Research progress in the role of gut microbiota in acute kidney injury. / è‚ é“èŒç¾¤åœ¨æ€¥æ€§è‚¾æŸä¼¤ä¸­ä½œç”¨çš„ç ”ç©¶è¿›å±•.

Acute kidney injury (AKI) remains a global public health problem with high incidence, high mortality rates, expensive medical costs, and limited treatment options. AKI can further progress to chronic kidney disease (CKD) and eventually end-stage renal disease (ESRD). Previous studies have shown that trauma, adverse drug reactions, surgery, and other factors are closely associated with AKI. With further in-depth exploration, the role of gut microbiota in AKI is gradually revealed. After AKI occurs, there are changes in the composition of gut microbiota, leading to disruption of the intestinal barrier, intestinal immune response, and bacterial translocation. Meanwhile, metabolites of gut microbiota can exacerbate the progression of AKI. Therefore, elucidating the specific mechanisms by which gut microbiota is involved in the occurrence and development of AKI can provide new insights from the perspective of intestinal microbiota for the prevention and treatment of AKI.

Estimated number of spine surgeries and related deaths in Japan from 2014 to 2020.

BACKGROUND: The total number of spine surgeries per year and their related deaths in Japan has not been adequately estimated in the literature. METHODS: We retrospectively reviewed the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) between April 2014 to March 2021, which covers 99.9 % of health insurance claim receipts by general practitioners. The annual number of surgeries was counted using K codes, a procedure classification unique to Japan, and classified into the following six categories; percutaneous vertebroplasty, endoscopic surgery, open discectomy, laminoplasty/laminectomy, instrumentation surgery, and others. The data distribution was also summarized by sex and age. Additionally, by reviewing DPC database-related papers for evaluation of the mortality rate after spine surgery in Japan, the number of spine surgery-related deaths was calculated. RESULTS: The NDB showed that the number of spine surgeries analyzed in this study increased from 170,081 in 2014 to 193,903 in 2019, with a slight decrease in 2020. The ratio of instrumentation surgery increased from 33.0 % in 2014 to 37.9 % in 2020. The rate of patients aged 75 or older increased 31.6 % to 39.6 %. Combining these findings with DPC data showing a mortality rate of 0.1 % to 0.4 % revealed that the estimated number of deaths related to spine surgery in Japan ranged from 200 to 800 per year. CONCLUSIONS: Approximately 200,000 spine surgeries and 200 to 800 spine surgery-related inpatient deaths were estimated to have occurred in Japan around 2020.

Trapdoor Deformity Correction Post Nasal Bilobed Flaps for Basal Cell Carcinoma Reconstruction With Multiple Laser Modalities.

ABSTRACT: In case of excision of nasal basal cell carcinoma (BCC), bilobed flaps are considered the criterion standard of reconstruction for defect less than 15 mm in size. However, there is still a risk of trapdoor deformity formation, of which its treatment is less discussed. A 44-year-old woman who was diagnosed with nasal BCC and underwent tumor excision with bilobed flap reconstruction presented with trapdoor deformity postoperatively. The computed Vancouver Scar Scale was 7. After early intervention of multiple laser modalities, including 2 sessions of 585-nm pulsed dye laser with a fluence of 9 J/cm2, pulse duration of 6 milliseconds, and spot size of 6 mm, 2940-nm Er-yttrium aluminum garnet (YAG) laser with a pulse energy of 800-900 mJ, repetition rate of 8-9 Hz, and laser spot size of 3-7 mm, and 5 sessions of 1064-nm Nd:YAG fractional picosecond laser with a pulse energy of 2.30-2.70 mJ, repetition rate of 8 Hz, and laser spot size of 6 mm from 5 to 23 weeks postoperatively, the Vancouver Scar Scale score improved to 1, with significant reduction of trapdoor scar erythema and puffiness. Although BCC is often curable, tumor excision causes unsatisfactory appearance satisfaction problem, owing to the apparent location of the lesion. Factors, such as sebaceous tissue thickness, reconstruction over multiple aesthetic subunits of nose, and damage to nasal cartilage framework structure during tumor removal, may increase the risk of trapdoor formation. Early intervention with multiple laser treatment can significantly revise the deformity.

