[Suprapubic lipectomy with a "Ω" incision for buried penis in obese adult men].

Objective: To investigate the application of suprapubic lipectomy with a "Ω" incision to removal of the prepubic fat pad for the management of buried penis in obese adult patients. METHODS: We retrospectively analyzed the clinical data on 20 obese adult patients with buried penis treated by suprapubic lipectomy via a "Ω" incision between August 2016 and September 2019. RESULTS: The operations were successfully completed in all the cases, with a mean operation time of 3.7 ± 0.6 hours and an average hospital stay of 8.3 ± 3.3 days. There were no such severe surgery-related complications as hematoma, urethral injury, or fat embolism in any of the cases. Fat liquefaction-related superficial wound infection developed in 1 patient postoperatively, which was cured by combined topical and systemic antibiotic therapy. A 3-month follow-up showed a 95% satisfaction of the patients with the postoperative appearance of the penis and suprapubic incision, but no complications such as ED, abnormal penile sensation, or penile retraction. CONCLUSIONS: Suprapubic lipectomy with a "Ω" incision to remove the prepubic fat pad is an effective surgical approach to the management of buried penis in obese adult males, which is an anatomy-based surgical correction and has the advantages of slight injury, rapid recovery and few complications./.

ROS Generated by Upconversion Nanoparticle-Mediated Photodynamic Therapy Induces Autophagy via PI3K/AKT/ mTOR Signaling Pathway in M1 Peritoneal Macrophage.

BACKGROUND/AIMS: Atherosclerosis is a chronic inflammatory cardiovascular disease. Macrophages are major components of atherosclerotic plaques and play a key role in the development of atherosclerosis by secreting a variety of pro-inflammatory factors. Our previous studies have confirmed that upconversion nanoparticles encapsulating chlorin e6 (UCNPs-Ce6) mediated photodynamic therapy (PDT) can promote cholesterol efflux and induce apoptosis in THP-1 macrophages. In this study, we investigated whether reactive oxygen species (ROS) generated by UCNPs-Ce6-mediated PDT can induce autophagy to inhibit the expression of pro-inflammatory factor in M1 peritoneal macrophages. METHODS: Peritoneal macrophages were collected from C57/BL6 mice injected with 3% thioglycollate broth medium and induced by lipopolysaccharides and interferon-γ. Intracellular ROS production was assessed by 2'-7'-dichloroflorescein diacetate and flow cytometry. Autophagy was assayed by western blot, transmission electron microscopy and immunofluorescence. Pro-inflammatory cytokines were detected by enzyme-linked immunosorbent assay and western blot. RESULTS: Model M1 peritoneal macrophages were established after 24 h induction. Protein expression levels of LC3 II and Beclin1, and degradation of p62 increased and peaked at 2 h in the PDT group. Meanwhile, levels of inflammatory cytokines iNOS, IL-12, and TNF-α markedly decreased after PDT. The increase in autophagy levels and decrease in pro-inflammatory cytokines were significantly inhibited by 3-methyladenine. Furthermore, ROS generated by UCNPs- Ce6 mediated PDT activated autophagy. The expression of autophagy related-protein and inflammatory cytokines iNOS, IL-12, and TNF-α were inhibited by the ROS inhibitor N-acetyl cysteine. CONCLUSION: ROS generated by UCNPs-Ce6-mediated PDT activated autophagy and inhibited the expression of pro-inflammatory factors of M1 peritoneal macrophage via the PI3K/AKT/mTOR signaling pathway.

[comIdiopathic scrotal calcinosis: A report of 10 cases and review of the literature].

OBJECTIVE: To investigate the clinical features, pathogenesis, diagnosis and scrotal reconstruction in the treatment of idiopathic scrotal calcinosis (ISC). METHODS: From March 2007 to October 2018, 10 ISC patients, aged 28－79 (mean 45) years and with a disease course of 6－497 (mean 128.4) months, were treated in our hospital. We retrospectively analyzed their clinical data and reviewed related literature. RESULTS: All the patients underwent physical examination and biochemical and parathyroid function tests. None of them had a history of endocrine or metabolic disease, or trauma, or a family member with similar diseases, and none had subjective symptoms except local pruritus in 1 case. All were treated surgically and post-operative follow-up revealed no recurrence. Histopathological examination of the excised lesion confirmed it to be ISC. CONCLUSIONS: ISC is a rare localized benign disease, of which surgery seems an effective option for the definite diagnosis and treatment. Occasionally scrotal reconstruction may be required in case of extensive involvement of the scrotal skin.

