Anti-Melanogenic Effects of Cnidium monnieri Extract via p38 Signaling-Mediated Proteasomal Degradation of Tyrosinase.

Cnidium monnieri fructus is widely used in traditional Oriental medicine for treating female genital disorders, male impotence, frigidity, and skin-related conditions in East Asia. However, the role of C. monnieri fructus extract (CMFE) in melanin synthesis is not well elucidated. This study aimed to investigate the anti-melanogenesis effect and mechanism of action of CMFE in α-MSH-stimulated B16F10 cells. Intracellular melanin content and tyrosinase activity were measured in α-MSH-stimulated B16F10 cells treated with various concentrations of CMFE (0.5-5 µg/mL). mRNA and protein levels of tyrosinase and MITF were evaluated using qRT-PCR and ting. CMFE's effect on the proteasomal degradation of tyrosinase was confirmed using a proteasomal degradation inhibitor, MG132. CMFE treatment activated p38, a protein associated with proteasomal degradation. Treatment with CMFE at up to 5 µg/mL showed no significant cytotoxicity. CMFE significantly reduced α-MSH-stimulated melanin production (43.29 ± 3.55% decrease, p < 0.05) and cellular tyrosinase activity (31.14 ± 3.15% decrease, p < 0.05). Although mRNA levels of MITF and tyrosinase increased, CMFE suppressed tyrosinase protein levels. The suppressive effect of CMFE on tyrosinase protein was blocked by MG132. CMFE inhibited melanogenesis by promoting the proteasome degradation of tyrosinase through p38 activation. These findings suggest that CMFE has the potential to be a natural whitening agent for inhibiting melanogenesis.

The Effects of Body Fat Reduction through the Metabolic Control of Steam-Processed Ginger Extract in High-Fat-Diet-Fed Mice.

The prevalence of metabolic syndrome is increasing globally due to behavioral and environmental changes. There are many therapeutic agents available for the treatment of chronic metabolic diseases, such as obesity and diabetes, but the data on their efficacy and safety are lacking. Through a pilot study by our group, Zingiber officinale rhizomes used as a spice and functional food were selected as an anti-obesity candidate. In this study, steam-processed ginger extract (GGE) was used and we compared its efficacy at alleviating metabolic syndrome-related symptoms with that of conventional ginger extract (GE). Compared with GE, GGE (25-100 µg/mL) had an increased antioxidant capacity and α-glucosidase inhibitory activity in vitro. GGE was better at suppressing the differentiation of 3T3-L1 adipocytes and lipid accumulation in HepG2 cells and promoting glucose utilization in C2C12 cells than GE. In 16-week high-fat-diet (HFD)-fed mice, GGE (100 and 200 mg/kg) improved biochemical profiles, including lipid status and liver function, to a greater extent than GE (200 mg/kg). The supplementation of HFD-fed mice with GGE (200 mg/kg) resulted in the downregulation of SREBP-1c and FAS gene expression in the liver. Collectively, our results indicate that GGE is a promising therapeutic for the treatment of obesity and metabolic syndrome.

Efficacy of Laparoscopic Iliopubic Tract Repair Plus Transabdominal Preperitoneal Hernioplasty for Treating Inguinal Hernia After Robot-assisted Radical Prostatectomy.

BACKGROUND: Robot-assisted radical prostatectomy (RARP) is a risk factor for inguinal hernia (IH). Furthermore, in patients who have undergone RARP, the fibrotic scar tissue in the RARP area limits preperitoneal dissection. This study aimed to evaluate the efficacy of performing laparoscopic iliopubic tract repair (IPTR) in addition to transabdominal preperitoneal hernioplasty (TAPPH) to treat IH after RARP. PATIENTS AND METHODS: A total of 80 patients with an IH after RARP were treated with TAPPH from January 2013 to October 2020 and were included in this retrospective study. Patients who underwent conventional TAPPH were categorized as the TAPPH group (25 patients with 29 hernias), whereas those who underwent TAPPH with IPTR were categorized as the TAPPH + IPTR group (55 patients with 63 hernias). The IPTR comprised suture fixation of the transversus abdominis aponeurotic arch to the iliopubic tract. RESULTS: All patients had indirect IH. The incidence of intraoperative complications was significantly higher in the TAPPH group than in the TAPPH + IPTR group [13.8% (4/29) vs 0.0% (0/63), P = 0.011]. The average operative time was also significantly shorter in the TAPPH + IPTR group than in the TAPPH group ( P < 0.001). There were no differences between the two groups in the duration of hospitalization, recurrence rate, and pain severity. CONCLUSIONS: The addition of laparoscopic IPTR to TAPPH for treating IH after RARP is safe and is associated with a minimal risk of intraoperative complications and a short operative time.

