Follistatin drives neuropathic pain in mice through IGF1R signaling in nociceptive neurons.

Neuropathic pain is a debilitating chronic condition that lacks effective treatment. The role of cytokine- and chemokine-mediated neuroinflammation in its pathogenesis has been well documented. Follistatin (FST) is a secreted protein known to antagonize the biological activity of cytokines in the transforming growth factor-ß (TGF-ß) superfamily. The involvement of FST in neuropathic pain and the underlying mechanism remain largely unknown. Here, we report that FST was up-regulated in A-fiber sensory neurons after spinal nerve ligation (SNL) in mice. Inhibition or deletion of FST alleviated neuropathic pain and reduced the nociceptive neuron hyperexcitability induced by SNL. Conversely, intrathecal or intraplantar injection of recombinant FST, or overexpression of FST in the dorsal root ganglion (DRG) neurons, induced pain hypersensitivity. Furthermore, exogenous FST increased neuronal excitability in nociceptive neurons. The biolayer interferometry (BLI) assay and coimmunoprecipitation (co-IP) demonstrated direct binding of FST to the insulin-like growth factor-1 receptor (IGF1R), and IGF1R inhibition reduced FST-induced activation of extracellular signal-regulated kinase (ERK) and protein kinase B (AKT), as well as neuronal hyperexcitability. Further co-IP analysis revealed that the N-terminal domain of FST exhibits the highest affinity for IGF1R, and blocking this interaction with a peptide derived from FST attenuated Nav1.7-mediated neuronal hyperexcitability and neuropathic pain after SNL. In addition, FST enhanced neuronal excitability in human DRG neurons through IGF1R. Collectively, our findings suggest that FST, released from A-fiber neurons, enhances Nav1.7-mediated hyperexcitability of nociceptive neurons by binding to IGF1R, making it a potential target for neuropathic pain treatment.

Is the transection of the hernia sac during laparoscopic inguinal hernioplasty safe and feasible? An updated systematic review and meta-analysis.

There is a debate over whether to transect or completely reduce the hernia sac during laparoscopic tension-free repair of inguinal hernia. This study endeavors to systematically assess the efficacy and safety of two approaches, namely transected sac (TS) and completely reduced sac (RS), in laparoscopic tension-free repair of inguinal hernia. Utilizing a meta-analysis methodology, we aim to provide a comprehensive analysis of these techniques. A comprehensive search was conducted across PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases to identify comparative studies focusing on laparoscopic tension-free repair of inguinal hernia, specifically comparing TS and RS techniques. The selected studies were subjected to meta-analysis using RevMan 5.3 software. A total of 8 studies, involving 2995 patients with inguinal hernia, were included in the analysis. The meta-analysis results revealed that the TS group had a higher incidence of seroma compared to the RS group [OR = 1.74, 95% CI (1.35, 2.25), P < 0.0001], and a prolonged time to return to normal activity postoperatively [MD = 0.99, 95% CI (0.85, 1.14), P < 0.00001]. However, no statistically significant differences were observed between the two groups in terms of operation time [MD = -1.75, 95% CI (- 8.72, 5.22), P = 0.62], incidence of postoperative pain [OR = 1.00, 95% CI (0.41, 2.44), P = 1.00], overall postoperative complication rate [OR = 0.98, 95% CI (0.43, 2.20), P = 0.95], and recurrence rate fOR = 2.53, 95% CI (0.61, 10.39), P = 0.20]. Transected sac in laparoscopic inguinal hernia repair is associated with an increased incidence of seroma and a longer recovery time for patients to return to normal activity. Clinical trial registration Registration number is INPLASY20223110070.

Efficacy of color Doppler ultrasound and contrast-enhanced ultrasound in identifying vascular invasion in pancreatic ductal adenocarcinoma.