ROS Generated by Upconversion Nanoparticle-Mediated Photodynamic Therapy Induces Autophagy Via PI3K/AKT/ mTOR Signaling Pathway in M1 Peritoneal Macrophage.

BACKGROUND/AIMS: Atherosclerosis is a chronic inflammatory cardiovascular disease. Macrophages are major components of atherosclerotic plaques and play a key role in the development of atherosclerosis by secreting a variety of pro-inflammatory factors. Our previous studies have confirmed that upconversion nanoparticles encapsulating chlorin e6 (UCNPs-Ce6) mediated photodynamic therapy (PDT) can promote cholesterol efflux and induce apoptosis in THP-1 macrophages. In this study, we investigated whether reactive oxygen species (ROS) generated by UCNPs-Ce6-mediated PDT can induce autophagy to inhibit the expression of pro-inflammatory factor in M1 peritoneal macrophages. METHODS: Peritoneal macrophages were collected from C57/BL6 mice injected with 3% thioglycollate broth medium and induced by lipopolysaccharides and interferon-γ. Intracellular ROS production was assessed by 2'-7'-dichloroforescein diacetate and flow cytometry. Autophagy was assayed by western blot, transmission electron microscopy and immunofluorescence. Pro-inflammatory cytokines were detected by enzyme-linked immunosorbent assay and western blot. RESULTS: Model M1 peritoneal macrophages were established after 24 h induction. Protein expression levels of LC3 II and Beclin1, and degradation of p62 increased and peaked at 2 h in the PDT group. Meanwhile, levels of inflammatory cytokines iNOS, IL-12, and TNF-α markedly decreased after PDT. The increase in autophagy levels and decrease in pro-inflammatory cytokines were significantly inhibited by 3-methyladenine. Furthermore, ROS generated by UCNPs-Ce6 mediated PDT activated autophagy. The expression of autophagy related-protein and inflammatory cytokines iNOS, IL-12, and TNF-α were inhibited by the ROS inhibitor N-acetyl cysteine. CONCLUSIONS: ROS generated by UCNPs-Ce6-mediated PDT activated autophagy and inhibited the expression of pro-inflammatory factors of M1 peritoneal macrophage via the PI3K/AKT/mTOR signaling pathway.

Survival analysis of patients with invasive extramammary Paget disease: implications of anatomic sites.

BACKGROUND: Extramammary Paget disease (EMPD) is a rare malignant dermatosis with poorly defined outcomes. We investigated clinical characteristics of invasive EMPD at different anatomic sites and by subject demographics to determine prognostic factors for overall survival (OS). METHODS: All patient data were collected from the Surveillance, Epidemiology, and End Results (SEER) program, 1973-2013, of the U.S. National Cancer Institute. Patients with invasive EMPD of skin, vulva/labia, vagina, scrotum/penis, or other sites were included. After excluding patients with unknown radiation status, data of 2001 patients were analyzed. Primary endpoint was EMPD mortality by anatomic sites. Independent variables included patients' demographic data, concurrent malignancy (ie, non-EMPD related cancers), tumor size, distant metastasis, and surgery and/or radiation or not. RESULTS: Multivariate regression analysis showed that mortality was significantly higher in patients with vaginal EMPD than in patients with vulvar/labial EMPD (adjusted hazard ratio [aHR] = 3.26, p < 0.001). Patients with distant metastasis had higher mortality than those without (aHR = 3.36, p < 0.001). Patients who received surgery had significantly lower mortality than those who did not receive surgery (aHR = 0.77, p = 0.030), and those treated with radiation had significantly higher mortality than those who did not receive radiation (aHR = 1.60, p = 0.002). Older age was associated with significantly increased mortality (aHR = 1.09, p < 0.001), and mortality was significantly higher in males than in females (aHR = 1.42, p = 0.008). CONCLUSIONS: In conclusion, among EMPD patients, mortality is higher in patients with vaginal EMPD than in those with vulvar/labial EMPD and higher in those who are older, those with concurrent malignancy or distant metastasis. Mortality is also higher in males than in females. Surgery is a protective factor and radiation is a risk factor for OS. Greater understanding of EMPD clinical characteristics, and considering EMPD in differential diagnosis of chronic genital and perianal dermatoses may provide support for early EMPD diagnosis and definitive surgical treatment.