Laparoscopic hydrocelectomy with transabdominal preperitoneal hernioplasty or iliopubic tract repair for treatment of encysted spermatic cord hydrocele.

BACKGROUND: An encysted spermatic cord hydrocele (ESCH) causes an inguinal swelling resembling an inguinal hernia (IH). An ESCH should be considered as a differential diagnosis of IH. Although laparoscopic operations have been performed to treat ESCHs in pediatric patients, such operations have not been reported in adults. This study was performed to evaluate the outcomes of laparoscopic hydrocelectomy for treatment of ESCHs in adults. METHODS: The medical charts of 49 patients who underwent laparoscopic transabdominal hydrocelectomy for ESCHs from January 2015 to December 2020 at a single institution were retrospectively reviewed. The patients were divided into those with and without an IH. Laparoscopic hydrocelectomy was performed, and the internal inguinal ring was closed with iliopubic tract repair (IPTR) or transabdominal preperitoneal (TAPP) hernioplasty depending on the presence of an IH. The patients' age, ESCH location, postoperative complications, recurrence, and operating time were examined. RESULTS: The patients' mean age was 46.7 (20-77) years. All patients underwent laparoscopic hydrocelectomy without open conversion. ESCHs were more common on the right side (35/49, 71.4%) than on the left (14/49, 28.6%). The presenting symptom in all patients was inguinal swelling. The ESCH was located inside the inguinal canal in 47 patients and protruded to the abdominal cavity from the inguinal canal in 2 patients. After laparoscopic hydrocelectomy, 32 patients without an IH underwent IPTR and 17 patients with an IH underwent TAPP hernioplasty. The mean operating time was shorter in the IPTR than TAPP hernioplasty group. The postoperative complications and hospital stay were not different between the two groups. There were no recurrences in either group. CONCLUSIONS: Laparoscopic hydrocelectomy with IPTR or TAPP hernioplasty is safe and feasible for treatment of ESCHs in adults.

Laparoscopic Hydrocelectomy of Encysted Hydrocele of the Canal of Nuck with High Ligation in Children or Iliopubic Tract Repair in Adults.

Background: Encysted hydrocele of the canal of Nuck (EHCN) is homologous to spermatic cord hydrocele in males. EHCN causes swelling in the inguinal region and should be considered in the differential diagnosis of inguinal hernias and masses in females. Complete excision and internal inguinal ring closure are the recommended treatments for symptomatic EHCN. In this study, we aimed at evaluating the safety and feasibility of laparoscopic hydrocelectomy, as well as age-appropriate procedures for EHCN. Materials and Methods: The medical records of 161 female adults and children, who underwent laparoscopic transabdominal hydrocelectomy from January 2014 to December 2020 at a single institution, were reviewed retrospectively and symptoms, location of EHCN, type of fluid in EHCN, postoperative complications, recurrence, and operating time were analyzed. Laparoscopic hydrocelectomy was performed and the internal inguinal ring was closed with high ligation in children and iliopubic tract repair (IPTR) in adults. Results: Fifty-two pediatric (age 2-11 years) and 109 adult (age 21-51 years) female patients were included. More adult patients had inguinal pain (34.9%, 38/109) compared with children (3.8% 2/52) (P < .001). More EHCNs were located in the inguinal canal than protruding into the abdominal cavity in both groups. Regarding the fluid characteristics, hemorrhagic and inflammatory hydroceles were more common in adults than in children (P < .001). There were no serious complications, neither recurrence nor chronic pain was observed in either group except for a surgical-site hematoma in 1 adult patient. Conclusion: Laparoscopic hydrocelectomy together with additional age-appropriate procedures, including high ligation in children and IPTR in adults, is a safe and feasible method for treating EHCN.

Adding Laparoscopic Iliopubic Tract Repair to Transabdominal Preperitoneal Hernioplasty for Treatment of Recurrent Inguinal Hernia After Totally Extraperitoneal Hernioplasty.

