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Abstract Arachidonic and adrenic acids in the membrane play key roles in ferroptosis. Here, we reveal that lipoprotein-associated phospholipase A2 (Lp-PLA2) controls intracellular phospholipid metabolism and contributes to ferroptosis resistance. A metabolic drug screen reveals that darapladib, an inhibitor of Lp-PLA2, synergistically induces ferroptosis in the presence of GPX4 inhibitors. We show that darapladib is able to enhance ferroptosis under lipoprotein-deficient or serum-free conditions. Furthermore, we find that Lp-PLA2 is located in the membrane and cytoplasm and suppresses ferroptosis, suggesting a critical role for intracellular Lp-PLA2. Lipidomic analyses show that darapladib treatment or deletion of PLA2G7, which encodes Lp-PLA2, generally enriches phosphatidylethanolamine species and reduces lysophosphatidylethanolamine species. Moreover, combination treatment of darapladib with the GPX4 inhibitor PACMA31 efficiently inhibits tumour growth in a xenograft model. Our study suggests that inhibition of Lp-PLA2 is a potential therapeutic strategy to enhance ferroptosis in cancer treatment.

Background Implant-based immediate breast reconstruction surgery with nipple-sparing mastectomy has recently been favored by patients. However, in patients who do not wish to undergo balancing procedures, it is difficult to select the appropriate implant size, making it challenging to achieve a symmetrical breast shape. Therefore, this study investigated the differences in breast asymmetry and other complications in patients who underwent a two-stage procedure or direct-to-implant (DTI) breast reconstruction to determine whether the two-stage procedure can produce more favorable outcomes. Methods The participants of this study were patients who underwent immediate two-stage breast reconstruction or DTI breast reconstruction from May 2018 to April 2022, did not receive postoperative radiotherapy, and did not wish to undergo any balancing procedures. An acellular dermal matrix was used for breast reconstruction in all patients, and a single reconstructive surgeon performed all the operations. Statistical significance was set at P

Background In recent years, breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) has emerged as an important concern. At our institution, patients who received breast reconstruction using Allergan implants were informed individually about BIA-ALCL. The present study analyzed correlations between patients’ level of satisfaction with their breast shape and whether they chose to undergo reoperation (implant removal or replacement). Methods Breast reconstruction with Allergan implants was performed between December 2014 and April 2018. In total, 107 patients were interviewed, excluding those who had died, were unreachable, or had already undergone reoperation. The mean follow-up period was 53 months (range, 26–73 months). Results After the interviews, 68 patients postponed reoperation, 29 had their implant replaced, and 10 had their implant removed. Nearly one-fifth (18.9%) of patients who were satisfied with their breast shape (13 out of 69) underwent reoperation due to anxiety over ALCL. Meanwhile, 68.4% of patients who were not satisfied due to capsular contracture or scar contracture (26 out of 38) underwent reoperation. Sixteen of the 30 patients who received postoperative radiotherapy (53.3%) chose to undergo reoperation. Conclusions Satisfaction with the cosmetic outcomes of implant placement played a meaningful role in patients’ decisions to undergo reoperation. This tendency may be linked to postoperative radiotherapy, which is a major contributor to complications such as contracture. Nonetheless, a substantial proportion of patients who were satisfied with the outcomes chose to undergo reoperation due to concerns regarding ALCL.

Background Breast reconstruction using an extended latissimus dorsi (eLD) flap can supplement more volume than reconstruction using various local flaps after partial mastectomy, and it is a valuable surgical method since the reconstruction area is not limited. However, when performing reconstruction, the surgeon should consider latissimus dorsi (LD) volume reduction due to postoperative chemotherapy (POCTx) and postoperative radiotherapy (PORTx). To evaluate the effect of POCTx and PORTx on LD volume reduction, the effects of each therapy—both separately and jointly—need to be demonstrated. The present study quantified LD volume reduction in patients who underwent POCTx and PORTx after receiving breast-conserving surgery (BCS) with an eLD flap. Methods This study included 48 patients who received immediate breast reconstruction using an eLD flap from January 2013 to March 2017, had chest computed tomography (CT) 7–10 days after surgery and 10–14 months after radiotherapy completion, and were observed for more than 3 years postoperatively. One surgeon performed the breast reconstruction procedures, and measurements of breast volume were obtained from axial CT views, using a picture archiving and communication system. A P-value