[Effects of different medications with tadalafil on erectile dysfunction in males with primary sexual failure].

OBJECTIVE: To evaluate the effects of three different medications with tadalafil on erectile dysfunction (ED) in young men with primary sexual failure. METHODS: This study included 76 male ED patients aged 21－35 years who had primary sexual failure but normal nocturnal penile tumescence and rigidity and failed to respond to psychotherapy. We randomly assigned them to receive oral tadalafil once daily, on demand, or once-daily + on-demand. After 2－3 months of treatment, we evaluated the effects based on the scores of the patients in the five domains of the International Index of Erectile Function (IIEF-5). RESULTS: After medication, all the patients showed significantly increased scores in the four domains of IIEF-5, namely, erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction. The on-demand group achieved even higher scores in erectile and orgasmic functions but a lower score in sexual desire than the once-daily group. However, the patients in the once-daily + on-demand group exhibited more significant improvement than those in the other two in all the five domains. CONCLUSIONS: Once-daily + on-demand medication with tadalafil can significantly enhance the therapeutic effect on psychogenic ED in young men with primary sexual failure.

Combination of Hydroxyl Acetylated Curcumin and Ultrasound Induces Macrophage Autophagy with Anti-Apoptotic and Anti-Lipid Aggregation Effects.

BACKGROUND/AIMS: Sonodynamic therapy (SDT) is considered a new approach for the treatment of atherosclerosis. We previously confirmed that hydroxyl acetylated curcumin (HAC) was a sonosensitizer. In this study, we investigated the mechanism of THP-1 macrophage apoptosis and autophagy induced by HAC mediated SDT (HAC-SDT). METHODS: Cell viability was measured using a CCK-8 assay. Laser scanning confocal microscopy was used to measure the levels of intracellular reactive oxygen species (ROS), sub-cellular HAC localization, BAX and cytochrome C translocation, LC3 expression, monodansylcadaverine staining and Dil-labeled oxidized low density lipoprotein (Dil-ox-LDL) uptake. Flow cytometry was used to analyze apoptosis and autophagy via Annexin V/propidium iodide and acridine orange staining, respectively. The expression levels of apoptosis- and autophagy-related proteins were detected by Western blot. Oil red O was used to measure intracellular lipid accumulation. RESULTS: We identified HAC (5.0 µg/mL) located in lysosomes, endoplasmic reticulum, Golgi apparatus and mitochondria after 4 h of incubation. Compared with other sonosensitizers (e.g., curcumin and emodin), HAC had a more obvious sonodynamic effect on macrophages. Furthermore, the mitochondrial-caspase pathway was confirmed to play a crucial role in the HAC-SDT-induced apoptosis; BAX translocated from the cytosol to the mitochondria during HAC-SDT. Subsequently, mitochondrial cytochrome C was released into the cytosol, activating the caspase cascade in a time-dependent manner. Furthermore, HAC-SDT could induce PI3K/AKT/mTOR pathway dependent autophagy, accompanied by a decrease in the lipid uptake of THP-1 macrophages. This mechanism was demonstrated by the formation of acidic vesicular organelles, the conversion of LC3 I to LC3 II, the expression of related proteins, and the attenuation of both Dil-ox-LDL and oil red O staining. Moreover, pre-treatment with the autophagy inhibitor 3-methyladenine enhanced the HAC-SDT-induced apoptosis. Additionally, HAC-SDT-induced autophagy and apoptosis were both blocked by ROS scavenger N-acetyl-l-cysteine. CONCLUSION: The results suggested that autophagy not only played an inhibitory role in the process of apoptosis but also could effectively attenuate lipid aggregation in THP-1 macrophages during HAC-SDT. As important intracellular mediators, the ROS generated by HAC-SDT also played a crucial role in initiating apoptosis and autophagy.

