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Purpose: To determine the morphology and postoperative outcomes of pediatric cataracts with thin (leptophakic) lenses., Design: Retrospective comparative clinical cohort study., Methods: We identified the records of pediatric patients who had undergone cataract surgery between 2018 and 2023 and lens thickness less than 2 standard deviations of age-stratified normal eyes in the general population. Matching controls were identified based on sex, age at surgery, and intraocular lens implant status. Data abstracted include axial length, anterior chamber depth, lens thickness, visual acuity, intraocular pressure, and surgical details., Results: A total of 13 eyes from 7 patients were identified to be leptophakic, 8 of which had matching controls. Compared with the control eyes, leptophakic eyes had thinner lenses (2.74 ± 0.39 mm vs 4.82 ± 1.01 mm, P < .01) with comparable anterior chamber depth (3.28 ± 0.76 mm vs 2.98 ± 1.28 mm, P = .13) and axial lengths (19.17 ± 2.61 mm vs 20.76 ± 1.76 mm, P = .20). Following cataract surgery, visual acuity improved for both the leptophakic and control cohorts within 2.5 months postoperatively (-0.68 ± 0.37 logMAR vs -0.06 ± 0.42 logMAR, P = .03) and at 1-2 years postoperatively (-1.58 ± 1.03 logMAR vs -0.60 ± 0.49 logMAR, P = .22) without any glaucoma-related adverse events. Of note, 5 of 13 leptophakic eyes (38%) were found to have posterior capsular ruptures intraoperatively., Conclusions: Leptophakic eyes demonstrated similar intraoperative and short-term postoperative outcomes when compared to control eyes, although vigilance for posterior capsular defects and ruptures may be necessary., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Repeated episodes of jaundice and pruritus are common in a group of autosomal recessive liver diseases known as benign recurrent intrahepatic cholestasis. Benign recurrent intrahepatic cholestasis (BRIC) is divided into two types, type 1 and type 2, and is caused by mutations in the ATP8B1 and ABCB11 genes. Here, we report a rare case of BRIC type 2 mutation., Case Presentation: A 45-year-old Chinese man had three frequent episodes of jaundice marked by extensive excoriation and severe pruritis, although he had no prior history of jaundice. Laboratory investigations showed no evidence of liver damage caused by viral, autoimmune, or acquired metabolic etiologies. The CT scan revealed an enlarged gallbladder with numerous punctate high-density shadows, while no wall thickening was observed. Endoscopic ultrasonography showed no evidence of dilation of the intrahepatic and extrahepatic bile duct, as well as the absence of gallstone., Diagnostic Evaluation: Immunohistochemical examinations of liver biopsy samples showed cytokeratin-7 positive hepatocytes, suggesting chronic intrahepatic cholestasis. The reticulin fiberstaining demonstrated that the portions of the hepatic plate in the center of the lobule were asymmetrically organized,and somewhat enlarged, with collapsed areas indicating intralobular inflammation. Moreover, there were areas of collapse that indicated the presence of intralobular inflammation. Whole exome sequencing revealed mutations in the ABCB11 gene; c.3084A>G, p.A1028A homozygous mutation (chr2-169789016), and c.2594C>T, p.A865V heterozygous mutation (chr2-169801131). Based on these findings, the final diagnosis of the patient was metabolism-related jaundice., Treatment: Apart from receiving tapering dosage of prednisone to lower bilirubin levels, the patient received no extra care., Conclusion: The comprehensive diagnosis of a middle-aged male patient with BRIC-2, which involved extensive radiological, hematological, and genetic investigations, informed a tailored tapering prednisone regimen, highlighting the importance of personalized medicine in managing atypical presentations of this rare cholestatic disorder.

Objectives: This study aims to explore the clinical significance of lateral pelvic sentinel lymph node biopsy (SLNB) using indocyanine green (ICG) fluorescence navigation in laparoscopic lateral pelvic lymph node dissection (LLND) and evaluate the accuracy and feasibility of this technique to predict the status of lateral pelvic lymph nodes (LPLNs). Methods: The clinical and pathological characteristics, surgical outcomes, lymph node findings and perioperative complications of 16 rectal cancer patients who underwent SLNB using ICG fluorescence navigation in laparoscopic LLND in the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College during April 2017 and October 2022 were retrospectively collected and analyzed. The patients did not receive preoperative neoadjuvant radiotherapy and presented with LPLNs but without LPLN enlargement (MRI showed the maximum short axes of the LPLNs were ≥5 mm and <10 mm at first visit). Results: All 16 patients were successfully performed SLNB using ICG fluorescence navigation in laparoscopic LLND. Three patients underwent bilateral LLND and 13 patients underwent unilateral LLND. The lateral pelvic sentinel lymph nodes (SLNs) were clearly fluorescent before dissection in 14 patients and the detection rate of SLNs for these patients was 87.5%. Lateral pelvic SLN metastasis was diagnosed in 2 patients and negative results were found in 12 patients by frozen pathological examinations. Among the 14 patients in whom lateral pelvic SLNs were detected, the dissected lateral pelvic non-SLNs were all negative. All dissected LPLNs were negative in two patients without fluorescent lateral pelvic SLNs. The specificity, sensitivity, negative predictive value, and accuracy was 85.7%, 100%, 100%, and 100%, respectively. Conclusions: This study indicates that lateral pelvic SLNB using ICG fluorescence navigation shows promise as a safe and feasible procedure with good accuracy. This technique may replace preventive LLND for locally advanced lower rectal cancer.

Objective: To study the changes of retinal function in type 2 diabetes mellitus(DM) patients without apparently diabetic retinopathy via multifocal electroretinogram., Methods: Thirty-six type 2 DM patients (72 eyes) without visible diabetic retinopathy were selected as the experimental group, and thirty-five healthy subjects (70 eyes) were selected as the control group. All subjects were underwent multifocal electroretinogram (mf- ERG)., Results: Compared with the control group, the implicit time delay of the P1 wave in the first ring, third ring, fourth ring, and fifth ring of the experimental group was significant (t = -3.154, p = 0.004, t = -8.21, p = 0.000, t = -3.067, p = 0.004, t = -4.443, p = 0.000, respectively). The implicit time of the N1 wave in the fourth- and fifth-ring were also significantly delayed compared with the control group (t = -3.549, p = 0.001, t = 2.961, p = 0.005, respectively). Compared with the control group, the implicit time of the P1 wave and N1 wave in the temporal region of the experimental group were delayed (t = -2.148, p = 0.037, t = -2.834, p = 0.007, respectively). There were no significant difference between the experimental group and the control group of the temporal area in the amplitude density of P1 wave, N1 wave. There was no difference in the implicit time and amplitude density of the N1 and P1 waves in the nasal region between the experimental group and the control group. The multifocal electroretinogram complex parameters showed better specificity and sensitivity in the diagnosis of diabetic retinopathy., Conclusion: The multifocal electroretinogram can detect abnormal changes in the retina of type 2 DM patients without visible diabetic retinopathy. The multifocal electroretinogram complex parameter is a potential indicator for the early diagnosis of diabetic retinopathy., (© 2024. The Author(s).)

Medicinal plants are invaluable resources for mankind and play a crucial role in combating diseases. Arbuscular mycorrhizal fungi (AMF) are widely recognized for enhancing the production of medicinal active ingredients in medicinal plants. However, there is still a lack of comprehensive understanding regarding the quantitative effects of AMF on the accumulation of medicinal active ingredients. Here we conducted a comprehensive global analysis using 233 paired observations to investigate the impact of AMF inoculation on the accumulation of medicinal active ingredients. This study revealed that AMF inoculation significantly increased the contents of medicinal active ingredients by 27%, with a particularly notable enhancement observed in flavonoids (68%) and terpenoids (53%). Furthermore, the response of medicinal active ingredients in belowground organs (32%) to AMF was more pronounced than that in aboveground organs (18%). Notably, the AMF genus Rhizophagus exhibited the strongest effect in improving the contents of medicinal active ingredients, resulting in an increase of over 50% in both aboveground and belowground organs. Additionally, the promotion of medicinal active ingredients by AMF was attributed to improvements in physiological factors, such as chlorophyll, stomatal conductance and net photosynthetic rate. Collectively, this research substantially advanced our comprehension of the pivotal role of AMF in improving the medicinal active ingredients of plants and provided valuable insights into the potential mechanisms driving these enhancements., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yuan, Zhang, Shi, Yang, Zhang, Wang, Wu and Gao.)

