Case report: Concomitant EGFR mutation and ALK rearrangement in non-small cell lung cancer.

In non-small cell lung cancer (NSCLC), two key genetic alterations, epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements, are commonly believed to be mutually exclusive. Studies have reported that concurrent EGFR/ALK co-mutation in non-small cell lung cancer patients is rare, with a prevalence ranging from 0.1% to 1.6%. However, the clinical and pathological characteristics of these patients are not well-defined, and the optimal treatment approach for such cases remains controversial. In this report, we present a case of stage IV lung adenocarcinoma with both epidermal growth factor receptor and anaplastic lymphoma kinase mutations, along with high PD-L1 expression. The patient initially received treatment with epidermal growth factor receptor tyrosine kinase inhibitors (TKIs), but the disease progressed. However, following a switch to ALK-TKI therapy and local radiotherapy, the lesion showed regression. Our report also provides a comprehensive summary of the clinical and pathological features, as well as treatment strategies, for non-small cell lung cancer patients with concurrent epidermal growth factor receptor mutation and anaplastic lymphoma kinase rearrangement.

Physiological and molecular mechanisms of boron in alleviating cadmium toxicity in Capsicum annuum.

Soil cadmium (Cd) contamination threatens food safety and human health, particularly in developing countries. Previously, we have proposed that boron (B) could reduce Cd uptake and accumulation in hot peppers (Capsicum annuum) by regulating the expression of genes related to Cd transport in roots. However, only few studies have examined the role of B in plant leaves under Cd stress. It is unclear how B induces the expression of relevant genes and metabolites in hot pepper leaves and to what extent B is involved in leaf growth and Cd accumulation. The purpose of this study was to investigate the effects of B on growth and Cd accumulation in hot pepper leaves by determining physiological parameters and transcriptome sequencing. The results showed that B application significantly improved the concentration of chlorophyll a and intercellular CO2, stomatal conductance, and photosynthetic and transpiration rates by 18-41 % in Cd-stressed plants. Moreover, B enhanced Cd retention in the cell wall by upregulating the expression levels of pectin-, lignin-, and callose-related genes and improving the activity of pectin methylesterase by 30 %, resulting in an approximate 31 % increase in Cd retention in the cell wall. Furthermore, B application not only enhanced the expression levels of genes related to antioxidant enzymes (superoxide dismutase, catalase, and peroxidase) and their activities by 28-40 %, thereby counteracting Cd-induced oxidative stress, but also improved Cd chelation, sequestration, and exclusion by upregulating the expression levels of genes related to sulfur metabolism, heavy metal-associated isoprenylated plant protein (HIPP), and transporters such as vacuolar cation/proton exchanger (CAX3), metal-nicotianamine transporter (YSL), ATP-binding cassette (ABC), zinc/iron transporters (ZIP) and oxic-compound detoxification (DTX), ultimately reinforcing Cd tolerance. Together, our results suggest that B application reduces the negative effects of Cd on leaf growth, promotes photosynthesis, and decreases Cd transfer to fruits through its sequestration and retention.

Molecular mechanism of HNTX-I activates the intermediate-conductance Ca2+-activated K+ (IK) channels.

The IK channel, a potassium ion channel regulated by calcium ions and voltages in a bidirectional manner, has been implicated in a range of diseases. However, there are currently few compounds available that can target the IK channel with high potency and specificity. Hainantoxin-I (HNTX-I) is the first peptide activator of IK channel discovered so far, but its activity is not ideal, and the underlying mechanism interaction between HNTX-I toxin and IK channel remains unclear. Thus, our study aimed to enhance the potency of IK channel activating peptides derived from HNTX-I and elucidate the molecular mechanism underlying the interaction between HNTX-I and the IK channel. By employing virtual alanine scanning mutagenesis, we generated 11 HNTX-I mutants using site-directed mutagenesis to pinpoint specific residues crucial for the HNTX-I and IK channel interaction. Subsequently, we identified key residues on the IK channel that are involved in the interaction with HNTX-I. Additionally, molecular docking was employed to guide the molecular engineering process and clarify the binding interface between HNTX-I and the IK channel. Our results demonstrate that HNTX-I primarily acts on the IK channel via the N-terminal amino acid, and its interaction with the IK channel is mediated by electrostatic and hydrophobic interactions, specifically the amino acid residues at positions 1, 3, 5, and 7 on HNTX-I. This study provides valuable insights into the peptide toxins that may serve as potential templates for the development of activators with enhanced potency and selectivity for the IK channel.

