cell invasion and suppressed the expression of genes related to bone metastasis in the highly invasive PC3-ML cells. The reduced invasive activity resulting from PKD2/3 depletion was in part mediated by the transcription factor Runx2, as its silencing decreased PKD2/3-mediated metastatic gene expression through the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase 1/2 signaling axis. Furthermore, inhibition of PKD by CRT0066101 potently decreased the frequency of bone micrometastases in a mouse model of bone metastasis based on intracardiac injection of PC3-ML cells. These results indicate that PKD2/3 plays an important role in the bone metastasis of prostate cancer cells, and its inhibition may be beneficial for the treatment of advanced prostate cancer.

[Comparison of mid-term effectiveness of unilateral biportal endoscopy-transforaminal lumbar interbody fusion with minimally invasive surgery-transforaminal lumbar interbody fusion assisted with three-dimensional microscope in treating lumbar spondylolisthesis].

Objective: To compare the mid-term effectiveness of unilateral biportal endoscopy (UBE)-transforaminal lumbar interbody fusion (TLIF) and minimally invasive surgery-transforaminal lumbar interbody fusion (MIS-TLIF) assisted with three-dimensional microscope in the treatment of single-level lumbar spondylolisthesis. Methods: A total of 41 single level lumbar spondylolisthesis patients who met the selection criteria were retrospectively collected between June 2018 and September 2019. Twenty-three patients were treated with UBE-TLIF (study group) and 18 with MIS-TLIF assisted with three-dimensional microscope (control group). There was no significant difference in gender, age, Meyerding degree of slippage, type of spondylolisthesis, lesion segment, course of disease, and preoperative hemoglobin (Hb) level, visual analogue scale (VAS) score, Oswestry disability index (ODI), lumbar lordosis (LL), and disc height (DH) between the two groups (P>0.05). The operation time, hospitalization time, intraoperative blood loss, Hb level between preoperative and postoperative at 1 day, and complications were compared between the two groups. The recovery of clinical sign and symptom was evaluated by VAS score and ODI before operation, and at 1 month, 3 months, 1 year, and 3 years after operation. The LL and DH were measured by radiography before operation and at last follow-up, and the fusion rate was calculated according to Suk grade at last follow-up. Results: All the operations were successfully completed. There was no significant difference in operation time between the two groups (P>0.05); the hospitalization time, intraoperative blood loss, and Hb difference between pre- and post-operation in the study group were significantly less than those in the control group (P<0.05). Both groups were followed up 36-48 months, with an average of 39.2 months. In the study group, 1 case of dural tear and 2 cases of Cage subsidence occurred, without postoperative infection and epidural hematoma; in the control group, infection occurred in 1 case, dural tear in 2 cases, Cage subsidence in 1 case, and no epidural hematoma occurred; there was no significant difference in the incidence of complications between the two groups (13.04% vs. 22.22%) (χ2=0.601, P=0.438). The VAS score and ODI at each time point after operation in both groups significantly improved when compared with those before operation, and further improved with time (P<0.05). There was no significant difference in VAS scores between the two groups at each time point after operation (P>0.05); the ODI of the study group was significantly lower than that of the control group at 1 and 3 months after operation (P<0.05), and there was no significant difference between the two groups at other time points (P>0.05). The imaging test showed that the intervertebral fusion rates were 95.7% in the study group and 94.4% in the control group at last follow-up, with no significant difference (χ2=0.032, P=0.859). At last follow-up, LL and DH in the two groups significantly improved when compared with those before operation (P<0.05), and the difference between before and after operation showed no significant difference between the two groups (P>0.05). Conclusion: Both UBE-TLIF and MIS-TLIF assisted with three-dimensional microscope have the advantages of clear intraoperative field and high surgical efficiency in treating lumbar spondylolisthesis, and can obtain satisfactory mid-term effectiveness. Compared with MIS-TLIF assisted with three-dimensional microscope, UBE-TLIF has the advantages of less bleeding and faster recovery.

Integrated network pharmacology and serum metabolomics approach deciphers the anti-colon cancer mechanisms of Huangqi Guizhi Wuwu Decoction.