Apoptosis of THP-1 Macrophages Induced by Pseudohypericin-Mediated Sonodynamic Therapy Through the Mitochondria-Caspase Pathway.

BACKGROUND/AIMS: Pseudohypericin (P-HY) and its congener hypericin are the major hydroxylated phenanthroperylenediones present in Hypericum species. Our previous study indicated that hypericin was able to function as a sonosensitizer. The potential use of P-HY as a sonosensitizer for sonodynamic therapy (SDT) requires further exploration. Thus, this study aimed to investigate the effects of P-HY-SDT on THP-1 macrophages. METHODS: THP-1 macrophages were incubated with P-HY, and cell viability was measured using a CCK-8 assay. Fluorescence microscopy assessed the intracellular reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm ) and mitochondrial permeability transition pore (mPTP) opening. Apoptotic and necrotic cell levels were measured by the flow cytometry analysis. Western blots were employed to assay BAX, Cytochrome C expression and apoptosis-related proteins. RESULTS: P-HY-SDT induced THP-1 macrophage apoptosis. The levels of ROS were significantly increased in the SDT group, resulting in both mPTP opening and ΔΨm loss, which led to apoptosis. In addition, the translocation of BAX, release of Cytochrome C and the upregulated expression of apoptosis-related proteins after P-HY-SDT were observed, all of which were reversed by N-acetyl cysteine (NAC). CONCLUSION: P-HY-SDT induced THP-1 macrophage apoptosis through the mitochondria-caspase pathway via ROS generation, the translocation of BAX and the release of Cytochrome C to regulate the mPTP opening.

Phospholipase A2-activating protein induces mitophagy through anti-apoptotic MCL1-mediated NLRX1 oligomerization.

Mitochondrial protein homeostasis is fine-tuned by diverse physiological processes such as mitochondria-associated degradation (MAD), which is regulated by valosin-containing protein (VCP) and its cofactors. As a cofactor of VCP, the mutation of phospholipase A-2-activating protein (PLAA) is the genetic cause of PLAA-associated neurodevelopmental disorder (PLAAND). However, the physiological and pathological roles of PLAA in mitochondria remain unclear. Here, we demonstrate that PLAA partially associates with mitochondria. Deficiency in PLAA increases mitochondrial reactive oxygen species (ROS) production, reduces mitochondrial membrane potential, inhibits mitochondrial respiratory activity and causes excessive mitophagy. Mechanically, PLAA interacts with myeloid cell leukemia-1 (MCL1) and facilitates its retro-translocation and proteasome-dependent degradation. The upregulation of MCL1 promotes the oligomerization of NLR family member X1 (NLRX1) and activation of mitophagy. Whereas downregulating NLRX1 abolishes MCL1 induced mitophagy. In summary, our data identify PLAA as a novel mediator of mitophagy by regulating MCL1-NLRX1 axis. We propose mitophagy as a target for therapeutic intervention in PLAAND.

Mitochondrial HSF1 triggers mitochondrial dysfunction and neurodegeneration in Huntington's disease.

Aberrant localization of proteins to mitochondria disturbs mitochondrial function and contributes to the pathogenesis of Huntington's disease (HD). However, the crucial factors and the molecular mechanisms remain elusive. Here, we found that heat shock transcription factor 1 (HSF1) accumulates in the mitochondria of HD cell models, a YAC128 mouse model, and human striatal organoids derived from HD induced pluripotent stem cells (iPSCs). Overexpression of mitochondria-targeting HSF1 (mtHSF1) in the striatum causes neurodegeneration and HD-like behavior in mice. Mechanistically, mtHSF1 facilitates mitochondrial fission by activating dynamin-related protein 1 (Drp1) phosphorylation at S616. Moreover, mtHSF1 suppresses single-stranded DNA-binding protein 1 (SSBP1) oligomer formation, which results in mitochondrial DNA (mtDNA) deletion. The suppression of HSF1 mitochondrial localization by DH1, a unique peptide inhibitor, abolishes HSF1-induced mitochondrial abnormalities and ameliorates deficits in an HD animal model and human striatal organoids. Altogether, our findings describe an unsuspected role of HSF1 in contributing to mitochondrial dysfunction, which may provide a promising therapeutic target for HD.