OBJECTIVES: To compare color Doppler ultrasound and contrast-enhanced ultrasound (CEUS) in evaluating vascular invasion in pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: This retrospective study included 210 patients with PDAC who were evaluated by color Doppler ultrasound, CEUS, and contrast-enhanced computed tomography (CECT) at our institution between January 2017 and December 2020. Pathologic results were used as the gold standard in patients who underwent surgical and intraoperative exploration. For nonsurgical patients, CECT results were used as the reference standard. The vessels evaluated included those in the peripancreatic arterial system and venous system. The diagnostic performances of color Doppler ultrasound and CEUS for vascular invasion were compared. RESULTS: In 51 patients who underwent surgery and intraoperative exploration, color Doppler ultrasound and CEUS differed only in assessing venous system invasion in patients with PDAC of the pancreatic body and tail, with the former being superior to the latter. In 159 nonsurgical patients, there was no difference between CEUS and color Doppler ultrasound in assessing superior mesenteric arteriovenous invasion. CEUS was superior to color Doppler ultrasound in evaluating the celiac artery and its branches, with an accuracy of up to 97.8% for some vessels. Color Doppler ultrasound was ideal for evaluating the splenic and portal veins. CONCLUSION: CEUS is more suitable for the evaluation of peripancreatic arteries than color Doppler. CEUS combined with color Doppler ultrasound can be used as a potential supplement to CECT and is also expected to be used to evaluate vascular invasion of PDAC after chemotherapy. CRITICAL RELEVANCE STATEMENT: Contrast-enhanced US and color Doppler in the assessment of vascular invasion in pancreatic ductal adenocarcinoma have their respective advantages, through standardized ultrasound processes are expected to improve the efficiency of inspection. KEY POINTS: Contrast-enhanced US has unique advantages in assessing pancreatic ductal adenocarcinoma invasion of the celiac artery. Doppler imaging is of high value in assessing venous system invasion. Standardization of ultrasound imaging procedures for pancreatic ductal adenocarcinoma is expected to improve efficiency.

Epidemiological investigation and diagnostic analysis of osteonecrosis of the femoral head in three northeastern provinces of China.

BACKGROUND: In this retrospective case investigation, we analysed the data of patients with osteonecrosis of the femoral head (ONFH) to reveal demographic and clinical diagnostic features of ONFH in three northeastern provinces of China and provide a reference for its prevention, diagnosis, and treatment. METHODS: We collected data from patients in Beijing Orthopaedic Hospital of Liaoning, focusing on the aetiology and diagnosis of ONFH. Medical records and self-designed questionnaires were used to collect information for statistical analysis, including age, aetiology, reason for glucocorticoid use, hospital level at first visit, and diagnosis. RESULTS: In total, 906 patients with complete medical records were included in the analysis. The mean patient age was 47.65 ± 12.12 years. The peak age distribution was in the 40s for men and the 50s for women. Among the total cohort, 72 patients (7.95%; 40 men and 32 women) had traumatic ONFH, 198 (21.85%; 131 men and 67 women) had steroid-induced ONFH, 230 (25.39%; 121 men and 109 women) had idiopathic ONFH, and 406 (44.81%; 397 men and 9 women) had alcohol-induced ONFH. Six hundred and twenty patients were diagnosed with ONFH at the first visit, while 286 patients were misdiagnosed, with a diagnosis rate of 68.43%. The diagnosis rate at the first visit in tertiary hospitals was 76.14%. The diagnosis rate at the first visit in second-class hospitals was 52.07%.ONFH was most likely to be misdiagnosed as lumbar disc herniation. CONCLUSIONS: Most patients with ONFH in three northeastern provinces of China were middle-aged, male, and had alcohol-induced ONFH. The misdiagnosis rate of ONFH at the first visit was very high, especially for misdiagnosis of lumbar disc herniation, indicating that the diagnosis of ONFH requires further improvement.

Dehydrozaluzanin C- derivative protects septic mice by alleviating over-activated inflammatory response and promoting the phagocytosis of macrophages.

Host-directed therapy (HDT) is a new adjuvant strategy that interfere with host cell factors that are required by a pathogen for replication or persistence. In this study, we assessed the effect of dehydrozaluzanin C-derivative (DHZD), a modified compound from dehydrozaluzanin C (DHZC), as a potential HDT agent for severe infection. LPS-induced septic mouse model and Carbapenem resistant Klebsiella pneumoniae (CRKP) infection mouse model was used for testing in vivo. RAW264.7 cells, mouse primary macrophages, and DCs were used for in vitro experiments. Dexamethasone (DXM) was used as a positive control agent. DHZD ameliorated tissue damage (lung, kidney, and liver) and excessive inflammatory response induced by LPS or CRKP infection in mice. Also, DHZD improved the hypothermic symptoms of acute peritonitis induced by CRKP, inhibited heat-killed CRKP (HK-CRKP)-induced inflammatory response in macrophages, and upregulated the proportions of phagocytic cell types in lungs. In vitro data suggested that DHZD decreases LPS-stimulated expression of IL-6, TNF-α and MCP-1 via PI3K/Akt/p70S6K signaling pathway in macrophages. Interestingly, the combined treatment group of DXM and DHZD had a higher survival rate and lower level of IL-6 than those of the DXM-treated group; the combination of DHZD and DXM played a synergistic role in decreasing IL-6 secretion in sera. Moreover, the phagocytic receptor CD36 was increased by DHZD in macrophages, which was accompanied by increased bacterial phagocytosis in a clathrin- and actin-dependent manner. This data suggests that DHZD may be a potential drug candidate for treating bacterial infections.

