Optical coherence tomography characteristics and prognostic predictors of acute macular neuroretinopathy following SARS-CoV-2 infection.

PURPOSE: To analyze the characteristics of optical coherence tomography in acute macular neuroretinopathy (AMN) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and discuss the prognostic predictors. METHODS: Patients with AMN following SARS-CoV-2 infection were divided into two groups according to the presence or absence of hyperreflective outer nuclear layer (ONL) lesion involving the fovea. RESULTS: The first visit included 14 eyes in the fovea-involved group and 20 eyes in the no fovea-involved group. Ellipsoid zone (EZ) hyporeflection and interdigitation zone (IZ) interruption were detected in all eyes. Other common manifestations were myoid zone (MZ) hyperreflection (76.5%), ONL hyperreflection (73.5%), outer plexiform layer (OPL) thickening (64.7%), and EZ interruption (50%). The follow-up period was 48.4 ± 55.3 days. At the last visit, 12 eyes were in the fovea-involved group and 13 eyes in the no fovea-involved group. IZ interruption was detected in all eyes. Other common manifestations were EZ hyporeflection (92.0%), ONL atrophy (40.0%), OPL thickening (36.0%), OPL linear (32.0%), and MZ hyperreflection (32%). The improvement of visual acuity (VA) was -0.5 ± 0.5 and -0.2 ± 0.4 in the fovea-involved group and the no fovea-involved group, respectively, with a statistically significant difference between them (P = 0.045). Initial VA, initial cotton wool spot, initial ONL cyst, final ONL cyst, and final OPL linear were associated with final VA (P = 0.000, P = 0.029, P = 0.044, P = 0.049, P = 0.049, respectively). CONCLUSIONS: In the early stage of AMN following SARS-CoV-2 infection, IZ interruption and EZ hyporeflection were the most common manifestations, and pathology of IZ was more serious than that of EZ. Subsequently, OPL and ONL atrophied, and ONL atrophied faster. Regardless of whether hyperreflective ONL involved the fovea, VA improved, with a more noticeable improvement found in the fovea-involved group. The presence of initial ONL cyst and initial cotton wool spot, rapid atrophy of OPL, and poorer initial VA indicating poorer VA outcome.

EBV promotes TCR-T-cell therapy resistance by inducing CD163+M2 macrophage polarization and MMP9 secretion.

BACKGROUND: Epstein-Barr virus (EBV) is a double-stranded DNA oncogenic virus. Several types of solid tumors, such as nasopharyngeal carcinoma, EBV-associated gastric carcinoma, and lymphoepithelioma-like carcinoma of the lung, have been linked to EBV infection. Currently, several TCR-T-cell therapies for EBV-associated tumors are in clinical trials, but due to the suppressive immune microenvironment of solid tumors, the clinical application of TCR-T-cell therapy for EBV-associated solid tumors is limited. Figuring out the mechanism by which EBV participates in the formation of the tumor immunosuppressive microenvironment will help T cells or TCR-T cells break through the limitation and exert stronger antitumor potential. METHODS: Flow cytometry was used for analyzing macrophage differentiation phenotypes induced by EBV-infected and EBV-uninfected tumors, as well as the function of T cells co-cultured with these macrophages. Xenograft model in mice was used to explore the effects of M2 macrophages, TCR-T cells, and matrix metalloprotein 9 (MMP9) inhibitors on the growth of EBV-infected tumors. RESULTS: EBV-positive tumors exhibited an exhaustion profile of T cells, despite the presence of a large T-cell infiltration. EBV-infected tumors recruited a large number of mononuclear macrophages with CCL5 and induced CD163+M2 macrophages polarization through the secretion of CSF1 and the promotion of autocrine IL10 production by mononuclear macrophages. Massive secretion of MMP9 by this group of CD163+M2 macrophages induced by EBV infection was an important factor contributing to T-cell exhaustion and TCR-T-cell therapy resistance in EBV-positive tumors, and the use of MMP9 inhibitors improved the function of T cells cocultured with M2 macrophages. Finally, the combination of an MMP9 inhibitor with TCR-T cells targeting EBV-positive tumors significantly inhibited the growth of xenografts in mice. CONCLUSIONS: MMP9 inhibitors improve TCR-T cell function suppressed by EBV-induced M2 macrophages. TCR-T-cell therapy combined with MMP9 inhibitors was an effective therapeutic strategy for EBV-positive solid tumors.