Background: In patients with recurrent inguinal hernia (IH) after totally extraperitoneal (TEP) hernioplasty, re-TEP hernioplasty is difficult because of fibrotic adhesions. Re-laparoscopic hernioplasty is possible by changing the approach from extraperitoneal to transabdominal. If iliopubic tract repair (IPTR), mainly used in the past for the open approach, is added as a laparoscopic procedure, re-laparoscopic hernioplasty is possible when treating recurrent IH. We aimed to evaluate the safety and feasibility of alternate transabdominal preperitoneal (TAPP) hernioplasty supplemented by IPTR for treating recurrent IH after TEP hernioplasty. Methods: We retrospectively evaluated 2600 patients with IHs who underwent TAPP hernioplasty from January 2015 to December 2020. Among patients with recurrent IH, those who underwent primary TEP were included in the study. For reoperation, TAPP hernioplasty was performed and IPTR was added. IPTR was performed by suture closure of the internal inguinal ring by the iliopubic tract and medial aponeurotic arch of the transversus abdominis muscle. Results: Of the 35 patients (33 males and 2 females) with recurrent IH after primary TEP hernioplasty, 51% (18/35) of patients had recurrence within 2 years of the first operation. There were 28 recurrent IHs of the same type as the original, and 7 cases of a different type. The mean TAPP operation time was 41 minutes. Chronic inguinodynia and re-recurrence was not observed. One patient had inferior epigastric vessel injury, which was successfully repaired. Conclusion: Adding laparoscopic IPTR to TAPP hernioplasty is safe feasible treatment for recurrent IH after TEP hernioplasty.

Clinical characteristics and treatment of chest submammary accessory breasts.

Accessory breast tissue is remnant mammary gland tissue resulting from a failure of regression during the embryonic development and can occur anywhere along the mammary ridge. Patients with accessory breast tissue may also have chest submammary accessory breasts, which are rare and painless, but are often removed for cosmetic reasons. Herein, we report the clinical characteristics and treatment of patients with chest submammary accessory breasts. This retrospective study included 104 women who had undergone liposuction for chest submammary accessory breast from January 2014 to December 2019. chest submammary accessory breasts were diagnosed by ultrasonography and physical examination. The overall satisfaction of patients with chest submammary accessory breast was evaluated using a 5-point Likert scale. The mean operation time was mean 20.7 min and the mean liposuction volume was mean 223.3 mL. The overall satisfaction score (incisional scar, pain and cosmesis) 6 months after chest submammary accessory breast liposuction was 4.7 (range 4-5). The chest submammary accessory breast consisted mainly of fatty tissue rather than mammary gland tissue; thus, chest submammary accessory breasts are painless and are treated purely for cosmetic reasons. In conclusion, liposuction is therefore a simple and effective treatment for chest submammary accessory breast.

Laparoscopic iliopubic tract repair to treat recurrent pediatric inguinal hernia.

BACKGROUND: Congenital defects, such as open processus vaginalis and the canal of Nuck, are common causes of primary pediatric inguinal hernia (PIH). However, in some patients, PIH occurs via acquired defects rather than congenital defects. The most representative cause of PIH is recurrent hernia. Recurrent PIH is treated with high ligation (HL), which is the same method that is used to treat primary PIH. However, the re-recurrence rate of recurrent PIH is high. This study aimed to compare laparoscopic iliopubic tract repair (IPTR) with laparoscopic HL for the treatment of recurrent PIH after primary PIH repair. METHODS: From June 2013 to March 2019, 126 patients (< 10 years old) with recurrent PIH were retrospectively enrolled. Patients were divided into two groups according to the operative technique: laparoscopic HL (58 patients) and laparoscopic IPTR (68 patients). With HL, the hernial sac was removed and the peritoneum closed. With IPTR, iliopubic tract and transversalis fascia sutures were applied. RESULTS: There were no cases of conversion to open surgery. Re-recurrence only occurred in the HL group; no patients in the IPTR group developed re-recurrence (8.6% [5/58] vs. 0.0% [0/68], respectively; p = 0.044). The mean duration from re-operation to re-recurrence in these five patients was 10.6 months. Other surgical outcomes and complications did not differ between the two groups. CONCLUSIONS: Laparoscopic IPTR is an effective surgical treatment for reducing re-recurrence of recurrent PIH.