A quantitative framework for patient-specific collision detection in proton therapy.

BACKGROUND: Beam modifying accessories for proton therapy often need to be placed in close proximity of the patient for optimal dosimetry. However, proton treatment units are larger in size and as a result the planned treatment geometry may not be achievable due to collisions with the patient. A framework that can accurately simulate proton treatment geometry is desired. PURPOSE: A quantitative framework was developed to model patient-specific proton treatment geometry, minimize air gap, and avoid collisions. METHODS: The patient's external contour is converted into the International Electrotechnique Commission (IEC) gantry coordinates following the patient's orientation and each beam's gantry and table angles. All snout components are modeled by three-dimensional (3D) geometric shapes such as columns, cuboids, and frustums. Beam-specific parameters such as isocenter coordinates, snout type and extension are used to determine if any point on the external contour protrudes into the various snout components. A 3D graphical user interface is also provided to the planner to visualize the treatment geometry. In case of a collision, the framework's analytic algorithm quantifies the maximum protrusion of the external contour into the snout components. Without a collision, the framework quantifies the minimum distance of the external contour from the snout components and renders a warning if such distance is less than 5 cm. RESULTS: Three different snout designs are modeled. Examples of potential collision and its aversion by snout retraction are demonstrated. Different patient orientations, including a sitting treatment position, as well as treatment plans with multiple isocenters, are successfully modeled in the framework. Finally, the dosimetric advantage of reduced air gap enabled by this framework is demonstrated by comparing plans with standard and reduced air gaps. CONCLUSION: Implementation of this framework reduces incidence of collisions in the treatment room. In addition, it enables the planners to minimize the air gap and achieve better plan dosimetry.

Coffea arabica Extract Attenuates Atopic Dermatitis-like Skin Lesions by Regulating NLRP3 Inflammasome Expression and Skin Barrier Functions.

Atopic dermatitis (AD) is a common skin disease worldwide. The major causes of AD are skin barrier defects, immune dysfunction, and oxidative stress. In this study, we investigated the anti-oxidation and anti-inflammation effects of Coffea arabica extract (CAE) and its regulation of the skin barrier and immune functions in AD. In vitro experiments revealed that CAE decreased the reactive oxygen species levels and inhibited the translocation of nuclear factor-κB (NF-κB), further reducing the secretion of interleukin (IL)-1ß and IL-6 induced by interferon-γ (IFN-γ)/tumor necrosis factor-α (TNF-α). Moreover, CAE decreased IFN-γ/TNF-α-induced NLR family pyrin domain-containing 3 (NLRP3), caspase-1, high-mobility group box 1 (HMGB1), and receptor for advanced glycation end products (RAGE) expression levels. It also restored the protein levels of skin barrier function-related markers including filaggrin and claudin-1. In vivo experiments revealed that CAE not only reduced the redness of the backs of mice caused by 2,4-dinitrochlorobenzene (DNCB) but also reduced the levels of pro-inflammatory factors in their skin. CAE also reduced transepidermal water loss (TEWL) and immune cell infiltration in DNCB-treated mice. Overall, CAE exerted anti-oxidation and anti-inflammation effects and ameliorated skin barrier dysfunction, suggesting its potential as an active ingredient for AD treatment.

With two episodes of right retromandibular angle subcutaneous emphysema during right upper molar crown preparation: A case report.