A 69-year-old woman with a history of a left orbital mass presented to the emergency room with progressive breakthrough pain in her left orbit despite medical therapy. On examination, there was extraocular motility restriction with diplopia upon left supraduction. Computed tomography (CT) scan of the orbits revealed soft tissue thickening of the left medial and superior periorbita and left lacrimal fossa; bony erosion of the left frontal bone, left orbital roof, and left lamina papyracea; and bilateral mass-like enlargement of the extraocular muscles. An orbitotomy with incisional biopsy was performed, and histopathological examination revealed non-caseating granulomatous inflammation consistent with sarcoidosis. Chest imaging demonstrated no sequela of pulmonary sarcoidosis, and her serum angiotensin converting enzyme (ACE) level was within normal range. She was treated with high-dose oral steroids with resolution of her symptoms. Her pain returned at the conclusion of the steroid taper, and it was controlled with chronic subcutaneous methotrexate and adalimumab injections.

Aim: To explore the nursing workforce allocation in intensive care units (ICUs) of COVID-19-designated hospitals during the epidemic peak in China., Design: A nationwide cross-sectional online survey., Methods: A total of 37 head nurses and 262 frontline nurses in 37 ICUs of COVID-19-designated tertiary hospitals located in 22 cities of China were surveyed. The self-reported human resource allocation questionnaire was used to assess the nursing workforce allocation., Results: The average patient-to-nurse ratio was 1.89 ± 1.14, and the median working hours per shift was 5 h. The top four majors of front-line nurses in ICUs were respiratory (31.30%), lemology (27.86%), intensive care (21.76%) and emergency (17.18%). We also found that a smaller average patient-to-nurse ratio (odds ratio [OR]: 0.328, 95% CI: 0.108, 1.000), longer average weekly rest time per person (OR: 0.193, 95% CI: 0.051, 0.729) and larger proportion of 6-9 working years (OR: 0.002, 95% CI: 0.001, 1.121) decreased the occurrence of nursing adverse events., (© 2023 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Background: Ulcerative colitis (UC) is an inflammatory disease of the colon that is characterized by mucosal ulcers. Given its increasing prevalence worldwide, it is imperative to develop safe and effective drugs for treating UC. Emodin, a natural anthraquinone derivative present in various medicinal herbs, has demonstrated therapeutic effects against UC. However, low bioavailability due to poor water solubility limits its clinical applications., Methods: Emodin-borate nanoparticles (EmB) were synthesized to improve drug solubility, and they modified with oligomeric mannitol into microgels (EmB-MO) for targeted delivery to intestinal macrophages that express mannose receptors. UC was induced in a mouse model using dextran sulfate sodium (DSS), and different drug formulations were administered to the mice via drinking water. The levels of inflammation-related factors in the colon tissues and fecal matter were measured using enzyme-linked immunosorbent assay. Intestinal permeability was evaluated using fluorescein isothiocyanate dextran. HE staining, in vivo imaging, real-time PCR, and western blotting were performed to assess intestinal barrier dysfunction., Results: Both EmB and EmB-MO markedly alleviated the symptoms of UC, including body weight loss, stool inconsistency, and bloody stools and restored the levels of pro- and anti-inflammatory cytokines. However, the therapeutic effects of EmB-MO on the macroscopic and immunological indices were stronger than those of EmB and similar to those of 5-aminosalicylic acid. Furthermore, EmB-MO selectively accumulated in the inflamed colon epithelium and restored the levels of the gut barrier proteins such as ZO-1 and Occludin., Conclusions: EmB-MO encapsulation significantly improved water solubility, which translated to greater therapeutic effects on the immune balance and gut barrier function in mice with DSS-induced UC. Our findings provide novel insights into developing emodin-derived drugs for the management of UC., (© 2023. International Society for Chinese Medicine and BioMed Central Ltd.)

Although primary tumors of the lacrimal gland are rare, adenoid cystic carcinoma (ACC) is the most common and lethal epithelial lacrimal gland malignancy. Traditional management of lacrimal gland adenoid cystic carcinoma (LGACC) involves the removal of the eye and surrounding socket contents, followed by chemoradiation. Even with this radical treatment, the 10-year survival rate for LGACC is 20% given the propensity for recurrence and metastasis. Due to the rarity of LGACC, its pathobiology is not well-understood, leading to difficulties in diagnosis, treatment, and effective management. Here, we integrate bulk RNA sequencing (RNA-seq) and spatial transcriptomics to identify a specific LGACC gene signature that can inform novel targeted therapies. Of the 3499 differentially expressed genes identified by bulk RNA-seq, the results of our spatial transcriptomic analysis reveal 15 upregulated and 12 downregulated genes that specifically arise from LGACC cells, whereas fibroblasts, reactive fibrotic tissue, and nervous and skeletal muscle account for the remaining bulk RNA-seq signature. In light of the analysis, we identified a transitional state cell or stem cell cluster. The results of the pathway analysis identified the upregulation of PI3K-Akt signaling, IL-17 signaling, and multiple other cancer pathways. This study provides insights into the molecular and cellular landscape of LGACC, which can inform new, targeted therapies to improve patient outcomes.

Objective: The purpose of this study was to analyze the techniques used to resection cervical extra-intraspinal neuromas (also known as cervical dumbbell neuromas) through the enlarged intervertebral foramen., Methods: A total of 34 consecutive patients (19 male, 15 female) with cervical dumbbell neuromas reviewed retrospectively between April 2008 and May 2020. Sixteen tumors were found in the intervertebral foramen of C 1 -C 3 , four in C 3 -C 4 , and 14 in C 4 -T 1 . The approach in all cases was to expose the tumors by intermuscular dissection and to remove them through the enlarged intervertebral foramen without excision of any bony structures. However, to expose tumors at different locations, the incisions shall be made accordingly. In this case series, the incisions were made along the posterior border of the sternocleidomastoid muscle for the C 1 -C 3 tumors and along the anterior border of the muscle for the C 3 -C 4 tumors. Transverse incisions were required for the C 4 -T 1 tumors., Results: Following the mentioned incising approach, all 34 tumors were completely exposed. 31 were completely removed in one stage, and 3 tumors underwent subtotal resection because of brachial plexus nerve adhesion. The vertebral artery and spinal cord were undamaged for all cases. The patients who had total tumor resection showed no sign of recurrence on enhanced magnetic resonance imaging during follow-ups. The status of patients who underwent subtotal resection was stable after radiation therapy. None of the patients developed spinal instability., Conclusions: Cervical dumbbell neuromas can be exposed and removed through the enlarged intervertebral foramen without causing spinal instability or injury to the spinal cord or vertebral artery. This operative approach can retain the integrity of the structures of spine and should be considered the ideal approach for cervical dumbbell neuromas., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Chang, Che and Zhang.)

Objective: To accelerate the onset of systemic lupus erythematosus in C57BL/6 mice by injecting cadmium chloride nanoemulsion and shorten the traditional modeling time., Methods: Pristane cadmium chloride nanoemulsion was prepared, and 66 C57BL/6 mice were randomly divided into four groups. The pristane group was intraperitoneally injected with 0.6 mL of pristane blank nanoemulsion, the model group was injected with 0.6 mL of pristane cadmium chloride nanoemulsion, the Cadmium chloride control group was injected with 0.6 mL of cadmium chloride nanoemulsion, and the control group was injected with the same amount of 0.9% sodium chloride solution. Urine protein content, anti-dsDNA antibody content, Th1 cell/Th2 cell ratio, and kidney staining were detected in each group., Results: The model group began to develop disease in the 4th week, the anti-dsDNA antibody level reached 566.71 ± 1.44 ng/L, and the proteinuria reached 245.38 ± 30.54 ng/mL. The model group showed an onset at least 5 weeks earlier than that in the pristane group. There was no significant difference in anti-dsDNA antibody content between Cadmium chloride control group and blank group. At the 12th week, the Th1/Th2 cell ratio in the model group significantly decreased, and the pathological changes in the kidneys were consistent with the typical manifestations of lupus in mouse models., Conclusion: These results suggest that cadmium chloride promotes earlier onset of pristane-induced systemic lupus erythematosus in a C57BL/6 mouse model.