Mild Allergic Reactions after Botulinum Toxin Injection: A Case Series and Literature Review.

Background: Botulinum toxin type A (BTA) is becoming more and more prevalent as an injection agent in cosmetic surgery. However, there is an increasing amount of cases reporting unexpected adverse reactions related to BTA injection. BTA can invoke many kinds of hypersensitive reactions, some of which can be delayed-type or even fatal; hence, it is of crucial importance to pay close attention to atypical and early symptoms that may indicate the presence of BTA allergy in patients. Methods: In this study, we reported three cases of mild and unexpected BTA-related hypersensitive reaction with a symptom of nonpruritic erythema on the chest that happened after BTA treatment of upper facial wrinkles and proposed several suggestions based on our practical experience and literature review. Results: Two patients' symptoms were alleviated spontaneously, and one patient's were alleviated after taking oral corticosteroid. According to our literature review, we believe that these incidences indicate a kind of unreported allergic reaction relevant to botulinum toxin. Conclusions: We suggest clinicians consider warily patients' subsequent BTA injection schedule if any suspicious reaction occurs after treatment. We suggest that patients who experience nonpruritic erythema after botulinum toxin injection should suspend subsequent injection plans for at least 3 months to prevent more severe consequences.

Adherence to an antioxidant diet and lifestyle is associated with reduced risk of cardiovascular disease and mortality among adults with nonalcoholic fatty liver disease: evidence from NHANES 1999-2018.

Background: Nonalcoholic fatty liver disease (NAFLD) stands a prevalent chronic liver condition significantly influenced by oxidative stress. We investigated the unclear relationship between antioxidant-rich diet and lifestyle and cardiovascular disease (CVD) prevalence rate and mortality in adult patients with NAFLD. Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHAENS) spanning from 1999 to 2018 to investigate the association between adherence to an antioxidant-rich diet and lifestyle and the cardiovascular disease (CVD) prevalence rate and mortality in adult patients with NAFLD. The study employed the Oxidative Balance Score (OBS) to define antioxidant diet and lifestyle. Results: Including 8,670 adult patients with NAFLD, the study revealed an inverse association between OBS and the prevalence of most CVD conditions. Fully adjusted models demonstrated that each unit increase in diet OBS, lifestyle OBS, and overall OBS corresponded to a 2, 7, and 2% reduction in all-cause mortality, respectively. In models 2, findings revealed that lifestyle Q2 and Q3 were linked to reduced cancer mortality, whereas diet and overall OBS did not exhibit an association. Additionally, Stratified analysis revealed that age (<45 years) and education level (> high school) significantly influenced the association between the OBS and the prevalence of CVD. Conclusion: These results underscore the protective link between adherence to an antioxidant diet and lifestyle and a diminished prevalence of CVD and mortality in adults with NAFLD, particularly among younger and higher-educated populations.

Trigeminal Neuralgia after Hyaluronic Acid and Botox Injection.

A rare case of trigeminal neuralgia following injections of Hyaluronic Acid and Botox was documented. In addressing the severe pain and swelling caused by the injection, a novel combination therapy was employed, notably including 5-fluorouracil. The significant improvement observed in this case not only provided clinical insights but also spurred further investigation into the underlying mechanisms linking trigeminal nerve damage to local dermal filler injections. The aim was to glean new medical perspectives and develop practical preventive strategies to mitigate such complications in future cases. This approach highlights the importance of understanding and addressing the potential neurological impacts of cosmetic procedures. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266 .

Identification of C1q/TNF-related protein 4 as a novel appetite-regulating peptide that reduces food intake in Siberian sturgeon (Acipenser baerii).