BACKGROUND: Subcutaneous emphysema is a well-known complication of oral surgery, especially during mandibular wisdom tooth extraction. However, subcutaneous emphysema secondary to dental procedures such as crown preparation is rare. The main symptom of emphysema is swelling and crepitus on palpation. Uncontrolled emphysema may spread along the fascial planes and cause deep space infections or a pneumomediastinum. CASE SUMMARY: In this paper, we report a 34-year-old female who underwent upper molar tooth preparation for crowns and subsequently developed extensive subcutaneous emphysema on the retromandibular angle on two different occasions. The treatment plan for this patient involved close observation of the airway, and administration of dexamethasone and antibiotics via intravenous drip or orally. Ice bag compression was quickly applied and medication was prescribed to alleviate discomfort and promote healing. Although the main reason is unclear, the presence of a fissure in the molar is an important clue which may contribute to the development of subcutaneous emphysema during crown preparation. It is imperative for dental professionals to recognize such pre-disposing factors in order to minimize the risk of complications. CONCLUSION: This case highlights the need for prompt diagnosis and management of subcutaneous emphysema because of the risk of much more serious complications. Awareness of relatively "benign" subcutaneous emphysema during any dental procedure is critical not only for inexperienced dentists, but also for those who work in rural and remote settings as members of surgical teams. In this study, we review the clinical presentation, mechanism, and differential diagnosis of subcutaneous emphysema.

Multiomics analyses reveal pathological mechanisms of HBV infection and integration in liver cancer.

Hepatitis B virus (HBV) infection and integration are important for hepatocellular carcinoma (HCC) initiation and progression, while disease mechanisms are still largely elusive. Here, we combined bulk and single-cell sequencing technologies to tackle the disease mechanisms of HBV-related HCC. We observed high HBV mutation rate and diversity only in tumors without HBV integration. We identified human somatic risk loci for HBV integration (VIMs). Transcription factors (TFs) enriched in VIMs were involved in DNA repair and androgen receptor (AR) signaling. Aberration of AR signaling was further observed by single-cell regulon analysis in HBV-infected hepatocytes, which showed remarkable interactions between AR and the complement system that, together with the X-linked ZXDB regulon that contains albumin (ALB), probably contribute to HCC male predominance. Complement system dysregulation caused by HBV infection was further confirmed by analyses of single-cell copy numbers and cell-cell communications. Finally, HBV infection-associated immune cells presented critical defects, including TXNIP in T cells, TYROBP in NK cells, and the X-linked TIMP1 in monocytes. We further experimentally validated our findings in multiple independent patient cohorts. Collectively, our work shed light on the pathogenesis of HBV-related HCC and other liver diseases that affect billions of people worldwide.

Adaptability of melanocytes post ultraviolet stimulation in patients with melasma.

BACKGROUND: Dynamic in vivo changes in melanin in melasma lesions after exposure to ultraviolet (UV) irradiation have not been described. OBJECTIVES: To determine whether melasma lesions and nearby perilesions demonstrated different adaptive responses to UV irradiation and whether the tanning responses were different among different locations on face. METHODS: We collected sequential images from real-time cellular resolution full-field optical coherence tomography (CRFF-OCT) at melasma lesions and perilesions among 20 Asian patients. Quantitative and layer distribution analyses for melanin were performed using a computer-aided detection (CADe) system that utilizes spatial compounding-based denoising convolutional neural networks. RESULTS: The detected melanin (D) is melanin with a diameter >0.5 µm, among which confetti melanin (C) has a diameter of >3.3 µm and corresponds to a melanosome-rich package. The calculated C/D ratio is proportional to active melanin transportation. Before UV exposure, melasma lesions had more detected melanin (p = 0.0271), confetti melanin (p = 0.0163), and increased C/D ratio (p = 0.0152) in the basal layer compared to those of perilesions. After exposure to UV irradiation, perilesions have both increased confetti melanin (p = 0.0452) and the C/D ratio (p = 0.0369) in basal layer, and this effect was most prominent in right cheek (p = 0.030). There were however no significant differences in the detected, confetti, or granular melanin areas before and after exposure to UV irradiation in melasma lesions in all the skin layers. CONCLUSIONS: Hyperactive melanocytes with a higher baseline C/D ratio were noted in the melasma lesions. They were "fixed" on the plateau and were not responsive to UV irradiation regardless of the location on face. Perilesions retained adaptability with a dynamic response to UV irradiation, in which more confetti melanin was shed, mainly in the basal layer. Therefore, aggravating effect of UV on melasma was mainly due to UV-responsive perilesions rather than lesions.