Objective: To investigate the safety, feasibility and short-term efficacy of total laparoscopic loop ileostomy reversal in patients after resection of rectal cancer. Methods: The clinical data of 20 patients who underwent total laparoscopic loop ileoscopic loop ileostomy after radical resection of rectal cancer at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, or Beijing Chaoyang District Sanhuan Cancer Hospital from October 2019 to June 2020 were collected and retrospectively analyzed. Results: All patients had successfully underwent total laparoscopic ileostomy reversal without conversion to open surgery or discontinued operation. No perioperative related death cases were found. In the whole group, the median operation time was 97 (60-145) minutes and the median intraoperative blood loss was 20 (10-100) milliliters. The median Visual Analogue Scale (VAS) score was 1.9 (1-5) one day after the operation. Nobody needed to use additional analgesic drugs. The median time to grand activities was 25 (16-42) hours, the median time to flatus was 44 (19-51) hours, and the median hospitalization after operation was 6.9 (5-9) days. No patients underwent operation related complications such as operative incision infection, abdominal and pelvic infection, intestinal obstruction, anastomotic leakage, bleeding and so on. Conclusions: Total laparoscopic loop ileostomy reversal appears to be safe, feasible and with promising efficacy for selected patients.

In this article, a 3D photocatalytic support with different Poisson's ratio was used for the first time to control the photocatalytic production rate of hydrogen. It was created by a stereo-lithography method, and the support with the most negative Poisson's ratio got the best result. The Poisson's ratio of the 3D structure influences the rate of hydrogen production, and it is important for the photocatalyst supports to be porous for light to penetrate into them. A series of Ce doped CdS photocatalysts were produced and immobilized on 3D multicellular Al 2 O 3 supports. By changing the proportion of Ce 3+ doped into the CdS photocatalysts 1 % of Ce 3+ exhibited optimal hydrogen production, which was 222.9 % compared to that of the pure CdS. Using the 3D photocatalytic support with different Poisson's ratio, the photocatalytic production rate of hydrogen increased by 128 %., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Retinoblastoma is the most common eye cancer in children and is fatal if left untreated. Over the past three decades, chemotherapy has become the mainstay of eye-sparing treatment. Nevertheless, chemoresistance continues to represent a major challenge leading to ocular and systemic toxicity, vision loss, and treatment failure. Unfortunately, the mechanisms leading to chemoresistance remain incompletely understood. Here, we engineered low-passage human retinoblastoma cells to study the early molecular mechanisms leading to resistance to carboplatin, one of the most widely used agents for treating retinoblastoma. Using single-cell next-generation RNA sequencing (scRNA-seq) and single-cell barcoding technologies, we found that carboplatin induced rapid transcriptomic reprogramming associated with the upregulation of PI3K-AKT pathway targets, including ABC transporters and metabolic regulators. Several of these targets are amenable to pharmacologic inhibition, which may reduce the emergence of chemoresistance. We provide evidence to support this hypothesis using a third-generation inhibitor of the ABCB1 transporter., Competing Interests: The authors declare no conflict of interest.

Retinoblastoma (Rb) is a deadly childhood eye cancer that is classically initiated by inactivation of the RB1 tumor suppressor. Clinical management continues to rely on nonspecific chemotherapeutic agents that are associated with treatment resistance and toxicity. Here, we analyzed 103 whole exomes, 20 whole transcriptomes, 5 single-cell transcriptomes, and 4 whole genomes from primary Rb tumors to identify previously unknown Rb dependencies. Several recurrent genomic aberrations implicate estrogen-related receptor gamma (ESRRG) in Rb pathogenesis. RB1 directly interacts with and inhibits ESRRG, and RB1 loss uncouples ESRRG from negative regulation. ESRRG regulates genes involved in retinogenesis and oxygen metabolism in Rb cells. ESRRG is preferentially expressed in hypoxic Rb cells in vivo. Depletion or inhibition of ESRRG causes marked Rb cell death, which is exacerbated in hypoxia. These findings reveal a previously unidentified dependency of Rb cells on ESRRG, and they implicate ESRRG as a potential therapeutic vulnerability in Rb.

Objectives: To study the clinical value of extracorporeal membrane oxygenation (ECMO) in the treatment of persistent pulmonary hypertension of the newborn (PPHN)., Methods: A retrospective analysis was performed on the medical data of 11 neonates with PPHN who were treated with ECMO in the Neonatal Intensive Care Unit of Zhongshan People's Hospital from January 2015 to December 2021, involving the neonates' general information, clinical diagnosis, laboratory results, duration of ECMO treatment, complications during ECMO treatment, length of hospital stay, and outcome., Results: Of the 11 neonates, 10 (91%) had successful weaning from ECMO, and 8 (73%) survived. For the 11 neonates, the mean duration of ECMO treatment was (81±50) hours (range: 26 to 185 hours), the mean duration of ventilator use was (198±105) hours (range: 57 to 392 hours), and the mean length of hospital stay was (22±15) days (range: 2 to 49 days). The oxygenation index and blood lactate level were significantly improved after 24 hours of ECMO treatment among the 11 neonates ( P <0.05). Ten neonates had significantly reduced pulmonary artery pressure after 24 hours of ECMO treatment ( P <0.05). One neonate had a progressive increase in the pulmonary artery pressure during EMCO treatment, succumbing to death. This neonate was diagnosed with alveolar capillary dysplasia based on the histopathological findings of the lung tissue and whole-exome sequencing results. Among the 11 children, 5 had intracranial hemorrhage, 1 had disseminated intravascular coagulation, 1 had gastric hemorrhage, 2 had pulmonary hemorrhage, 1 had renal insufficiency, and 3 had bleeding at the puncture site during ECMO treatment., Conclusions: ECMO is effective for the treatment of PPHN, however, the high incidence of complications of ECMO treatment suggests that it is important to carefully assess the indications and timing of ECMO treatment and improve the management of ECMO, which can improve the weaning rate and survival rate.

Objective: To analyze the level and changing trend of significant injury-caused deaths in the Chinese population from 2010 to 2019 and provide evidence for related intervention. Methods: Data on notable injury-caused deaths in areas under National Disease Surveillance Programs were collected from 2010 to 2019. Crude and standardized mortality rates of four significant injuries were calculated to describe the status of injury-caused deaths. The trend of changes in standardized mortality rates was analyzed using the Joinpoint regression model. Results: The overall trend of standardized mortality rate on an injury during 2010-2019 was consistently decreasing (AAPC=-3.5%, P <0.001) while the general direction of accidental fall standardized mortality rate was increasing (AAPC=1.0%, P =0.104). The standardized mortality rate for significant injuries fluctuated with age, increasing for those aged 50-79 years (AAPC=3.9% for the 50- group, AAPC=5.6% for the 60- group, and AAPC=4.6% for the 70- group, all P <0.001). The standardized mortality rates for all major injuries were higher in males than those in females, with road traffic accidents and drowning declining faster in males than that in females (AAPC=-5.3% in the male road traffic accident group, AAPC=-3.8% in the female road traffic accident group, AAPC=-4.0% in the male drowning group, AAPC=-3.5% in the female drowning group, all P <0.001), and suicide and sequelae declining faster in females than that in males (AAPC=-6.4% in female, AAPC=-4.7% in male, all P <0.001). The standardized mortality rate for significant injuries was higher in rural than that in urban areas and decreased faster than that in urban areas. The central region had the highest standardized mortality rate for suicide and sequelae. The western part had the highest standardized mortality rates for road traffic accidents, accidental falls, and drowning, with the fastest decline in road traffic accidents and drowning (AAPC=-5.3% in the road traffic accident group and AAPC=-5.3% in the drowning group, both P <0.001). Conclusions: The mortality rate from significant injuries in the Chinese population showed a continuous downward trend from 2010 to 2019, with a rebound in the standardized mortality rate from accidental falls in recent years among the elderly, males, rural residents, and central and western regions being the focus of future prevention and control.