This review of national and international randomized controlled trials of Salviae miltiorrhizae radix pharmacopuncture for lumbar herniated intervertebral discs was performed to assess its clinical efficacy. There were 5 online databases (PubMed, EMBASE, CNKI, NDSL, OASIS, and RISS) searched on June 1st, 2020. Studies were selected according to the inclusion and exclusion criteria and were reviewed by risk of bias assessment. This review included 14 Chinese studies. The sample sizes ranged from 50 to 100. The numbers of treatments ranged from 20 to 30, with most patients receiving 20 treatments. The longest treatment periods were 10–15 and 15–20 days, of which each accounted for 29% of the studies. The most frequently used evaluation indices were the Japanese Orthopedic Association and the Visual Analog Scale scoring method. The most frequently used acupoints were EX18 and BL25, which accounted for 31% of the total number of acupoints. In 50% of the studies, the pharmacopuncture injection volume was 2 mL. Acupuncture treatment was the most common control group. Eleven studies reported that the intervention group had significantly improved symptoms. However, most of the included studies were of low quality.

Background Reduction mammoplasty or mastopexy is performed as an additional balancing procedure in patients with large or ptotic breasts who undergo breast-conserving surgery (BCS). Radiation therapy on breasts that have undergone surgery may result in changes in the volume. This study presents a comparative analysis of patients who received post-BCS balancing procedures to determine whether volume changes were larger in breasts that received radiation therapy than on the contralateral side. Methods Thirty-six participants were selected among patients who received BCS using the inverted-T scar technique between September 2012 and July 2017, were followed up for 2 or more years, and had pre-radiation therapy computed tomography images and post-radiation therapy images taken between 12 and 18 months after completion. The average age of the participants was 53.5 years, their average body mass index was 26.62 kg/m2. Results The pre- and post-radiation therapy volumes of the breasts receiving BCS were 666.08±147.48 mL and 649.33±130.35 mL, respectively. In the contralateral breasts, the volume before radiation therapy was 637.69±145.72 mL, which decreased to 628.14±166.41 mL after therapy. The volume ratio of the affected to the contralateral breasts was 1.05±0.10 before radiation therapy and 1.06±0.12 after radiation therapy. Conclusions The ratio of the volume between the two breasts immediately after surgery and at roughly 18 months postoperatively was not significantly different (P=0.98). For these reasons, we recommend a simultaneous single-stage balancing procedure as a reasonable option for patients who require radiation therapy after BCS without concerns regarding volume change.

Background Implant-based dual-plane augmentation mammoplasty requires accurate separation of the pectoralis major muscle (PMM) at its origins. The authors identified the PMM origins during breast reconstruction surgery with the goal of providing additional information on subpectoral implant insertion for reconstructive or aesthetic purposes. Methods This study was conducted on 67 patients who underwent breast reconstruction surgery at the breast center of our hospital between November 2016 and June 2018. In total, 34 left and 39 right hemithoraces were examined. The left and right hemithoraces were each divided into 15 zones to determine the percentage of PMM attachments in each zone. The distribution of PMM origins in each zone was examined to identify any statistically significant differences. Results There were no statistically significant differences in the origins of the PMM between the right and left hemithoraces. The percentage of attachments increased moving from the fourth to the sixth rib and from the lateral to the medial aspect. Conclusions The anatomical findings of this study could be used as a reference for accurate dissection of the origins of the PMM for the preparation of the subpectoral pocket for subpectoral implant placement.