Intrathyroid thymic carcinoma: clinicopathological features and whole exome sequencing analysis.

Intrathyroid thymic carcinoma (ITC) is a rare malignant tumour. We present nine cases of ITC that were analysed by immunohistochemical staining, of which five were analysed using whole exome sequencing (WES). These cases included six women and three men with an age range of 31-66 years. The average postoperative follow-up term was 37.8 months (range, 7-95 months), and all patients survived well except for one case with lung metastasis. Microscopically, ITC showed solid islands of tumour cells separated by fibrous connective tissue containing lymphocytes and other inflammatory cells. Tumour cells strongly expressed Ckpan (AE1/AE3), P63, and CD117. And all cases but one were positive for CD5. The median value of Ki-67 was 32% (range 10-60%). We observed partial positivity of Syn and CgA in only one case. ITC shares morphological and immunohistochemical similarities with thymic squamous cell carcinoma. In situ hybridization of EBER showed negative results. All cases were microsatellite stable, and the tumour mutational burden of the 5 cases was all < 1 mutations/Mb. WES showed higher mutation rates for N4BP1 (2/5), and many genetic alterations were related to the NF-kB signalling pathway, which is crucial for insight into the molecular mechanisms of the occurrence and development of ITC.

Effect of boron supply on the uptake and translocation of cadmium in Capsicum annuum.

Large areas of soil in southern China are contaminated with cadmium (Cd) and are deficient in boron (B). Previously, we suggested that B supplementation could reduce Cd accumulation in hot peppers (Capsicum annuum L.); however, the physiological mechanisms underlying this reduction remain unclear. In this study, the uptake and translocation of Cd in hot pepper plants were investigated using hydroponic experiments with different B and Cd treatments. A pot experiment was performed to verify whether B decreased the Cd concentration in hot peppers by minimizing the Cd translocation rate. The results of the dose- and time-dependent experiments showed that B supplementation reduced root Cd uptake and root-to-shoot Cd translocation. Additionally, B supplementation increased the root length, diameter, volume, surface area, and number of root forks and tips, as well as improving the relative absorbance of carboxyl groups under Cd exposure, leading to enhanced Cd fixation in the cell walls of the roots. As a result, the fruit Cd concentration decreased because B inhibited Cd translocation from the roots. Overall, the results demonstrate that B supplementation can reduce Cd accumulation in hot peppers by promoting normal root growth and development and by limiting the uptake and translocation of Cd.

Effects of a Dulaglutide plus Calorie-Restricted Diet versus a Calorie-Restricted Diet on Visceral Fat and Metabolic Profiles in Women with Polycystic Ovary Syndrome: A Randomized Controlled Trial.

The effects of dulaglutide and a calorie-restricted diet (CRD) on visceral adipose tissue (VAT) and metabolic profiles in polycystic ovary syndrome (PCOS) have not been extensively investigated. In this study, we investigated whether dulaglutide combined with CRD could further reduce VAT and promote clinical benefits as compared with a CRD regimen alone in overweight or obese PCOS-affected women. Between May 2021 and May 2022, this single-center, randomized, controlled, open-label clinical trial was conducted. Overall, 243 participants with PCOS were screened, of which 68 overweight or obese individuals were randomly randomized to undergo dulaglutide combined with CRD treatment (n = 35) or CRD treatment alone (n = 33). The duration of intervention was set as the time taken to achieve a 7% weight loss goal from baseline body weight, which was restricted to 6 months. The primary endpoint was the difference in the change in VAT area reduction between the groups. The secondary endpoints contained changes in menstrual frequency, metabolic profiles, hormonal parameters, liver fat, and body composition. As compared with the CRD group, the dulaglutide + CRD group had a considerably shorter median time to achieve 7% weight loss. There was no significant between-group difference in area change of VAT reduction (-0.97 cm2, 95% confidence interval from -14.36 to 12.42, p = 0.884). As compared with CRD alone, dulaglutide + CRD had significant advantages in reducing glycated hemoglobin A1c and postprandial plasma glucose levels. The results of the analyses showed different changes in menstruation frequency, additional metabolic profiles, hormonal markers, liver fat, and body composition between the two groups did not differ significantly. Nausea, vomiting, constipation, and loss of appetite were the main adverse events of dulaglutide. These results emphasize the value of dietary intervention as the first line of treatment for PCOS-affected women, while glucagon-like peptide 1 receptor agonist therapy provides an efficient and typically well tolerated adjuvant therapy to aid in reaching weight targets based on dietary therapy in the population of overweight/obese PCOS-affected women.