Emerging findings point to a role for C1q/TNF-related protein 4 (CTRP4) in feeding in mammals. However, it remains unknown whether CTRP4 regulates feeding in fish. This study aimed to determine the feeding regulation function of CTRP4 in Siberian sturgeon (Acipenser baerii). In this study, the Siberian sturgeon ctrp4 (Abctrp4) gene was cloned, and Abctrp4 mRNA was shown to be highly expressed in the hypothalamus. In the hypothalamus, Abctrp4 mRNA decreased during fasting and reversed after refeeding. Subsequently, we obtained the AbCTRP4 recombinant protein by prokaryotic expression and optimized the expression and purification conditions. Siberian sturgeon (81.28 ± 14.75 g) were injected intraperitoneally using 30, 100, and 300 ng/g Body weight (BW) AbCTRP4 to investigate its effect on feeding. The results showed that 30, 100, and 300 ng/g BW of the AbCTRP4 significantly reduced the cumulative food intake of Siberian sturgeon at 1, 3, and 6 h. Finally, to investigate the potential mechanism of CTRP4 feeding inhibition, 300 ng/g BW AbCTRP4 was injected intraperitoneally. The findings demonstrated that AbCTRP4 treatment for 1 h significantly promoted the mRNA levels of anorexigenic peptides (pomc, cart, and leptin) while suppressing the mRNA abundances of orexigenic peptides (npy and agrp).In addition, the jak2/stat3 pathway in the hypothalamus was significantly activated after 1 h of AbCTRP4 treatment. In conclusion., this study confirms the anorexigenic effect of CTRP4 in Siberian sturgeon.

Lactate dehydrogenase A promotes nasopharyngeal carcinoma progression through the TAK1/NF-κB Axis.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant tumor that originates in the nasopharyngeal mucosa and is common in China and Southeast Asian countries. Cancer cells reprogram glycolytic metabolism to promote their growth, survival and metastasis. Glycolysis plays an important role in NPC development, but the underlying mechanisms remain incompletely elucidated. Lactate dehydrogenase A (LDHA) is a crucial glycolytic enzyme, catalyzing the last step of glycolysis. This study aims to investigate the exact role of LDHA, which catalyzes the conversion of pyruvate into lactate, in NPC development. METHODS AND RESULTS: The western blot and immunohistochemical (IHC) results indicated that LDHA was significantly upregulated in NPC cells and clinical samples. LDHA knockdown by shRNA significantly inhibited NPC cell proliferation and invasion. Further knockdown of LDHA dramatically weakened the tumorigenicity of NPC cells in vivo. Mechanistic studies showed that LDHA activated TGF-ß-activated kinase 1 (TAK1) and subsequent nuclear factor κB (NF-κB) signaling to promote NPC cell proliferation and invasion. Exogenous lactate supplementation restored NPC cell proliferation and invasion inhibited by LDHA knockdown, and this restorative effect was reversed by NF-κB inhibitor (BAY 11-7082) or TAK1 inhibitor (5Z-7-oxozeaenol) treatment. Moreover, clinical sample analyses showed that LDHA expression was positively correlated with TAK1 Thr187 phosphorylation and poor prognosis. CONCLUSIONS: Our results suggest that LDHA and its major metabolite lactate drive NPC progression by regulating TAK1 and its downstream NF-κB signaling, which could become a therapeutic target in NPC.

Botulinum Toxin A Injection for Hemihypertrophy-related Unilateral Gastrocnemius Hypertrophy.

Hemihypertrophy is a rare congenital disorder that causes unequal growth of the extremities, trunk, face, or half of the body. We report a case of a 32-year-old woman with hemihypertrophy-related gastrocnemius hypertrophy treated with botulinum toxin A injection. The patient has received two botulinum toxin A injections, and we measured the thickness of the gastrocnemius muscle using ultrasound and measured the maximum circumference around the calf with the patient in the prone position. The patient's maximum calf circumference was reduced by 1 cm. The thickness of the medial head of the gastrocnemius was reduced by 0.3 cm, and the thickness of the lateral head of the gastrocnemius was reduced by 0.6 cm. Botulinum toxin A injection therapy was effective in treating hemihypertrophy-related gastrocnemius hypertrophy.

Comparative efficacy of aflibercept and ranibizumab in the treatment of age-related macular degeneration with retinal pigment epithelial detachment: a systematic review and network meta-analysis.

OBJECTIVES: To evaluate the efficacy of anti-vascular endothelial growth factor (VEGF) in treatment of age-related macular degeneration (AMD) with retinal pigment epithelial detachment (PED). METHODS: Systematic review identifying studies comparing intravitreal ranibizumab (IVR), intravitreal aflibercept (IVA) and intravitreal conbercept (IVC) published before Mar 2022. RESULTS: One randomized controlled trial and 6 observational studies were selected for meta-analysis (1,069 patients). The change of best corrected visual acuity (BCVA) in IVA 2.0 mg group was better than IVR 0.5 mg (average difference 0.07) and IVR 2.0 mg (average difference 0.10), the differences were statistically significant. The change of the height of PED in IVA 2.0 group was better than IVR 0.5 group (average difference 45.30), the difference was statistically significant. The proportion of patients without PED at last visit in IVA 2.0 group were better than those in IVR 2.0 group (hazard ratio 1.91), the difference was statistically significant. There was no significant difference compared with IVR 0.5 group (hazard ratio 1.45). IVA required fewer injections than IVR, with a mean difference of -1.58. CONCLUSIONS: IVA appears to be superior to IVR in improvement of BCVA, height decrease of PED and regression of PED with less injections in nAMD with PED.