Huangqi Guizhi Wuwu Decoction (HGWD), as a classic Chinese herbal decoction, has been widely used in treating various diseases for hundreds of years. However, systematically elucidating its mechanisms of action remains a great challenge to the field. In this study, taking advantage of the network pharmacology approach, we discovered a potential new use of HGWD for patients with colon cancer (CC). Our in vivo result showed that orally administered HGWD markedly inhibited the growth of CC xenografts in mice. The subsequent enrichment analyses for the core therapeutic targets revealed that HGWD could affect multiple biological processes involving CC growth, such as metabolic reprogramming, apoptosis and immune regulation, through inhibiting multiple cell survival-related signalings, including MAPK and PI3K-AKT pathways. Notably, these in silico analysis results were most experimentally verified by a series of in vitro assays. Furthermore, our results based on serum metabolomics showed that the lipid metabolic pathways, including fatty acid biosynthesis and cholesterol metabolism, play key roles in delivery of the anti-CC effect of HGWD on tumor-bearing mice, and that cytochrome P450 family 2 subfamily E member 1 (CYP2E1) is a potential therapeutic target. Together, our integrated approach reveals a therapeutic effect of HGWD on CC, providing a valuable insight into developing strategies to predict and interpret the mechanisms of action for Chinese herbal decoctions.

Identification of the collagen family as prognostic biomarkers in papillary thyroid carcinoma.

OBJECTIVE: The aim of this study was to construct a collagen-related prognostic model for thyroid cancer and to investigate prognostic value of collagen family genes for thyroid cancer. METHODS: A LASSO Cox regression model for thyroid cancer was developed based on the expression profiles of collagen-related genes. Kaplan-Meier survival analysis was performed for high and low risk groups. The ROC method was used to assess its predictive performance. Predictive independence was verified by multivariate Cox regression analysis. The relationship between this feature and immune cell infiltration was analyzed by tumor microenvironment. COL18A1 was validated by immunohistochemistry and RT-PCR in thyroid cancer tissues. The effect of COL18A1 on cell proliferation, migration and invasion ability of tumor cells were further valuated by CCK-8 assay and transwell assay. The effect of COL18A1 on the immune escape ability of tumor cells was further valuated by cytotoxicity assays. RESULTS: A model including 4 collagen family genes was developed to predict thyroid cancer prognosis. Patients with high-risk score had a poorer prognosis than those with low-risk scores for 1-, 2-, 3-, and 5- year survival. The model independently predicted prognosis after adjusting for other prognostic factors. A nomogram combining risk score and age was constructed with high sensitivity and specificity. This feature was significantly associated with immune cell infiltration. COL18A1 was aberrantly over-expressed in thyroid cancer compared with control tissues and significantly increased proliferative capacity, migration capacity, invasion capacity, and immune escape ability of tumor cells. CONCLUSION: Our findings establish a signature associated with collagen family genes that can be a promising tool to predict the prognosis of thyroid cancer. High COL18A1 expression significantly correlates with the poor prognosis of patients and enhances the immune escape ability of tumor cells.

Bankart Repair With Remplissage Restores Better Shoulder Stability Than Bankart Repair Alone, and Medial or Two Remplissage Anchors Increase Stability but Decrease Range of Motion: A Finite Element Analysis.

PURPOSE: To investigate the effects of the number and location of anchors for remplissage on postoperative glenohumeral biomechanics. METHODS: A biomechanical study was conducted involving finite element model constructed based on data from the intact glenohumeral joint. Seven models were established, including a normal model, a model of Bankart lesion combined with "off-track" Hill-Sachs lesion, a model of Bankart repair alone, and 4 models of Bankart repair with remplissage based on different remplissage anchor numbers and locations. The effects of the number and location of the remplissage anchors on glenohumeral stability were studied through calculation and comparison of (1) the stress and its distribution on the joint capsule, cartilage, labrum and anchors as well as (2) the displacement of the humeral head. RESULTS: Finite element analysis demonstrated that contact stress on the glenohumeral cartilage decreased when medial or 2 anchors were used and was minimized in the combined repair model with 2 medial anchors. The stress on remplissage anchors was greater when the anchors were placed medially. The humeral head displacement was maximized in the combined lesion model. The combined repair models with 2 medially placed anchors showed the largest slope on the force-displacement curve, indicating the largest strain on the humeral head. CONCLUSIONS: Based on a finite element analysis, Bankart repair with remplissage restored better shoulder stability compared with Bankart repair alone in the treatment of anterior shoulder instability involving Bankart lesion combined with "off-track" Hill-Sachs lesion. When the anchor for remplissage was medially placed or 2 anchors were used, the stability of the glenohumeral joint increased but with a loss of range of motion. CLINICAL RELEVANCE: The results of this study will assist in choosing the number and location of anchors for remplissage during shoulder stabilization surgery although with some limitations.