Diapause arrest in animals such as Caenorhabditis elegans is tightly regulated so that animals make appropriate developmental decisions amidst environmental challenges. Fully understanding diapause requires mechanistic insight of both entry and exit from the arrested state. Although a steroid hormone pathway regulates the entry decision into C. elegans dauer diapause, its role in the exit decision is less clear. A complication to understanding steroid hormonal regulation of dauer has been the peculiar fact that steroid hormone mutants such as daf-9 form partial dauers under normal growth conditions. Here, we corroborate previous findings that daf-9 mutants remain capable of forming full dauers under unfavorable growth conditions and establish that the daf-9 partial dauer state is likely a partially exited dauer that has initiated but cannot complete the dauer exit process. We show that the steroid hormone pathway is both necessary for and promotes complete dauer exit, and that the spatiotemporal dynamics of steroid hormone regulation during dauer exit resembles that of dauer entry. Overall, dauer entry and dauer exit are distinct developmental decisions that are both controlled by steroid hormone signaling., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

The accurate determination of the risk of cancer recurrence is a critical unmet need in managing thyroid cancer (TC). Although numerous studies have successfully demonstrated the use of high throughput molecular diagnostics in TC prediction, it has not been successfully applied in routine clinical use, particularly in Chinese patients. In our study, we objective to screen for characteristic genes specific to PTC and establish an accurate model for diagnosis and prognostic evaluation of PTC. We screen the differentially expressed genes by Python 3.6 in The Cancer Genome Atlas (TCGA) database. We discovered a three-gene signature Gap junction protein beta 4 (GJB4), Ripply transcriptional repressor 3 (RIPPLY3), and Adrenoceptor alpha 1B (ADRA1B) that had a statistically significant difference. Then we used Gene Expression Omnibus (GEO) database to establish a diagnostic and prognostic model to verify the three-gene signature. For experimental validation, immunohistochemistry in tissue microarrays showed that thyroid samples' proteins expressed by this three-gene are differentially expressed. Our protocol discovered a robust three-gene signature that can distinguish prognosis, which will have daily clinical application., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer XS declared a shared parent affiliation with the author(s) to the handling editor at the time of the review., (Copyright © 2022 Zhong, Deng, Shen, Cai, Feng, Gan, Jiang, Liu, Zhang, Deng, Zheng, Xie, Ning, Huang, Chen, Miao and Xu.)

Rectal cancer is a common malignant tumor of the digestive tract, and surgery is the main treatment strategy. Disorders of bowel, anorectal and urogenital function remain common problems after total mesorectal resection (TME), which seriously decreases the quality of life of patients. Surgical nerve damage is one of the main causes of the complications, while TME with pelvic autonomic nerve preservation is an effective way to reduce the occurrence of adverse outcomes. Intraoperative nerve monitoring (IONM) is a promising method to assist the surgeon to identify and protect the pelvic autonomic nerves. Nevertheless, the monitoring methods and technical standards vary, and the clinical use of IONM is still limited. This review aims to summarize the researches on IONM in rectal and pelvic surgery. The electrical nerve stimulation technique and different methods of IONM in rectal cancer surgery are introduced. Also, the authors discuss the limitations of current researches, including methodological disunity and lack of equipment, then prospect the future direction in this field.

Background: Appropriate allocation of nursing staff is key to ensuring efficient nursing in hospitals, and is significantly correlated with patient safety, nursing quality, and nurse job satisfaction. However, there are few studies on nursing workforce allocation in the isolation wards of COVID-19 designated hospitals globally. This study aims to better understand the nursing workforce allocation in the isolation wards of COVID-19 designated hospitals in China, and provide a theoretical basis for efficiently deploying first-line nurses in China and across the world in the future., Methods: An online survey was conducted among the head nurses (n = 229) and nurses (n = 1378) in the isolation wards of 117 hospitals (selected by stratified sampling), using a self-reported human resource allocation questionnaire., Results: The average bed-to-nurse ratios of different isolation wards were different (Z = 36.742, P = 0.000). The bed-to-nurse ratios of the ICU, suspected COVID-19 cases ward, and confirmed COVID-19 cases ward, were 1:1.88, 1:0.56, and 1:0.45, respectively. The nurse work hours per shift in different isolation wards were also different (Z = 8.468, P = 0.014), with the specific values of the ICU, suspected COVID-19 cases ward, and confirmed COVID-19 cases ward, being 5, 6, and 6 h, respectively. A correlation analysis showed that the average work hours per shift was proportional to the overtime work of nurses (r s  = 0.146), the proportion of nurse practitioners was proportional to the overall utilization rate of nursing human resources in the wards (r s  = 0.136), and the proportion of nurses with college degrees was proportional to teamwork (r s  = 0.142). The proportion of nurses above grade 10 was inversely proportional to teamwork and psychological problems (r s  = 0.135, r s  = 0.203). The results of multiple stepwise regression analyses showed that the work hours of nurses per shift was the main factor affecting nurse satisfaction and that the proportion of nurses and the work hours of nurses per shift were both independent factors affecting the length of stay (LOS) of patients., Conclusion: Hospitals in China have made good nursing workforce allocations during the COVID-19 pandemic, but there are certain shortcomings. Therefore, scientific and efficient nursing workforce allocation practice plans should be established to improve the ability of hospitals to deal with public health emergencies and are urgent problems that need to be addressed soon., (© 2022. The Author(s).)

In the past, people summarized and invented a series of surgical procedures for the treatment of colorectal cancer after continuous thinking and exploration. Some of these surgical procedures, such as Miles, Dixon, and Hartmann procedures, are considered to be classic and still in use today. In general, the surgical development has gone through roughly four stages: palliative surgery, radical surgery, extended radical surgery, and tumor functional surgery. As far as the surgical procedure of colorectal surgery is concerned, it mainly includes five elements: surgical approach, intestinal segment resection, degree of lymph node dissection, digestive tract reconstruction, and specimen removal. Only by fully understanding the five elements of surgical procedures and seeking for variables from them can innovation be achieved and benefit patients. This article will discuss the evolution of colorectal surgery according to development of medicine and surgery. "Taking history as a mirror, we can know the rise and fall." Only by correctly understanding history can we objectively understand the nature of things and the laws of their development. This is true for humans, and it is true for medicine.