Feasibility of Laparoscopic Transabdominal Preperitoneal Hernioplasty for Incarcerated Inguinal Hernia.

BACKGROUND/OBJECTIVES: An incarcerated inguinal hernia (IncIH) is defined as an irreducible inguinal hernia. The problems caused by long-term incarceration are adhesion between the incarcerated organ and hernial sac and difficulty in reduction of the edematous incarcerated organ. The present study was performed to evaluate the feasibility of laparoscopic transabdominal preperitoneal (TAPP) hernioplasty to treat chronic IncIH. METHODS: This retrospective study included 154 patients aged >20 years who were treated for IncIH from January 1, 2015 to October 31, 2020. Patients were categorized into those with symptoms for ≥ 3 months (chronic IncIH group, 134 patients) and those with symptoms for < 3 months (acute IncIH group, 20 patients). RESULTS: The type of incarcerated organ differed between groups. The most frequently incarcerated organ was the intestine (85%, 17/20) in the acute IncIH group and the omentum (98%, 131/134) in the chronic IncIH group (p < 0.000). Compared with the chronic IncIH group, the acute IncIH group had a higher prevalence of pre-operative inguinal pain (85%, 17/20 vs 3%, 4/134; p < 0.000) and a lower prevalence of adhesion between the incarcerated organ and the hernial sac (5%, 1/20 vs 37%, 49/134; p = 0.011). Organ resection was performed in 1 patient in the acute IncIH group and 19 in the chronic IncIH group. CONCLUSION: In patients with chronic IncIH, TAPP hernioplasty was used to successfully resolve adhesion between the incarcerated organ and the hernial sac, avoiding organ resection by enabling intra-abdominal reduction in many patients. TAPP hernioplasty may be a feasible surgical method for the treatment of IncIH.

Comparison of laparoscopic transabdominal preperitoneal hernioplasty and laparoscopic iliopubic tract repair for Nyhus type II hernia in women.

BACKGROUND: Indirect inguinal hernia with a dilated internal ring but an intact posterior inguinal wall is classified as Nyhus type II. Females have a higher incidence of indirect hernia than direct hernia. The purpose of this study was to evaluate the efficacy of laparoscopic iliopubic tract repair (IPTR) compared with laparoscopic transabdominal preperitoneal (TAPP) hernioplasty in treating women with Nyhus type II hernia. METHODS: This retrospective study included 318 women aged ≥ 20 years who were treated for Nyhus type II hernia from January 2013 to December 2018. The patients were categorized into two groups in accordance with the operative technique: the TAPP group (33 patients) and the IPTR group (285 patients). In the IPTR group, intraabdominal suturing of the iliopubic tract and transversalis fascia arch was performed without mesh implantation. RESULTS: The mean operation time was shorter in the IPTR group (17.2 ± 3.9 min) than the TAPP group (20.5 ± 8.1 min, p = 0.028). The postoperative complication rate was higher in the TAPP group than the IPTR group [6.1% (2/33) vs. 0.4% (1/285), respectively; p = 0.001]. Inguinodynia occurred in one patient in the TAPP group and no patients in the IPTR group. The hospital stay did not significantly differ between the two groups. The numeral rating scale pain scores at 1 day and 1 week postoperatively did not significantly differ between the two groups. There was no recurrence in either group. CONCLUSIONS: Laparoscopic IPTR was safe and feasible for treating Nyhus type II hernia in women.

Phosphorylation in Novel Mitochondrial Creatine Kinase Tyrosine Residues Render Cardioprotection against Hypoxia/Reoxygenation Injury.

