2017年 · 第130卷第24期

Prior studies have reported controversial conclusions regarding the risk of adverse cardiovascular events in patients using proton-pump inhibitors (PPIs) combined with clopidogrel therapy, causing much uncertainty in clinical practice. We sought to evaluate the safety of PPIs use among high-risk cardiovascular patients who underwent percutaneous coronary intervention (PCI) in a long-term follow-up study.

A total of 7868 consecutive patients who had undergone PCI and received dual antiplatelet therapy (DAPT) at a single center from January 2013 to December 2013 were enrolled. Adenosine diphosphate (ADP)-induced platelet aggregation inhibition was measured by modified thromboelastography (mTEG) in 5042 patients. Propensity score matching (PSM) was applied to control differing baseline factors. Cox proportional hazards regression was used to evaluate the 2-year major adverse cardiovascular and cerebrovascular events (MACCEs), as well as individual events, including all-cause death, myocardial infarction, unplanned target vessel revascularization, stent thrombosis, and stroke.

Among the whole cohort, 27.2% were prescribed PPIs. The ADP-induced platelet aggregation inhibition by mTEG was significantly lower in PPI users than that in non-PPI users (42.0±30.9% vs. 46.4±31.4%, t = 4.435, P< 0.001). Concomitant PPI use was not associated with increased MACCE through 2-year follow-up (12.7% vs. 12.5%, χ² = 0.086, P= 0.769). Other endpoints showed no significant differences after multivariate adjustment, regardless of PSM.

In this large cohort of real-world patients, the combination of PPIs with DAPT was not associated with increased risk of MACCE in patients who underwent PCI at up to 2 years of follow-up.

Debate on treatment for young patients with coronary artery disease still exists. This study aimed to investigate the intermediate- and long-term outcomes between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in patients aged 18–45 years with diabetes mellitus (DM).

Between January 2006 and March 2016, a total of 2018 DM patients aged 18–45 years including 517 cases of CABG and 1501 cases of PCI were enrolled in the study. Using propensity score matching (PSM), 406 patients were matched from each group. The intermediate- and long-term data were collected. The primary end point of this study was long-term death. The secondary end points included long-term major adverse cardiovascular and cerebrovascular events (MACCEs), stroke, angina, myocardial infarction (MI), and repeat revascularization.

Before PSM, the in-hospital mortality was 1.2% in the CABG group and 0.1% in the PCI group, with statistically significant difference (P < 0.0001). The 10-year follow-up outcomes including long-term survival rate and freedom from MACCEs were better in the CABG group than those in the PCI group (97.3% vs. 94.5%, P= 0.0072; 93.2% vs. 86.3%, P< 0.0001), but CABG group was associated with lower freedom from stoke compared to PCI group (94.2% vs. 97.5%, P= 0.0059). After propensity score-matched analysis, these findings at 10-year follow-up were also confirmed. Freedom from MACCEs was higher in CABG group compared to PCI group, but no significant difference was observed (93.1% vs. 89.2%, P= 0.0720). The freedom from recurrent MI was significantly higher in CABG patients compared with PCI patients (95.6% vs. 92.5%, P= 0.0260). Furthermore, CABG was associated with a higher rate of long-term survival rate than PCI (97.5% vs. 94.6%, P= 0.0403). There was no significant difference in the freedom from stroke between CABG and PCI groups (95.3% vs. 97.3%, P= 0.9385). The hospital cost was greater for CABG (13,936±4480 US dollars vs. 10,926±7376 US dollars, P< 0.0001).

In DM patients aged 18–45 years, the cumulative survival rate, and freedom from MI and repeat revascularization for CABG were superior to those of PCI. However, a better trend to avoid stroke was observed with PCI.

For patients with a brain metastasis (BM), systemic therapy is usually administered after the completion of radiotherapy, especially in cases of multiple BMs. However, the role of systemic therapy in patients with a limited number of BMs is not clear. Therefore, we conducted a retrospective study to explore this question.

Consecutive patients with a pathologically confirmed malignancy and 1–3 intracranial lesions that had been documented within the last decade were selected from the databases of three hospitals in China.