Intermittent fasting protects against food allergy in a murine model via regulating gut microbiota.

Background: The prevalence of food allergy (FA) is increasing. Decreases in the diversity of gut microbiota may contribute to the pathogenesis of FA by regulating IgE production of B cells. Intermittent fasting (IF) is a popular diet with the potential to regulate glucose metabolism, boosting immune memory and optimizing gut microbiota. The potential effect of long-term IF on the prevention and treatment of FA is still unknown. Methods: Two IF protocols (16 h fasting/8 h feeding and 24 h fasting/24 h feeding) were conducted on mice for 56 days, while the control mice were free to intake food (free diet group, FrD). To construct the FA model, all mice were sensitized and intragastrical challenged with ovalbumin (OVA) during the second half of IF (day 28 to day 56). Rectal temperature reduction and diarrhea were recorded to evaluate the symptoms of FA. Levels of serum IgE, IgG1, Th1/Th2 cytokines, mRNA expression of spleen T cell related transcriptional factors, and cytokines were examined. H&E, immunofluorescence, and toluidine blue staining were used to assess the structural changes of ileum villi. The composition and abundance of gut microbiota were analyzed by 16srRNA sequencing in cecum feces. Results: The diarrhea score and rectal temperature reduction were lower in the two fasting groups compared to the FrD groups. Fasting was associated with lower levels of serum OVA-sIgE, OVA-sIgG1, interleukin (IL)-4 and IL-5, and mRNA expression of IL-4, IL-5, and IL-10 in the spleen. While no significant association was observed in interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-6, IL-2 levels. Less mast cell infiltration in ileum was observed in the 16h/8h fasting group compared to the FrD group. ZO-1 expression in the ileum of the two fasting groups was higher in IF mice. The 24h/24h fasting reshaped the gut microbiota, with a higher abundance of Alistipes and Rikenellaceae strains compared to the other groups. Conclusion: In an OVA-induced mice FA model, long-term IF may attenuate FA by reducing Th2 inflammation, maintaining the integrity of the intestinal epithelial barrier, and preventing gut dysbiosis.

Adaptation and Limitations of painDETECT Questionnaire Score Approach Before and After Posterior Cervical Decompression Surgery.

BACKGROUND: The painDETECT questionnaire (PDQ) is one of the available screening tools for neuropathic pain (NeP), with a cut-off score of 13. This study aimed to investigate changes in PDQ scores in patients undergoing posterior cervical decompression surgery for degenerative cervical myelopathy (DCM). METHODS: Patients with DCM undergoing cervical laminoplasty or laminectomy with posterior fusion were recruited. They were asked to complete a booklet questionnaire including PDQ and Numerical Rating Scales (NRS) for pain at baseline and one year after surgery. Patients with a preoperative PDQ score ≥13 were further investigated. RESULTS: A total of 131 patients (mean age = 70.1 years; 77 male and 54 female) were analyzed. After posterior cervical decompression surgery for DCM, mean PDQ scores decreased from 8.93 to 7.28 (P = 0.008) in all patients. Of the 35 patients (27%) with preoperative PDQ scores ≥13, mean PDQ changed from 18.83 to 12.09 (P < 0.001). Comparing the NeP improved group (17 patients with postoperative PDQ scores ≤12) with the NeP residual group (18 patients with postoperative PDQ scores ≥13), the NeP improved group showed less preoperative neck pain (2.8 vs. 4.4, P = 0.043) compared to the NeP residual group. There was no difference in the postoperative satisfaction rate between the two groups. CONCLUSIONS: Approximately 30% of patients exhibited preoperative PDQ scores ≥13, and about half of these patients demonstrated improvements to below to the cut-off value for NeP after posterior cervical decompression surgery. The PDQ score change was relatively associated with preoperative neck pain.