Meta-analysis of the effectiveness and safety of robotic-assisted versus laparoscopic transabdominal preperitoneal repair for inguinal hernia.

BACKGROUND: Inguinal hernia is a common global disease. This study aims to investigate the effectiveness and safety of robot-assisted transabdominal preperitoneal repair (RTAPP) and laparoscopic transabdominal preperitoneal repair (LTAPP) for inguinal hernia. METHODS: We conducted a thorough search in Cochrane Library, Embase, and PubMed for relevant clinical studies. After applying inclusion and exclusion criteria, the quality of selected studies was assessed using the Jadad scale for randomized controlled studies and the Newcastle-Ottawa scale for observational studies. Meta-analysis was performed using RevMan 5.3 software. RESULTS: A total of ten studies were included, comprising two randomized controlled studies and eight non-randomized controlled studies. Meta-analysis results revealed no statistically significant differences between the RTAPP group and the LTAPP group regarding hospital stay [MD = 0.21 days, 95% CI (-0.09, 0.51), P = 0.17], incidence of seroma [OR = 0.85, 95% CI(0.45, 1.59), P = 0.61], overall complication rate [OR = 1.22, 95% CI(0.68, 2.18), P = 0.51], readmission rate [OR = 1.31, 95% CI(0.23, 7.47), P = 0.76], and recurrence rate [OR = 0.82, 95% CI(0.22, 3.07), P = 0.77]. However, the RTAPP group had longer operation time compared to the LTAPP group [MD = 14.02 minutes, 95% CI (6.65, 21.39), P = 0.0002], and the cost of the RTAPP procedure was higher than that of the LTAPP procedure [MD = $4.17 thousand, 95% CI (2.59, 5.76), P<0.00001]. CONCLUSION: RTAPP for inguinal hernia is a safe and feasible approach, however, it is associated with increased operation time and treatment costs.

Chemoprotective effect of baicalin against cyclophosphamide induced ovarian toxicity in mice via inhibition of TGF-ß.

Ovarian toxicity is most common gynecologically related malignancy, arising for most cases owing to the advanced stage of diagnosis. The aim of the current study was to explore the anticancer potential of baicalin against cyclophosphamide (CP) induced ovarian toxicity in mice and explore the possible mechanism. ovarian cancer cells (Hey, SKOv3ip and HO891PM) were treated with different doses of baicalin and examined via flow cytometry and cell proliferation assay. Subcutaneous administration of CP (200 mg/kg) was used to induce the ovary toxicity and mice were received the oral administration of baicalin. Oxidative, pro-inflammatory, inflammatory, apoptosis parameters, progesterone, estrogen hormones and histopathological were also estimated at end of the study. Baicalin increased the apoptosis and caused the cell cycle arrest at the G2/M stage in ovarian cancer cells. Baicalin significantly (P < 0.001) reduced the level of TGF-ß in the HO8910PM, SKOv3ip and Hey cell lines. Baicalin significantly (P < 0.001) increased the body weight and reduced the tumor volume in mice. Baicalin significantly (P < 0.001) increased the level of estrogen and progesterone. Baicalin significantly (P < 0.001) reduced the level of malonaldehyde (MDA) and increased the level of superoxide dismutase (SOD) and catalase (CAT). Baicalin significantly (P < 0.001) decreased the level of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and inflammatory parameter such as nuclear kappa B factor (NF-κB), respectively. Baicalin significantly (P < 0.001) reduced the level of the caspase-3. Baicalin, act as the potential agent against the ovarian toxicity by alteration of TGF-ß and inflammatory pathways.

Appropriateness and Comprehensiveness of Using ChatGPT for Perioperative Patient Education in Thoracic Surgery in Different Language Contexts: Survey Study.