A total of 250 patients were enrolled; of them, 135 received radiotherapy alone and 115 received radiotherapy plus systemic therapy. In patients receiving whole-brain radiation therapy (WBRT) as radiotherapy, 28 received WBRT alone and 35 patients received WBRT plus systemic therapy. Of the patients treated with stereotactic radiosurgery (SRS), 107 received SRS alone and 80 received SRS plus systemic therapy. Multivariate analysis revealed that systemic therapy significantly reduced the risk of mortality compared with radiotherapy alone (hazard ratio [HR] = 0.294, 95% confidence interval [CI] = 0.158- 0.548). Further, when the analysis was conducted in subgroups of WBRT (HR = 0.230, 95% CI = 0.081- 0.653) or SRS (HR = 0.305, 95% CI = 0.127–0.731), systemic therapy still showed the ability to reduce the risk of mortality in patients with BMs.

Systemic therapy after either SRS or WBRT radiotherapy may significantly reduce the risk of mortality of patients with 1–3 BMs.

The location of facial port-wine stain (PWS) may be helpful for predicting some associated anomalies; high glaucoma incidence is found in patients with eyes close to PWS-affected areas (V1, ophthalmic branch area of the trigeminal nerve). This study aimed to investigate the characteristics of glaucoma in V1-affected PWS.

A total of 569 patients with V1 area-affected PWS were reviewed in the study. The large series was based on the referral system between the Department of Plastic and Reconstructive Surgery and the Department of Ophthalmology. All patients were screened for glaucoma with assessments of intraocular pressure, cup-to-disc ratio, corneal diameter (only for infants), and axial length.

Of the 569 patients, 110 (19.3%) patients had glaucoma. Among the patients, 18.1% (76/420) had early-onset glaucoma (under 4-year-old group). In the 4 to 18-year-old age group, 29.3% (29/99) of the patients had glaucoma. Compared with right lateral and bilateral PWS, left-sided PWS had a lower risk of glaucoma in this study (odds ratio = 0.432 [95% confidence interval, 0.264- 0.706], P= 0.01). The under 4-year-old group showed a slight predominance of males (61.8%) in glaucoma.

High glaucoma incidence was observed in patients with eyes close to PWS. More attention should be paid to glaucoma screening for right lateral and bilateral PWS patients. The predominance of males in Sturge–Weber syndrome (SWS) early-onset glaucoma patients might be due to the limitation of the case number; however, it might also provide us a new clue of potential relationship between SWS and PCG.

Descemet’s stripping automated endothelial keratoplasty (DSAEK) surgery offers a more standardized approach and reliable method to create corneal grafts with an instrument such as a microkeratome. With the development of Descemet’s membrane endothelial keratoplasty, an excellent clinical outcome is seen in the treatment of corneal endothelial dysfunctions, which indicates that thinner corneal graft results in better clinical outcome. With the recent development of the femtosecond laser, ultrathin corneal graft preparation has become possible. This study aimed to report corneal graft endothelial cell loss (ECL) in a large series of cases undergoing DSAEK with femtosecond laser-assisted corneal graft preparation within a 12-month period.

This study was designed as a prospective, noncomparative, interventional case series. Totally 126 consecutive eyes with endothelial failure of 120 patients, who had corneal endothelial decompensation and underwent femtosecond-assisted DSAEK using the VisuMax femtosecond laser system, were included in the study. Central endothelial cell density (ECD) was recorded postoperatively at 2 weeks (n = 126), 1 month (n = 126), 3 months (n = 110), 6 months (n = 101), and 12 months (n = 71) and then compared with the preoperative eye bank measurements. Pre- and postoperative central ECDs were evaluated using Heidelberg retina tomography-III confocal microscopy. ECL was calculated for each postoperative time point. Graft thickness was examined using anterior segment-optical coherence tomography.