Management of an Unusual Avulsion Trauma of Total Esophagus During Upper Gastrointestinal Endoscopy.

BACKGROUND: An esophageal defect usually resulted from surgical ablation of tumors or corrosive injury. Staged reconstructions are required usually in extensive defects. AIM AND OBJECTIVES: This study aimed to present a rare iatrogenic complication of total esophageal avulsion injury during upper gastrointestinal endoscopic treatment and to perform staged reconstructions to create a neoesophagus. MATERIALS AND METHODS: In the presented case, staged reconstructions with a tubed deltopectoral flap and a supercharged colon interposition flap were performed to reconstruct the hypopharynx and esophagus. However, recurrent choking occurred because of the extent of injury involving the epiglottis. A tubed free radial forearm flap connected to the lower buccogingival sulcus was used to create a new route for food passage. RESULTS: The patient resumed oral intake after rehabilitation. CONCLUSIONS: The avulsion injury of the total esophagus is rare and devastating. Staged reconstructions with a tubed deltopectoral flap, a supercharged colon interposition flap, and a tubed free radial forearm flap would be a safe and reliable method.

RHOA-regulated IGFBP2 promotes invasion and drives progression of BCR-ABL1 chronic myeloid leukemia.

The Philadelphia 9;22 chromosome translocation has two common isoforms that are preferentially associated with distinct subtypes of leukemia. The p210 variant is the hallmark of chronic myeloid leukemia (CML) whereas p190 is frequently associated with B-cell acute lymphoblastic leukemia. The only sequence difference between the two isoforms is the guanidine exchange factor domain. This guanidine exchange factor is reported to activate RHO family GTPases in response to diverse extracellular stimuli. It is not clear whether and, if so, how RHOA contributes to progression of p210 CML. Here we show that knockout of RHOA in the K562 and KU812, p210-expressing cell lines leads to suppression of leukemogenesis in animal models in vivo. RNA-sequencing analysis of the mock control and null cells demonstrated a distinct change in the gene expression profile as a result of RHOA deletion, with significant downregulation of genes involved in cell activation and cell adhesion. Cellular analysis revealed that RHOA knockout leads to impaired cell adhesion and migration and, most importantly, the homing ability of leukemia cells to the bone marrow, which may be responsible for the attenuated leukemia progression. We also identified IGFBP2 as an important downstream target of RHOA. Further mechanistic investigation showed that RHOA activation leads to relocation of the serum response factor (SRF) into the nucleus, where it directly activates IGFBP2. Knockout of IGFBP2 in CML cells suppressed cell adhesion/invasion, as well as leukemogenesis in vivo. This elevated IGFBP2 expression was confirmed in primary CML samples. Thus, we demonstrate one mechanism whereby the RHOA-SRF-IGFBP2 signaling axis contributes to the development of leukemia in cells expressing the p210 BCR-ABL1 fusion kinase.

Free extended anterolateral thigh myocutaneous flap versus combined pedicled pectoralis major-latissimus dorsi myocutaneous flaps in deep and extensive sternal wound reconstruction.