Effect of potassium intake on cadmium transporters and root cell wall biosynthesis in sweet potato.

Large areas of farmland soil in southern China are deficient in potassium (K) and are contaminated with cadmium (Cd). Previously, we suggested that the K supplementation could reduce Cd accumulation in sweet potatoes (Ipomoea batatas (L.) Lam). In the present study, we investigated the underlying physiological and molecular mechanisms. A hydroponic experiment with different K and Cd treatments was performed to compare the transcriptome profile and the cell wall structure in the roots of sweet potato using RNA sequencing, Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM). The results showed that K supply inhibits the expressions of IRT1 and YSL3, which are responsible for root Cd uptake under Cd exposure. Furthermore, the expressions of COPT5 and Nramp3 were downregulated by K, which increased Cd retention in the root vacuoles. The upregulation of POD, CAD, INT1 and SUS by K contributed to lignin and cellulose biosynthesis and thickening of root xylem cell wall, which further reduced Cd translocation to the shoot. In addition, K affected the expressions of LHT, ACS, TPS and TPP associated with the production of ethylene and trehalose, which involved in plant resistance to Cd toxicity. In general, K application could decrease the uptake and translocation of Cd in sweet potatoes by regulating the expression of genes associated with Cd transporters and root cell wall components.

Invasive Bordetella pertussis Infection in Infants: A Case Report.

Infants are more likely to develop severe pertussis. We report a malignant pertussis case in a 2-month-old boy with respiratory failure, severe pneumonia, septic shock, and encephalopathy. Bordetella pertussis was detected from nasopharyngeal secretions by polymerase chain reaction, as well as both blood and cerebrospinal fluid samples via metagenomics next-generation sequencing.

Distinct clinicopathological and genomic features in solid and basaloid adenoid cystic carcinoma of the breast.

Adenoid cystic carcinoma (AdCC) of the breast is a rare indolent carcinoma of salivary gland-type tumors, frequently associated with MYB genetic alteration. Solid and basaloid adenoid cystic carcinoma (SB-AdCC) is considered a sparse variant of AdCC. This study sought to search for clinicopathological and genomic features in SB-AdCC. Registered clinicopathological data on a cohort of 13 AdCC of the breast cases, including six conventional adenoid cystic carcinoma (C-AdCC) cases and seven SB-AdCC cases, were collected. MYB gene rearrangement via fluorescent in situ hybridization was investigated and MYB protein expression was evaluated by immunohistochemistry. Compared with C-AdCC, we found that the distribution of SB-AdCC cases were shifted to older age and were more frequently distant metastasis. Moreover, metastasis cases also showed a high (exceed 30%) Ki-67 index. Both groups showed MYB rearrangements and MYB protein expression, but they were less frequent in SB-AdCC than C-AdCC. To conclude, our results suggest that SB-AdCC is an aggressive variant of mammary AdCC with a higher incidence of distant metastases compared with C-AdCC, though they share common molecular features. A high Ki-67 index may be an adverse prognostic factor for metastasis.

A novel alectinib-sensitive CTNND1-ALK fusion in a lung adenocarcinoma patient: a case report.

Genomic fusions of anaplastic lymphoma kinase (ALK) are a well-established therapeutic target in non-small-cell lung cancer (NSCLC). Although various ALK fusion variants have been identified in NSCLC, their responses to ALK tyrosine-kinase inhibitors (TKIs) are heterogeneous. We report the case of a 71-year-old female patient diagnosed with lung adenocarcinoma with liver metastases. A novel CTNND1 (exon 14)-ALK (exon 20) fusion was identified from the biopsy sample by next-generation sequencing (NGS) and validated by immunohistochemistry (IHC) staining. Alectinib was administered, and the patient soon achieved partial response (PR). The progression-free survival (PFS) exceeded 15 months as of January 25, 2022. Our findings expand the spectrum of ALK rearrangements and provide a potential treatment option for lung adenocarcinoma patients with CTNND1-ALK fusions.