OBJECTIVE: Ischemic cardiomyopathy (ICM) is the leading cause of heart failure. Proteomic and genomic studies have demonstrated ischemic preconditioning (IPC) can assert cardioprotection against ICM through mitochondrial function regulation. Considering IPC is conducted in a relatively brief period, regulation of protein expression also occurs very rapidly, highlighting the importance of protein function modulation by post-translational modifications. This study aimed to identify and analyze novel phosphorylated mitochondrial proteins that can be harnessed for therapeutic strategies for preventing ischemia/reperfusion (I/R) injury. METHODS: Sprague-Dawley rat hearts were used in an ex vivo Langendorff system to simulate normal perfusion, I/R, and IPC condition, after which the samples were prepared for phosphoproteomic analysis. Employing human cardiomyocyte AC16 cells, we investigated the cardioprotective role of CKMT2 through overexpression and how site-directed mutagenesis of putative CKMT2 phosphorylation sites (Y159A, Y255A, and Y368A) can affect cardioprotection by measuring CKMT2 protein activity, mitochondrial function and protein expression changes. RESULTS: The phosphoproteomic analysis revealed dephosphorylation of mitochondrial creatine kinase (CKMT2) during ischemia and I/R, while preserving its phosphorylated state during IPC. CKMT2 overexpression conferred cardioprotection against hypoxia/reoxygenation (H/R) by increasing cell viability and mitochondrial adenosine triphosphate level, preserving mitochondrial membrane potential, and reduced reactive oxygen species (ROS) generation, while phosphomutations, especially in Y368, nullified cardioprotection by significantly reducing cell viability and increasing ROS production during H/R. CKMT2 overexpression increased mitochondrial function by mediating the proliferator-activated receptor γ coactivator-1α/estrogen-related receptor-α pathway, and these effects were mostly inhibited by Y368A mutation. CONCLUSION: These results suggest that regulation of quantitative expression and phosphorylation site Y368 of CKMT2 offers a unique mechanism in future ICM therapeutics.

Surgery for fibroadenoma arising from axillary accessory breast.

BACKGROUND: Patients with fibroadenomas in axillary accessory breasts (AABs) have a palpable mass, cyclic axillary pain, and aesthetic concerns that must be addressed. We compared the baseline patient characteristics, AAB characteristics, and surgical outcomes of patients with AABs with and without fibroadenomas undergoing surgical excision. We also monitored the patients for recurrence of axillary fibroadenomas. METHODS: This retrospective study involved 2310 women who underwent AAB excision from 2014 to 2019. Patients with and without a palpable fibroadenoma were divided into a fibroadenoma group and non-fibroadenoma group, respectively. All patients underwent complete excision of accessory mammary gland (AMG) tissue, including fibroadenomas in the AABs. We removed the fibroadenoma and the AMG tissue with a minimal axillary incision. RESULTS: Thirty-nine patients had a palpable fibroadenoma in the AAB, and all patients in the fibroadenoma group had cyclic axillary pain and a palpable axillary mass. There were no significant differences in the patients' age, weight of the AMG tissue, liposuction volume, or fibroadenoma laterality between the two groups. The body mass index in the fibroadenoma group was lower than that in the non-fibroadenoma group (19.9 vs. 22.3 kg/m2, respectively; P < 0.000). Concurrent fibroadenoma excision in a normal breast on the chest was performed more often in the fibroadenoma group than in the non-fibroadenoma group (35.9% (14/39) vs. 4.1% (92/2271), respectively; P < 0.000). The mean fibroadenoma size was 2.1 cm (range, 1.1-9.1 cm). All patients were satisfied with the degree of postoperative pain relief, disappearance of palpable lesions, and cosmetic improvement. No patients developed fibroadenoma recurrence. CONCLUSIONS: Complete excision of the AMG tissue and fibroadenoma is appropriate in patients with an AAB with a fibroadenoma. Surgeons should also consider the high incidence of concurrent fibroadenomas in the normal breasts on the chest.

Reoperation Because of Dissatisfaction with the Aesthetic Results of Gynecomastia Surgery: Technical Considerations.

BACKGROUND: Gynecomastia is a common disease in male patients that is characterized by benign breast enlargement. Gynecomastia may involve fibroglandular tissue (FGT), supramammary fat tissue, and retromammary fat tissue (RMFT). Gynecomastia is usually treated surgically; however, some patients undergo reoperation because of dissatisfaction with the results of the first operation. This study aimed to analyze the breast conditions requiring reoperation and to identify factors requiring attention during the first gynecomastia surgery. METHODS: We retrospectively evaluated 98 patients who underwent reoperation because of unsatisfactory esthetic outcomes from January 2014 to April 2020. According to the reasons for dissatisfaction, patients were divided into undercorrection and overcorrection groups. Patients with remnant breast tissue were assigned to the undercorrection group, while those in whom excess breast tissue was removed and was assigned to the overcorrection group. RESULTS: The undercorrection and overcorrection groups comprised 81 and 17 patients, respectively. In the undercorrection group, 49 (60.5%) patients had residual FGT and fat tissue necessitating simultaneous FGT excision and liposuction, while 32 (39.5%) patients had no residual FGT and were treated with liposuction only. In the overcorrection group, 13 (76.5%) patients had undergone excessive removal of RMFT at the inferolateral aspect of the pectoralis major muscle margin and were treated by autologous fat grafting. CONCLUSIONS: The most common cause of undercorrection was incomplete FGT removal, and the most common cause of overcorrection was excessive RMFT removal. Complete FGT excision and proper RMFT preservation can reduce the reoperation rate after gynecomastia surgery. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Laparoscopic Iliopubic Tract Repair with Transabdominal Preperitoneal Hernioplasty after Radical Prostatectomy.

