Histone chaperone HIRA, Promyelocytic Leukemia (PML) protein and p62/SQSTM1 coordinate to regulate inflammation during cell senescence.

Cellular senescence, a stress-induced stable proliferation arrest associated with an inflammatory Senescence-Associated Secretory Phenotype (SASP), is a cause of aging. In senescent cells, Cytoplasmic Chromatin Fragments (CCFs) activate SASP via the anti-viral cGAS/STING pathway. PML protein organizes PML nuclear bodies (NBs), also involved in senescence and anti-viral immunity. The HIRA histone H3.3 chaperone localizes to PML NBs in senescent cells. Here, we show that HIRA and PML are essential for SASP expression, tightly linked to HIRA's localization to PML NBs. Inactivation of HIRA does not directly block expression of NF-κB target genes. Instead, an H3.3-independent HIRA function activates SASP through a CCF-cGAS-STING-TBK1-NF-κB pathway. HIRA physically interacts with p62/SQSTM1, an autophagy regulator and negative SASP regulator. HIRA and p62 co-localize in PML NBs, linked to their antagonistic regulation of SASP, with PML NBs controlling their spatial configuration. These results outline a role for HIRA and PML in regulation of SASP.

Evaluation of the Time Difference Method in Identifying Hepatocellular Carcinoma in Current CEUS LR-M Category Nodules.

OBJECTIVE: The aim of the work described here was to explore a potential method for improving the diagnostic detection of hepatocellular carcinoma (HCC) based on the contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) Version 2017. METHODS: We retrospectively evaluated 585 liver nodules in 427 patients at risk for HCC from December 2020 to March 2023. The nodules were categorized as LR-1 to LR-M based on CEUS LI-RADS Version 2017 and were randomly subclassified into a developmental cohort (DC) and a validation cohort (VC) at 3:1. In the DC, the cutoff value of the time difference (∆T) for differentiating HCC from other malignancies by LR-M was calculated and used to reclassify nodules in the VC. The diagnostic effect on HCC detection before and after reclassification was further assessed. RESULTS: According to the current CEUS LI-RADS, 140 of 426 (32.9%) confirmed HCC nodules were misclassified as LR-M. In the DC (439 nodules), the receiver operating characteristic (ROC) curve revealed that the cutoff value of ∆T (wash-out onset time minus contrast arrival time) recommended for HCC diagnosis was greater than 21 s. In the VC (146 nodules), 34 HCCs were correctly categorized as LR-5 according to the cutoff value, and after reclassification, LR-5 had higher accuracy (67.1% vs. 89.0%, p < 0.001) and sensitivity (56.0% vs. 87.2%, p < 0.001) for HCC diagnosis with high specificity (100% vs. 94.6%, p = 0.500). CONCLUSION: Using the time difference method could identify HCC nodules misdiagnosed as LR-M and improve the diagnostic performance of current CEUS LI-RADS.

Assessment of legacy and alternative halogenated organic pollutants in outdoor dust and soil from e-waste sites in Nigeria: Concentrations, patterns, and implications for human exposure.

E-waste is often processed informally, particularly in developing countries, resulting in the release of harmful chemicals into the environment. This study investigated the co-occurrence of selected persistent organic pollutants (POPs), including legacy and alternative halogenated flame retardants (10 polybrominated diphenyl ethers (PBDEs), decabromodiphenyl ethane (DBDPE), syn and anti-dechlorane plus (DP)), 32 polychlorinated biphenyls (PCBs) and 12 organochlorine pesticides (OCPs), in 20 outdoor dust and 49 soil samples from 7 e-waste sites in Nigeria. This study provides the first report on alternative flame retardants (DBDPE and DP) in Nigeria. The total concentration range of the selected classes of compounds was in the order: ∑10PBDEs (44-12300 ng/g) > DBDPE (4.9-3032 ng/g) > ∑2DP (0.7-278 ng/g) > ∑32PCBs (4.9-148 ng/g) > ∑12OCPs (1.9-25 ng/g) for dust, and DBDPE (4.9-9647 ng/g) > ∑10PBDEs (90.3-7548 ng/g) > ∑32PCBs (6.1-5025 ng/g) > ∑12OCPs (1.9-250 ng/g) > ∑2DP (2.1-142 ng/g) for soil. PBDEs were the major contributors to POP pollution at e-waste dismantling sites, while PCBs were the most significant contributors at e-waste dumpsites. DBDPE was found to be significantly associated with pollution at both e-waste dismantling and dumpsites. Estimated daily intake (EDI) via dust and soil ingestion and dermal adsorption routes ranged from 1.3 to 2.8 ng/kg bw/day and 0.2-2.9 ng/kg bw/day, respectively. In the worst-case scenario, EDI ranged from 2.9 to 10 ng/kg bw/day and 0.8-5.8 ng/kg bw/day for dust and soil, respectively. The obtained intake levels posed no non-carcinogenic risk, but could increase the incidence of cancer at some of the studied e-waste sites, with values exceeding the USEPA cancer risk lower limit (1.0 × 10-6). Overall, our results suggest that e-waste sites act as emission point sources of POPs.