BACKGROUND: The combined pedicled pectoralis major-latissimus dorsi (PM-LD) and free extended anterolateral thigh (ALT) myocutaneous flaps provide well-vascularized tissues for extensive sternal wound reconstruction. However, the outcomes and postoperative complications between the two surgical techniques are different. Thus, the aim of this study is to evaluate the feasibility of these two reconstructive options. METHODS: This single-center, retrospective study was conducted between August 2011 and May 2019. Forty-four patients diagnosed with deep sternal wound infection (DSWI) and presented with grade four complications (sternal instability and necrotic bone tissue) were enrolled. Two reconstructive strategies, namely, combined pedicled PM-LD (n = 24) and free extended ALT (n = 20) myocutaneous flaps, were used according to the patients' hemodynamics. Data including age, gender, body mass index (BMI), hospital stay, follow-up, defect/flap size, number of surgical procedures before reconstruction, duration from the last debridement to flap coverage, comorbidities, and postoperative complications, were obtained for statistical analysis. RESULTS: The mean defect size in the combined PM-LD myocutaneous flap group was 188.4 (5*17-10*23) cm2 , and the mean flap size was 150.0 (8*12-15*15) cm2 and 205.0 (8*15-10*25) cm2 in PM and LD flap, respectively. The mean defect size in the free extended ALT myocutaneus flap group was 202.5 (6*16-10*21) cm2 , and the mean flap size was 285.2 (9*30-12*25) cm2 . No significant differences were observed between the free extended ALT and the combined pedicled PM-LD myocutaneous flaps in relation to age, gender, BMI, hospital days, follow-up, defect size, preoperative procedures, and comorbidities, except for the average operative time (443.2 ± 31.2 vs. 321.3 ± 54.3 mins, p = .048). The combined pedicled PM-LD myocutaneous flap had significantly more donor site complications, including seroma (21% vs. 0%, p = .030), bilateral nipple-areolar complex asymmetry (100% vs. 0%, p < .0001), and skin graft loss with infection (33% vs. 0%; p = .044) than the free extended ALT myocutaneous flap. CONCLUSION: The free extended ALT and the combined pedicled PM-LD myocutaneous flaps were both feasible and effective options for sternal wound reconstruction. Our findings suggested that the free extended ALT myocutaneous flap may be a better alternative for a comprehensive and extensive reconstruction of sternal wounds. Further studies based on these findings can be conducted.

Nano Modification of Antrodia Cinnamomea Exhibits Anti-Inflammatory Action and Improves the Migratory Potential of Myogenic Progenitors.

The skeletal muscle progenitors' proliferation and migration are crucial stages of myogenesis. Identifying drug candidates that contribute to myogenesis can have a positive impact on atrophying muscle. The purpose of the study is to synthesize the Antrodia cinnamomea (AC)-ß-cyclodextrin (BCD) inclusion complex (IC) and understand its in vitro pro-regenerative influence in murine skeletal C2C12 myoblasts. The IC was subjected to various nano-characterization studies. Fluorescent IC was synthesized to understand the cellular uptake of IC. Furthermore, 25 µg/mL, 12.5 µg/mL, and 6.25 µg/mL of IC were tested on murine C2C12 skeletal muscle cells for their anti-inflammatory, pro-migratory, and pro-proliferative action. The cellular internalization of IC occurred rapidly via pinocytosis. IC (252.6 ± 3.2 nm size and -37.24 ± 1.55 surface charge) exhibited anti-inflammatory action by suppressing the secretion of interleukin-6 and enhanced cell proliferation with promising cytocompatibility. A 12.5 µg/mL dose of IC promoted cell migration in 24 h, but the same dose of AC significantly reduced cell migration, suggesting modification by BCD. Molecular studies revealed that IC promoted C2C12 myoblasts migration by upregulating long non-coding RNA (lncRNA) NEAT-1, SYISL, and activating the pPKC/ß-catenin pathway. Our study is the first report on the pro-proliferative and pro-migratory effects of BCD-modified extracts of AC.

A truncated derivative of FGFR1 kinase cooperates with FLT3 and KIT to transform hematopoietic stem cells in syndromic and de novo AML.