Functional deficiency of succinate dehydrogenase promotes tumorigenesis and development of clear cell renal cell carcinoma through weakening of ferroptosis.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinomas, with high mortality and poor prognoses worldwide. Succinate dehydrogenase (SDH) consists of four nuclear-encoded subunits and it is the only complex involved in both the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS). Previous studies have shown decreased SDH activity in ccRCC. However, the role and underlying molecular mechanisms of SDH in ccRCC initiation and development remain unclear. In the present study, pan-cancer analysis of SDH gene expression was analyzed and the relationship between SDH gene expression and clinicopathological parameters was assessed using different databases. cBioPortal, UACLAN, and Tumor Immune Estimation Resource (TIMER) were subsequently utilized to analyze genetic alterations, methylation, and immune cell infiltration of SDH genes in ccRCC patients. We found SDHs were significantly downregulated in ccRCC tissues and correlated with ccRCC progression. Increased methylation and high SDH promoter mutation rates may be the cause of reduced expression of SDHs in ccRCC. Moreover, the interaction network showed that SDH genes were correlated with ferroptosis-related genes. We further demonstrated that SDH inhibition dampened oxidative phosphorylation, reduced ferroptotic events, and restored ferroptotic cell death, characterized by eliminated mitochondrial ROS levels, decreased cellular ROS and diminished peroxide accumulation. Collectively, this study provides new insights into the regulatory role of SDH in the carcinogenesis and progression of ccRCC, introducing a potential target for advanced antitumor therapy through ferroptosis.

Defects and countermeasures in laboratory diagnosis of rare IgE multiple myeloma.

BACKGROUND: IgE multiple myeloma (MM) is a rare subtype of MM that is easily misdiagnosed. We report a rare case of IgE-MM and investigate the application of the SLiM-CRAB criteria to screen for high-risk smoldering MM (SMM) patients, so as to summarize the causes and methods used to prevent missed diagnosis or misdiagnosis in IgE-MM. METHODS: The serum monoclonal protein (M-protein) classification and IgE quantification was performed and sent to several individual institutions. The results were collected and the causes of IgE detection defects were analyzed. RESULTS: Upon admission to our hospital, the patient's serum free kappa light chain was 1069.9 mg/L, free lambda light chain was 9.2 mg/L, and free kappa/lambda ratio was 115.9, which met the SLiM criteria, but without CRAB features. Immunofixation electrophoresis (IF) showed "M-like protein aggregation bands" in all lanes. After pretreatment with 1% ß-mercaptoethanol to depolymerize the aggregation of monoclonal protein, the "M-like protein aggregation bands disappeared. The other five institutions did not provide the correct typing results. The quantification of serum IgE was as high as 2.06 × 107 IU/mL, whereas 7 other testing institutions reported IgE levels ranging from 1.0 to 1100 IU/mL. CONCLUSION: High-risk biomarkers in SLiM criteria can achieve good therapeutic effects in rare IgE-MM patients. Serum immunofixation performed without antisera against IgE, insufficient identification of the lytic bands produced by high macromolecule aggregation in IF, and the absence of a prozone effect avoidance procedure during IgE quantitative detection are the primary causes of missed diagnosis or misdiagnosis in patients with IgE-MM.

Temperature-compensated optical fiber sensor for volatile organic compound gas detection based on cholesteric liquid crystal.

External temperature variations inevitably affect the accuracy of a liquid crystal sensor. Therefore, we propose a novel temperature-compensated fiber volatile organic compound (VOC, using acetone as a model compound) gas sensor. The proposed sensor consists of a short segment of hollow-core fiber (HCF), which is spliced on a multimode fiber. Cholesteric liquid crystal (CLC) is sealed into HCF to sense the temperature, and another type of CLC is coated on the end face of HCF for VOC gas detection. The VOC gas concentration and ambient temperature can be simultaneously measured by monitoring the wavelength shifts of two Bragg reflection peaks caused by two types of CLCs. The effects of the CLC thickness on the sensitivities of temperature and acetone concentration are investigated, and optimal parameters are chosen. An optimal sensor can reach a temperature sensitivity of 2.53 nm/°C and acetone concentration sensitivity of 48.46 nm·L/mmol at 8-44°C. In addition, temperature compensation capability, repeatability, response time, and stability are also researched. The experimental results prove this sensor has great application potential in high-precision real-time VOC gas monitoring and detection.