Objective: To compare the postoperative function, the short-term and long-term outcomes between fascia-oriented and vascular-oriented lateral lymph node dissection (LLND) in patients with rectal cancer. Methods: A retrospective cohort study was performed. Clinical data of patients who received total mesorectal excision (TME) with LLND at National Cancer Center, Cancer Hospital of Chinese Academy of Medical Science from January 2014 to December 2019 were retrospectively collected. Inclusion criteria were as follows: (1) rectal cancer was pathologically diagnosed, and the lower margin was below the peritoneal reflection. (2) resectable advanced rectal cancer with suspected lateral lymph node metastasis was evaluated based on rectal MRI assessment. (3) preoperative MRI showed lateral lymph node short diameter ≥5 mm and/or lymph node morphology (spike, blur, irregular) as well as heterogenous signal intensity. Lymph node shrinkage was less than 60% after receiving neoadjuvant therapy based on the reassessment of rectal MRI. (4) TME+LLND surgery was performed synchronously. Exclusion criteria were as follows: (1) previous history of pelvic surgery; (2) preoperative cystitis, urethritis, moderate and severe prostatic hyperplasia and other diseases resulting in abnormal urination function; (3) preoperative sexual dysfunction or loss of function; (4) patients receiving LLND due to lateral recurrence after TME; (5) distant metastasis of the tumor at initial diagnosis; (6) Incomplete collection of clinical data. A total of 73 consecutive patients were enrolled in this study. Based on the surgical approaches in performing LLND, patients were divided into fascia-oriented group ( n =30) and vascular-oriented group ( n =43). There were no significant differences in baseline data between the two groups (all P >0.05). The main outcome indicators of this study were the incidence of postoperative urinary and male sexual dysfunction, the efficacy, the number of lateral lymph nodes harvested and the detection rate of positive lymph nodes. Overall survival (OS) rates and progression free survival (PFS) rates were calculated by the Kaplan-Meier method and compared by log-rank test. Results: All patients in both groups completed surgery successfully. There were no significant differences in operation time, intraoperative blood loss, postoperative complications, and the length of hospital stay between the two groups (all P >0.05). In the whole group, the incidence of postoperative urinary dysfunction and male sexual dysfunction was 43.8% (32/73) and 62.5% (25/40), respectively. The median number of lateral lymph nodes harvested was 8.0(4.0,11.0) with a positive rate of 20.5%(15/73). Compared to the vascular-oriented group, the fascia-oriented group demonstrated a decreased rate of urinary dysfunction [26.7% (8/30) vs. 55.8% (24/43), χ(2)=6.098, P =0.014], lower rate of sexual dysfunction in males [6/15 vs. 76% (19/25), χ(2)=5.184, P =0.023], more harvested lateral lymph nodes [ M ( P 25, P 75): 9.5 (6.8, 15.3) vs. 6.0 (3.0, 9.0), Z =-2.849, P =0.004]. There was no significant difference in the positvie rate of lateral lymph nodes between the two groups [20% (6/30) versus 20.9% (9/43), χ(2)=0.009, P =0.923]. Three(4.1%) patients were lost during a median follow-up of 34 (1-66) months. The 3-year PFS and OS of the whole cohort were 69.5% and 88.3%, respectively. No significant difference in 3-year PFS rates (79.6% vs. 62.0%, P =0.172) and 3-year OS rates (91.2% vs. 85.9%, P =0.333) were observed between the fascia-oriented group and the vascular-oriented group (both P >0.05). Conclusion: Fascia-oriented LLND is associated with lower risk of postoperative urinary and male sexual dysfunction in patients with rectal carcinoma, and harvest of more lymph nodes, but no significant advantage in long-term survival.

Colorectal cancer ranks within the top three cancers both in terms of incidence as well as deaths. Metastasis is often the major cause of mortality and liver is the primary and most common site to which colorectal cancers metastasize. We tested the prognostic ability of a long non-coding RNA (lncRNA) signature in liver metastatic colorectal cancers. We first evaluated expression levels of several lncRNAs in eight excised liver metastases from primary colorectal cancers and found significantly upregulated lncRNAs HOTAIR and MALAT1 along with significantly downregulated LOC285194. We further compared the expression levels of HOTAIR, MALAT1 and LOC285194 in primary colorectal tumors at the time of initial diagnosis and correlated them with disease progression and liver metastasis. HOTAIR and MALAT1 were significantly upregulated and LOC285194 was significantly downregulated in twelve patients who were diagnosed with liver metastasis within 5 years of initial diagnosis, compared to the five patients with no metastasis. A positive signature comprising of high HOTAIR/MALAT1 and low LOC285194 also correlated with progression to higher grade tumors. Thus, the lncRNA signature comprising of high HOTAIR/MALAT1 and low LOC285194 could be a prognostic signature for liver metastasis as well as overall poor survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Song, Wang, Du, Peng, Zhou and Zhang.)

N- trans -Feruloyloctopamine (FO), a natural compound, was reported in our previous study to inhibit a tumor cell malignant phenotype by AKT- and EMT-related signals and might be used as a promising drug for HCC treatment. However, the specific targets and detailed mechanisms still need to be clarified. Screening with RNA-Seq in Huh7 cells treated with FO revealed that 317 genes were modulated, of which 188 genes were upregulated and 129 genes were downregulated. Real-time cell analyzer and flow cytometry data reveal that tumor cell proliferation and apoptosis were impacted by FO. DAVID bioinformatic data showed that most of the biological process GO terms are related to proliferation and apoptosis. KEGG enrichment analysis showed that FO mainly regulates PI3K-AKT- and apoptosis-related signals, in which BBC3, DDIT3, NOXA, and CDKN1A on the surface serve as the novel targets of FO inducing HCC cell apoptosis. The result implied that FO might exacerbate HCC cell apoptosis by regulating BBC3, DDIT3, CDKN1A, and NOXA signals. The obstacle effect of FO can provide new targets and new credibility for the treatment of liver cancer., Competing Interests: All authors declare that they have no conflicts of interest., (Copyright © 2021 Bin Ma et al.)

Purpose: Sebaceous carcinoma (SC) is a malignant eyelid tumor of the ocular adnexa that is primarily treated via surgical excision. Few therapies exist in advanced cases, and medical therapy is limited because of our incomplete understanding of SC biology. Herein, we describe a technique to culture human ocular adnexal SC for use as an in vitro model., Methods: Human ocular adnexal SC tumor cells were isolated from a patient undergoing orbital exenteration surgery and named Bascom Palmer 50 (BP50). They were cultured in Dulbecco's modified Eagle medium/nutrient mixture F-12 supplemented with 10% fetal bovine serum and antibiotics and were maintained at 37°C in humidified 5% CO2. The cells were characterized by immunohistochemistry, exome sequencing, and short tandem repeats analysis. In vitro drug screening against mitomycin-C (MMC) was performed using a cell viability assay., Results: BP50 grew past 40 passages with a doubling time of 52.3 hours. Immunocytochemical staining revealed expression of SC-associated markers adipophilin, epithelial membrane antigen, p53, and androgen receptor. Whole exome sequencing showed a significant carryover in somatic mutations between the tumor tissue and corresponding cell line, revealing genetic markers consistent with SC. MMC affected cell viability in a dose-dependent manner., Conclusions: BP50 displays characteristics of ocular adnexal SC and therefore may facilitate improved understanding of SC biology and the high throughput assessment of novel therapeutic compounds and new drug combinatorial approaches targeted for this disease., Translational Relevance: Drug screening with MMC against these cells shows in vitro evidence to support its continued clinical use in SC.

Background: Preoperative computed tomography (CT)-guided coil localization (CL) is commonly used to facilitate video-assisted thoracoscopic surgery (VATS)-guided diagnostic wedge resection (WR) of pulmonary nodules (PNs). When a scapular-blocked PN (SBPN) is localized, the trans-scapular CL (TSCL) is commonly performed. In this study, we investigated the safety, feasibility, and clinical efficacy of preoperative CT-guided TSCL for SBPNs., Materials and Methods: From January 2014 to September 2020, a total of 152 patients with PNs underwent CT-guided CL prior to VATS-guided WR. Of these patients, 14 had SBPNs and underwent the TSCL procedure., Results: A total of 14 SBPNs were localized in the 14 patients. The mean diameter of the 14 SBPNs was 7.4 ± 2.4 mm. The technical success rate of the scapula puncture was 100%. No complications occurred near the scapula. The technical success rate of CL was 92.9%. One coil dropped off when performing the VATS procedure. The mean duration of the TSCL was 14.2 ± 2.7 min. Two patients (14.3%) developed asymptomatic pneumothorax after TSCL. The technical success rate of VATS-guided WR was 92.9%. The patient who experienced technical failure of TSCL directly underwent lobectomy. The mean duration of the VATS was 90.0 ± 42.4 min and the mean blood loss was 62.9 ± 37.2 ml. The final diagnoses of the 14 SBPNs included invasive adenocarcinoma (n = 4), adenocarcinoma in situ (n = 9), and benign disease (n = 1)., Conclusions: Preoperative CT-guided TSCL is a safe and simple procedure that can facilitate high success rates of VATS-guided WR of SBPNs.