[Small-dose vardenafil restores erectile function after penile surgery].

OBJECTIVE: To investigate the impact of penile surgery on the erectile function of the patient and to evaluate the role of small-dose vardenafil in restoring the impaired penile erection. METHODS: Sixty cases of penile cavernosum surgery were equally and randomly divided into a vardenafil and a control group, the former treated 5 - 7 days after surgery with 10 mg vardenafil every other day, while the latter given vitamin E at 100 mg once a day, both for 12 weeks. The penile erectile function of the patients was evaluated with the IIEF-5 questionnaire before surgery and at 3 and 6 months after vardenafil medication. RESULTS: The mean IIEF-5 scores of the vardenafil group were 18.83 +/- 2.98 and 20.13 +/- 2.98 at 3 and 6 months after vardenafil medication, significantly higher than 14.21 +/- 3.62 before surgery (P > 0.05), while that of the control group was significantly decreased at 3 months as compared with the preoperative score (13.38 +/- 2.82 versus 15.80 +/- 3.02, P < 0.05). The vardenafil group showed the highest IIEF-5 score after surgery (P < 0.05). CONCLUSION: Long-term administration of small-dose vardenafil after penile surgery helps to restore and maintain penile erectile function.

[Tapping at acupoints along meridian combined with thunder-fire moxibustion for upper-limb hemiplegia after stroke].

OBJECTIVE: To observe the effect of tapping at acupoints along meridian combined with thunder-fire moxibustion on upper-limb muscle strength and activities of daily living in patients with upper-limb hemiplegia after stroke. METHODS: A total of 140 patients with upper-limb hemiplegia after stroke were randomly divided into a combination group (35 cases, 2 cases dropped off), an acupoint-tapping group (35 cases), a moxibustion group (35 cases, 2 cases dropped off) and a routine group (35 cases). The patients in the routine group were only treated with routine treatment and nursing. On the basis of the treatment in the routine group, the patients in the acupoint-tapping group were treated with tapping along the large intestine meridian of hand yangming, with Hegu (LI 4), Shousanli (LI 10), Quchi (LI 11), Shouwuli (LI 13) and Jianyu (LI 15) as the key acupoints, once a day, 10 min each time; the patients in the moxibustion group were treated with thunder-fire moxibustion at the affected-side Shousanli (LI 10), Quchi (LI 11) and their surrounding area, once a day, 15 min each time. The patients in the combination group were treated with tapping at acupoints along meridian, followed by thunder-fire moxibustion. The treatment was 6 days a week for 4 weeks in the 4 groups. The body mass index of joint activity (shoulder abduction, elbow extension, wrist flexion) and Barthel index (BI) score were observed before and after treatment in the four groups. RESULTS: Compared before treatment, body mass indexs of shoulder abduction, elbow extension, wrist flexion as well as BI scores in the four groups were significantly increased after treatment (P<0.05). After treatment, the body mass indexs of joint activity in the combination group were higher than those in the other three groups (P<0.05). The BI scores in the acupoint-tapping group, the moxibustion group and the combination group were higher than those in the routine group (P<0.05). The BI score in the combination group was higher than the acupoint-tapping group and the moxibustion group (P<0.05). CONCLUSION: Tapping at acupoints along meridian combined with thunder-fire moxibustion could effectively improve the upper-limb muscle strength and activities of daily living in patients with upper-limb hemiplegia after stroke, and its effect is superior to simple tapping at acupoints along meridian or thunder-fire moxibustion.

[Duckett's procedure of one-stage urethroplasty for hypospadias].

