Search

Aim: To explore the clinical factors associated with pathologic complete response (pCR) for locally advanced rectal cancer (LARC) patients treated with neoadjuvant chemoradiotherapy (nCRT) and develop a web‐based dynamic nomogram. Methods: Retrospective analysis of patients with examination confirmed LARC from 2011 to 2022. Patients from the Union Hospital of Fujian Medical University were included as the training cohort (n = 1579) and Zhangzhou Hospital of Fujian Medical University as the external validation cohort (n = 246). Results: In the training cohort, after nCRT, 350 (22.2%) patients achieved pCR. More stomas were avoided in pCR patients (73.9% vs. 69.7%, p = 0.043). After a median follow‐up time of 47.7 months (IQR 2–145) shown OS (5‐year: 93.7% vs. 81.0%, HR = 0.310, 95%CI: 0.189–0.510, p < 0.001) and DFS (5‐year: 91.2% vs. 75.0%, HR = 0.204, 95%CI: 0.216–0.484, p < 0.001) were significantly better among patients with pCR than non‐pCR. Multivariable Logistic analysis shown pCR was significantly associated with Pre‐CRT CEA (HR = 0.944, 95%CI: 0.921–0.968; p < 0.001), histopathology (HR = 4.608, 95%CI: 2.625–8.089; p < 0.001), Pre‐CRT T stage (HR = 0.793, 95%CI: 0.634–0.993; p = 0.043), Pre‐CRT N stage (HR = 0.727, 95%CI: 0.606–0.873; p = 0.001), Pre‐CRT MRI EMVI (HR = 0.352, 95%CI: 0.262–0.473; p < 0.001), total neoadjuvant therapy (HR = 2.264, 95%CI: 1.280–4.004; p = 0.005). Meanwhile, the online version of the nomogram established in this study was publicized on an open‐access website (URL: https://pcrpredict.shinyapps.io/LARC2/). The model predicted accuracy with a C‐index of 0.73 (95% CI: 0.70–0.75), with an average C‐index of 0.73 for the internal cross validation and 0.78 (95% CI: 0.72–0.83) for the external validation cohort, showing excellent model accuracy. Delong test results showed the model has an important gain value for clinical characteristics to predict pCR in rectal cancer. Conclusions: Patients with pCR had a better prognosis, including OS and DFS, and were independently associated with Pre‐CRT CEA, histopathology, Pre‐CRT T/N stage, Pre‐CRT MRI EMVI, and TNT. A web‐based dynamic nomogram was successfully established for clinical use at any time. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion The management of the infrapatellar fat pad (IPFP) during total knee arthroplasty (TKA) remains controversial. This study aimed to evaluate a novel IPFP preservation technique—“the medially pedicled IPFP flap”—for reducing postoperative pain, wound complications, and improving functional recovery after TKA.A retrospective analysis was conducted on TKA cases at our institution from 2018 to 2021, including those with IPFP preservation (medially pedicled flap) versus IPFP complete resection. Patient demographics, perioperative parameters (blood loss, operative time, length of hospital stay, visual analogue scale [VAS] score, white cell count [WBC], C‐reactive protein [CRP], erythrocyte sedimentation rate [ESR], and wound oozing), and postoperative follow‐up data (VAS, Knee Society [KSS], or Knee Society functional assessment [KSFA] scores) were compared between groups. Independent sample t‐tests were used to compare continuous data and chi‐squared tests were used to compare categorical data between groups.Six hundred thirty patients were included, with 278 in the medial pedicled IPFP flap group (preservation group) and 352 in the IPFP resection group (resection group). The operative time was significantly shorter in the preservation versus resection group (125.5 ± 23.2 vs 130.3 ± 28.7 mins, p = 0.03), as was the length of hospital stay (8.4 ± 2.7 vs 9.2 ± 2.3 days, p < 0.01). Regarding pain, the preservation group had significantly lower VAS scores on postoperative day 2 (2.0 ± 0.8 vs 2.4 ± 1.2, p < 0.001) and day 3 (1.5 ± 0.5 vs 1.8 ± 1.0, p < 0.001). CRP and ESR levels on postoperative day 5 were also significantly lower in the preservation group. Wound oozing rates were significantly lower in the preservation versus resection group (0.7% vs 2.8%, p = 0.04). No significant differences existed in VAS, KSS, or KSFA scores at the last follow‐up.The novel IPFP preservation technique significantly improved surgical exposure, shortened operative time and length of hospital stay. It also reduced wound pain and oozing compared to IPFP resection. [ABSTRACT FROM AUTHOR]