BACKGROUND: ChatGPT, a dialogue-based artificial intelligence language model, has shown promise in assisting clinical workflows and patient-clinician communication. However, there is a lack of feasibility assessments regarding its use for perioperative patient education in thoracic surgery. OBJECTIVE: This study aimed to assess the appropriateness and comprehensiveness of using ChatGPT for perioperative patient education in thoracic surgery in both English and Chinese contexts. METHODS: This pilot study was conducted in February 2023. A total of 37 questions focused on perioperative patient education in thoracic surgery were created based on guidelines and clinical experience. Two sets of inquiries were made to ChatGPT for each question, one in English and the other in Chinese. The responses generated by ChatGPT were evaluated separately by experienced thoracic surgical clinicians for appropriateness and comprehensiveness based on a hypothetical draft response to a patient's question on the electronic information platform. For a response to be qualified, it required at least 80% of reviewers to deem it appropriate and 50% to deem it comprehensive. Statistical analyses were performed using the unpaired chi-square test or Fisher exact test, with a significance level set at P<.05. RESULTS: The set of 37 commonly asked questions covered topics such as disease information, diagnostic procedures, perioperative complications, treatment measures, disease prevention, and perioperative care considerations. In both the English and Chinese contexts, 34 (92%) out of 37 responses were qualified in terms of both appropriateness and comprehensiveness. The remaining 3 (8%) responses were unqualified in these 2 contexts. The unqualified responses primarily involved the diagnosis of disease symptoms and surgical-related complications symptoms. The reasons for determining the responses as unqualified were similar in both contexts. There was no statistically significant difference (34/37, 92% vs 34/37, 92%; P=.99) in the qualification rate between the 2 language sets. CONCLUSIONS: This pilot study demonstrates the potential feasibility of using ChatGPT for perioperative patient education in thoracic surgery in both English and Chinese contexts. ChatGPT is expected to enhance patient satisfaction, reduce anxiety, and improve compliance during the perioperative period. In the future, there will be remarkable potential application for using artificial intelligence, in conjunction with human review, for patient education and health consultation after patients have provided their informed consent.

Cytokine Storm in Acute Viral Respiratory Injury: Role of Qing-Fei-Pai-Du Decoction in Inhibiting the Infiltration of Neutrophils and Macrophages through TAK1/IKK/NF-[Formula: see text]B Pathway.

COVID-19 has posed unprecedented challenges to global public health since its outbreak. The Qing-Fei-Pai-Du decoction (QFPDD), a Chinese herbal formula, is widely used in China to treat COVID-19. It exerts an impressive therapeutic effect by inhibiting the progression from mild to critical disease in the clinic. However, the underlying mechanisms remain obscure. Both SARS-CoV-2 and influenza viruses elicit similar pathological processes. Their severe manifestations, such as acute respiratory distress syndrome (ARDS), multiple organ failure (MOF), and viral sepsis, are correlated with the cytokine storm. During flu infection, QFPDD reduced the lung indexes and downregulated the expressions of MCP-1, TNF-[Formula: see text], IL-6, and IL-1[Formula: see text] in broncho-alveolar lavage fluid (BALF), lungs, or serum samples. The infiltration of neutrophils and inflammatory monocytes in lungs was decreased dramatically, and lung injury was ameliorated in QFPDD-treated flu mice. In addition, QFPDD also inhibited the polarization of M1 macrophages and downregulated the expressions of IL-6, TNF-[Formula: see text], MIP-2, MCP-1, and IP-10, while also upregulating the IL-10 expression. The phosphorylated TAK1, IKK[Formula: see text]/[Formula: see text], and I[Formula: see text]B[Formula: see text] and the subsequent translocation of phosphorylated p65 into the nuclei were decreased by QFPDD. These findings indicated that QFPDD reduces the intensity of the cytokine storm by inhibiting the NF-[Formula: see text]B signaling pathway during severe viral infections, thereby providing theoretical and experimental support for its clinical application in respiratory viral infections.

Reliability and repeatability of 2021 ARCO classification and its guiding significance in treatment of nontraumatic osteonecrosis of the femoral head.