Background and Objectives: In patients with inguinal hernias who have undergone radical prostatectomy, dissecting the medial preperitoneal space is difficult because of the presence of fibrotic scars. It is also difficult to guarantee sufficient space for mesh implantation. We added laparoscopic iliopubic tract repair (IPTR) to transabdominal preperitoneal (TAPP) hernioplasty, and evaluated this for the treatment of inguinal hernias after radical prostatectomy. Methods: This retrospective study included 29 male patients with inguinal hernias after radical prostatectomy who underwent TAPP hernioplasty between January 1, 2015 and October 31, 2018. Laparoscopic IPTR was performed first, followed by TAPP hernioplasty. Results: All patients had an indirect inguinal hernia. The mean time from radical prostatectomy to TAPP hernioplasty was 2.1 years (range, 0.3-11 years). In one patient, the peritoneal flap was insufficient, and the operation was performed using a dual-layer mesh. All other patients underwent conventional TAPP hernioplasty. The mean operation time was 42 min (range, 30-50 min), and the mean duration until return to normal activities was 8.4 days. There were two minor postoperative complications (one hematoma and one seroma). The mean follow-up period was 45.8 ± 14.0 months (range, 22-67 months), and chronic pain or recurrence was not observed. Conclusion: Adding laparoscopic IPTR to TAPP hernioplasty in patients with a history of radical prostatectomy is feasible and safe, with a low risk of chronic pain and recurrence.

Adding iliopubic tract repair to high ligation reduces recurrence risk in pediatric laparoscopic transabdominal inguinal hernia repair.

BACKGROUND: Many laparoscopic methods are available for treating pediatric inguinal hernias. Recurrence after laparoscopic pediatric inguinal hernia repair (LPIHR) is one of the greatest concerns for surgeons. The present study was performed to evaluate the effects of iliopubic tract repair in LPIHR with respect to the recurrence rate, surgical outcomes, and complications. METHODS: LPIHR was performed in 3386 pediatric patients aged < 10 years from January 2016 to June 2018. The patients were categorized into two groups according to the operative techniques: high ligation alone (1736 patients) and additional iliopubic tract repair (1650 patients). In high ligation surgery, the hernia sac was removed and the peritoneum was closed. In iliopubic tract repair surgery, iliopubic tract and transversalis fascia arch sutures were added. RESULTS: Recurrence only occurred in the high ligation group; no patients in the iliopubic tract repair group developed recurrence [0.35% (6/1736) vs. 0.00% (0/1650), respectively; p = 0.014]. Other surgical outcomes and complications did not differ between the two groups. Six patients in the high ligation group developed recurrence: four infants aged < 1 year and two children aged > 1 year. The mean duration from the first operation to reoperation in these six patients was 11.8 months; five patients developed recurrence within 1 year after the initial operation. All patients had a recurrent indirect hernia, and the location of the hernial defects was on the medial side of the previous stitch. The logistic regression indicated that the difference between the two groups affected the recurrence rate. This finding predicted that iliopubic tract repair is associated with a lower recurrence rate than high ligation (odds ratio 0.996, 95% confidence interval 0.994-0.999, p = 0.015). CONCLUSIONS: This study of transabdominal LPIHR indicates that iliopubic tract repair results in a small but significant decrease in the risk of recurrence.

Ovarian Incarceration and Torsion in Single-Ovary Versus Multiple-Reproductive Organ Prolapse in Female Inguinal Hernia: A Retrospective Study of 510 Infants Who Underwent Laparoscopic Hernia Repair.