Relationship Between Age at Initial Shoulder Instability and Overall Outcomes After Arthroscopic Bankart Repair: Mean 6-Year Follow-up.

BACKGROUND: Age at surgery plays a crucial role in the frequency of recurrent shoulder instability. However, there are few studies that evaluate the relationship between age at initial shoulder instability and overall outcomes after stabilization surgery. PURPOSE: To compare clinical outcomes and structural changes after arthroscopic Bankart repair in patients who experienced initial shoulder instability during adolescence versus those with later onset instability. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study included patients who underwent arthroscopic Bankart repair at a single institution between 2007 and 2017. Comparisons were made between patients who experienced initial shoulder instability during adolescence (age 13-19 years; group A) and those with later onset instability (age 20-35 years; group B). Clinical outcomes (recurrence rate, postoperative pain, functional scores, active range of motion, and return to sports) and structural changes demonstrated by magnetic resonance imaging (MRI) were evaluated at minimum 2-year follow-up. In addition, functional outcomes within each group were compared between the patients with and without postoperative recurrence. RESULTS: A total of 58 patients were included (24 patients in group A and 34 patients in group B). The mean follow-up was 72.1 months. Group A demonstrated a significantly higher recurrence rate than group B (41.7% vs 11.8%, respectively; P = .009; risk ratio, 5.36 [95% CI, 1.43-20.09]) as well as significantly lower Rowe (76.9 ± 20.1 vs 88.7 ± 13.2, respectively; P = .01) and Constant-Murley scores (92.2 ± 7.6 vs 96.3 ± 4.2, respectively; P = .01). Postoperative MRI revealed no significant structural differences between the groups regarding the glenoid labrum, glenohumeral cartilage, or osseous reaction around the implanted anchors. In group A, patients with recurrence had less satisfaction regarding postoperative sports level than those without recurrence, whereas in group B, patients with recurrence had more postoperative pain and functional impairment compared with those without recurrence. CONCLUSION: Initial shoulder instability during adolescence was associated with a higher recurrence rate and lower functional scores after arthroscopic Bankart repair compared with later onset instability, although no significant structural differences were found between the groups on MRI at a mean 6-year follow-up.

Neutrophil infiltration and whole-cell vaccine elicited by N-dihydrogalactochitosan combined with NIR phototherapy to enhance antitumor immune response and T cell immune memory.

Melanoma is one of the deadliest malignancies with a high risk of relapse and metastasis. Long-term, tumor-specific, and systemic immunity induced by local intervention is ideal for personalized cancer therapy. Laser immunotherapy (LIT), a combination of local irradiation of laser and local administration of an immunostimulant, was developed to achieve such an immunity. Although LIT showed promising efficacy on tumors, its immunological mechanism is still not understood, especially its spatio-temporal dynamics. Methods: In this study, we investigated LIT-induced immunological responses using a 980-nm laser and a novel immunostimulant, N-dihydrogalactochitosan (GC). Then we followed the functions of key immune cells spatially and temporally using intravital imaging and immunological assays. Results: Immediately after LIT, GC induced a rapid infiltration of neutrophils which ingested most GC in tumors. The cytokines released to the serum peaked at 12 h after LIT. Laser irradiations produced photothermal effects to ablate the tumor, release damage-associated molecular patterns, and generate whole-cell tumor vaccines. LIT-treated tumor-bearing mice efficiently resisted the rechallenged tumor and prevented lung metastasis. Intravital imaging of tumor at rechallenging sites in LIT-treated mice revealed that the infiltration of tumor-infiltrating lymphocytes (TILs) increased with highly active motility. Half of TILs with arrest and confined movements indicated that they had long-time interactions with tumor cells. Furthermore, LIT has synergistic effect with checkpoint blockade to improve antitumor efficacy. Conclusion: Our research revealed the important role of LIT-induced neutrophil infiltration on the in situ whole-cell vaccine-elicited antitumor immune response and long-term T cell immune memory.

Retears and Concomitant Functional Impairments After Rotator Cuff Repair: Shoulder Activity as a Risk Factor.