In this work, the relationships between air quality and pollutant emissions were investigated during the COVID-19 pandemic in Shandong Province. During the quarantine period (from January 24 to February 7, 2020), the concentrations of atmospheric pollutants decreased significantly relative to the period before controls were imposed (from January 15 to 23, 2020). Specifically, except for an increase in the concentration of O 3 , concentrations of PM 10 , PM 2.5 , NO 2 , SO 2 , and CO decreased for 72.6 μg·m -3 (45.86%), 47.4 μg·m -3 (41.24%), 25.6 μg·m -3 (58.00%), 3.0 μg·m -3 (17.71%), and 0.5 mg·m -3 (31.40%), respectively. RAMS-CMAQ simulation showed that meteorological diffusion had an essential role in improving air quality. Influenced by meteorological factors, emissions of PM 10 , PM 2.5 , NO 2 , SO 2, and CO were reduced 26.04%, 33.03%, 28.35%, 43.27%, and 23.29%, respectively. Furthermore, the concentrations of PM 10 , PM 2.5 , NO 2 , SO 2 , and CO were reduced by 19.82%, 8.21%, 29.65%, -25.56%, and 8.12%, respectively, due to pollution emissions reductions during the quarantine period. O 3 concentrations increased by 20.51% during quarantine, caused by both meteorological factors (10.47%) and human activities (10.04%). These results indicate that primary pollutants were more sensitive to emissions reductions; however, secondary pollutants demonstrated a lagged response the emissions reduction and were significantly affected by meteorological factors. The linear relationship between ozone and the emissions reduction was not significant, and was inverse overall. Further investigation are now required on the impact of emissions reduction on ozone pollution control.

Although PD-1/PD-L1 immunotherapy has been used successfully in treating many cancers, metastatic colorectal cancer (CRC) patients are not as responsive. B7-H3 is a promising target for immunotherapy and we found it to have the highest expression among B7-CD28 family members in CRC. Thus, the aim of the present study was to investigate B7-H3 expression in a large CRC cohort. B7-H3, B7-H4, and PD-L1 protein levels and differential lymphocyte infiltration were evaluated in tissue microarrays from 805 primary tumors and matched metastases. The relationships between immune markers, patient characteristics, and survival outcomes were determined. B7-H3 (50.9%) was detected in more primary tumors than B7-H4 (29.1%) or PD-L1 (29.2%), and elevated B7-H3 expression was associated with advanced overall stage. Co-expression of B7-H3 only with B7-H4 or PD-L1 was infrequent in primary tumors (6.3%, 5.7%, respectively). Moreover, B7-H3 in primary tumors was positively correlated with their respective expression at metastatic sites (ρ = 0.631; p < 0.001). No significant relationships between B7-H4 and PD-L1 and survival were observed; however, B7-H3 overexpression in primary tumors was significantly related to decreased disease-free survival. A positive relationship between B7-H3 expression and high density CD45RO T cell was observed in primary tumors, whereas B7-H4 and PD-L1 overexpression were related to CD3 T-cell infiltration. In conclusion, compared with B7-H4 and PD-L1, B7-H3 expression exhibited a higher prevalence and was significantly related to aggressiveness, worse prognosis and CD45RO T-cell infiltration in primary tumors. Further exploration of this potential target of immunotherapy in CRC patients is warranted.

Objective: To investigate the relationship between human cytomegalovirus (HCMV) infection and peripheral blood CD14 + CD16 + monocytes in the pathogenesis of coronary heart disease (CHD), and to elucidate the mechanism of pathogenesis in CHD by analyzing the correlation between infection, inflammation, and CHD, to provide a basis for the prevention, evaluation, and treatment of the disease., Methods: In total, 192 patients with CHD were divided into three groups: latent CHD, angina pectoris, and myocardial infarction. HCMV-IgM and -IgG antibodies were assessed using ELISA; CD14 + CD16 + monocytes were counted using a five-type automated hematology analyzer; mononuclear cells were assessed using fluorescence-activated cell sorting; and an automatic biochemical analyzer was used to measure the levels of triglyceride, cholesterol, high- and low-density lipoprotein cholesterols, lipoprotein, hs-CRp and Hcy., Results: The positive rates of HCMV-IgM and -IgG were significantly higher in the CHD groups than in the control group. HCMV infection affects lipid metabolism to promote immune and inflammatory responses., Conclusion: HCMV infection has a specific correlation with the occurrence and development of CHD. The expression of CD14 + CD16 + mononuclear cells in the CHD group was increased accordingly and correlated with acute HCMV infection. Thus, HCMV antibody as well as peripheral blood CD14 + CD16 + mononuclear cells can be used to monitor the occurrence and development of CHD., (Copyright © 2020 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Objective: Meta-analysis to evaluate complications in the use of autogenous bone and bone substitutes and to compare bone substitutes, specifically HA, polyetheretherketone (PEEK) and titanium materials. Methods: Search of PubMed, Cochrane, Embase and Google scholar to identify all citations from 2010 to 2019 reporting complications regarding materials used in cranioplasty. Results: 20 of 2266 articles met the inclusion criteria, including a total of 2913 patients. The odds of overall complication were significantly higher in the autogenous bone group ( n  = 214/644 procedures, 33.2%) than the bone substitute groups ( n  = 116/436 procedures, 26.7%, CI 1.29-2.35, p < 0.05). In bone substitutes groups, there was no significant difference in overall complication rate between HA and Ti (OR, 1.2; 95% CI, 0.47-3.14, p  = 0.69). PEEK has lower overall complication rates (OR, 0.51; 95% CI, 0.30-0.87, p  = 0.01) and lower implant exposure rates (OR, 0.17; 95% CI, 0.06-0.53, p  = 0.002) than Ti, but there was no significant difference in infection rates and postoperative hematoma rates. Conclusions: Cranioplasty is associated with high overall complication rates with the use of autologous bone grafts compared with bone substitutes. PEEK has a relatively low overall complication rates in substitutes groups, but still high infection rates and postoperative hematoma rates. Thus, autologous bone grafts should only be used selectively, and prospective long-term studies are needed to further refine a better material in cranioplasty.

The use of synthetic bridges as surrogates for disulfide bonds has emerged as a practical strategy to obviate the poor stability of some disulfide-containing peptides. However, peptides incorporating large-span synthetic bridges are still beyond the reach of existing methods. Herein, we report a native chemical ligation (NCL)-assisted diaminodiacid (DADA) strategy that enables the robust generation of disulfide surrogate peptides incorporating surrogate bridges up to 50 amino acids in length. This strategy provides access to some highly desirable but otherwise impossible-to-obtain disulfide surrogates of bioactive peptide. The bioactivities and structures of the synthetic disulfide surrogates were verified by voltage clamp assays, NMR, and X-ray crystallography; and stability studies established that the disulfide replacements effectively overcame the problems of disulfide reduction and scrambling that often plague these pharmacologically important peptides., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Human activities have shaped large-scale distributions of many species, driving both range contractions and expansions. Species differ naturally in range size, with small-range species concentrated in particular geographic areas and potentially deviating ecologically from widespread species. Hence, species' responses to human activities may be influenced by their geographic range sizes, but if and how this happens are poorly understood. Here, we use a comprehensive distribution database and species distribution modeling to examine if and how human activities have affected the extent to which 9,701 vascular plants fill their climatic potential ranges in China. We find that narrow-ranged species have lower range filling and widespread species have higher range filling in the human-dominated southeastern part of China, compared with their counterparts distributed in the less human-influenced northwestern part. Variations in range filling across species and space are strongly associated with indicators of human activities (human population density, human footprint, and proportion of cropland) even after controlling for alternative drivers. Importantly, narrow-ranged and widespread species show negative and positive range-filling relationships to these human indicators, respectively. Our results illustrate that floras risk biotic homogenization as a consequence of anthropogenic activities, with narrow-ranged species becoming replaced by widespread species. Because narrow-ranged species are more numerous than widespread species in nature, negative impacts of human activities will be prevalent. Our findings highlight the importance of establishing more protected areas and zones of reduced human activities to safeguard the rich flora of China.