The corneal epithelium is the outermost transparent barrier of the eyeball and undergoes continuous self‐renewal by limbal stem cells (LSCs) during its lifetime; however, the impact of aging on LSCs remains largely unknown. Here, we showed that the healing ability of the cornea in elderly macaques (Macaca fascicularis) was significantly decreased compared to that of younger macaques. This delayed wound closure accompanied a disordered cell arrangement and corneal opacity. A novel cytokine, Secreted and Transmembrane 1 (SECTM1), was found to facilitate corneal healing and was upregulated in young macaques upon wounding. Mechanistically, SECTM1 is essential for LSC migration and proliferation, and may partially function through Cell Division Cycle Associated 7 (CDCA7). Notably, the topical application of SECTM1 to aged wounded corneas dramatically promoted re‐epithelialization and improved corneal transparency in both mice and macaques. Our work suggests that aging may impair the expression of healing response factors and injury repair in non‐human primate corneas, and that SECTM1 application could potentially benefit corneal wound healing in clinical treatment. [ABSTRACT FROM AUTHOR]

Objectives: Primary pulmonary lymphoepithelioma‐like carcinoma (PLELC) is a subtype of lung carcinoma associated with the Epstein–Barr virus (EBV). The clinical predictive biomarkers of immune checkpoint blockade (ICB) in PLELC require further investigation. Methods: We prospectively analysed EBV levels in the blood and immune tumor biomarkers of 31 patients with ICB‐treated PLELC. Viral EBNA‐1 and BamHI‐W DNA fragments in the plasma were quantified in parallel using quantitative polymerase chain reaction. Results: Progression‐free survival (PFS) was significantly longer in EBNA‐1 high or BamHI‐W high groups. A longer PFS was also observed in patients with both high plasma EBNA‐1 or BamHI‐W and PD‐L1 ≥ 1%. Intriguingly, the tumor mutational burden was inversely correlated with EBNA‐1 and BamHI‐W. Plasma EBV load was negatively associated with intratumoral CD8+ immune cell infiltration. Dynamic changes in plasma EBV DNA level were in accordance with the changes in tumor volume. An increase in EBV DNA levels during treatment indicated molecular progression that preceded the imaging progression by several months. Conclusions: Plasma EBV DNA could be a useful and easy‐to‐use biomarker for predicting the clinical activity of ICB in PLELC and could serve to monitor disease progression earlier than computed tomography imaging. [ABSTRACT FROM AUTHOR]

Accumulation of abnormal chondroitin sulfate (CS) chains in breast cancer tissue is correlated with poor prognosis. However, the biological functions of these CS chains in cancer progression remain largely unknown, impeding the development of targeted treatment focused on CS. Previous studies identified chondroitin polymerizing factor (CHPF; also known as chondroitin sulfate synthase 2) is the critical enzyme regulating CS accumulation in breast cancer tissue. We then assessed the association between CHPF‐associated proteoglycans (PGs) and signaling pathways in breast cancer datasets. The regulation between CHPF and syndecan 1 (SDC1) was examined at both the protein and RNA levels. Confocal microscopy and image flow cytometry were employed to quantify macropinocytosis. The effects of the 6‐O‐sulfated CS‐binding peptide (C6S‐p) on blocking CS functions were tested in vitro and in vivo. Results indicated that the expression of CHPF and SDC1 was tightly associated within primary breast cancer tissue, and high expression of both genes exacerbated patient prognosis. Transforming growth factor beta (TGF‐β) signaling was implicated in the regulation of CHPF and SDC1 in breast cancer cells. CHPF supported CS–SDC1 stabilization on the cell surface, modulating macropinocytotic activity in breast cancer cells under nutrient‐deprived conditions. Furthermore, C6S‐p demonstrated the ability to bind CS‐SDC1, increase SDC1 degradation, suppress macropinocytosis of breast cancer cells, and inhibit tumor growth in vivo. Although other PGs may also be involved in CHPF‐regulated breast cancer malignancy, this study provides the first evidence that a CS synthase participates in the regulation of macropinocytosis in cancer cells by supporting SDC1 expression on cancer cells. [ABSTRACT FROM AUTHOR]