Mean preoperative cell count was 3383±350 cells/mm². Mean postoperative cell counts were 2382±707 cells/mm², 2179 ± 685 cells/mm², 2074 ± 688 cells/mm², 1884 ± 662 cells/mm², and 1723 ± 624 cells/mm² at 2 weeks, 1, 3, 6, and 12 months, respectively; these represented the ECL of 29.7 ± 19.7%, 35.4 ± 19.5%, 38.6 ± 19.8%, 44.3 ± 18.9%, and 48.9 ± 18.4% at the each corresponding time point. The mean corneal graft thickness after surgery was 142 ± 48µm, 118 ± 41 µm, 108 ± 37 µm, 100 ± 32 µm, and 99 ± 32 µm at each corresponding study visit, respectively. There was no correlation between corneal graft thickness and corneal ECL (R = 0.039).

Corneal ECL remained relatively stable up to 12 months after femtosecond laser-assisted ultrathin DSAEK in a large case series. No correlation between cell loss and corneal graft thickness was found, which indicated that corneal graft preparation by the femtosecond laser was safe. ECL was faster within the first 6 months and relatively stable thereafter.

Some problems have been found in the usually adopted combined approach for the removal of intra-extracranial tumors in skull base. Herein, we described a pure endoscopic transnasal or transoral approach (ETA) for the removal of intra-extracranial tumors in various skull base regions.

Retrospectively, clinical data, major surgical complications, pre- and postoperative images, and follow-up information of a series of 85 patients with intra-extracranial tumors in various skull base regions who were treated by surgery via ETA in our skull base center during the past 10 years were reviewed and analyzed.

Gross total tumor removal was achieved in 80/85 cases (94.1%) in this study. All 37 cases with tumors in anterior skull base and all 14 cases with tumors in jugular foramen received total tumor removal. Thirteen and three cases with tumors in clivus received total and subtotal tumor removal, respectively. Total and subtotal tumor removal was performed for 16 cases and 2 cases in lateral skull base, respectively. The complications in this study included: cerebrospinal fluid leakage (n = 3), meningitis (n = 3), and new cranial nerve deficits (n = 3; recovered in 3 months after surgery). In the follow-up period of 40–151 months (median: 77 months), seven patients (8.8%) out of the 80 cases of total tumor removal experienced recurrence.

Complete resection of intra-extracranial growing tumors in various skull base regions can be achieved via the pure ETA in one stage in selected cases. Surgical procedure for radical removal of tumors is feasible and safe.

Amyloid-β deposition and accumulation of autophagic vacuoles are pathologic features of Alzheimer’s disease (AD). Dysregulation of the endosomal–autophagic–lysosomal (EAL) pathway, which impairs amyloid precursor protein processing, is one of the earliest changes in AD. However, the precise role of EAL pathway in neurodegeneration remains unclear. This study aimed to investigate the role of EAL pathway in AD and further study the mechanism of EAL dysfunction.

We used 3-, 7-, and 12-month-old APPswe/PSEN1dE9 (APP/PS1) mice to model different stages of AD with age- and gender-matched wild-type littermates as controls (4–7 mice per group) and detected the changes of EAL markers, endosomal organizers Rab5 and Rab7, autophagosome marker LC3B, and lysosomal proteins Lamp1/2 in cortex and hippocampus by immunohistochemistry and Western blotting analysis. To further explore the mechanism of EAL dysregulation in AD, components of the class III phosphatidylinositol 3-kinase (PI3KC3) complex, activators of Rab7 (Beclin1 and UVRAG), and the negative regulator of Rab7 (Rubicon) were also measured in this two brain regions.

In 7-month-old APP/PS1 brain that amyloid beta initiated to accumulate intracellularly, EAL pathway, and related PI3KC3 members, UVRAG and Beclin1 were upregulated both in cortex and hippocampus (all P< 0.05). By the age of 12 months old, when abundant amyloid plaques formed, EAL markers, UVRAG, and Beclin1 were also upregulated in the cortex (all P< 0.05). However, Rab7 was decreased significantly (P = 0.0447), accompanied by a reduction of its activating PI3KC complex component Beclin1 (P = 0.0215) and enhancement of its inhibiting component Rubicon (P = 0.0055) in the hippocampus.