Cigarette smoke-induced oxidative stress activates NRF2 to mediate fibronectin disorganization in vascular formation.

Cigarette smoke significantly induces oxidative stress, resulting in cardiovascular disease. NRF2, a well-known antioxidative stress response factor, is generally considered to play protective roles in cardiovascular dysfunction triggered by oxidative stress. Interestingly, recent studies reported adverse effects of NRF2 on the cardiovascular system. These unfavourable pathogenic effects of NRF2 need to be further investigated. Our work shows that cigarette smoke extract (CSE)-induced oxidative stress disturbs fibronectin (FN) assembly during angiogenesis. Furthermore, this effect largely depends on hyperactive NRF2-STAT3 signalling, which consequently promotes abnormal FN deposition. Consistently, disruption of this pathway by inhibiting NRF2 or STAT3 prevents CSE-induced FN disorganization and vasculature disruption in human umbilical vein endothelial cells or zebrafish. Taken together, these findings demonstrate the cardiovascular dysfunction caused by CSE from a novel perspective that NRF2-dependent signalling engages in FN disorganization.

Fish oil-containing lipid emulsions prevention on parenteral nutrition-associated cholestasis in very low birth weight infants: a meta-analysis.

BACKGROUND: The effect of fish oil-containing lipid emulsions on preventing parenteral nutrition-associated cholestasis (PNAC) in very low birth weight (VLBW) infants is not known. Thus, we conducted a meta-analysis to identify any prevention effect. METHODS: PubMed, EMBASE, and CENTRAL were searched up to 26 January 2021 for studies related to the preventive effect of fish oil-containing lipid emulsions and fish oil-free lipid emulsions on cholestasis in VLBW infants. Revman 5.3 was used to synthesize the results. A fixed-effect model was used to summarize the data when the heterogeneity was non-significant (I2 < 50%), and a random-effects model was used when the heterogeneity was significant (I2 > 50%). RESULTS: Of 728 articles, 11 randomized controlled trials met the inclusion criteria. The meta-analysis indicated that fish oil-containing lipid emulsion reduced the occurrence of PNAC significantly with risk ratio (RR) = 0.53, 95% confidence interval (CI) 0.36-0.80, P = 0.002. The heterogeneity was non-significant with I2 = 23%. Subgroup analysis based on parenteral nutrition duration and median birth weight was performed. The synthesis results for patients with parenteral nutrition duration exceeding 14 days revealed I2 = 35% (P = 0.15) and pooled RR = 0.47, 95% CI 0.30-0.73, P = 0.0008; and for patients with duration less than 14 days revealed I2 = 0% (P = 0.72) and pooled RR = 1.14, 95% CI 0.39-3.35, P = 0.81. The synthesis for patients with birth weight more than 1000 g revealed I2 = 0% (P = 0.41) and pooled RR = 0.55, 95% CI 0.26-1.18, P = 0.12; and for patients with birth weight below 1000 g revealed I2 = 44% (P = 0.11) and pooled RR = 0.53, 95% CI 0.33-0.85, P = 0.009. CONCLUSIONS: The fish oil-containing lipid emulsion can reduce the occurrence of PNAC in VLBW infants based on the available original randomized controlled trial studies, especially for patients with parenteral nutrition duration exceeding 14 days and extremely low birth weight infants. Future studies should be performed before a definitive conclusion can be established.

Boron supplying alters cadmium retention in root cell walls and glutathione content in Capsicum annuum.