Background: Thermage is a monopolar radiofrequency (RF). It has become an indispensable part of facial and body youthful methods. Although the current device is constantly improving in epidermal cooling techniques and even automatically measures the local impedance value, applying surface anesthesia can take some of the pain away caused by thermage, and the patient's severe pain in the jaw and neck areas is still difficult to resolve. Methods: The author describes how he uses the combination of the buccal nerve block (BNB) and the superficial cervical plexus block (SCPB) to improve the comfort of the patient's face and neck treatment of patients. It can improve the quality, elasticity, and texture of the skin. Results: According to the author's knowledge of oral and maxillofacial surgery, the combination of BNB and SCPB is applied to the neck and facial analgesia. Combining the BNB and SCPB effectively provides facial and neck anesthesia. The BNB in this technique provides pain relief to the facial skin in the mandibular area and SCPB offers pain relief to the skin of the neck. RF facial rejuvenation treatment often involves the junction of the face and neck to improve the contour of the mandibular margin. Therefore, Whether the RF treatment is aimed at the face or neck, or the treatment is performed simultaneously, we advocate the block both of the buccal nerve and the superficial cervical plexus nerves to achieve perfect analgesia. Still, the dosage of anesthetic medication for the nerve block can be adjusted according to the treatment area. Conclusion: We applied these two nerve blocks and their combination to improve skin laxity with RF therapy for the first time. [ABSTRACT FROM AUTHOR]

Aims: Basolateral amygdala (BLA), as a center for stress responses and emotional regulation, is involved in visceral hypersensitivity of irritable bowel syndrome (IBS) induced by stress. In the present study, we aimed to investigate the role of EphB2 receptor (EphB2) in BLA and explore the underlying mechanisms in this process. Methods: Visceral hypersensitivity was induced by water avoidance stress (WAS). Elevated plus maze test, forced swimming test, and sucrose preference test were applied to assess anxiety‐ and depression‐like behaviors. Ibotenic acid or lentivirus was used to inactivate BLA in either the induction or maintenance stage of visceral hypersensitivity. The expression of protein was determined by quantitative PCR, immunofluorescence, and western blot. Results: EphB2 expression was increased in BLA in WAS rats. Inactivation of BLA or downregulation of EphB2 in BLA failed to induce visceral hypersensitivity as well as anxiety‐like behaviors. However, during the maintenance stage of visceral pain, visceral hypersensitivity was only partially relieved but anxiety‐like behaviors were abolished by inactivation of BLA or downregulation of EphB2 in BLA. Chronic WAS increased the expression of EphB2, N‐methyl‐D‐aspartate receptors (NMDARs), and postsynaptic density protein (PSD95) in BLA. Downregulation of EphB2 in BLA reduced NMDARs and PSD95 expression in WAS rats. However, activation of NMDARs after the knockdown of EphB2 expression still triggered visceral hypersensitivity and anxiety‐like behaviors. Conclusions: Taken together, the results suggest that EphB2 in BLA plays an essential role in inducing visceral hypersensitivity. In the maintenance stage, the involvement of EphB2 is crucial but not sufficient. The increase in EphB2 induced by WAS may enhance synaptic plasticity in BLA through upregulating NMDARs, which results in IBS‐like symptoms. These findings may give insight into the treatment of IBS and related psychological distress. [ABSTRACT FROM AUTHOR]

Background: Diabetic foot ulcer (DFU) is a common and serious complication of diabetes, and its treatment is challenging. Platelet‐rich plasma (PRP) gel and umbilical cord mesenchymal stem cells (UC‐MSCs) gel have been concerned as new therapies for DFU in recent years, and comparative studies on the efficacy and mechanisms of these methods, however, are rarely reported. Methods: Thirty patients with DFU were selected and divided into the PRP group and the UC‐MSCs group, and wound healing, foot blood vessels (ABI index), infection index (CRP), neuropathy symptoms (TCSS score), and foot skin temperature before and after treatment were compared between the two groups. SPSS 21.0 was used for statistical analysis. Results: The results showed that the efficacy of the UC‐MSCs gel group was significantly better than that of the PRP group in terms of wound healing rate, time to complete wound closure, ABI index, CRP level and TCSS score. No statistically significant difference in foot skin temperature was observed between the two groups. Conclusion: The efficacy of UC‐MSCs gel is significantly superior to that of PRP gel in the treatment of DFU, with shortened time to complete wound closure, increased wound healing rate, better pain and infection control, and improved vascular and neurological symptoms. [ABSTRACT FROM AUTHOR]