Our study implies that EAL pathway, represented as Rab7 and its PI3KC3 regulators’ expressions, showed temporal and spatial variation in brains at different stages of AD. It provides new insights into the role of EAL pathway in pathogenesis and indicates potential therapeutic targets in neurodegenerative diseases.

Both Mitofusin 2 (Mfn2) and pelvic organ prolapse (POP) are related to aging. The aim of the present study was to investigate the variations of Mfn2 expression in the uterosacral ligaments of patients with and/or without POP and their correlations with the expression of procollagen.

Fibroblasts were cultured using tissue specimens that were harvested from the uterosacral ligaments of POP and non-POP (NPOP) patients (n = 10 for each group) from September 2016 to December 2016. The Cell Counting Kit-8 (CCK-8) assay was used to compare the differences in cell proliferation between the two groups. Relative quantitative reverse transcription-polymerase chain reaction and Western blotting assays were employed to assess the differences in the mRNA and protein expression levels of Mfn2 and procollagen 1A1/1A2/3A1 between the two groups. The changes in procollagen expression were assessed following the downregulation of Mfn2 in the POP group using RNAi. The data were assessed with independent sample t-test or general linear model univariate analysis using the SPSS 13.0 software.

The results from CCK-8 assay indicated that cell viability in the POP group was significantly lower compared with that of the NPOP group (t_d5,7,9,11= −5.925, −6.851, −9.129, and −9.661, respectively, all P< 0.001, from D5 to D11). The mRNA and protein expression levels of Mfn2 in the cultured fibroblasts of the POP group were significantly higher compared with those of the NPOP group (mRNA: t = 2.425, P= 0.032; protein: t = 2.392, P= 0.037, respectively), whereas only the expression levels of procollagen 1A1/1A2/3A1 were significantly higher in the NPOP group (mRNA: t= −2.165, P_1A1 = 0.041; t= −2.741, P_1A2 = 0.026; t= −2.147, P_3A1 = 0.045, respectively; protein: t= −2.418, P_1A1 = 0.029; t= −2.405, P_1A2 = 0.033; t= −2.470, P_3A1 = 0.012, respectively). The expression levels of procollagen in the POP group increased following the downregulation of Mfn2.

The proliferation rate and cell viability of the fibroblasts in the POP group were significantly lower compared with those in the NPOP group. In the POP fibroblasts, Mfn2 expression was increased, while procollagen expression was decreased.

Root avulsion to all 5 roots of the brachial plexus is a common presentation and keeps a major reconstructive challenge. The contralateral C7 (CC7) nerve transfer has been used in treating brachial plexus avulsion injury (BPAI) since 1986. However, the effectiveness of the procedure remains a subject of controversy. The aim of this meta-analysis was to study surgical outcomes regarding motor and sensory recovery after CC7 nerve transfer.

Chinese or English (i.e., "contralateral c-7" , "contralateral c7" , "c7 nerve root" , and "seventh cervical nerve root" ) keywords were used for a literature search for articles related to CC7 nerve transfer in several databases (i.e., PubMed, Cochrane, Embase, CNKI, CQVIP, and Wanfang Data). Clinical research articles were screened, and animal studies as well as duplicate publications were excluded. Muscle strength and sensory recovery were considered to be effective only when the scores on the United Kingdom Medical Research Council scale were equal to or higher than M3 and S3, respectively.

The overall ipsilateral recipient nerve recovery rates were as follows: the efficiency rate for muscle strength recovery after CC7 nerve transfer was 0.57 (95% confidence interval [CI]: 0.48- 0.66) and for sensory recovery was 0.52 (95% CI: 0.46–0.58). When the recipient nerve was the median nerve, the efficiency rate for muscle strength recovery was 0.50 (95% CI: 0.39- 0.61) and for sensory was 0.56 (95% CI: 0.50–0.63). When the recipient nerve was the musculocutaneous nerve and the radial nerve, the efficiency rate for muscle strength recovery was 0.74 (95% CI: 0.65- 0.82) and 0.50 (95% CI: 0.31- 0.70), respectively.