Large areas of farmland in southern China are facing environmental problems such as cadmium (Cd) contamination and boron (B) deficiency. The aim of this study was to investigate the biochemical and molecular mechanisms underlying the reduction in Cd accumulation in hot pepper (Capsicum annuum) by B application. A hydroponic experiment was conducted to compare the subcellular distribution of Cd, transcriptome profile, degree of pectin methylation, and glutathione (GSH) synthesis in the roots of hot pepper under different B and Cd conditions. Boron supply promoted root cell wall biosynthesis and pectin demethylation by upregulating related genes and increasing cell wall Cd concentration by 28%. In addition, with the application of B, the proportion of Cd in root cell walls increased from 27% to 37%. Boron supplementation upregulated sulfur metabolism-related genes but decreased cysteine and GSH contents in the roots. As a result, shoot Cd concentration decreased by 27% due to the decrease in GSH, a critical long-distance transport carrier of Cd. Consequently, B supply could reduce the uptake, translocation, and accumulation of Cd in hot pepper by retaining Cd in the root cell walls and decreasing GSH content.

Characterization of cadmium accumulation mechanism between eggplant (Solanum melongena L.) cultivars.

Excessive cadmium (Cd) accumulation in vegetables due to farmland pollution constitutes a serious threat to human health. Eggplant has a tendency to accumulate Cd. To investigate the mechanism of the differences in Cd accumulation levels between high-Cd (BXGZ) and low-Cd (MYQZ) eggplant cultivar, physiological and biochemical indicators and mRNA expression of eggplant were examined using photosynthetic apparatus, biochemical test kits, Fourier transform infrared (FTIR) spectroscopy and transcriptome sequencing, etc. The results of biochemical test kits and FTIR revealed that MYQZ enhanced pectin methylesterase (PME) activity, and lignin and pectin content in the root cell wall, which was associated with the upregulation of PME, cinnamyl-alcohol dehydrogenase and peroxidase (PODs). Higher levels of cysteine and glutathione (GSH) contents and upregulation of genes associated with sulfur metabolism, as well as higher expression of ATP-binding cassette transporters (ABCs), cation exchangers (CAX) and metal tolerance proteins (MTPs) were observed in MYQZ. In BXGZ, the higher stomatal density and stomatal aperture as well as higher levels of Ca2+ binding protein-1 (PCaP1) and aquaporins and lower levels of A2-type cyclins (CYCA2-1) are consistent with an enhanced transpiration rate in BXGZ. Furthermore, a more developed root system was shown to be associated with higher levels of auxin response factor (ARF19), GATA transcription factors (GATA4, 5 and 11) and auxin efflux carrier component (PIN5) in BXGZ. In conclusion, highly active PME, and higher levels of lignin and pectin in MYQZ are expected to reduce Cd toxicity, while Cd translocation can be inhibited with the help of ABC and other Cd transporters. As for BXGZ, the uptake and translocation of Cd were enhanced by the developed root system and stronger transpiration.

Gene Expression Profiling for Differential Diagnosis of Liver Metastases: A Multicenter, Retrospective Cohort Study.

BACKGROUND: Liver metastases (LM) are the most common tumors encountered in the liver and continue to be a significant cause of morbidity and mortality. Identification of the primary tumor of any LM is crucial for the implementation of effective and tailored treatment approaches, which still represents a difficult problem in clinical practice. METHODS: The resection or biopsy specimens and associated clinicopathologic data were archived from seven independent centers between January 2017 and December 2020. The primary tumor sites of liver tumors were verified through evaluation of available medical records, pathological and imaging information. The performance of a 90-gene expression assay for the determination of the site of tumor origin was assessed. RESULT: A total of 130 LM covering 15 tumor types and 16 primary liver tumor specimens that met all quality control criteria were analyzed by the 90-gene expression assay. Among 130 LM cases, tumors were most frequently located in the colorectum, ovary and breast. Overall, the analysis of the 90-gene signature showed 93.1% and 100% agreement rates with the reference diagnosis in LM and primary liver tumor, respectively. For the common primary tumor types, the concordance rate was 100%, 95.7%, 100%, 93.8%, 87.5% for classifying the LM from the ovary, colorectum, breast, neuroendocrine, and pancreas, respectively. CONCLUSION: The overall accuracy of 93.8% demonstrates encouraging performance of the 90-gene expression assay in identifying the primary sites of liver tumors. Future incorporation of the 90-gene expression assay in clinical diagnosis will aid oncologists in applying precise treatments, leading to improved care and outcomes for LM patients.

Molecular and biochemical mechanisms underlying boron-induced alleviation of cadmium toxicity in rice seedlings.