Vibrio cholerae , the facultative pathogen responsible for cholera disease, continues to pose a global health burden. Its persistence can be attributed to a flexible genetic tool kit that allows for adaptation to different environments with distinct carbon sources, including the six-carbon sugar alcohol mannitol. V. cholerae takes up mannitol through the transporter protein MtlA, whose production is downregulated at the posttranscriptional level by MtlS, a cis antisense small RNA (sRNA) whose promoter lies within the mtlA open reading frame. Though it is known that mtlS expression is robust under growth conditions lacking mannitol, it has remained elusive as to what factors govern the steady-state levels of MtlS. Here, we show that manipulating mtlA transcription is sufficient to drive inverse changes in MtlS levels, likely through transcriptional interference. This work has uncovered a cis -acting sRNA whose expression pattern is predominantly controlled by transcription of the sRNA's target gene. IMPORTANCE Vibrio cholerae is a bacterial pathogen that relies on genetic tools, such as regulatory RNAs, to adapt to changing extracellular conditions. While many studies have focused on how these regulatory RNAs function, fewer have focused on how they are themselves modulated. V. cholerae expresses the noncoding RNA MtlS, which can regulate mannitol transport and use, and here we demonstrate that MtlS levels are controlled by the level of transcription occurring in the antisense direction. Our findings provide a model of regulation describing how bacteria like V. cholerae can modulate the levels of an important regulatory RNA. Our work contributes to knowledge of how bacteria deploy regulatory RNAs as an adaptive mechanism to buffer against environmental flux., (Copyright © 2019 Zhang and Liu.)

Background and Objective: The benefit from adjuvant chemotherapy for patients treated with neoadjuvant chemoradiotherapy (NCRT) and curative surgery remains controversial, particularly among those responding well to NCRT. This retrospective study aimed to clarify the benefits of adjuvant chemotherapy in terms of the oncological outcomes of patients with ypT0-2N0 rectal cancer after NCRT and curative surgery., Methods: All patients with ypT0-2N0 rectal cancer after NCRT and curative resection between 2005 and 2014 were examined. The oncological outcomes between patients treated with adjuvant chemotherapy and those without any chemotherapy were compared., Results: The clinicopathological characteristics of 110 patients were reviewed in this study; one patient was excluded due to lack of follow-up. Of the 109 patients included, 58 (53.2%) underwent adjuvant chemotherapy (chemo group), whereas the remaining 51 (46.8%) did not receive any chemotherapy (non-chemo group). After a median follow-up of 50 months, there were no significant differences in the 5-year overall survival (OS) or recurrence-free survival (RFS) rates between the groups (OS: 92.1 vs 86.3%, P  =   0.375; RFS: 80.9 vs 74.7%, P  =   0.534). Subgroup analysis also demonstrated no significant differences in 5-year OS and RFS rates between patients with ypT0N0 rectal cancer ( P  =   0.712 and P  =   0.599, respectively) and those with ypT1-2N0 disease ( P  =   0.255 and P  =   0.278, respectively)., Conclusions: These results indicate that patients with ypT0-2N0 rectal cancer after NCRT followed by curative surgery may not derive significant benefit from adjuvant chemotherapy. However, further prospective randomized trials, with larger sample sizes, are warranted to confirm this conclusion.

Risk of gene flow from canola (Brassica napus) to species of wild relatives was used as an example to evaluate the risk of gene flow of transgenic crops. B. juncea and B. rapa were the most common weedy Brassica species in China, which were both sexually compatible with canola. Data on canola cultivation in China were collected and analyzed using geographic information system (GIS), and the distribution of its wild relatives was predicted by MaxEnt species distribution model. Based on biological and phenological evidence, our results showed that gene flow risk exists in most parts of the country, especially in places with higher richness of wild Brassica species. However, risk in dominant canola cultivation regions is relatively low owing to the reduced distribution density of wild species in these regions. Three regions of higher risk of gene flow had been identified. Risk of gene flow is relatively high in certain areas. China has been assumed to be the original center of B. juncea and B. rapa, and gene flow may lead to negative effects on the conservation of biodiversity of local species. Strategies had been proposed to reduce the possibility of gene flow either by monitoring introgression from crops to wild relatives in the areas of high adoption of the crop or by taking measures to limit the releasing of new crops or varieties in the areas with abundant wild relatives.

Hereditary nonsyndromic hearing loss is extremely heterogeneous. Mutations in the POU class 4 transcription factor 3 (POU4F3) are known to cause autosomal dominant nonsyndromic hearing loss linked to the loci of DFNA15. In this study, we describe a pathogenic missense mutation in POU4F3 in a four-generation Chinese family (6126) with midfrequency, progressive, and postlingual autosomal dominant nonsyndromic hearing loss (ADNSHL). By combining targeted capture of 129 known deafness genes, next-generation sequencing, and bioinformatic analysis, we identified POU4F3 c.602T>C (p.Leu201Pro) as the disease-causing variant. This variant cosegregated with hearing loss in other family members but was not detected in 580 normal controls or the ExAC database and could be classified as a "pathogenic variant" according to the American College of Medical Genetics and Genomics guidelines. We conclude that POU4F3 c.602T>C (p.Leu201Pro) is related to midfrequency hearing loss in this family. Routine examination of POU4F3 is necessary for the genetic diagnosis of midfrequency hearing loss.

Carcinogenesis has a multifactorial etiology, and the underlying molecular pathogenesis is still not entirely understood, especially for eye cancers. Primary malignant intraocular neoplasms are relatively rare, but delayed detection and inappropriate management contribute to poor outcomes. Conventional treatment, such as orbital exenteration, chemotherapy, or radiotherapy, alone results in high mortality for many of these malignancies. Recent sequential multimodal therapy with a combination of high-dose chemotherapy, followed by appropriate surgery, radiotherapy, and additional adjuvant chemotherapy has helped dramatically improve management. Transcription factors are proteins that regulate gene expression by modulating the synthesis of mRNA. Since transcription is a dominant control point in the production of many proteins, transcription factors represent key regulators for numerous cellular functions, including proliferation, differentiation, and apoptosis, making them compelling targets for drug development. Natural compounds have been studied for their potential to be potent yet safe chemotherapeutic drugs. Since the ancient times, plant-derived bioactive molecules have been used to treat dreadful diseases like cancer, and several refined pharmaceutics have been developed from these compounds. Understanding targeting mechanisms of oncogenic transcription factors by natural products can add to our oncologic management toolbox. This review summarizes the current findings of natural products in targeting specific oncogenic transcription factors in various types of eye cancer., (Published by Elsevier Ltd.)

The phosphoenopyruvate:carbohydrate phosphotransferase system (PTS) enables Vibrio cholerae - and other bacteria - to recognize and transport exogenous carbon sources for energy, including the six-carbon sugar alcohol, mannitol. The mannitol-specific PTS transporter is encoded by mtlA and its expression is expected to be regulated by the putative repressor encoded by the mtlR gene. Here, we show that mtlR overexpression inhibits V. cholerae growth in medium supplied with mannitol as the sole carbon source and represses MtlA-mediated biofilm formation. We demonstrate that when V. cholerae is grown in non-mannitol medium, knocking out mtlR leads to both increased MtlA protein and mtlA mRNA levels, with these increases being especially pronounced in non-glucose sugars. We propose that in non-mannitol, non-glucose growth conditions, MtlR is a major regulator of mtlA transcription. Surprisingly, with regard to mtlR expression, transcript and protein levels are highest in mannitol medium, conditions where mtlA expression should not be repressed. We further show that MtlR levels increase during growth of the bacteria and linger in cells switched from mannitol to non-mannitol medium. Our data suggests an expression paradigm for mtlA where MtlR acts as a transcriptional repressor responsible for calibrating MtlA levels during environmental transitions.