Preoperative low muscle mass and malnutrition affect the clinical prognosis of locally advanced gastric cancer patients undergoing radical surgery.

Background: Gastric cancer is a common and highly aggressive malignant tumor of the gastrointestinal tract that poses a serious threat to human life and health. As the clinical symptoms of early gastric carcinoma are not obvious, many patients are diagnosed in the middle or late stages. With the advancement of medical technology, gastrectomy has become a safer surgical procedure, but it still has a high recurrence and mortality rate after surgery. The prognosis of gastric cancer patients after surgery is not only related to tumor-related factors (i.e., tumor stage) but the patient's nutritional status. This study aimed to investigate the effect of preoperative muscle mass combined with the prognostic nutritional index (PNI) on clinical prognosis in locally advanced gastric carcinoma. Methods: The clinical data of 136 patients with locally advanced gastric carcinoma diagnosed by pathology and undergoing radical gastrectomy were retrospectively reviewed. To analyze the influencing factors of preoperative low muscle mass and its correlation with the prognostic nutritional index. Patients with both low muscle mass and low PNI (≤46.55) were assigned a score of 2, and those with only one or neither of these abnormalities were assigned a score of 1 or 0, respectively, according to the new prognostic score (PNIS). The relationship between PNIS and clinicopathological characteristics was analyzed. Univariate and multivariate analyses were performed to identify risk factors for overall survival (OS). Results: Low muscle mass was associated with a lower PNI (P < 0.01). The optimal cut-off value of PNI was 46.55, the sensitivity was 48%, and the specificity was 97.1%. There were 53 (38.97%), 59 (43.38%), and 24 patients (17.65%) in the PNIS 0, 1, and 2 groups, respectively. A higher PNIS and advanced age were independent risk factors for postoperative complications (P < 0.01). The overall survival rate in patients with PNIS 2 score was significantly poorer than in patients with scores of 1 or 0 (3-year OS: 45.8% vs 67.8% vs 92.4%, P < 0.001). A Multivariate Cox hazards analysis showed that PNIS 2, depth of tumor invasion, vascular invasion, and postoperative complications were independent predictors of the poor 3-year survival in patients with locally advanced gastric cancer. Conclusions: The combination of muscle mass and the PNI score system can be used to predict the survival outcome of patients with locally advanced gastric cancer.

Characterization of the metabolism of eupalinolide A and B by carboxylesterase and cytochrome P450 in human liver microsomes.

Eupalinolide A (EA; Z-configuration) and eupalinolide B (EB; E-configuration) are bioactive cis-trans isomers isolated from Eupatorii Lindleyani Herba that exert anti-inflammatory and antitumor effects. Although one pharmacokinetic study found that the metabolic parameters of the isomers were different in rats, metabolic processes relevant to EA and EB remain largely unknown. Our preliminary findings revealed that EA and EB are rapidly hydrolyzed by carboxylesterase. Here, we investigated the metabolic stability and enzyme kinetics of carboxylesterase-mediated hydrolysis and cytochrome P450 (CYP)-mediated oxidation of EA and EB in human liver microsomes (HLMs). We also explored differences in the hydrolytic stability of EA and EB in human liver microsomes and rat liver microsomes (RLMs). Moreover, cytochrome P450 reaction phenotyping of the isomers was performed via in silico methods (i.e., using a quantitative structure-activity relationship model and molecular docking) and confirmed using human recombinant enzymes. The total normalized rate approach was considered to assess the relative contributions of five major cytochrome P450s to EA and EB metabolism. We found that EA and EB were eliminated rapidly, mainly by carboxylesterase-mediated hydrolysis, as compared with cytochrome P450-mediated oxidation. An inter-species difference was observed as well, with faster rates of EA and EB hydrolysis in rat liver microsomes. Furthermore, our findings confirmed EA and EB were metabolized by multiple cytochrome P450s, among which CYP3A4 played a particularly important role.