Both cadmium (Cd) contamination and boron (B) deficiency in farmland soils pose a threat to the yield and quality of crops in Southern China. The present study investigated the mechanisms by which B reduces Cd accumulation in rice (Oryza sativa) seedlings. Boron supplementation partially restored the decline in shoot and root biomass caused by Cd treatment (26% and 33%, respectively), with no significant difference between the B+Cd and control groups. We also found that B significantly reduced shoot and root Cd concentrations (by 64% and 25%, respectively) but increased Cd concentration (by 43%) and proportion (from 38% to 55%) in root cell walls. Transcriptome analysis and biochemical tests suggested that B supplementation enhanced lignin and pectin biosynthesis, pectin demethylation, and sulfur and glutathione metabolism. Moreover, B decreased the expression of some Cd-induced transporter-related genes (i.e., HMA2, Nramp1, and several ABC genes). These results indicate that B relieved Cd toxicity and reduced Cd accumulation in rice seedlings by restraining Cd uptake and translocation from root to shoot by improving Cd tolerance and chelation ability. These novel findings would benefit further investigations into how B influences Cd uptake, translocation, detoxification, and accumulation in crops.

Transcriptome analysis and physiological indicators reveal the role of sulfur in cadmium accumulation and transportation in water spinach (Ipomoea aquatica Forsk.).

Cadmium (Cd) contamination of croplands has become a threat to crop food safety and human health. In this study, we investigated the effect of sulfur on the growth of water spinach under Cd stress and the amount of Cd accumulation by increasing the soil sulfate content. We found that the biomass of water spinach significantly increased after the application of sulfur while the shoot Cd concentration was considerably reduced (by 31%). The results revealed that sulfur could promote the expression of PME and LAC genes, accompanied by an increase in PME activity and lignin content. Also, the cell wall Cd content of water spinach roots was significantly increased under sulfur treatment. This finding suggests that sulfur could enhance the adsorption capacity of Cd by promoting the generation of cell wall components, thereby inhibiting the transportation of Cd via the apoplastic pathway. In addition, the higher expression of Nramp5 under the Cd1S0 (concentration of Cd and sulfur are 2.58 and 101.31 mg/kg respectively) treatment led to increased Cd uptake. The CAX3 and ABC transporters and GST were expressed at higher levels along with a higher cysteine content and GSH/GSSR value under Cd1S1 (concentration of Cd and sulfur are 2.60 and 198.36 mg/kg respectively) treatment, which contribute to the Cd detoxification and promotion of Cd compartmentalization in root vacuoles, thereby reducing the translocation of Cd to the shoot via the symplastic pathway.

Selection for low-cadmium cultivars and cadmium subcellular distribution comparison between two selected cultivars of eggplant (Solanum melongena L.).

Excessive accumulation of cadmium (Cd) in vegetables poses a serious threat to human health; therefore, it is urgent to screen and cultivate vegetable cultivars with low Cd accumulation in the edible parts. Eggplant has a high tendency for Cd accumulation, but research on its low Cd accumulation cultivars is still rare. In this study, to screen low-Cd cultivars, 30 eggplant cultivars were screened using soils containing 0.22 mg/kg, 2.9 mg/kg (low-Cd), and 4.7 mg/kg of Cd (high-Cd). MYCQ and ZGQ were confirmed as low-Cd cultivars, BXGZ and WCCQ were confirmed as high-Cd cultivars, and a 2.52-3.88-fold difference in Cd concentration was observed in their fruits. The subcellular distribution revealed that the root cell wall and vacuole Cd concentrations of a typical low-Cd cultivar (MYCQ) were significantly higher than those of a typical high-Cd cultivar (BXGZ); however, the Cd concentrations in the cell wall and vacuole in fruits, leaves, and stems were significantly lower in MYCQ than in BXGZ. These results indicated that the low-Cd cultivars of eggplant could lessen Cd toxicity through the elevated Cd retention and sequestration levels of root cell walls and vacuoles, thus reducing Cd transport from roots to aboveground tissues, leading to low Cd accumulation. The findings of this study can provide a physiological and biochemical foundation for the screening and breeding of low-Cd cultivars of fruit vegetables and demonstrates that the application of low-Cd cultivars is necessary for food safety in humans.