BACKGROUND: Myeloid and lymphoid malignancies associated with chimeric FGFR1 kinases are the hallmark of stem cell leukemia and lymphoma syndrome (SCLL). In all cases, FGFR1 kinase is constitutively phosphoactivated as a result of chromosome translocations, which lead to acquisition of dimerization motifs in the chimeric proteins. Recently, we demonstrated that these chimeric kinases could be cleaved by granzyme B to generate a truncated derivative, tnFGFR1, which localized exclusively into the nucleus and was not phosphorylated. METHODS: Stem cell transduction and transplantation in syngeneic mice was used to assess the transforming ability of tnFGFR1 in bone marrow stem cells, and RPPA and RNA-Seq was used to examine the related signaling pathways and regulated target genes. RESULTS: For the first time, we show that this non-classical truncated form of FGFR1 can independently lead to oncogenic transformation of hematopoietic stem cells in an animal model in vivo. These leukemia cells show a mixed immunophenotype with a B-cell B220 + Igm- profile in the majority of cells and Kit+ in virtually all cells, suggesting a stem cell disease. tnFGFR1, however, does not activate classic FGFR1 downstream signaling pathways but induces a distinct profile of altered gene expression with significant upregulation of transmembrane signaling receptors including FLT3 and KIT. We further show that de novo human AML also express tnFGFR1 which correlates with upregulation of FLT3 and KIT as in mouse leukemia cells. ChIP analysis demonstrates tnFGFR1 occupancy at the Flt3 and Kit promoters, suggesting a direct transcriptional regulation. Cells transformed with tnFGFR1 are insensitive to FGFR1 inhibitors but treatment of these cells with the Quizartinib (AC220) FLT3 inhibitor, suppresses in vitro growth and development of leukemia in vivo. Combined treatment with FGFR1 and FLT3 inhibitors provides increased survival compared to FGFR1 inhibition alone. CONCLUSIONS: This study demonstrates a novel model for transformation of hematopoietic stem cells by chimeric FGFR1 kinases with the combined effects of direct protein activation by the full-length kinases and transcriptional regulation by the truncated nuclear tnFGFR1 derivative, which is associated with GZMB expression levels. Genes significantly upregulated by tnFGFR1 include Flt3 and Kit which promote a leukemia stem cell phenotype. In human AML, tnFGFR1 activation leads to increased FLT3 and KIT expression, and higher FLT3 and GZMB expression levels are associated with an inferior prognosis. These observations provide insights into the relative therapeutic value of targeting FGFR1 and FLT3 in treating AML with this characteristic gene expression profile.

The effect of medication on serum anti-müllerian hormone (AMH) levels in women of reproductive age: a meta-analysis.

OBJECTIVE: The study aims to address whether serum anti-müllerian hormone (AMH) levels fluctuate in the short term after medication application, including oral contraceptives (OCs), metformin (MET), Gonadotropin-releasing hormone agonist (GnRH-a), dehydroepiandrosterone (DHEA), vitamin D (VD), clomiphene citrate (CC), and letrozole (LET). METHODS: Published literature from PubMed, Embase, and Cochrane central was retrieved up until 19 September 2021. A total of 51 self-control studies with an average Newcastle-Ottawa quality assessment scale (NOS) score of 6.90 were analyzed. The extracted data were entered into Stata software, and the weighted mean difference/standardized mean difference (WMD/SMD) and 95% confidence interval (CI) were used for data analysis. RESULTS: After OCs treatment the AMH level showed a significant decline in women with normal ovarian function, which was significant within 3 months (WMD = -1.43, 95% CI: -2.05 to -0.80, P < 0.00001). After MET treatment, the serum AMH decreased in polycystic ovary syndrome (PCOS) patients (WMD = -1.79, 95% CI: -2.32 to -1.26, P < 0.00001), in both obese and non-obese patients. GnRH-a treatment in endometriosis patients led to dynamic changes in the serum AMH levels, that is, ascent at 1 month (P = 0.05), and descent at 3 months (P = 0.02). After DHEA treatment the serum AMH increased in diminished ovarian reserve (DOR) / poor ovarian response (POR) patients (WMD = 0.18, 95% CI: 0.09 to 0.27, P < 0.0001). After VD treatment the serum AMH increased, and it was obvious in non-PCOS patients (WMD = 0.78, 95% CI: 0.34 to 1.21, P = 0.0004). After CC treatment the serum AMH decreased significantly in PCOS patients, specifically in non-obese patients (WMD = -1.24, 95% CI: -1.87 to -0.61, P = 0.0001). CONCLUSIONS: Serum AMH levels may be affected in the short term after drug application. Specifically, OC, MET and CC lead to decreased AMH level, DHEA and VD lead to increased AMH level, and GnRH-a leads to dynamic variation, which is correlated with PCOS, obesity, age, and duration of medication. The impacts of these medications should be taken into consideration when AMH is used as a marker of ovarian reserve.