Molecular mechanisms and physiological responses of rice leaves co-exposed to submicron-plastics and cadmium: Implication for food quality and security.

The effects of co-exposure to aged submicron particles (aSMPs) and Cd as model contaminants on rice leaves via the foliar route were investigated. Thirty-day-old rice seedlings grown in soil were exposed to Cd (nitrate) through foliar spraying at concentrations of 1, 10, 50, 100, and 500 µM, with or without aSMP at a rate of 30 µg d-1. It was observed that Cd translocated from leaves to roots via stems even without co-exposure to SMP. Co-exposure can reduce cadmium levels in leaves. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) analysis confirmed a significant reduction (29.3 - 77.9%) in Cadmium accumulation in the leaves of rice plants during co-exposure. Exposure to Cd resulted in physiological, transcriptomic, and metabolomic changes in rice leaves, disrupting 28 metabolism pathways, and impacting crop yield and quality. Exposure to both Cd and aSMPs can interfere with the Cd distribution in plants. Rice leaves exposed solely to Cd exhibit higher toxicity and Cd accumulation, compared to those co-exposed to Cd and aSMPs. The accumulation of Cd in plant leaves is enhanced with aSMPs, which may lead to more pronounced gene expression regulation and changes in metabolic pathways, compared to Cd exposure. Our study found that the independent Cd exposure group had higher Cd accumulation and toxicity in rice leaves compared to the combined exposure of Cd and aSMPs. We hypothesize that aged negatively charged SMPs can capture Cd and reduce its exposure in the free state while jointly inhibiting Cd-induced oxidative and chloroplast damage, thereby reducing the potential risk of Cd exposure in rice plants.

Comparison of the 2005 Montreal Criteria and the 2019 Cirrhotic Cardiomyopathy Consortium Criteria for the Diagnosis of Cirrhotic Cardiomyopathy.

The comparison between the diagnostic criteria for cirrhotic cardiomyopathy (CCM) first proposed in 2005 (2005 Montreal criteria), and those redefined in the 2019 Cirrhotic Cardiomyopathy Consortium (2019 CCC criteria) has generated significant controversy. Importantly, the predictive value of these criteria in cirrhotic patients (CPs) remains unclear to this date. Thus, the present study aims to compare the 2 sets of criteria and investigate their predictive value in CPs. Between April 2021 and April 2023, a total of 104 CPs with an average age of 46.4 ± 8.9 years, who had no history of other cardiac diseases or malignancies were enrolled in this prospective single-center observational cohort study, conducted at the Third Affiliated Hospital of Sun Yat-Sen University. Various echocardiographic indicators were measured and assessed for their prognostic value and association with clinical outcomes. The prevalence of CCM was found to be comparable when evaluated using both the 2019 CCC and 2005 Montreal criteria (54.8% vs 44.2%, p = 0.161). However, the diagnosis of systolic dysfunction was significantly different between the 2 criteria (52.9% vs 1.0%, p <0.001). Among patients with systolic dysfunction, 27.9% had reduced left ventricular global longitudinal strain, while 25% had increased left ventricular global longitudinal strain. Moreover, fewer patients were diagnosed with diastolic dysfunction (DD) using the 2019 CCC criteria (4.8% vs 44.2%, p <0.001). Multivariate Cox analysis revealed that CPs who had encephalopathy, a high model for end-stage liver disease score, and DD diagnosed using the 2019 CCC criteria exhibited a poorer prognosis. In conclusion, although the prevalence of CCM according to both criteria is similar, the consistency is poor, indicating that they are not the same group of patients. Importantly, CPs with DD diagnosed according to the 2019 CCC criteria might be associated with increased adverse events.