Transfer of CC7 nerves to musculocutaneous nerves leads to the best results. CC7 is a reliable donor nerve, which can be safely used for upper limb function reconstruction, especially for entirely BPAI. When modifying procedures, musculocutaneous nerves and median nerve can be combined as recipient nerves.

Antiplatelet therapy (APT) was prevalently being used in the prevention of vascular disease, but the influence of prior APT on the prognosis of patients with intracerebral hemorrhage (ICH) remains controversial. This meta-analysis was to explore the effects of prior APT on the prognosis of patients with primary ICH.

PubMed and Embase were searched to identify the eligible studies. The studies comparing the mortality of ICH patients with or without prior APT were included. The quality of these studies was evaluated by the Newcastle–Ottawa quality assessment scale. The adjusted or unadjusted odds ratio (OR) for mortality between ICH patients with and without prior APT were pooled with 95% confidence interval (95% CI) as the effect of this meta-analysis.

Twenty-two studies fulfilled the inclusion criteria and exhibited high qualities. The pooled OR was 1.37 (95% CI: 1.13–1.66, P= 0.001) for univariate analysis and 1.41 (95% CI: 1.05–1.90, P= 0.024) for multivariate analysis. The meta-regression indicated that for each 1-day increase in the time of assessment, the adjusted OR for the mortality of APT patients decreased by 0.0049 (95% CI: 0.0006–0.0091, P= 0.026) as compared to non-APT patients.

Prior APT was associated with high mortality in patients with ICH that might be attributed primarily to its strong effect on early time.

To review recent research advances on tau, a major player in Alzheimer’s disease (AD) pathogenesis, a biomarker for AD onset, and potential target for AD therapy.

This review was based on a comprehensive search using online literature databases, including PubMed, Web of Science, and Google Scholar.

Literature search was based on the following keywords: Alzheimer’s disease, tau protein, biomarker, cerebrospinal fluid (CSF), therapeutics, plasma, imaging, propagation, spreading, seeding, prion, conformational templating, and posttranslational modification. Relevant articles were carefully reviewed, with no exclusions applied to study design and publication type.

Amyloid plaques enriched with extracellular amyloid beta (Aβ) and intracellular neurofibrillary tangles comprised of hyperphosphorylated tau proteins are the two main pathological hallmarks of AD. Although the Aβ hypothesis has dominated AD research for many years, clinical Aβ-targeting strategies have consistently failed to effectively treat AD or prevent AD onset. The research focus in AD has recently shifted to the role of tau in AD. In addition to phosphorylation, tau is acetylated and proteolytically cleaved, which also contribute to its physiological and pathological functions. Emerging evidence characterizing pathological tau propagation and spreading provides new avenues for research into the molecular and cellular mechanisms underlying AD pathogenesis. Techniques to detect tau at minute levels in CSF and blood have been developed, and improved tracers have facilitated tau imaging in the brain. These advances have potential to accurately determine tau levels at early diagnostic stages in AD. Given that tau is a potential therapeutic target, anti-tau immunotherapy may potentially be a viable treatment strategy in AD intervention.

Detecting changes in tau and targeting tau pathology represent a promising lead in the diagnosis and treatment of AD.

The optimal management strategy for prostate cancer (PCa) remains controversial. We performed a systemic review of current progress and controversies regarding the diagnosis and treatment of PCa.

We searched PubMed for recently published articles up to July 2017 using the following key words: "prostate cancer," "progress," "controversy," "immunotherapy," and "prevention."

Articles were obtained and reviewed to provide a systematic review of the current progress and controversies regarding PCa management.

The value of serum prostate-specific antigen (PSA) screening remains controversial, but PSA screening is recommended to facilitate the early diagnosis of PCa in high-risk groups. Prostate biopsy via the transrectal or perineal approach has both advantages and disadvantages. There was a significant correlation between testosterone levels and PCa prognosis. The current research is focused on the mechanisms responsible for PCa. Active surveillance has been proposed as a management strategy for low-risk, localized PCa, but there is an urgent need for further clinical studies to establish the criteria for recommending this approach. The main complications of radical resection for PCa are urinary incontinence and erectile dysfunction, though three-dimensional laparoscopic and robot-assisted laparoscopic techniques have obvious advantages over radical surgery. Radiotherapy is also a therapeutic option for PCa, while immunotherapies may alter the prostate tumor microenvironment. Ongoing studies aim to provide guidance on effective sequential and combination strategies. Prevention remains an important strategy for reducing PCa morbidity and mortality.