Clinical features of sodium-taurocholate cotransporting polypeptide deficiency in pediatric patients: case series and literature review.

Sodium-taurocholate cotransporting polypeptide (NTCP) deficiency is a newly reported hereditary bile acid metabolic disease. Here we describe the clinical characteristics of 12 cases of pediatric NTCP deficiency, as well as review 60 previously reported cases in the literature in order to provide better guidance for pediatricians. The clinical records, laboratory and imaging data were collected of 12 cases who were treated at the pediatric infectious disease department of the West China Second University Hospital of Sichuan University, China, from December 2018 to July 2020. PubMed and Wanfang databases were searched and 11 studies including 60 pediatric NTCP deficiency patients from January 2015 to November 2020 were retrieved. In our center, there were 4 girls and 8 boys, with a median age at admission of 9.9 months (range, 2.2 to 70 months). Six patients (50%) had prolonged neonatal jaundice. All of the patients (12/12; 100%) had normal growth and development. The reason for the first visit was prolonged neonatal jaundice (4/12, 33.3%), non-liver related diseases (6/12, 50%) and routine checkup (2/12, 16.7%). Hypercholanemia was documented in 12/12 (100%), elevated aspartate aminotransferase (AST) in 6/12 (50%), and elevated alanine aminotransferase (ALT) in 1/12 (8.3%). All of the patients (12/12; 100%) had homozygous mutations of c.800C>T in SLC10A1. Sixty patients (22 girls and 38 boys) were included in the literature review; 36 (60%) had hyperbilirubinemia after 1 month. The reasons for testing for hypercholanemia were identified in 47/60 cases, and included prolonged neonatal jaundice and neonatal transient cholestasis in 26 (26/47, 55.3%); non-liver related diseases in 14 (14/47, 29.8%); routine medical examination in 3 (3/14, 6.4%); volunteer recruitment in 1 (1/14, 7.1%); dark urine in 1 (1/47, 2.1%). Hypercholanemia was confirmed in 60/60 (100%); 31 (51.7%) had elevated AST, and 10 (16.7%) had elevated ALT. Among 59 Chinese patients, 52 (88.1%) had homozygous mutations of c.800C>T in SLC10A1. The most common symptom of pediatric NTCP deficiency is jaundice. NTCP deficiency can also be detected during routine check-ups. The common biochemical features are hypercholanemia and elevated AST. Screening for c.800C>T mutation in SLC10A1 is useful for primary genetic screening in Chinese infants with persistent hypercholanemia after infectious, structural, and immunological factors are excluded.

Moderately differentiated esophageal squamous cell carcinoma has a poor prognosis after neoadjuvant chemoradiotherapy.

BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) plus surgery is the standard treatment for esophageal squamous cell carcinoma (ESCC); however, further analysis is needed to detail the histopathological characteristics of ESCC and their clinical significance after NCRT. This study aimed to present the pathological characteristics of ESCC and their association with prognosis after NCRT. METHODS: All patients with ESCC who underwent NCRT followed by surgical resection at Sichuan Cancer Hospital (China) from January 2018 to December 2019 were included. Resection specimens of both the primary disease and lymph nodes were re-evaluated by an experienced pathologist. After NCRT, the pathological characteristics of the residual tumor were evaluated based on the Japanese residual tumor pattern, Mandard tumor regression grade (Mandard-TRG), local inflammatory infiltration classification, and lymph node status. RESULTS: Among the 103 patients with ESCC included in this study, the pathological complete response (pCR) rate was 34% (35/103). The pCR rate of patients with poorly differentiated tumors (31/72) was higher (43.1%) than that of patients with well or moderately differentiated tumors (P<0.05). The residual tumor rate was 66% (68/103). A positive correlation was noted between the Japanese residual tumor pattern and Mandard-TRG (Kendall's tau-b =0.857, P<0.001). Tumor infiltration depth, lymph node positivity, moderate differentiation, and tumor recurrence were associated with poor oncological outcomes (P<0.05). CONCLUSIONS: Patients with poorly differentiated tumors can obtain an excellent short-term response; however, they have extremely poor long-term survival. For patients with moderately differentiated tumors, both the short- and long-term outcomes are poor. Lymph node status after NCRT is a prognostic factor for ESCC treated with NCRT.