Background This study aimed to determine the magnitude of volume reduction of the latissimus dorsi (LD) muscle after treatment using only postoperative radiotherapy (PORTx) in patients who underwent immediate breast reconstruction using an extended LD musculocutaneous (eLDMC) flap after partial mastectomy. Methods We retrospectively reviewed 28 patients who underwent partial mastectomy and an eLDMC flap, received only PORTx, and underwent chest computed tomography (CT) 7 to 10 days after surgery and 18±4 months after the end of radiotherapy, from March 2011 to June 2016. The motor nerve to the LD was resected in all patients. One plastic surgeon performed the procedures, and the follow-up period was at least 36 months (mean, 46.6 months). The author obtained LD measurements from axial CT views, and the measurements were verified by an experienced radiologist. The threshold for statistical significance was set at P

The effectiveness of fire needling or warm needling treatment in clinical studies for the treatment of ankle sprains was reviewed using 4 international (PubMed, Cochrane library, EMBASE, CNKI) and 5 Korean databases (NDSL, RISS, KISS, OASIS, KTKP). Randomized controlled trials, that performed fire needling or warm needling treatment for ankle sprains until October, 2018 were retrieved (n = 8). All studies were performed in China, and 7 out of 8 studies were published within the last 5 years. There were 4 studies that used fire needling treatment, 3 studies used warm needling treatment, and 1 study used fire and warm needling treatment. The ashi-points and gallbladder meridian were the most frequently selected acupoint and meridian each. All intervention groups in the 8 studies showed statistically significant beneficial effects compared with control groups. The results of this study could provide preliminary data as the basis for welldesigned randomized controlled trials on fire needling or warm needling treatment for ankle sprains.

The aim of this study was to examine pharmacopuncture treatment for lateral epicondylitis, and to contribute to developing a standardized treatment regimen by reviewing trends in clinical trials. Five randomized controlled trials, 1 case-control study, and 8 cohort studies published after 1999, that involved pharmacopuncture for lateral epicondylitis, were selected from Korean and international online databases (n = 8). The type of pharmacopuncture, dose, frequency, efficacy, and adverse events were analyzed. Seven types of pharmacopuncture were used, namely Bee Venom, Illicium henryi Diels, Akebiae Caulis, Angelicae sinensis Diels, Ligusticum chuanxiong Hort, Hominis Placenta, and Salviae Miltiorrhizae Radix. Dose, treatment duration, and treatment frequency varied widely. One study assessed the treatment efficacy according to frequency. Nine studies lacked data on adverse events. The quality of 5 randomized controlled trials was low. Although pharmacopuncture treatment appeared to be effective for lateral epicondylitis, it was difficult to standardize the regimen for lateral epicondylitis.

Background Pain caused by nasal pack removal after closed reduction of nasal bone fractures is a common problem. This study investigated the effect of infiltrating lidocaine into nasal packs on the pain caused by pack removal after closed reduction of nasal bone fractures. Methods Seventy-five patients who underwent closed reduction of nasal bone fractures between March 2016 and March 2018 were enrolled in this prospective, randomized, single-blind study. Merocel (hydroxylated polyvinyl acetate) packs were applied bilaterally and retained for 5 days. Twenty minutes before removal, both packs were rehydrated with 6 mL of 2% lidocaine in 26 patients and with 6 mL of saline in 24 patients; the packs were not rehydrated in 25 patients. Visual analog scale (VAS) scores for pain on removal were recorded. Results The mean VAS score was 5.3±2.0 in all patients, 3.8±1.5 in the lidocaine group, 5.8±1.4 in the saline group, and 6.3±2.1 in the non-rehydrated group. There was a significant difference in the pain score between the lidocaine and saline groups (P