OBJECTIVE: To study the clinical effect of Duckett's procedure of one-stage urethroplasty with the transverse preputial island flap in the treatment of hypospadias. METHODS: We retrospectively studied 20 cases of hypospadias treated by Duckett's procedure of one-stage urethroplasty with the transverse preputial island flap (Group A) from 2003 to 2007. The patients ranged in age from 2 to 22 years (mean 11.3 years). Another 30 hypospadias patients aged 7 to 34 (mean 16.1) years underwent urethroplasty with mucous membrane of the bladder (Group B) in the same period. Of the 50 cases, 13 were the penile type, 33 the penoscrotal type, 2 the scrotal type, and 2 the perineal type. Catheters were indwelled in Group A, but both cystostomy and catheter indwelling were used in Group B. RESULTS: For Duckett's procedure, surgery succeeded in 17 cases (85%), urethra stenosis developed in 1 (5%) and urinary fistula in 2 (10%), which were successfully repaired 6 months after the operation. The mean operation frequency was 1.1 per patient. In Group B, the operation was accomplished in 2 stages and succeeded in 26 cases (86.7%), with postoperative development of urinary fistula in 3 (10%) and urethra stenosis in 1 (3.3%). The mean operation frequency was 2.1 per patient. The 2 cases of postoperative urethra stenosis were both cured by urethral sounding. CONCLUSION: Duckett's procedure of one-stage urethroplasty with the transverse preputial island flap is effective in hypospadias repair, with a success rate close to that of other types of operations and a low rate of postoperative complications. Compared with the use of mucous membrane of the bladder, it has the advantages of one-move accomplishment and gives a better penile appearance.

[Repair and functional reconstruction of the penis (a report of 62 cases)].

OBJECTIVE: To investigate the effects of surgery treatment on serious penile lesions and malformation. METHODS: Sixty-two patients, aged from 19 to 63 years old (mean 35 ys), were included in the study. Among them, 4 patients suffered from penis partial defection were respectively treated with restoring defective penis, penis lengthening and urethroplasty; three patients with penis completely missing were treated with penis reconstruction surgery; 22 cases with serious penile curvature were treated with the 16-dot plication technique (Lue's procedure); 15 cases with penile fracture were treated with conservative treatment for 1 case and with patch penis, corpus spongiosum, and deep penile dorsal vein ligation for 14 cases; 5 cases with post-operative complications of 3-pieces of penile prosthesis, including the prosthesis perforating to the urethra, water pump failure, broken connection tube, erection angle < 60 degrees and failure to expansion the corpus cavernosum, were treated by taking out prostheses, urethral repair cracks, replacement of the prostheses, excision of fibrosis scar and re-implantation prostheses respectively. Four cases with penis complete amputation were treated with the penis replantation; three cases of avulsion injury were treated with the replantation and free flap skin; 6 with Paget's disease of penises were treated with the lesion free skin buried in the scrotum and penis. RESULTS: All these patients were followed up for 3 months to 4 years, with the average of 9 months. Among the 4 cases of penis partial defection, 2 patients were satisfied with the penile appearance and sexual function; 1 got some satisfactory and 1 was unsatisfied. Three cases with the loss of the penis completely were satisfied with both the postoperative appearance and urination, and 1 was not satisfied. Twenty-two cases of penile curvature deformities were corrected, and one case was recurrence. Fourteen of the 15 patients with penile fracture were followed, and all got the restoration of sexual function. Among them, 5 cases with post-operative complications, including mild bending, algopareunia, subcutaneous induration, poor hardness and poor sexual pleasure, were not further treated, and another case lost; Five cases with post-operative complications of three-pieces penile prosthesis were treated successfully, and 4 of their spouses were satisfied with their sexual function after operation, only 1 of their spouse not satisfied. Among four cases with complete amputation of penis, two cases of penis were replanted successfully while two necrosis. Three cases with avulsion were treated with skin grafting successfully. All 6 cases with penile Paget's disease were followed for 2 -4 years, and free skin grafts were all survival. One patient died of brain metastases 18 months after operation and five cases were disease-free survival. CONCLUSION: The patients should be treated based on the procedure of andrological and urological surgery, together with microsurgical, flap or skin graft technique. The urologist should design personalized surgical procedure. Most of the patient's penis shape and erectile dysfunction can be reconstructed by our procedures, but some patients can not achieve the desired appearance or function of penis. New approaches of the treatment ought to be developed to restore both of the shape and function for those severe injury of the penis.

Mutant huntingtin inhibits the mitochondrial unfolded protein response by impairing ABCB10 mRNA stability.