Synovitis, acne, pustulosis, hyperostosis, osteitis syndrome with invisible organizing pneumonia: A case report.

We report the case of a 59-year-old female patient, presenting with pustular rash on both hands and pain in the lumbosacral part and left lower limb. A magnetic resonance imaging examination of the left leg was undertaken and the result showed that a malignant lesion with bone destruction of the left femoral shaft could not be excluded. Subsequently, bone tumor was excluded by pathological examination. Lung computed tomography scan showed patchy consolidation and cord shadow in the middle left lung. Subsequently, lung cancer was excluded by pathological examination, and the histopathological changes of lung were consistent with those of organized pneumonia. Blood tests revealed elevated C-reactive protein and erythrocyte sedimentation rate. Antinuclear antibody, rheumatoid factor, and human leukocyte antigen-B27 were unremarkable. Whole body bone scintigraphy via technetium 99m-methyl diphosphonate showed increased radionuclide uptake in the left middle femur. Based on her clinical manifestations, imaging results and bone scintigraphy, the patient was diagnosed as having synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome. Loxoprofen and Tripterygium wilfordii Hook F led to impressive clinical and radiologic improvement.

Genomic alteration profile and PD-L1 expression among different breast cancer subtypes in Chinese population and their correlations.

BACKGROUD: There were limitations existing in programmed cell-death ligand 1 (PD-L1) as predictive biomarkers for breast cancer (BC), hence exploring the correlation between PD-L1 levels and other biomarkers in BC may become a very useful therapeutic clinical tool. METHODS: A total of 301 Chinese patients with different BC subtypes including 47 HR+/HER2+, 185 HR+/HER2-, 38 HR-/HER2+, and 31 triple-negative breast cancer (TNBC) were enrolled in our study. Next-generation sequencing based Yuansu450 gene panel was used for genomic alteration identification and PD-L1 expression was tested using immunohistochemistry. RESULTS: The most prevalent BC-related mutations were TP53 mutations, followed by mutations in PIK3CA, ERBB2, CDK12, and GATA3 in our Chinese cohort. We found that mutations DDR2 and MYCL were only mutated in HR-/HER2+ subtype, whereas H3-3A and NRAS mutations were only occurred in HR-/HER2- subtype. The percentage of patients with PD-L1-positive expression was higher in patients with HR-/HER2- mainly due to the percentage of PD-L1-high level. Mutational frequencies of TP53, MYC, FAT4, PBRM1, PREX2 were observed to have significant differences among patients with different BC subtypes based on PD-L1 levels. Moreover, a positive correlation was observed between TMB and PD-L1 level in HR+/HER2- subtype, and showed that the proportion of patients with high PD-L1 expression was higher than that of patients with low PD-L1 expression in the HR+/HER2- and HR+/HER2+ cohorts with high Ki67 expression. CONCLUSIONS: The genomic alterations based on PD-L1 and other biomarkers of different cohorts may provide more possibilities for the treatment of BC with different subtypes.

Validation of a natural language processing algorithm to identify adenomas and measure adenoma detection rates across a health system: a population-level study.

BACKGROUND AND AIMS: Measuring adenoma detection rates (ADRs) at the population level is challenging because pathology reports are often reported in an unstructured format; further, there is significant variation in reporting methods across institutions. Natural language processing (NLP) can be used to extract relevant information from text-based records. We aimed to develop and validate an NLP algorithm to identify colorectal adenomas that could be used to report ADR at the population level in Ontario, Canada. METHODS: The sampling frame included pathology reports from all colonoscopies performed in Ontario in 2015 and 2016. Two random samples of 450 and 1000 reports were selected as the training and validation sets, respectively. Expert clinicians reviewed and classified reports as adenoma or other. The training set was used to develop an NLP algorithm (to identify adenomas) that was evaluated using the validation set. The NLP algorithm test characteristics were calculated using expert review as the reference. We used the algorithm to measure ADR for all endoscopists in Ontario in 2019. RESULTS: The 1450 pathology reports were derived from 62 laboratories, 266 pathologists, and 532 endoscopists. In the training set, the NLP algorithm for any adenoma had a sensitivity of 99.60% (95% confidence interval (CI), 97.77-99.99), specificity of 99.01% (95% CI, 96.49-99.88), positive predictive value of 99.19% (95% CI, 97.12-99.90), and F1 score of .99. Similar results were obtained for the validation set. The median ADR was 33% (interquartile range, 26%-40%). CONCLUSIONS: When we used a population-based sample from Ontario, our NLP algorithm was highly accurate and was used at the system level to measure ADR.