BACKGROUND: Most patients return successfully to shoulder involving sports or activity after rotator cuff repairs. It has not been decided yet whether postoperative participation in shoulder activity adds to the risk of retear. PURPOSE/HYPOTHESIS: The purpose was to verify whether patients who participate in shoulder activities after rotator cuff repair have a higher risk of structural failure than nonactive patients and to investigate the relationship between postoperative shoulder function and tendon integrity in active and nonactive patients. The hypotheses were that (1) active patients have a higher retear rate than nonactive patients and (2) structural failure is associated with worse functional outcomes in active patients. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A cohort study was performed using 145 patients who underwent arthroscopic rotator cuff repair from 2015 to 2017. Functional assessments and magnetic resonance imaging were performed at least 24 months postoperatively. Shoulder activities since 6 months after surgery were rated in 4 categories (sports, job, activities of daily life, and weight of general lifting) as sedentary, light, moderate, or strenuous. The activity level of each patient was defined by the highest rated category. Patients who were involved in light, moderate, and strenuous activity were identified as active for the present study, and the rest were defined as sedentary. The proportion of retears between groups and the functional conditions between retorn and intact tendons were compared. RESULTS: A total of 48 patients were enrolled in the active group, and 97 were enrolled in the sedentary group. The active group demonstrated a significantly higher retear rate than the sedentary group (27.1% vs 11.3%, respectively; P = .016; risk ratio, 2.39 [95% CI, 1.16-4.93]). In the active group, patients with retears showed higher visual analog scale scores for pain, decreased abduction strength, and lower shoulder functional scores (American Shoulder and Elbow Surgeons score, Fudan University Shoulder Score, and Constant-Murley score) than those with healed tendons, whereas in the sedentary group, functional outcomes were generally similar across patients with and without retears. CONCLUSION: Shoulder activity after the early postoperative period was associated with a high risk of retears in patients who underwent rotator cuff repair. A correlation between inhibited function and structural failure was detected but only in active patients, while sedentary patients with retears retained functional improvements similar to those with intact tendons.

Effect of electroacupuncture at the ST36 and GB39 acupoints on apoptosis by regulating the p53 signaling pathway in adjuvant arthritis rats.

p53 and mouse double minute 2 homolog (MDM2) serve key regulatory roles in the apoptosis of synovial cells. The present study aimed to investigate the effects of electroacupuncture (EA) at the 'Zusanli' (ST36) and 'Xuanzhong' (GB39) acupoints on apoptosis in an adjuvant arthritis (AA) rat model. A total of 40 male Sprague­Dawley rats were randomly divided into Control, AA, AA + EA and AA + sham EA groups (n=10 rats in each group). Rats in all the groups, with the exception of the control group, were injected with Complete™ Freund's adjuvant into the bilateral hindlimb footpad to establish the AA model. Rats in the AA + EA group were treated with EA at the ST36 and GB39 acupoints. Rats in the AA + sham EA group were treated with percutaneous electrical stimulation at a position of 5 mm away from the ST36 and GB39 acupoints. The arthritis index scores and hindlimb paw volumes of the rats in each group were recorded. Subsequently, pathological changes in the synovial tissue were evaluated by hematoxylin and eosin (H&E) staining, and the apoptotic rate of the synovial cells was detected by TUNEL staining. In addition, the expression levels of the apoptosis­associated proteins, Bax, phorbol­12­myristate­13­acetate­induced protein 1 (Noxa) and p53 upregulated modulator of apoptosis (PUMA), were determined by western blot analysis. The expression of both the gene and protein of p53 and MDM2 in synovial tissue was detected by reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and western blot analysis, respectively. The results indicated that the arthritis index scores and hindlimb paw volumes upon EA stimulation were significantly decreased compared with those of the AA group (P<0.05). H&E staining revealed that the synovial inflammation of EA stimulation was significantly decreased compared with the AA group (P<0.05). The TUNEL assay results indicated that the apoptotic rate of synovial cells in the AA + EA group was significantly increased compared with that in the AA group (P<0.05). Furthermore, an increased expression of proapoptotic proteins was confirmed by the increased expression levels of Bax, Noxa and PUMA in the AA + EA group. The results of RT­qPCR and western blot analysis demonstrated that, compared with the AA group, EA stimulation led to a marked increase in p53 (P<0.05) and a significant decrease in MDM2 (P<0.05) gene and protein expression. Taken together, these results demonstrated that EA performed on the ST36 and GB39 acupoints led to a significant amelioration in AA injury of model rats, by regulating the p53 signaling pathway and inducing apoptosis.