Toward automatic beam angle selection for pencil-beam scanning proton liver treatments: A deep learning-based approach.

BACKGROUND: Dose deposition characteristics of proton radiation can be advantageous over photons. Proton treatment planning, however, poses additional challenges for the planners. Proton therapy is usually delivered with only a small number of beam angles, and the quality of a proton treatment plan is largely determined by the beam angles employed. Finding the optimal beam angles for a proton treatment plan requires time and experience, motivating the investigation of automatic beam angle selection methods. PURPOSE: A deep learning-based approach to automatic beam angle selection is proposed for the proton pencil-beam scanning treatment planning of liver lesions. METHODS: We cast beam-angle selection as a multi-label classification problem. To account for angular boundary discontinuity, the underlying convolution neural network is trained with the proposed Circular Earth Mover's Distance-based regularization and multi-label circular-smooth label technique. Furthermore, an analytical algorithm emulating proton treatment planners' clinical practice is employed in post-processing to improve the output of the model. Forty-nine patients that received proton liver treatments between 2017 and 2020 were randomly divided into training (n = 31), validation (n = 7), and test sets (n = 11). AI-selected beam angles were compared with those angles selected by human planners, and the dosimetric outcome was investigated by creating plans using knowledge-based treatment planning. RESULTS: For 7 of the 11 cases in the test set, AI-selected beam angles agreed with those chosen by human planners to within 20° (median angle difference = 10°; mean = 18.6°). Moreover, out of the total 22 beam angles predicted by the model, 15 (68%) were within 10° of the human-selected angles. The high correlation in beam angles resulted in comparable dosimetric statistics between proton treatment plans generated using AI- and human-selected angles. For the cases with beam angle differences exceeding 20°, the dosimetric analysis showed similar plan quality although with different emphases on organ-at-risk sparing. CONCLUSIONS: This pilot study demonstrated the feasibility of a novel deep learning-based beam angle selection technique. Testing on liver cancer patients showed that the resulting plans were clinically viable with comparable dosimetric quality to those using human-selected beam angles. In tandem with auto-contouring and knowledge-based treatment planning tools, the proposed model could represent a pathway for nearly fully automated treatment planning in proton therapy.

miR-4731-5p Enhances Apoptosis and Alleviates Epithelial-Mesenchymal Transition through Targeting RPLP0 in Non-Small-Cell Lung Cancer.

Background/Aim. MircoRNA-4731-5p (miR-4731-5p) is a new miRNA involved in different human cancers, but its function has not been clarified in non-small-cell lung cancer (NSCLC). The present study attended to resolve the role of miR-4731-5p in NSCLC. Materials and Methods. The expression level of miR-4731-5p or ribosomal protein large P0 (RPLP0) and NSCLC clinicopathologic characteristics were analyzed. The binding between miR-4731-5p and RPLP0 was confirmed by TargetScan prediction and luciferase reporter experiment. Also, the probable role of miR-4731-5p in NSCLC via RPLP0 was elaborated by the MTT, western blotting, immunofluorescence, transwell, flow cytometry, and TUNEL assays. Moreover, in vivo verification was conducted in xenografted nude mice. Results. The level of miR-4731-5p was notably declined in vivo and in vitro, which was involved in the prognosis of lung cancer patients. The miR-4731-5p mimic could remarkably restrain cell viability, invasion, and the translational expression level of vimentin and e-cadherin, with promoted cell apoptosis in NSCLC, which were notably reversed by RPLP0 overexpression. Conclusion. miR-4731-5p/RPLP0 axis might be an underlying therapeutic target for NSCLC.