Objective: To evaluate the effect of proton pump inhibitors (PPIs) therapy on severe acute pancreatitis (SAP) patients., Methods: Forty five patients with SAP recruited in our center from October 2015 to October 2016,were randomly assigned into two groups: convention group (C group, n =21) and convention+esomeprazole group (C+E group, n =24). C+E group received esomeprazole 40 mg/d intravenously for 1 week,whereas C group only received baseline treatment. Serum C-reactive protein (CRP),interleukin-6 (IL-6) and interleukin-8 (IL-8),tumor necrosis factor-α (TNF-α) and procalcitonin (PCT) were detected by ELISA on the first day (baseline) and the seventh day. Acute physiology and chronic health evaluation Ⅱ scores (APACHE Ⅱ),systemic inflammatory response syndrome scores (SIRS) and modified Marshall scoring system (Marshall) were obtained at 1 d (baseline),3 d and 7 d. Upper gastrointestinal manifestation (peptic ulcer) and gastric pH were detected by endoscopic examination at 7 d. Fecal occult blood test was performed at 7 d., Results: No significant difference was found in CRP,IL-6,IL-8,TNF-α and PCT between the two groups ( P >0.05),also no difference in APACHE Ⅱ,SIRS and Marshall scores ( P >0.05). The gastric pH was remarkably higher in C+E group when compared to C group (5.02±1.61 vs.2.83±1.08, P <0.001). There was no significant difference in the incidence of peptic ulcer and the rate of positive fecal occult blood between the two groups., Conclusion: PPIs therapy did not show benefit on alleviating systemic inflammatory response and clinical scores in SAP patients,and didn't improve the prevention of peptic ulcer and gastrointestinal hemorrhage.

Recurrence of hepatocellular carcinoma (HCC) after transarterial chemoembolisation (TACE) is common due to neoangiogenesis. Cyclooxygenase-2 inhibitors and somatostatin analogues were reported to inhibit tumour angiogenesis. The pilot randomized controlled trial was aimed to prospectively evaluate the protocol of TACE combined with celecoxib and lanreotide (TACE+C+L) in patients with unresectable and advanced HCC. A total of 71 patients with HCC were enrolled and randomly assigned to either TACE (n=35) or TACE+C+L (n=36) group. Overall survival, disease control rate (DCR), and adverse events were assessed during a 3-year follow-up period. The median overall survival of the TACE+C+L group (15.0 months) was doubled compared to that of TACE group (7.5 months), p = 0.012. DCR of the TACE+C+L group was significantly higher than that of the TACE group either at 6 months (72.2% vs 42.9%, p = 0.012) or at 12 months (61.1% vs 28.6%, p = 0.006). The median overall survivals (13 months vs 4.5 months, p = 0.013) and DCR at 12 months (50% vs 13.6%, p = 0.008) of patients with advanced HCC in TACE+C+L groups were significantly higher than those in TACE group. No significant difference of adverse events was observed between the two groups. The occurrence of post-embolisation syndrome in TACE+C+L group was significantly lower than that in TACE group (16.7% vs 60.0%, p = 0.001). In conclusion, the regimen of TACE+C+L prolonged overall survival, enhanced tumour response, reduced post-embolisation syndrome and was well-tolerable in the patients with unresectable HCC. It may be more beneficial for advanced HCC.

Low birth weight is associated with adverse health outcomes. If birth weight records are not available, studies may use recalled birth weight. It is unclear whether this is reliable. We performed a systematic review and meta-analysis of studies comparing recalled with recorded birth weights. We followed the Meta-Analyses of Observational Studies in Epidemiology (MOOSE) statement and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched MEDLINE, EMBASE and Cumulative Index to Nursing and Allied Health Literature (CINAHL) to May 2015. We included studies that reported recalled birth weight and recorded birth weight. We excluded studies investigating a clinical population. Two reviewers independently reviewed citations, extracted data, assessed risk of bias. Data were pooled in a random effects meta-analysis for correlation and mean difference. In total, 40 studies were eligible for qualitative synthesis (n=78,997 births from 78,196 parents). Agreement between recalled and recorded birth weight was high: pooled estimate of correlation in 23 samples from 19 studies (n=7406) was 0.90 [95% confidence interval (CI) 0.87-0.93]. The difference between recalled and recorded birth weight in 29 samples from 26 studies (n=29,293) was small [range -86-129 g; random effects estimate 1.4 g (95% CI -4.0-6.9 g)]. Studies were heterogeneous, with no evidence for an effect of time since birth, person reporting, recall bias, or birth order. In post-hoc subgroup analysis, recall was higher than recorded birth weight by 80 g (95% CI 57-103 g) in low and middle income countries. In conclusion, there is high agreement between recalled and recorded birth weight. If birth weight is recalled, it is suitable for use in epidemiological studies, at least in high income countries.

Hereditary hearing loss is characterized by a high degree of genetic heterogeneity. Mutations in the TMPRSS3 (transmembrane protease, serine 3) gene cause prelingual (DFNB10) or postlingual (DFNB8) deafness. In our previous study, three pathogenic mutations in TMPRSS3 were identified in one Chinese family. To evaluate the importance of TMPRSS3 mutations in recessive deafness among the Chinese, we screened 150 autosomal recessive nonsyndromic hearing loss (ARNSHL) families and identified 6 that carried seven causative TMPRSS3 mutations, including five novel mutations (c.809T>A, c.1151T>G, c.1204G>A, c.1244T>C, and c.1250G>A) and two previously reported mutations (c.323-6G>A and c.916G>A). Each of the five novel mutations was classified as severe, by both age of onset and severity of hearing loss. Together with our previous study, six families were found to share one pathogenic mutation (c.916G>A, p.Ala306Thr). To determine whether this mutation arose from a common ancestor, we analyzed six short tandem repeat (STR) markers spanning the TMPRSS3 gene. In four families, we observed linkage disequilibrium between p.Ala306Thr and STR markers. Our results indicate that mutations in TMPRSS3 account for about 4.6% (7/151) of Chinese ARNSHL cases lacking mutations in SLC26A4 or GJB2 and that the recurrent TMPRSS3 mutation p.Ala306Thr is likely to be a founder mutation.

Anisotropic gold nanostructures with unique plasmonic properties, specifically the strong absorption of light in the near-infrared region (650-900 nm) due to the excitation of plasmon oscillations, have been widely employed as photothermal conversion agents (PTCAs) for cancer photothermal therapy (PTT). However, the reported PTCAs show suboptimal photothermal conversion efficiency (η), even gold nanocages (η = 63%), which limits their biomedical applications. Herein, we fabricated gold bellflowers (GBFs) with an ultrahigh photothermal conversion efficiency (η = 74%) via a novel liquid/liquid/gas triphasic interface system, using chloroauric acid as a gold source, and o-phenetidine as a reducing agent. The well-defined GBFs with multiple-branched petals show adjustable localized surface plasmon resonance (LSPR) from 760 to 1100 nm by tuning the petal length and circular bottom diameter. Originating from the monophasic and biphasic systems used in the creation of gold nanourchins (GNUs) and gold microspheres (GMPs) respectively, the triphasic interface system successfully produced GBFs. The possible formation mechanisms of GNUs, GMPs, and GBFs in the different systems were also investigated and discussed. We found that the formation mechanism of GNUs and GBFs followed classical crystallization, while the formation of GMPs followed non-classical crystallization.

There is a growing recognition of the association between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and erectile dysfunction (ED); however, most of the reports are based on questionnaires which cannot distinguish between organic and functional ED. The purpose of this study was to determine the exact relationship between CP/CPPS and ED, and to investigate the changes in erectile organ structure and function in a rat model of CP/CPPS. We established a rat model of experimental autoimmune prostatitis (EAP), which is a valid model for CP/CPPS. Erectile function in EAP and normal rats was comparable after cavernous nerve electrostimulation. The serum testosterone and oestradiol levels, ultrastructure of the corpus cavernosum and expression of endothelial nitric oxide synthase and neuronal nitric oxide synthase in the two groups were similar; however, there was a decrease in smooth muscle-to-collagen ratio and alpha-smooth muscle actin expression and an increase in transforming growth factor-beta 1 expression was observed in EAP rats. Thus, organic ED may not exist in EAP rats. We speculate that ED complained by patients with CP/CPPS may be psychological, which could be caused by impairment in the quality of life; however, further studies are needed to fully understand the potential mechanisms underlying the penile fibrosis in EAP rats., (© 2015 Blackwell Verlag GmbH.)