Single-cell profile of tumor and immune cells in primary breast cancer, sentinel lymph node, and metastatic lymph node.

PURPOSE: Little is known about the host-tumor interaction in the lymph-node basin at a single cell level. This study examines single cell sequences in breast cancer nodal metastases of a patient with triple-negative breast cancer. METHODS: The primary breast tumor, sentinel lymph node, an adjacent lymph node with metastatic involvement and a clinically normal-appearing lymph node were collected during surgery. Single-cell sequencing was performed on all four specimens. RESULTS: 14,016 cells were clustered into 6 cell subpopulations. Cancer cells demonstrated the molecular characteristics of TNBC basal B subtype and highly expressed genes in the MAPK signaling cascade. Tumor-associated macrophages regulated antigen processing and presentation and other immune-related pathways to promote tumor invasion. CD8 + and CD4 + T lymphocytes concentrated more in sentinel lymph node and mainly stratified into two transcriptional states. The immune-cell amount variation among primary tumor, sentinel and normal lymph nodes showed a similar tendency between the sc-RNA-seq profile of TNBC samples and a previous reported bulk RNA-seq profile of a breast cancer cohort, including all four breast cancer subtype samples. DISCUSSION: Single-cell sequencing analysis suggested that the sentinel lymph node was the initial meeting site of tumor infiltration and immune response, where partial T lymphocytes perform anti-tumor activity, while other T cells exhibit an exhausted state. We proposed a molecular explanation to the well-established clinical principle that the 5-year and 10-year survival outcomes were noninferior between SLND and ALND.

GFAT1-linked TAB1 glutamylation sustains p38 MAPK activation and promotes lung cancer cell survival under glucose starvation.

Reprogrammed cell metabolism is deemed as one of the hallmarks of cancer. Hexosamine biosynthesis pathway (HBP) acts as an "energy sensor" in cells to regulate metabolic fluxes. Glutamine-fructose-6-phosphate amidotransferase 1 (GFAT1), the rate-limiting enzyme of HBP, is broadly found with elevated expression in human cancers though its exact and concrete role in tumorigenesis still remains unknown and needs further investigation. P38 mitogen-activated protein kinase (MAPK) is an important component of stress-signaling pathway and plays a critical role in cell fate decision, whereas the underlying mechanism of its activation under nutrient stress also remains elusive. In this study, we show that glucose deprivation induces the interaction of GFAT1 with transforming growth factor ß-activated kinase 1 binding protein 1 (TAB1) in a TAB1 S438 phosphorylation-dependent manner. Subsequently, the binding of GFAT1 to TAB1 facilitates TTLL5-GFAT1-TAB1 complex formation, and the metabolic activity of GFAT1 for glutamate production further contributes to TTLL5-mediated TAB1 glutamylation. In consequence, TAB1 glutamylation promotes the recruitment of p38α MAPK and thus drives p38 MAPK activation. Physiologically, GFAT1-TAB1-p38 signaling promotes autophagy occurrence and thus protects tumor cell survival under glucose deficiency. Clinical analysis indicates that both GFAT1 and TAB1 S438 phosphorylation levels correlate with the poor prognosis of lung adenocarcinoma patients. These findings altogether uncover an unidentified mechanism underlying p38 MAPK signaling regulation by metabolic enzyme upon nutrient stress and provide theoretical rationality of targeting GFAT1 for cancer treatment.

One-stage transanal endorectal pull-through for Hirschsprung disease: experience with 229 neonates.

OBJECTIVE: To evaluate the safety and efficacy of transanal endorectal pull-through (TEPT) and the long-term outcomes in newborns with Hirschsprung disease (HD). METHODS: A total of 229 newborns with HD underwent one-stage TEPT between 2007 and 2020, and the diagnoses were confirmed by rectal biopsy. The perioperative clinical course for all patients was reviewed, and the postoperative short- and long-term outcomes were assessed. RESULTS: A total of 229 neonates (187 male and 42 female) had a median age at TEPT of 17 days (range 6-28 days). Sixty-eight patients (29.7%) underwent TEPT combined with an abdominal approach or laparoscopy. Early postoperative complications (using the Clavien-Dindo grading system) were documented in 36 patients (15.7%), and late postoperative complications were noted in 9 patients (3.9%). The follow-up period in the remaining 165 children ranged from 1.2 to 14.0 years (median 5.0 years). A total of 106 of the patients older than four years old took part in an interview about bowel function, and 85 patients (80.2%) had bowel function scores (BFS) ≥ 18. CONCLUSION: TEPT is effective and safe for HD in the neonatal period and presents with a low rate of complications and an acceptable outcome.