Purpose: Although inguinal hernia repair is common in infants, few studies have focused on the condition in female infants. In female infantile inguinal hernia, there is a risk of oophorectomy when torsion and strangulation occur due to ovarian prolapse. We aimed to evaluate the risks of ovarian incarceration and torsion in single-ovary versus multiple-reproductive organ prolapse in female infantile inguinal hernia. Methods: Females ≤12 months old who underwent laparoscopic transabdominal inguinal hernia repair from September 2012 to December 2019 were retrospectively analyzed. If manual reduction failed at initial diagnosis, surgery was performed within 24 hours in all incarceration cases. The clinical characteristics and surgical outcomes were compared between those with single-organ versus multiple-organ prolapse. Results: Of 510 patients, 465 (91.2%) had single-organ prolapse, most commonly a single ovary (381/465), followed by intestine (84/465). Forty-five patients (8.8%) had multiple-organ prolapse, most commonly a single ovary plus intestine (27/45), followed by both ovaries plus the uterus (10/45). The manually irreducible incarceration rate was higher in patients with multiple-organ prolapse (57.8%) than single-organ prolapse (23.4%; P < .000). In patients with ovarian incarceration, the ovarian torsion rate was higher in the single-ovary group (38/109, 34.9%) than the multiple-organ group (1/26, 3.8%; P < .000). There was no significant difference between the two groups in recurrence or oophorectomy rate. Conclusion: Most female infantile inguinal hernias involve ovarian prolapse. There is a high risk of incarceration in multiple-organ prolapse and a high risk of ovarian torsion in single-ovary prolapse.

BH4 activates CaMKK2 and rescues the cardiomyopathic phenotype in rodent models of diabetes.

Diabetic cardiomyopathy (DCM) is a major cause of mortality/morbidity in diabetes mellitus patients. Although tetrahydrobiopterin (BH4) shows therapeutic potential as an endogenous cardiovascular target, its effect on myocardial cells and mitochondria in DCM and the underlying mechanisms remain unknown. Here, we determined the involvement of BH4 deficiency in DCM and the therapeutic potential of BH4 supplementation in a rodent DCM model. We observed a decreased BH4:total biopterin ratio in heart and mitochondria accompanied by cardiac remodeling, lower cardiac contractility, and mitochondrial dysfunction. Prolonged BH4 supplementation improved cardiac function, corrected morphological abnormalities in cardiac muscle, and increased mitochondrial activity. Proteomics analysis revealed oxidative phosphorylation (OXPHOS) as the BH4-targeted biological pathway in diabetic hearts as well as BH4-mediated rescue of down-regulated peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC-1α) signaling as a key modulator of OXPHOS and mitochondrial biogenesis. Mechanistically, BH4 bound to calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) and activated downstream AMP-activated protein kinase/cAMP response element binding protein/PGC-1α signaling to rescue mitochondrial and cardiac dysfunction in DCM. These results suggest BH4 as a novel endogenous activator of CaMKK2.

Anti-osteoporotic effects of Salvia miltiorrhiza Bunge EtOH extract both in ovariectomized and naturally menopausal mouse models.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza is a traditional oriental medicine widely used for preventing and treating disorders of the liver, menstrual, and blood circulation systems. Osteoporosis, loss of bone with age and/or estrogen deficiency, is an important causal factor of fracture. S. miltiorrhiza extract has been used to alleviate dysmenorrhea and painful osteoarthritis. AIM OF THE STUDY: This study was performed to investigate the anti-osteoporosis activity of the Salvia miltiorrhiza ethanol extract (SME) in osteoporosis-prone conditions: ovariectomized (OVX) and naturally menopaused (NM) ICR mice. MATERIALS AND METHODS: Anti-osteoporotic potentials of SME (50-200 mg/kg) were evaluated based on bone mineral density using microCT analysis, biochemical parameters, and changes in the gene expressions involved in bone resorption. RESULTS: SME ameliorated the loss of trabecular bone both in OVX and NM mice. SME was effective in correcting aberrant levels of RANKL, osteocalcin, and BALP, which are critically involved in bone resorption. In addition, SME suppressed the expression of TRAF6 and NFATc1, which play a role in osteoclast differentiation. CONCLUSIONS: SME suppressed the loss of trabecular bone via suppressing bone resorption and osteoclast differentiation both in OVX and NM mice. SME is likely to be developed as a therapeutic agent for osteoporosis.