BACKGROUND: The study was designed to evaluate the interobserver reliability and intraobserver repeatability of the 2021 Association Research Circulation Osseous (ARCO) classification and explore its guiding significance in the treatment of nontraumatic osteonecrosis of the femoral head (ONFH). METHODS: In this retrospective study, we randomly selected and investigated 50 sets of preoperative computed tomography or magnetic resonance imaging scans from 96 patients (139 hips) to validate the reliability and repeatability of the 2021 ARCO classification. Patients with a nano-hydroxyapatite/polyamide-66 support rod were included in the clinical efficacy study. The Harris hip score (HHS) was used to assess hip function. Femoral head collapse of > 2 mm was considered radiological failure. Total hip arthroplasty (THA) was performed for clinical failure, and follow-up was discontinued. RESULTS: The average kappa value of interobserver consistency was 0.652. The average rate of consistency was 90.25%, and the average kappa value of intraobserver consistency was 0.836. Eighty-two patients (122 hips) were enrolled and followed up for a mean of 43.57 ± 9.64 months. There was no significant difference in the HHS among the three groups before surgery, but the difference was statistically significant at the last follow-up. Among them, types 1 and 2 had significantly higher scores at the last follow-up than preoperatively (P < 0.05), whereas type 3 had a lower score at the last follow-up than preoperatively, although the difference was not statistically significant (P > 0.05).According to the imaging evaluation, the failure rate of type 1, 2, and 3 at the last follow-up was 0%, 19%, and 87%, respectively. Univariate analysis showed that the femoral head survival rate of radiography was significantly affected by the new classification system (P = 0.00). At the last follow-up, the incidence rate of THA in type 1, 2, and 3 was 5%, 7%, and 31%, respectively. Univariate analysis showed that the femoral head survival rate was significantly affected by the new classification system (P = 0.001). CONCLUSIONS: The 2021 ARCO classification for early-stage ONFH shows substantial consistency and repeatability. We do not recommend femoral head-preserving surgery for patients with type 3 ONFH.

Pancreatic ductal adenocarcinoma with synchronous and metachronous hepatic metastasis predicted by contrast-enhanced ultrasound.

Background: Contrast-enhanced ultrasound (CEUS) has proven valuable in diagnosing benign and malignant pancreatic diseases, but its value in evaluating hepatic metastasis remains to be further explored. This study investigated the relationship between CEUS features of pancreatic ductal adenocarcinoma (PDAC) and concomitant or recurrent liver metastases after treatment. Methods: This retrospective study included 133 participants with PDAC who were diagnosed with pancreatic lesions with CEUS at Peking Union Medical College Hospital from January 2017 to November 2020. According to the CEUS classification methods in our center, all the pancreatic lesions were classified as either with rich or poor blood supply. Additionally, quantitative ultrasonographic parameters were measured in the center and periphery of all pancreatic lesions. CEUS modes and parameters of the different hepatic metastasis groups were compared. The diagnostic performance of CEUS was calculated for diagnosing synchronous and metachronous hepatic metastasis. Results: The proportions of rich blood supply and poor blood supply were 46% (32/69) and 54% (37/69), respectively, in the no hepatic metastasis group; 42% (14/33) and 58% (19/33), respectively, in the metachronous hepatic metastasis (MHM) group; and 19% (6/31) and 81% (25/31), respectively, in the synchronous hepatic metastasis (SHM) group. The wash-in slope ratio (WIS ratio) between the center of the lesion and around the lesion and peak intensity ratio (PI ratio) between the center of the lesion and around the lesion had higher values in the negative hepatic metastasis group (P<0.05). In predicting synchronous and metachronous hepatic metastasis, the WIS ratio had the best diagnostic performance. The sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) were 81.8%, 95.7%, 91.2%, 90.0%, and 91.7%, respectively, for MHM; and 87.1%, 95.7%, 93.0%, 90.0%, and 94.3%, respectively, for SHM. Conclusions: CEUS would be helpful in image surveillance for synchronous or metachronous hepatic metastasis of PDAC.

Abnormal glycosylation in glioma: related changes in biology, biomarkers and targeted therapy.

Glioma is a rapidly growing and aggressive primary malignant tumor of the central nervous system that can diffusely invade the brain tissue around, and the prognosis of patients is not significantly improved by traditional treatments. One of the most general posttranslational modifications of proteins is glycosylation, and the abnormal distribution of this modification in gliomas may shed light on how it affects biological behaviors of glioma cells, including proliferation, migration, and invasion, which may be produced by regulating protein function, cell-matrix and cell‒cell interactions, and affecting receptor downstream pathways. In this paper, from the perspective of regulating protein glycosylation changes and abnormal expression of glycosylation-related proteins (such as glycosyltransferases in gliomas), we summarize how glycosylation may play a crucial role in the discovery of novel biomarkers and new targeted treatment options for gliomas. Overall, the mechanistic basis of abnormal glycosylation affecting glioma progression remains to be more widely and deeply explored, which not only helps to inspire researchers to further explore related diagnostic and prognostic markers but also provides ideas for discovering effective treatment strategies and improving glioma patient survival and prognosis.

Efficacy and safety of glue mesh fixation for laparoscopic inguinal hernia: A meta-analysis of randomized controlled trials.