Concentrations and homologue patterns of SCCPs and MCCPs in the serum of the general population of adults in Hangzhou, China.

Due to their ubiquitous presence in the environment and humans, chlorinated paraffins (CPs) are a major environmental and public health concern. CPs are known to persist, bioaccumulate and potentially threaten human health, but reports on their internal exposure in the adult general population are still scarce. In this study, serum samples collected from adults living in Hangzhou, China, were quantified for SCCPs and MCCPs using GC-NCI-MS methods. A total of 150 samples were collected and subjected to analysis. ∑SCCPs were detected in 98% of the samples with a median concentration of 721 ng/g lw. MCCPs were found in all serum samples with a median concentration of 2210 ng/g lw, indicating that MCCPs were the dominant homologous group. For SCCPs and MCCPs, ∑C10 and ∑C14 were found to be the dominant carbon chain length homologues. Our results showed that age, BMI and lifestyle were not found to be significantly associated with internal exposure to CPs for the samples in this study. Based on PCA analysis, an age-specific distribution of CP homologues was observed. This suggests that internal exposure to CPs in the general population is related to exposure scenarios and history. The results of this study may contribute to a better understanding of the internal exposure to CPs in the general population and may provide a direction for the investigation of the source of exposure to CPs in the environment and daily life.

Transmembrane nuclease NUMEN/ENDOD1 regulates DNA repair pathway choice at the nuclear periphery.

Proper repair of DNA damage lesions is essential to maintaining genome integrity and preventing the development of human diseases, including cancer. Increasing evidence suggests the importance of the nuclear envelope in the spatial regulation of DNA repair, although the mechanisms of such regulatory processes remain poorly defined. Through a genome-wide synthetic viability screen for PARP-inhibitor resistance using an inducible CRISPR-Cas9 platform and BRCA1-deficient breast cancer cells, we identified a transmembrane nuclease (renamed NUMEN) that could facilitate compartmentalized and non-homologous end joining-dependent repair of double-stranded DNA breaks at the nuclear periphery. Collectively, our data demonstrate that NUMEN generates short 5' overhangs through its endonuclease and 3'→5' exonuclease activities, promotes the repair of DNA lesions-including heterochromatic lamina-associated domain breaks as well as deprotected telomeres-and functions as a downstream effector of DNA-dependent protein kinase catalytic subunit. These findings underline the role of NUMEN as a key player in DNA repair pathway choice and genome-stability maintenance, and have implications for ongoing research into the development and treatment of genome instability disorders.

Isoalantolactone mediates the degradation of BCR-ABL protein in imatinib-resistant CML cells by down-regulating survivin.

Isoalantolactone (Iso) is a bioactive lactone isolated from the root of Inula helenium L, which has been reported to have many pharmacological effects. To investigate the role and mechanism of isoalantolactone in chronic myeloid leukemia (CML), we first investigated isoalantolactone's anti-proliferative effects on imatinib-sensitive and imatinib-resistant CML cells by CCK8. Flow cytometry was used to detect isoalantolactone-induced cell apoptosis. Survivin was overexpressed in KBM5 and KBM5T315I cells using the lentivirus vector pSIN-3×flag-PURO. In KBM5 and KBM5T315I cells, shRNA was used to knockdown survivin. Cellular Thermal Shift Assay (CETSA) was used to detect the interaction between isoalantolactone and survivin. The ubiquitin of survivin induced by isoalantolactone was detected through immunoprecipitation. Quantitative polymerase-chain reaction (Q-PCR) and western blotting were used to detect the levels of mRNA and protein. Isoalantolactone inhibits the proliferation and promotes apoptosis of imatinib-resistant CML cells. Although isoalantolactone inhibits the proteins of BCR-ABL and survivin, it cannot inhibit survivin and BCR-ABL mRNA levels. Simultaneously, it was shown that isoalantolactone can degrade survivin protein by increasing ubiquitination. It was demonstrated that isoalantolactone-induced survivin mediated downregulation of BCR-ABL protein. It was also revealed that isoalantolactone triggered BCR-ABL protein degradation via caspase-3. Altogether, isoalantolactone inhibits survivin through the ubiquitin proteasome pathway, and mediates BCR-ABL downregulation in a caspase-3 dependent manner. These data suggest that isoalantolactone is a natural compound, which can be used as a potential drug to treat TKI-resistant CML.