Numerous studies have shown that mitochondrial dysfunction contributes to consequential phenotypes of Huntington's disease (HD), a fatal and inherited neurodegenerative disease caused by the expanded CAG repeats in the N-terminus of the huntingtin (Htt) gene. To maintain proper function, mitochondria develop a dedicated protein quality control mechanism by activating a stress response termed the mitochondrial unfolded protein response (UPRmt). Defects in the UPRmt have been linked to aging and are also associated with neurodegenerative diseases. However, little is known about the role of the UPRmt in HD. In this study, we find that ABCB10, a mitochondrial transporter involved in the UPRmt pathway, is downregulated in HD mouse striatal cells, HD patient fibroblasts, and HD R6/2 mice. Deletion of ABCB10 causes increased mitochondrial reactive oxygen species (ROS) production and cell death, whereas overexpression of ABCB10 reduces these aberrant events. Moreover, the mitochondrial chaperone HSP60 and mitochondrial protease Clpp, two well-established markers of the UPRmt, are reduced in the in vitro ABCB10-deficienct HD models. CHOP, a key transcription factor of HSP60 and Clpp, is regulated by ABCB10 in HD mouse striatal cells. Furthermore, we find that mutant huntingtin (mtHtt) inhibits the mtUPR by impairing ABCB10 mRNA stability. These findings demonstrate a suppression of the UPRmt by mtHtt, suggesting that disturbance of mitochondrial protein quality control may contribute to the pathogenesis of HD.

Author Correction: Hypericin-mediated sonodynamic therapy induces autophagy and decreases lipids in THP-1 macrophage by promoting ROS-dependent nuclear translocation of TFEB.

The authors wish to point out that in Figure 1f, the picture of DAPI in the ATG5 siRNA group is incorrect. During the process of image synthesis, the authors mixed the pictures of DAPI in the control group and ATG5 siRNA group, leading to the duplicate between them of DAPI. Furthermore, the AMPK blot and the AKT blot in Figure 2a were inadvertently duplicated with the third ß-actin in Figure 2a and AKT in Figure 4e, respectively. The authors would like to apologize for any inconvenience this may have caused.

Penile and scrotal Paget's disease: 130 Chinese patients with long-term follow-up.

OBJECTIVES: To report a retrospective series of 130 Chinese patients with penoscrotal extramammary Paget's diseases (EMPD), with a long-term follow-up, and thus improve the diagnosis and therapy of this disease. PATIENTS AND METHODS: The history, clinical presentation, pathology, treatment, and prognosis of 130 patients were analysed. All cases were confirmed by skin biopsy, and then the patients had local wide resection to remove the involved skin and subcutaneous tissue. The large defective wound was reconstructed using a split-thickness skin graft or local flap. RESULTS: Forty-five patients were evaluated by frozen-section biopsy of the margins during surgery, five of whom had positive margins and then had an extended resection immediately. Most of these patients had local skin or adjacent scrotal flaps to cover their skin defects. Of the 130 patients, 81 had a mean (range) follow-up of 3.2 (0.5-10) years after surgery. Five of nine patients with positive margins and three (4%) of 72 with negative margins had tumour recurrence. Five patients died from metastatic disease. CONCLUSIONS: Penoscrotal EMPD needs be differentiated from other chronic dermatitis. A 3 cm surgical margin should be sufficient and frozen-section pathological examinations are necessary for some complicated conditions. Skin grafts or local flaps are good for large skin defects.

Variations in climatic suitability and planting regionalization for potato in northern China under climate change.