The diagnosis, treatment, and prevention of PCa are complex issues, worthy of intensive study. Further studies are needed to improve the management of PCa.

Peripheral nerve injury is a common clinical problem because the dysfunction of distal limb seriously affects patients’ quality of life, and it results in a huge social and economic burden.^[1]Repair of peripheral nerve injury is a very complex pathological process. Due to slow nerve regeneration, Wallerian degeneration of nerve stump, tissue adhesion, atrophy of muscles and motor end plates and other constraints, functional rehabilitation of the damaged nerve is always restricted. The ultimate goal of repairing peripheral nerve injuries is to restore the function of the distal target organs to their original level in both sensory and motor aspect. At present, the foreign as well as the domestic researches on peripheral nerve injury mainly focus on the methods of nerve repair, promotion of axonal growth, and the functional remodeling paralleled with anatomical restoration.

Reportedly, maxillary premolars are the most complex teeth for performing endodontic treatment,^[1]with root canals varying based on race, genetic predisposition, diet, region, gender,^[2]and perhaps age. To date, few detailed studies have been conducted to assess number of roots and root canal morphology of maxillary premolars in the elderly. The present study analyzed root canal morphology of maxillary premolars in elderly individuals using cone-beam computed tomography (CBCT), which has substantial clinical value in guiding endodontic treatment.^[3]

Mild thyroid stimulating hormone (TSH) elevations are highly prevalent whereas large proportion of individuals with TSH elevations is without chronic autoimmune thyroid diseases. TSH secretion exhibits a daily circadian rhythm, and we previously reported that individuals with sleep disorders have significantly higher TSH levels than controls.^[1]In this study, we evaluated the ratio of isolated TSH elevation in individuals with night-sleep restricted and re-evaluate which when night-sleep was recovered.

Mercury is usually added to skin-lightening products due to its whitening effect. The Food and Drug Administration (FDA) limits the amount of mercury in cosmetics to trace amounts under 1 ppm. Nevertheless, many cosmetics contain mercury above 1000 ppm to increase the whitening effect. In a group of special patients in the study, pain, renal damage, and neuropsychiatric symptoms were the cardinal symptoms observed.

Drug-induced liver injury (DILI) is one of the most common and serious adverse drug reactions. Idiosyncratic DILI is more common than intrinsic DILI and can be classified into hepatocellular injury, cholestatic injury, mixed hepatocellular-cholestatic injury, and vascular injury.^[1]Lepidium meyenii(Maca) has been intensively studied since its diverse repertoire of pharmacological properties. These experimental studies have not found any evidence ofin vivoorin vitrotoxicity associated with either long- or short-term consumption.^[2]Here, we reported a case of liver injury that was probably directly induced by Maca, suggesting that the safety of Maca should be evaluated by further studies.

The major mechanism for ring chromosome formation is thought to result from breakage and reunion at the breakpoints on the long and short arms of a chromosome. This fusion event can produce terminal arm inversions, deletions, and duplications that determine the resulting phenotype.^[1]Ring chromosome 13 is relatively uncommon, with an estimated incidence of 1/58,000 live births. Clinical severity of ring chromosome 13 syndrome is broad and influenced by the stability of the ring as well as the extent of the deletions and/or duplications along chromosome 13.^[2]Prenatal diagnosis of ring chromosome 13 is very rare. Here, we present a prenatal case with molecular cytogenetic characterization of mosaic ring chromosome 13 syndrome in a fetus with multiple abnormal ultrasound findings.