It is still controversial whether glue can be used for mesh fixation in laparoscopic inguinal hernia repair. The aim of this meta-analysis was used to systematically evaluate the effectiveness and safety of glue mesh fixation in laparoscopic tension-free inguinal hernia repair. The PubMed database, EMBASE database and Cochrane Library were searched to collect published randomized controlled trials (RCTs) on laparoscopic tension-free inguinal hernia repair with glue mesh fixation. Sixteen RCTs and 2409 patients with inguinal hernia were included. The meta-analysis showed that compared with the mechanical mesh fixation group(MMFG), the glue mesh fixation group(GMFG) had significantly reduced incidences of chronic pain[relative risk (RR) = 0.40, 95% confidence interval (CI) (0.28,0.57), P < 0.00001], urinary retention[RR = 0.53, 95% CI(0.29,0.97), P = 0.04], haematoma[RR = 0.23, 95% CI(0.09,0.58), P = 0.002] and total complications[RR = 0.28, 95% CI(0.18,0.44), P < 0.00001]; there were no significant differences in pain score on postoperative day 1[MD = -1.33, 95% CI(-2.93,0.26), P = 0.10], operation time[MD = 1.46, 95% CI(-3.97,6.88), P = 0.60] and recurrence rate[RR = 0.72, 95% CI(0.35,1.47), P = 0.37] between the two groups. In conclusion, the application of glue mesh fixation in laparoscopic inguinal hernia repair is safe and reliable with fewer complications. Moreover, it can reduce the incidence of chronic pain without increasing the recurrence rate. However, due to the small number of cases in this analysis and limitations in the quality of the included studies, the findings need to be further verified by multicentre, large-sample and high-quality RCTs in the future.

DNMT3b affects colorectal cancer development by regulating FLI1 through DNA hypermethylation.

Friend leukemia integration 1 (FLI1) is an ETS transcription factor family member. Here, we identified cg11017065 as the most hyper-methylated cytosine and guanine (CpG) in colorectal cancer (CRC), which belongs to the FLI1 gene. Moreover, integrated bioinformatics prediction and analysis of our cohort showed that FLI1 expression was downregulated and DNA methylation was elevated in CRC. Bioinformatics prediction also indicated that patients overexpressing FLI1 had higher survival rates than those with low FLI1 expression. CRC cells with ectopic expression of FLI1 had reduced invasion, migration, cloning ability and increased apoptosis. Furthermore, DNA-methyltransferase 3b (DNMT3b) was found to be significantly overexpressed in CRC, and low DNMT3b expression predicted a prolonged survival. DNMT3b bound to the FLI1 promoter. Inhibition of DNMT3b increased FLI1 expression and inhibited the malignant phenotype of CRC cells. Inhibition of FLI1 reversed the phenotypic modulation by DNMT3b depletion in vitro and in vivo. In conclusion, our data indicate that DNMT3b potentiates CRC cell proliferation, migration, and invasion through downregulating FLI1.

Injectable Carbon Dots-Based Hydrogel for Combined Photothermal Therapy and Photodynamic Therapy of Cancer.

Hydrogel has been widely used in modern biotherapeutics due to its excellent biocompatibility, degradability, and high drug loading capacity. Among them, the construction of a phototherapy system including photosensitizer and hydrogel has aroused great interest in tumor therapy. Unfortunately, complex modifications are necessary to integrate different photosensitizers into the hydrogel. In this work, an injectable hydrogel was proposed by the Schiff base reaction between HA-CHO and carbon dots (CDs), which can realize PTT and PTT simultaneously. Notably, the CDs with rich -NH2 can be used not only as a photosensitizer but also as an efficient cross-linking agent for the Schiff base reaction to form a hydrogel network. The CD@Hydrogel with outstanding biosafety showed a high antitumor effect after 660 nm laser irradiation in in vitro and in vivo experiments. In summary, the CD@Hydrogel can not only realize PTT and PDT synergistic treatment under one light source but also act as a cross-linking agent to react with HA-CHO to form hydrogel, which is simple and efficient, providing a new strategy for cancer phototherapy.

[Reduning Injection protects flu-infected mice by inhibiting infiltration of inflammatory cells in lung and down-regulating cytokine storm].