Contrast-Enhanced Ultrasound With SonoVue and Sonazoid for the Diagnosis of Colorectal Liver Metastasis After Chemotherapy.

PURPOSE: To compare the diagnostic efficacy of SonoVue and Sonazoid contrast-enhanced ultrasound (CEUS) in correctly detecting and characterizing colorectal liver metastasis (CRLM) after chemotherapy. MATERIALS AND METHODS: Patients with CRLMs treated with chemotherapy and subsequently scheduled for hepatic resection were prospectively enrolled from April 2020 to January 2021. Lesions detected by SonoVue or Sonazoid CEUS were recorded as and characterized as metastases or non-metastatic lesions respectively. Histopathology or intraoperative ultrasound with MRI were the reference standard. RESULTS: A total of 348 focal liver lesions in 42 patients were investigated, including 297 CRLMs and 51 non-metastatic lesions. SonoVue showed significantly higher diagnostic accuracy (64.7% versus 54.0%; P < .001) and sensitivity (63.3% versus 50.5%; P < .001) in the diagnosis of CRLMs than Sonazoid, both methods presented with similar specificity (72.5% versus 74.5%; P = 1.0). Forty metastases appeared non-hypoenhancing (hyperenhancing or isoenhancing) in the late phase and postvascular phase of Sonazoid CEUS and were mischaracterized as benign lesions. CONCLUSION: SonoVue performed significantly better than Sonazoid in the diagnosis of CRLMs after chemotherapy.

Aryl-, halogenated- and alkyl- organophosphate esters induced oxidative stress, endoplasmic reticulum stress and NLRP3 inflammasome activation in HepG2 cells.

Organophosphate esters (OPEs) are a group of extensively used man-made chemicals with diverse substituents that are ubiquitously detected in human-related samples including serum, breastmilk, food and house dust. The understanding of their toxicological effects and potential mechanisms on hepatocytes is still limited. In this study, nine most frequently detected OPEs were selected and divided into three subgroups (aryl-, halogenated- and alkyl-OPEs) based on their substituents. The cytotoxicity, apoptosis, oxidative stress, endoplasmic reticulum (ER) stress and NLRP3 inflammasome activation induced by OPEs were evaluated in human hepatocellular carcinomas HepG2 cells. All OPEs induced apoptosis likely through a caspase-dependent apoptotic pathway. The activities of anti-oxidative enzyme SOD and CAT exhibited sensitive responses after OPEs treatment for 6 h. The OPEs induced ROS overproduction, DNA damage, endoplasmic reticulum (ER) stress and NLRP3 inflammasome activation varied among aryl-, halogenated- and alkyl-OPEs. Halogenated- and alkyl- OPEs induced overproduction of ROS and DNA damage, and elevated ER stress and NLRP3 inflammasome activation are observed aryl-OPEs induced cytotoxicity.

Prospect of neoadjuvant/adjuvant immunotherapy in early-stage triple-negative breast cancer.

China is bearing the growing burden of breast cancer globally, accounting for 18% of all new cases. Triple-negative breast cancer (TNBC) is aggressive, prone to early recurrence and metastasis, with a poor prognosis. Improving the prognosis at the early-stage of TNBC remains a challenge, due to the limited efficacy of traditional neoadjuvant/adjuvant chemotherapy. Early studies revealed that early-stage TNBC is more immunogenic. Several current clinical trials revealed that the combination with immunotherapy in the form of immune checkpoint inhibitors (ICIs) expands the treatment options for early-stage TNBC by improving the pathologic complete response (pCR), as well as long-term survival benefits. Correspondingly, Chinese Society of Clinical Oncology (CSCO) updated the breast cancer guidelines to include several recommendations regarding neoadjuvant/adjuvant immunotherapy. However, relevant immunotherapy data in Chinese patients with early-stage TNBC remain scarce. The cTRIO clinical trial (ChiCTR2100041675) is a multicenter phase II trial initiated by investigators to evaluate tislelizumab combined with nab-paclitaxel and carboplatin in neoadjuvant/ adjuvant therapy for Chinese patients with TNBC. In this review, we discuss the latest advances in clinical studies of neoadjuvant/adjuvant immunotherapy for early-stage TNBC, as well as potential challenges and strategies to improve the clinical outcomes. We introduce the study design of the cTRIO trial, which aims to make the clinical benefits more robust for early-stage TNBC patients in China.