Primary pigmented nodular adrenocortical disease (PPNAD) causes adrenocorticotropic hormone (ACTH)-independent Cushing’s syndrome (CS), which is the most frequent endocrine manifestation of Carney complex (CNC).^[1]In the disease process of PPNAD, both presadrenal glands are involved and feature small brown-black nodules separated by the atrophic adrenal cortex. Endocrine lesions in CNC include testicular neoplasms, PPNAD, growth hormone (GH) and prolactin-producing pituitary tumors, and thyroid cancer.^[2]It is a genetically heterogeneous autosomal dominant disease. Mutations of the regulatory subunit type 1A of the cAMP-dependent protein kinase (PRKAR1A) gene are found in nearly 60% of individuals with CNC, whereas an uncharacterized gene at the CNC2 locus on chromosome 2p16 is similarly implicated in disease pathogenesis.^[2]Here, we present the case of a Chinese young girl with PPNAD.

Left atrial appendage aneurysm (LAAA) is an extremely rare cardiac anomaly which is mainly characterized by localized or diffuse dilatation of left atrial appendage.^[1]This condition with diverse symptoms including arrhythmia, thromboembolic events, and heart failure confuses physician and is easily misdiagnosed.^[2]We herein report a case of huge LAAA which is misdiagnosed originally.

Intra-abdominal pregnancy is rare and affects approximately 1 in 10,000 births. It occurs in 1.4% of ectopic pregnancies and carries a mortality rate of 5.1/1000 cases, 7.7 times higher compared with nonabdominal ectopic pregnancies. This study aimed to present a case of a live 14-week primary hepatic ectopic pregnancy diagnosed using ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) and managed using laparoscopic microsurgery.

To the Editor: Permethrin is a great handmade of chemical agents, pyrethroid Type I, which exists in two main isomers, Cis and Trans.^[1]Its application in farming and building is due to well availability and repelling of pests. It may be easy absorbed from the gastrointestinal and skin tract and by inhalation of dust.^[2,3]They are great chemicals with high producing of reactive oxygen species and inducer of necrosis pathway. Inadequate information of using permethrin resulted in many side effects on biological systems. Spermatogenesis is one of the main vital systems susceptible to reactive oxygen species and oxidative stress.^[4]Since spermatogenesis takes place in the testis, any chemical agent like permethrin could be destroyed cellular structure and function and leads to infertility.^[5]On the other hand, done studies for confronting these effects were mostly focused on reducing infertility rate and proposing the best way to treatment. Most studies represent a varied range of antioxidants to solving male infertility.Allium cepa(onion), a natural antioxidant, was used in traditional medicine. It protects DNA and other important molecules from oxidative stress and improves sperm parameters, so leads to increase fertility rate.^[6]

To the Editor: Tuberous sclerosis complex (TSC), a rare autosomal dominant and variable penetrance, affects about 10 in every 100,000 people.^[1]In general, it is described as a clinical triad of adenomas, mental disorders, and seizures. However, due to incomplete penetrance, symptoms may be involved in isolated organs, which may manifest as mild incomplete diseases or involve multiple organs. Pulmonary lymphangiomyomatosis (LAM) associated with both renal and hepatic angiomyolipomas (AMLs) in a TSC patient is very rare. To the best of our knowledge, only one case has been reported by Ciftciet al.^[2]Here, we present such a case with clinical and pathological analysis.

To the Editor: Synovial sarcoma (SS) is a relatively rare type of soft tissue sarcoma that constitutes approximately 8% of all soft tissue sarcomas. SS frequently occurs in the para-articular structures of the limbs and is predominantly found in the lower limbs. The other involved locations of invasion are lung, lymph nodes, and bone. However, the skin is rarely involved.^[1,2,3]Here, we reported an extremely rare case of biphasic SS presenting with disseminated cutaneous metastases.

To the Editor: Mutations in the mitochondrial alanyl-tRNA synthetase 2 gene (AARS2) have been recently found to lead to chronic progressive leukodystrophy or infantile cardiomyopathy. Up to date, there have been 15 patients reported with chronic progressive leukodystrophy. Notably, all the female patients (9/15) present with ovarian failure, described as "ovarioleukodystrophy."^[1,2,3,4]Herein, we report a female patient with progressive adult-onset leukodystrophy without ovarian failure due to compound heterozygous mutations inAARS2.