This study aimed to explore the protective effect of Reduning Injection(RDN) on mice infected by influenza virus A/PR/8(PR8) and its immune regulatory roles during viral infection. In in vivo experiments, female C57 BL/6 mice were randomly divided into phosphate buffered saline(PBS) group, PR8-infected group, oseltamivir treatment group(OSV) and RDN treatment group. After 2 h of PR8 infection, mice in the oseltamivir group were gavaged with oseltamivir 30 mg·kg~(-1), and those in the RDN treatment group were injected intraperitoneally with RDN 1.5 mL·kg~(-1)once per day for seven consecutive days. The body weight of mice in each group was recorded at the same time every morning for 16 consecutive days. The line chart of body weight change was created to analyze the protective effect of RDN on flu-infected mice. The relative mRNA expression of different cytokines(IL-6, TNF-α, MCP-1, IL-1ß, MIP-2, IP-10 and IL-10) in lung samples of flu-infected mice was detected by PCR. Flow cytometry was utilized to analyze the composition of immune cells of mouse BALF samples on day 5 after infection. Mouse macrophage cell line RAW264.7 was planted and treated by different concentrations of RDN(150, 300, 600 µg·mL~(-1)) for 24 h or 48 h, and cell proliferation was detected by CCK-8 assay. RAW264.7 cells and mouse primary peritoneal macrophages were stimulated with synthetic single stranded RNA(R837), which elicited the inflammatory response by mimicking the infection of single-stranded RNA viruses. The expression of cytokines and chemokines in the supernatants of above culture system was detected by ELISA and qPCR. On days 4, 5, 6, 7 and 15 after infection, the body weight loss of mice in the RDN treatment group was alleviated compared with that of PR8-infected mice(P<0.05). RDN treatment obviously reduced lung index and the production of IL-6, TNF-α, MCP-1 and MIP-2 in lung tissues of flu-infected mice(P<0.05). The proportions of macrophages, neutrophils and T cells in mouse BALF samples were analyzed by flow cytometry, and compared with PR8-infected mice, RDN decreased the proportion of macrophages in BALF of flu-infected mice(P<0.05), and the proportion of T cells was recovered dramatically(P<0.001). In CCK-8 assay, the concentrations of RDN(150, 300, 600 µg·mL~(-1)) failed to cause cytotoxicity to RAW264.7 cells. In addition, RDN lowered the expression of inflammatory cytokines such as IL-6, TNF-α,MCP-1, IL-1ß, RANTES, and IP-10 and even anti-inflammatory cytokine IL-10 in R837-induced macrophages. RDN reduced the infiltration of inflammatory macrophages and the production of excessive inflammatory cytokines, alleviated the body weight loss of flu-infected mice. What's more, RDN restored the depletion of T cells, which might prevent secondary infection and deteriorative progression of the disease. Taken together, RDN may inhibit cytokine production and therefore down-regulate cytokine storm during the infection of influenza virus.

Involvement of Histone Lysine Crotonylation in the Regulation of Nerve-Injury-Induced Neuropathic Pain.

Histone lysine crotonylation (KCR), a novel epigenetic modification, is important in regulating a broad spectrum of biological processes and various diseases. However, whether KCR is involved in neuropathic pain remains to be elucidated. We found KCR occurs in macrophages, sensory neurons, and satellite glial cells of trigeminal ganglia (TG), neurons, astrocytes, and microglia of the medulla oblongata. KCR in TG was detected mainly in small and medium sensory neurons, to a lesser extent in large neurons. Peripheral nerve injury elevated KCR levels in macrophages in the trigeminal and dorsal root ganglia and microglia in the medulla oblongata but reduced KCR levels in sensory neurons. Inhibition of histone crotonyltransferases (p300) by intra-TG or intrathecal administration of C646 significantly alleviated partial infraorbital nerve transection (pIONT)- or spinal nerve ligation (SNL)-induced mechanical allodynia and thermal hyperalgesia. Intra-TG or intrathecal administration of Crotonyl coenzyme A trilithium salt to upregulate KCR dose-dependently induced mechanical allodynia and thermal hyperalgesia in mice. Mechanismly, inhibition of p300 alleviated pIONT-induced macrophage activation and reduced the expression of pain-related inflammatory cytokines Tnfα, Il1ß and chemokines Ccl2 and Cxcl10. Correspondingly, exogenous crotonyl-CoA induced macrophage activation and the expression of Tnfα, Il1ß, Il6, Ccl2 and Ccl7 in TG, which C646 can repress. These findings suggest that histone crotonylation might be functionally involved in neuropathic pain and neuroinflammation regulation.

Effects of psychological nursing care on anxiety and depression in perioperative patients with lung cancer: A systematic review and meta-analysis.