The role of aging in cancer.

Many cancers show an increase in incidence with age, and age is the biggest single risk factor for many cancers. However, the molecular basis of this relationship is poorly understood. Through a collection of review articles, our thematic issue discusses the link between aging and cancer in aspects including somatic mutations, proteostasis, mitochondria, metabolism, senescence, epigenetic regulation, immune regulation, DNA damage, and telomere function.

Immature tertiary lymphoid structure formation was increased in the melanoma tumor microenvironment of IKZF1 transgenic mice.

Background: IKZF1 promotes the occurrence of lymphoma and is also related to the development of breast cancer, liver cancer, and ovarian cancer. It was hypothesized that IKZF1 influences tertiary lymphoid structures (TLSs) formation and development in the tumor immune microenvironment, and this effect of IKZF1 on the tumor immune microenvironment has not been explored. Using melanoma grafts as a model, we investigated the effect of IKZF1 on the immune microenvironment of melanoma. Methods: The Cell Count Kit-8 (CCK8) assay was used to detect the effect IKZF1 overexpression in melanoma cells on cell proliferation. The IKZF1 overexpression vector was constructed by homologous recombination. After linearization, the overexpression vector was microinjected into the fertilized egg. Transgenic mice overexpressing IKZF1 were screened by tail identification. After melanoma B16 mouse cells were digested into single cells, the tumor was subcutaneously implanted in C57BL6/J-wild type (WT) mice and IKZF1 transgenic mice, and the tumor growth of the 2 groups was compared. The number of TLSs in the tumor tissues of mice was analyzed after hematoxylin-eosin (HE) staining. Results: Overexpression of IKZF1 in melanoma cells did not affect cell proliferation. The IKZF1 overexpression vector pcDNA3.1-CAG-IKAROS was successfully constructed. Viable fertilized eggs were obtained after microinjection. Transgenic mice stably expressing IKZF1 were identified by polymerase chain reaction (PCR). Compared with WT mice, the tumor load of IKZF1 transgenic mice increased significantly. HE staining showed that the number of immature TLSs in melanomas of IKZF1 transgenic mice increased significantly. Conclusions: IKZF1 does not affect the proliferation of melanoma cells. Transgenic mice overexpressing IKZF1 were successfully constructed. IKZF1 is a key driver gene of the formation of immature TLS.

CEUS and CT/MRI LI-RADS in Association With Serum Biomarkers for Differentiation of Combined Hepatocellular-Cholangiocarcinoma From Hepatocellular Carcinoma.

Background: Combined Hepatocellular-cholangiocarcinoma (cHCC-CCAs) are with both unambiguously differentiated hepatocellular and biliary components. cHCC-CCAs show various imaging features similar to hepatocellular carcinoma (HCCs) and intrahepatic cholangiocarcinoma (ICCs), which makes the differential diagnosis between them challenging. The accurate diagnosis of cHCC-CCAs is of great importance in selecting treatment methods and performing patient management. Purpose: To investigate the diagnostic efficacy of CEUS and CT/MRI LI-RADS in association with tumor biomarkers for differentiation of cHCC-CCAs from HCCs. Methods: A total of 54 cHCC-CCAs and 55 HCCs in two centers were retrospectively collected. The diagnostic criteria for cHCC-CCAs if one or more of the following conditions were satisfied: (1) arterial phase hyperenhancement (APHE) on CEUS and LR-M on CT/MRI; (2) LR-5 on both CEUS and CT/MRI with elevated carbohydrate antigen 19-9 (CA19-9); (3) LR-M on both CEUS and CT/MRI with elevated alphafetoprotein (AFP). The sensitivity, specificity, accuracy and area under the receiver operating characteristic curve (AUC) were calculated. Results: The rates of APHE and Rim-APHE on CEUS in cHCC-CCAs were 81.5% and 9.3%, respectively. The rate of early and marked washout on CEUS in cHCC-CCAs were 59.3% and 27.8%, respectively. 64.8% and 25.9% of cHCC-CCAs showed APHE and Rim-APHE on CT/MRI, respectively. 46.3% and 35.2% of cHCC-CCAs showed washout and delay enhancement on CT/MRI, respectively. The kappa value of LI-RADS categories of cHCC-CCAs on CEUS and CT/MRI was 0.319 (P=0.008). The sensitivity, specificity, accuracy and AUC of the aforementioned diagnostic criteria for cHCC-CCAs were 64.8%, 84.4%, 76.1% and 0.746, respectively. Conclusion: The combination of the CEUS and CT/MRI LI-RADS with serum tumor markers shows promising diagnostic performance of cHCC-CCAs.