To the Editor: A 65-year-old woman presented with a cutaneous red-brown plaque on the left posterior thigh for the past 7 years. Initially, the lesion was a slightly elevated, well-demarcated plaque with a smooth surface and was about 1 cm in diameter, without any symptoms. Over the years, it slowly extended into an elevated plaque with rough surface, frequently bleeding after slight friction. Physical examination revealed an obviously elevated, well-demarcated red-brown plaque (3.0 cm × 2.7 cm) covered by crusts on the left posterior thigh [Figure 1a], with slightly tenderness. Biopsy showed hyperkeratosis and parakeratosis. Acanthosis with irregular elongation of the rete ridges was in the involved epidermis [Figure 1b]. There were clear cells (some contained large cytologically atypical nuclei stained dark) [Figure 1c] in the stratum spinosum, and the basement membrane was not involved. Immunohistochemical findings revealed negative for PAS [Figure 1d], S100, HMB-45, CEA, and GCDFP15 [Figure 1e], positive for Ki-67 (<30%), CK34βE12 [Figure 1f], and P63 [Figure 1g], and weakly positive for CAM5.2 [Figure 1h]. The diagnosis of pagetoid Bowen’s disease (BD) is definite. Later, a wide local excision (1.0 cm margin) was performed with negative margins of resection. Among all the histological variants of BD, pagetoid BD has been reported to occur in only 4.6% of BD. Unlike typical BD, pagetoid BD commonly presents in the upper and lower extremities, followed by head/neck and trunk area, with very rare cases appearing in the external genitalia location.^[1]In this case, the lesion first appeared to be nevoid, suggesting that it might be secondary to a preexisting nevocellular nevus. It is also reported that a few cases of classic BD arise in the preexisting skin lesions such as seborrheic keratosis.^[2]Histologically, pagetoid BD is characterized by nests of atypical keratinocytes with round nuclei and abundant pale cytoplasm located either singularly or in groups within the epidermis, and the main differential diagnosis of pagetoid cells includes extra-mammary pagetoid disease (EMPD) and malignant melanomain situ(MIS). Similar to classic BD, pagetoid BD always shows full-level involvement of the epidermis, scattered multinucleated tumor giant cells, keratohyalin granules, single-cell keratinization, and intercellular bridges visible between pagetoid cells, while EMPD lesion contains pagetoid cells well demarcated from nearby epidermal cells, flattened basal layer, stratum corneum involved, acinar structures, and no intercellular bridge. Well-demarcated pagetoid cells and stratum corneum involved can occur in MIS lesion; in contrast, follicular extension shows up in MIS only. Immunohistochemical tests are always helpful. The melanocytic markers such as S100, melan-A, and HMB-45 show great value in distinguishing MIS from pagetoid BD as only MIS lesions tend to be stained positive. CK34βE12 shows that the cells may stem from keratinocyte. CEA and GCDFP15 illustrate that the cells are probably from sweat glands. CAM5.2 and Ber-EP4 are generally considered to support the diagnosis of EMPD;^[3]however, some cases of pagetoid BD show positive for them.^[4]Recent studies suggest that p63 might be a useful marker as it stains atypical keratinocytes of BD but not EMPDs.^[5]This patient’s tissue [Supplementary Table 1] shows positive for P63, Ki-67 (<30%), and CK34βE12, weakly positive for CAM5.2, and negative for PAS, S100, HMB-45, CEA, and GCDFP15. Based on these findings, MIS and EMPD can be excluded; a diagnosis of pagetoid BD was confirmed.

In the article titled "Shanghai Score: A Prognostic and Adjuvant Treatment-evaluating System Constructed for Chinese Patients with Hepatocellular Carcinoma after Curative Resection" , published on pages 2650-2660, Issue 22, Volume 130 inChinese Medical Journal,^[1]the website address "http://115.28.66.83/pro/theme/admin_4/shanghai.php" was incorrectly written as "http://www.115.28.66.83/pro/theme/admin_4/shanghai.php" on page 2, 5^thline, under Introduction paragraph.