Investigating the variations in crop climatic suitability and planting regionalization can provide scientific evidence for ensuring food security under climate change. In this study, variations in climatic suitability and planting regionalization for the potato in northern China were investigated based on daily data from 1965 to 2014 collected at 321 agro-meteorological observation stations located throughout the region. Northern China was divided into three areas, including Northwest China, North China and Northeast China. The agricultural climatic suitability theory and the fuzzy mathematics method were applied. The potato growth seasons were divided into threestages:from sowing to emergence, from emergence to flowering and from flowering to maturity. The comprehensive climatic suitabilityindex (C), which varied from 0 to 1, was established to evaluate the effects of climate change on potato planting. The results showed that, from 1965 to 2014, the C value in the study area increased 0.002 every ten years over the past 50 years with an average of 0.706, benefitting potato growth in the vast area of northern China. Nonetheless, precipitation was found to be the main climatic factor restricting potato growth in northern China. For spatial distribution, the C value showed a gradually declining trend from east to west, decreasing westward and southward over the past 50 years. For the growth season, the C value varied during different potato growth stages over the past 50 years. The C value increased during the sowing-emergence stage and decreased during the emergence-flowering stage and the flowering-maturity stage. The decreased C during the later growth stages would directly affect the quality and yield of the potato, mainly because the flowering-maturity stage was associated with potato tuber enlargement and starch accumulation. Variations in potato planting regionalization in northern China over the past 50 years were evident. Climate change was more beneficial to potato cultivation in northeast China where the highly suitable areas had clearly expanded. However, potato cultivation was most negatively affected in northwest China where the middle suitable areas had receded. Our findings have important implications for improving climate change impact studies and agricultural production to cope with ongoing climate change.

ROS-Dependent Activation of Autophagy through the PI3K/Akt/mTOR Pathway Is Induced by Hydroxysafflor Yellow A-Sonodynamic Therapy in THP-1 Macrophages.

Monocyte-derived macrophages participate in infaust inflammatory responses by secreting various types of proinflammatory factors, resulting in further inflammatory reactions in atherosclerotic plaques. Autophagy plays an important role in inhibiting inflammation; thus, increasing autophagy may be a therapeutic strategy for atherosclerosis. In the present study, hydroxysafflor yellow A-mediated sonodynamic therapy was used to induce autophagy and inhibit inflammation in THP-1 macrophages. Following hydroxysafflor yellow A-mediated sonodynamic therapy, autophagy was induced as shown by the conversion of LC3-II/LC3-I, increased expression of beclin 1, degradation of p62, and the formation of autophagic vacuoles. In addition, inflammatory factors were inhibited. These effects were blocked by Atg5 siRNA, the autophagy inhibitor 3-methyladenine, and the reactive oxygen species scavenger N-acetyl cysteine. Moreover, AKT phosphorylation at Ser473 and mTOR phosphorylation at Ser2448 decreased significantly after HSYA-SDT. These effects were inhibited by the PI3K inhibitor LY294002, the AKT inhibitor triciribine, the mTOR inhibitor rapamycin, mTOR siRNA, and N-acetyl cysteine. Our results demonstrate that HSYA-SDT induces an autophagic response via the PI3K/Akt/mTOR signaling pathway and inhibits inflammation by reactive oxygen species in THP-1 macrophages.

Berberine-sonodynamic therapy induces autophagy and lipid unloading in macrophage.

Impaired autophagy in macrophages accompanies the progression of atherosclerosis and contributes to lipid loading in plaques and ineffective lipid degradation. Therefore, evoking autophagy and its associated cholesterol efflux may provide a therapeutic treatment for atherosclerosis. In the present study, berberine-mediated sonodynamic therapy (BBR-SDT) was used to induce autophagy and cholesterol efflux in THP-1 macrophages and derived foam cells. Following BBR-SDT, autophagy was increased in the macrophages, autophagy resistance in the foam cells was prevented, and cholesterol efflux was induced. The first two effects were blocked by the reactive oxygen species scavenger, N-acetyl cysteine. BBR-SDT also reduced the phosphorylation of Akt and mTOR, two key molecules in the PI3K/AKT/mTOR signaling pathway, which is responsible for inducing autophagy. Correspondingly, treatment with the autophagy inhibitor, 3-methyladenine, or the PI3K inhibitor, LY294002, abolished the autophagy-induced effects of BBR-SDT. Furthermore, induction of cholesterol efflux by BBR-SDT was reversed by an inhibition of autophagy by 3-methyladenine or by a small interfering RNA targeting Atg5. Taken together, these results demonstrate that BBR-SDT effectively promotes cholesterol efflux by increasing reactive oxygen species generation, and this subsequently induces autophagy via the PI3K/AKT/mTOR signaling pathway in both 'normal' macrophages and lipid-loaded macrophages (foam cells). Thus, BBR-SDT may be a promising atheroprotective therapy to inhibit the progression of atherosclerosis and should be further studied.