Corrigendum: Efficacy of Initial vs. Delayed Photodynamic Therapy in Combination With Conbercept for Polypoidal Choroidal Vasculopathy.

[This corrects the article DOI: 10.3389/fmed.2021.791935.].

Clinicopathologic and Genomic Features in Triple-Negative Breast Cancer Between Special and No-Special Morphologic Pattern.

Background: Triple-negative breast cancer (TNBC) is refractory and heterogeneous, comprising various entities with divergent phenotype, biology, and clinical presentation. As an aggressive subtype, Chinese TNBC patients with special morphologic patterns (STs) were restricted to its incidence of 10-15% in total TNBC population. Methods: We recruited 89 patients with TNBC at Guangdong Provincial People's Hospital (GDPH) from October 2014 to May 2021, comprising 72 cases of invasive ductal carcinoma of no-special type (NSTs) and 17 cases of STs. The clinical data of these patients was collected and statistically analyzed. Formalin-fixed, paraffin-embedded (FFPE) tumor tissues and matched blood samples were collected for targeted next-generation sequencing (NGS) with cancer-related, 520- or 33-gene assay. Immunohistochemical analysis of FFPE tissue sections was performed using anti-programmed cell death-ligand 1(PD-L1) and anti-androgen receptor antibodies. Results: Cases with NSTs presented with higher histologic grade and Ki-67 index rate than ST patients (NSTs to STs: grade I/II/III 1.4%, 16.7%,81.9% vs 0%, 29.4%, 58.8%; p<0.05; Ki-67 ≥30%: 83.3% vs. 58.8%, p<0.05), while androgen receptor (AR) and PD-L1 positive (combined positive score≥10) rates were lower than of STs cases (AR: 11.1% vs. 47.1%; PD-L1: 9.6% vs. 33.3%, p<0.05). The most commonly altered genes were TP53 (88.7%), PIK3CA (26.8%), MYC (18.3%) in NSTs, and TP53 (68.8%), PIK3CA (50%), JAK3 (18.8%), KMT2C (18.8%) in STs respectively. Compared with NSTs, PIK3CA and TP53 mutation frequency showed difference in STs (47.1% vs 19.4%, p=0.039; 64.7% vs 87.5%, p=0.035). Conclusions: In TNBC patients with STs, decrease in histologic grade and ki-67 index, as well as increase in PD-L1 and AR expression were observed when compared to those with NSTs, suggesting that TNBC patients with STs may better benefit from immune checkpoint inhibitors and/or AR inhibitors. Additionally, lower TP53 and higher PIK3CA mutation rates were also found in STs patients, providing genetic evidence for deciphering at least partly potential mechanism of action.

Helicobacter pylori Biofilm-Related Drug Resistance and New Developments in Its Anti-Biofilm Agents.

Helicobacter pylori is one of the most common pathogenic bacterium worldwide, infecting about 50% of the world's population. It is a major cause of several upper gastrointestinal diseases, including peptic ulcers and gastric cancer. The emergence of H. pylori resistance to antibiotics has been a major clinical challenge in the field of gastroenterology. In the course of H. pylori infection, some bacteria invade the gastric epithelium and are encapsulated into a self-produced matrix to form biofilms that protect the bacteria from external threats. Bacteria with biofilm structures can be up to 1000 times more resistant to antibiotics than planktonic bacteria. This implies that targeting biofilms might be an effective strategy to alleviate H. pylori drug resistance. Therefore, it is important to develop drugs that can eliminate or disperse biofilms. In recent years, anti-biofilm agents have been investigated as alternative or complementary therapies to antibiotics to reduce the rate of drug resistance. This article discusses the formation of H. pylori biofilms, the relationship between biofilms and drug resistance in H. pylori, and the recent developments in the research of anti-biofilm agents targeting H. pylori drug resistance.