Natural Product Library Screens Identify Sanguinarine Chloride as a Potent Inhibitor of Telomerase Expression and Activity.

Reverse transcriptase hTERT is essential to telomerase function in stem cells, as well as in 85-90% of human cancers. Its high expression in stem cells or cancer cells has made telomerase/hTERT an attractive therapeutic target for anti-aging and anti-tumor applications. In this study, we screened a natural product library containing 800 compounds using an endogenous hTERT reporter. Eight candidates have been identified, in which sanguinarine chloride (SC) and brazilin (Braz) were selected due to their leading inhibition. SC could induce an acute and strong suppressive effect on the expression of hTERT and telomerase activity in multiple cancer cells, whereas Braz selectively inhibited telomerase in certain types of cancer cells. Remarkably, SC long-term treatment could cause telomere attrition and cell growth retardation, which lead to senescence features in cancer cells, such as the accumulation of senescence-associated ß-galactosidase (SA-ß-gal)-positive cells, the upregulation of p16/p21/p53 pathways and telomere dysfunction-induced foci (TIFs). Additionally, SC exhibited excellent capabilities of anti-tumorigenesis, both in vitro and in vivo. In the mechanism, the compound down-regulated several active transcription factors including p65, a subunit of NF-κB complex, and reintroducing p65 could alleviate its suppression of the hTERT/telomerase. Moreover, SC could directly bind hTERT and inhibit telomerase activity in vitro. In conclusion, we identified that SC not only down-regulates the hTERT gene's expression, but also directly affects telomerase/hTERT. The dual function makes this compound an attractive drug candidate for anti-tumor therapy.

TIN2 deficiency leads to ALT-associated phenotypes and differentiation defects in embryonic stem cells.

Telomere integrity is critical for embryonic development, and core telomere-binding proteins, such as TIN2, are key to maintaining telomere stability. Here, we report that homozygous Tin2S341X resulted in embryonic lethality in mice and reduced expression of Tin2 in the derived mouse embryonic stem cells (mESCs). Homozygous mutant mESCs were able to self-renew and remain undifferentiated but displayed many phenotypes associated with alternative lengthening of telomeres (ALT), including excessively long and heterogeneous telomeres, increased ALT-associated promyelocytic leukemia (PML) bodies, and unstable chromosomal ends. These cells also showed upregulation of Zscan4 expression and elevated targeting of DAXX/ATRX and H3K9me3 marks on telomeres. Furthermore, the mutant mESCs were impeded in their differentiation capacity. Upon differentiation, DAXX/ATRX and PML bodies disassociated from telomeres in these cells, where elevated DNA damage was also apparent. Our results reveal differential responses to telomere dysfunction in mESCs versus differentiated cells and highlight the critical role of TIN2 in embryonic development.

Exposure patterns, chemical structural signatures, and health risks of pesticides in breast milk: A multicenter study in China.