Background The aim of this study was to review clinical efficacy of acupuncture treatment of mild cognitive impairment. Methods Randomized controlled trials that performed acupuncture treatment for mild cognitive impairment were retrieved from 6 online databases (PubMed, Cochrane Library, EMBASE, CNKI, NDSL, OASIS) on September 30th, 2018. Studies were selected according to inclusion and exclusion criteria, and were reviewed by Risk of Bias assessment. Results In total, 21 studies were included in this review. All studies were Chinese (19 studies published in Chinese and 2 in English). The sample size, 50 to 100, and the number of treatment times, 20 to 30, were the largest range in all studies. The most treatments performed was 30. The longest treatment period was 56 days, which accounted for 33% of the studies. The most frequently used evaluation index was the Mini Mental State Examination followed by the Montreal Cognitive Assessment, each used 17 times and 15 times, respectively. The most frequently used acupoints were GV20, EX-HN1, GB20, and GV24, which accounted for 47% of total number of acupoints used. In 48% of the studies, needle retention time was 30 minutes. Western medicine treatment was the most common control group. Most studies reported that the intervention group was statistically significantly different to the control group. Conclusions These results suggest that acupuncture for mild cognitive impairment was effective. However, it is difficult to confirm this conclusion because the quality of most of these studies were of low quality.

Background The dorsolateral branch of the posterior intercostal artery (DLBPI) can be easily found while harvesting a latissimus dorsi (LD) musculocutaneous flap for breast reconstruction. However, it remains unknown whether this branch can be used for a free flap and whether this branch alone can provide perfusion to the skin. We examined whether the DLBPI could be reliably found and whether it could provide sufficient perfusion. Methods We dissected 10 fresh cadavers and counted DLBPIs with a diameter larger than 2 mm. For each DLBPI, the following parameters were measured: distance from the lateral margin of the LD muscle, level of the intercostal space, distance from the spinal process, and distance from the inferior angle of the scapula. Results The DLBPI was easily found in all cadavers and was reliably located in the specified area. The average number of DLBPIs was 1.65. They were located between the seventh and eleventh intercostal spaces. The average length of the DLBPI between the intercostal space and the LD muscle was 4.82 cm. To assess the perfusion of the DLBPIs, a lead oxide mixture was injected through the branch and observed using X-rays, and it showed good perfusion. Conclusions The DLBPI can be used as a pedicle in free flaps for small defects. DLBPI flaps have some limitations, such as a short pedicle. However, an advantage of this branch is that it can be reliably located through simple dissection. For women, it has the advantage of concealing the donor scar underneath the bra band.

Cathepsin K (Cat K) is expressed in cancer cells, but the effect of Cat K on apoptosis is still elusive. Here, we showed that inhibition of Cat K sensitized the human carcinoma cells to anti-cancer drug through up-regulation of Bim. Inhibition of Cat K increased USP27x expression, and knock down of USP27x markedly blocked Cat K-induced up-regulation of Bim expression. Furthermore, inhibition of Cat K induced proteasome-dependent degradation of regulatory associated protein of mammalian target of rapamycin (Raptor). Down-regulation of Raptor expression increased mitochondrial ROS production, and mitochondria specific superoxide scavengers prevented USP27x-mediated stabilization of Bim by inhibition of Cat K. Moreover, combined treatment with Cat K inhibitor (odanacatib) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) reduced tumor growth and induced cell death in a xenograft model. Our results demonstrate that Cat K inhibition enhances anti-cancer drug sensitivity through USP27x-mediated the up-regulation of Bim via the down-regulation of Raptor. Keywords: Apoptosis, Bim, Cathepsin K, USP27x, Mitochondria, Raptor