BACKGROUND: This study aimed to investigate the effects of psychological nursing care (PNC) on anxiety relief in perioperative lung cancer (LC) patients. METHODS: We searched the Cochrane Library, PubMed, Embase, CNKI, CBM, and Wangfang electronic databases from inception to May 1, 2022. Eligible randomized controlled trials (RCTs) investigating the effects and safety of PNC on anxiety relief in perioperative LC patients. Anxiety was the primary outcome measure. The secondary outcomes were depression, length of hospital stay, and the occurrence of adverse events. RESULTS: Six eligible RCTs with 494 patients were included in this study. Compared with routine nursing care, PNC showed better outcomes in terms of anxiety relief (mean difference [MD] = -13.24; random 95% confidence interval (CI), -18.28 to -8.20; P<.001), depression decrease (MD = -11.84; random 95% CI, -18.67 to -5.01; P < .001), and length of hospital stay (MD = -2.6; fixed 95% CI, -3.13 to -2.07; P < .001). No data on adverse events were pooled because only 1 trial reported this outcome. CONCLUSIONS: This study showed that PNC may benefit more than routine nursing care for patients with LC in anxiety, depression, and length of hospital stay. High-quality RCTs are needed to validate the current findings in the future.

Evaluation of the diagnostic performance of the EFSUMB CEUS Pancreatic Applications guidelines (2017 version): a retrospective single-center analysis of 455 solid pancreatic masses.

OBJECTIVES: To explore the diagnostic performance of EFSUMB CEUS Pancreatic Applications guidelines (version 2017) before and after the addition of iso-enhancement and very fast/fast washout as supplementary diagnostic criteria for PDAC. METHODS: In this retrospective study, patients diagnosed with solid pancreatic lesions from January 2017 to December 2020 were evaluated. Pancreatic ductal adenocarcinoma (PDAC) is reported to show hypo-enhancement in all phases according to the EFSUMB guidelines. First, based on this definition, all lesions were categorized as PDAC and non-PDAC. Then, iso-enhancement and very fast/fast washout were added as supplementary diagnostic criteria, and all lesions were recategorized. The diagnostic performance was assessed in terms of the accuracy (ACC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV). The reference standard consisted of histologic evaluation or composite imaging and clinical follow-up findings. RESULTS: A total of 455 nodules in 450 patients (median age, 58.37 years; 250 men) were included. The diagnostic performance using the EFSUMB CEUS guidelines for PDAC had an ACC of 69.5%, SEN of 65.4%, SPE of 84%, PPV of 93.5%, NPV of 40.6%, and ROC of 0.747. After recategorization according to the supplementary diagnostic criteria, the diagnostic performance for PDAC had an ACC of 95.8%, SEN of 99.2%, SPE of 84%, PPV of 95.7%, NPV of 96.6%, and ROC of 0.916. CONCLUSION: The EFSUMB guidelines and recommendations for pancreatic lesions can effectively identify PDAC via hypo-enhancement on CEUS. However, the diagnostic performance may be further improved by the reclassification of PDAC lesions after adding iso-enhancement and very fast/fast washout mode. KEY POINTS: • In the EFSUMB guidelines, the only diagnostic criterion for PDAC is hypo-enhancement, to which iso-enhancement and very fast/fast washout mode were added in our research. • Using hypo-enhancement/iso-enhancement with very fast/fast washout patterns as the diagnostic criteria for PDAC for solid pancreatic masses on CEUS has high diagnostic accuracy. • The blood supply pattern of PDAC can provide important information, and CEUS has unique advantages in this respect due to its real-time dynamic attenuation ability.

Case Report: Torsade de Pointes Induced by the Third-Generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Osimertinib Combined With Litsea Cubeba.

Torsades de Pointes (TdP) occurred in a 68-year-old female with epidermal growth factor receptor (EGFR) mutant lung cancer administered osimertinib, the third-generation EGFR tyrosine kinase inhibitor (TKI). Electrocardiogram (ECG) recorded at Tdp showed QT prolongation (QTc = 515 ms), to which a Traditional Chinese Medicine (TCM) named "Litsea Cubeba" may have contributed. After discontinuation of osimertinib and Litsea Cubeba, magnesium supplementation, potassium supplementation, lidocaine infusion, and the pacemaker frequency adjustment, Tdp terminated. However, QT prolongation sustained at discharge (QTc = 528 ms), partly because of the emergency use of amiodarone. Osimertinib may prolong the QT interval leading to TdP, especially when multiple risk factors to lengthen QT interval are incidentally overlapped. Thus, regular monitoring of ECG and appropriate management of concomitant drugs are highly recommended.