China is the world's largest pesticide user. These chemicals are bioaccumulative in the human body, and eventually could be transferred from the mother to the fetus/infant via placental and breastfeeding transport, which might pose developmental deficiency risks. In this study, human biomonitoring of legacy pesticides was conducted in three Chinese cities using 60 breast milk samples. The patterns, chemical structural signatures, and the estimated daily intake of pesticides were assessed. The median concentration of HCB (57.8 ng g-1 lw, Interquartile range: 28.5-76.9 ng g-1 lw) was the highest among all pesticides, whereas the HCHs, DDXs, TCVP, and heptachlor were also detected. A significantly different pattern of pesticides was found among three sampling cities: the Mianyang cases were mostly DDXs oriented while the Wuhan and Hangzhou cases were under HCB, HCHs, TCVP, and heptachlor influences. Maternal age and pre-pregnancy BMI were found to be the influencing factors for the pesticides in the breast milk, and dietary preferences were an important factor in the exposure scenario. Chemical structural signatures indicated that for HCHs and DDXs the exposure was mostly historical, while the lindane and dicofol exposure may exist among the volunteering mothers. The EF for chiral pesticides did not deviate significantly from the racemic value. The risk from breastfeeding was negligible according to the Chinese and UN standard, while some cases from Hangzhou and Wuhan exceeded the Canadian restrictions. Thus, the adverse health effects of chemical exposure by dietary intake for infants need to be closely monitored in future studies.

The top 50 most cited articles in carpal tunnel syndrome research: A bibliometrics study.

BACKGROUND: Citation analysis was applied to identify the influential studies in the specific field. More and more literature related to carpal tunnel syndrome (CTS) have been published in recent years. To our knowledge, no one has performed a citation analysis of CTS. Thus, our study identified the top 50 influential articles pertaining to CTS and conduct an analysis of their characteristics. METHODS: The Web of Science database was used to identify all the articles from 1900 to 2020. We obtained the top 50 articles ranked by citation times, and articles were included and excluded based on the relevance to CTS. Also, we collected the information about journal name, level of evidence, source country and institution, and research type for further analysis. RESULTS: The top 50 articles were published between 1959 and 2012. The number of citations ranged from 151 to 1083. The citation density was between 3.23 and 40.27 per year. Muscle Nerve published most articles in CTS research, followed by Journal of Bone and Joint Surgery American Volume. The USA was the leading country, and all the top 5 institutions were from the USA. Katz JN with the highest h-index published most articles. Level III was the most common evidence level. CONCLUSIONS: We identified the top 50 cited articles related to CTS. These influential articles might provide researchers with a comprehensive list of the major contribution related to CTS research.

Diagnostic value of color parametric imaging and contrast-enhanced ultrasound in the differentiation of hepatocellular adenoma and well-differentiated hepatocellular carcinoma.

PURPOSE: To investigate the differential diagnostic value of computer-aided color parametric imaging (CPI) and contrast-enhanced ultrasound (CEUS) in hepatocellular adenoma (HCA) and well-differentiated hepatocellular carcinoma (wHCC). METHOD: A total of 38 patients who underwent CEUS and were pathologically diagnosed with HCA (10 cases) and wHCC (28 cases) were reviewed retrospectively. The differences between the radiological features of HCA and wHCC were compared by two readers, blinded to the final diagnosis. RESULTS: (a) Sonographic features: on gray-scale ultrasound, halo sign was more common in wHCC than in HCA (60.7% vs. 10.0%, p = 0.009). On CEUS, hyper- or isoenhancement was more common in HCA in the portal phase (90.0% vs. 50.0%; p = 0.022). On CPI mode, HCA was inclined toward centripetal enhancement (60.0% vs. 14.3% p = 0.010). HCA was characterized by the presence of pseudocapsule enhancement (50.0% vs. 14.3%; p = 0.036). Quantitative analysis showed that the arrival time of HCA was earlier than that of wHCC (12.4 ± 3.7 s vs. 15.9 ± 3.2 s; p = 0.006). (b) Interobserver agreement was improved by using CPI compared with CEUS. The diagnostic sensitivity, specificity, and accuracy of the combination were 80.0%, 85.7%, and 84.2%, respectively. CONCLUSIONS: CEUS combined with CPI can provide effective information for the differential diagnosis of HCA and wHCC, especially for the non-experienced radiologists.

Acupuncture combined with metformin for polycystic ovary syndrome: A protocol for systematic review and meta-analysis.

BACKGROUND: Polycystic ovary syndrome is an endocrine disorder that occurs mostly in women of reproductive age and has lifelong effects on their health. METHODS: Randomized controlled clinical trials that met the inclusion criteria were screened by searching multiple databases. Relevant data were extracted, and meta-analysis was performed using Reviewer Manager 5.4. RESULTS: The results of this study will be submitted to peer-reviewed journals. CONCLUSION: This study provides evidence for the efficacy and safety of the clinical application of acupuncture combined with metformin in the treatment of polycystic ovary syndrome.