Background This study was performed to review the efficacy of national and international randomized controlled trials (RCT) investigating Chuna manipulative treatment for ankle sprains. Methods Online databases (PubMed, Cochrane, EMBASE, CNKI, NDSL, OASIS), were searched for studieswhere Chuna treatment was performed for ankle sprains up to October 12th, 2017. Only RCT were selectedthat fulfilled the inclusion/exclusion criteria. Data were analyzed using the Cochrane risk of bias tool. Results There were 676 studies retrieved from the databases, resulting in analysis of 24 RCT. There was an average of 7 treatment visits over a 7 day period and the most frequent evaluation tool used was efficacy rate,with drug therapy being the most common control used in the trials. In 15 RCT, several Chuna methods were used in combination, amongst which, the osteopathic technique was most common. Statistically significant improvement in evaluation indices was reported in 19 RCT, and in 3 RCT, statistically significant improvement was reported, but not for all indices. In the remaining 2 RCT, there were no significant differences in any of the evaluation indices. No adverse reactions were reported in any of the RCT, although it was book whether all the trial protocols indicated that adverse reactions should be monitored, and for this reason, the risk of bias was unclear. Conclusions The review of 24 studies suggest that Chuna manipulative treatment for ankle sprains waseffective in most cases, although, potential bias in these studies was difficult to evaluate.

Human papillomaviruses (HPVs) are causative agents of various diseases associated with cellular hyperproliferation, including cervical cancer, one of the most prevalent tumors in women. E7 is one of the two HPV-encoded oncoproteins and directs recruitment and subsequent degradation of tumor-suppressive proteins such as retinoblastoma protein (pRb) via its LxCxE motif. E7 also triggers tumorigenesis in a pRb-independent pathway through its C-terminal domain, which has yet been largely undetermined, with a lack of structural information in a complex form with a host protein. Herein, we present the crystal structure of the E7 C-terminal domain of HPV18 belonging to the high-risk HPV genotypes bound to the catalytic domain of human nonreceptor-type protein tyrosine phosphatase 14 (PTPN14). They interact directly and potently with each other, with a dissociation constant of 18.2 nM. Ensuing structural analysis revealed the molecular basis of the PTPN14-binding specificity of E7 over other protein tyrosine phosphatases and also led to the identification of PTPN21 as a direct interacting partner of E7. Disruption of HPV18 E7 binding to PTPN14 by structure-based mutagenesis impaired E7's ability to promote keratinocyte proliferation and migration. Likewise, E7 binding-defective PTPN14 was resistant for degradation via proteasome, and it was much more effective than wild-type PTPN14 in attenuating the activity of downstream effectors of Hippo signaling and negatively regulating cell proliferation, migration, and invasion when examined in HPV18-positive HeLa cells. These results therefore demonstrated the significance and therapeutic potential of the intermolecular interaction between HPV E7 and host PTPN14 in HPV-mediated cell transformation and tumorigenesis.

Objective: Dysphagia is a common clinical condition characterized by difficulty in swallowing. It is sub-classified into oropharyngeal dysphagia, which refers to problems in the mouth and pharynx, and esophageal dysphagia, which refers to problems in the esophageal body and esophagogastric junction. Dysphagia can have a significant negative impact one’s physical health and quality of life as its severity increases. Therefore, proper assessment and management of dysphagia are critical for improving swallowing function and preventing complications. Thus a guideline was developed to provide evidence-based recommendations for assessment and management in patients with dysphagia. Methods: Nineteen key questions on dysphagia were developed. These questions dealt with various aspects of problems related to dysphagia, including assessment, management, and complications. A literature search for relevant articles was conducted using Pubmed, Embase, the Cochrane Library, and one domestic database of KoreaMed, until April 2021. The level of evidence and recommendation grade were established according to the Grading of Recommendation Assessment, Development and Evaluation methodology. Results: Early screening and assessment of videofluoroscopic swallowing were recommended for assessing the presence of dysphagia. Therapeutic methods, such as tongue and pharyngeal muscle strengthening exercises and neuromuscular electrical stimulation with swallowing therapy, were effective in improving swallowing function and quality of life in patients with dysphagia. Nutritional intervention and an oral care program were also recommended. Conclusion: This guideline presents recommendations for the assessment and management of patients with oropharyngeal dysphagia, including rehabilitative strategies. [ABSTRACT FROM AUTHOR]