Demonstration of a trapped-ion atomic clock in space.

Atomic clocks, which lock the frequency of an oscillator to the extremely stable quantized energy levels of atoms, are essential for navigation applications such as deep space exploration1 and global navigation satellite systems2, and are useful tools with which to address questions in fundamental physics3-6. Such satellite systems use precise measurement of signal propagation times determined by atomic clocks, together with propagation speed, to calculate position. Although space atomic clocks with low instability are an enabling technology for global navigation, they have not yet been applied to deep space navigation and have seen only limited application to space-based fundamental physics, owing to performance constraints imposed by the rigours of space operation7. Methods of electromagnetically trapping and cooling ions have revolutionized atomic clock performance8-13. Terrestrial trapped-ion clocks operating in the optical domain have achieved orders-of-magnitude improvements in performance over their predecessors and have become a key component in national metrology laboratory research programmes13, but transporting this new technology into space has remained challenging. Here we show the results from a trapped-ion atomic clock operating in space. On the ground, NASA's Deep Space Atomic Clock demonstrated a short-term fractional frequency stability of 1.5 × 10-13/τ1/2 (where τ is the averaging time)14. Launched in 2019, the clock has operated for more than 12 months in space and demonstrated there a long-term stability of 3 × 10-15 at 23 days (no drift removal), and an estimated drift of 3.0(0.7) × 10-16 per day. Each of these exceeds current space clock performance by up to an order of magnitude15-17. The Deep Space Atomic Clock is particularly amenable to the space environment because of its low sensitivity to variations in radiation, temperature and magnetic fields. This level of space clock performance will enable one-way navigation in which signal delay times are measured in situ, making near-real-time navigation of deep space probes possible18.

Retraction Note: Quantification of ocean heat uptake from changes in atmospheric O2 and CO2 composition.

This Article has been retracted; see accompanying Retraction Note.

What do women undergoing in vitro fertilization (IVF) understand about their chance of IVF success?

STUDY QUESTION: How well informed are Australian women who undergo IVF about their chances of having a baby? SUMMARY ANSWER: Only one in four women estimated their individual chance of success with IVF accurately, with most women overestimating their chance. WHAT IS KNOWN ALREADY: Limited knowledge about infertility and infertility treatment in the general population is well-documented. The few studies that have investigated patients' knowledge about the chance of IVF success suggest that while IVF patients are aware of average success rates, they tend to be unrealistic about their own chance of success. STUDY DESIGN, SIZE, DURATION: We conducted an anonymous online survey of 217 women who had started IVF since 2018 in Australia. The survey was advertised on social media, enabling women from across Australia to participate. Responses were collected in June 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: The survey included questions on demographic characteristics and IVF history. It asked what participants thought their chance of having a baby from one IVF treatment cycle was, how they rated their knowledge about chance of success, and about their experience of receiving IVF-related information. Participants' estimations of their chance of success were compared with their chance as calculated by the Society for Assisted Reproductive Technology's (SART) online calculator. Responses to a free-text question about what information women wished they had been given when they started treatment were analysed thematically. MAIN RESULTS AND THE ROLE OF CHANCE: Only about a quarter (58/217, 27%) of participants accurately estimated their chance of having a baby within 20% relative to their SART calculated chance, with more than half (118/217, 54%) overestimating their chance. Ninety percent of women indicated that their preferred source of treatment information was a consultation with their doctor, despite less than half (44%) reporting that doctors explained the probability of having a baby with IVF well (mean 5.9/10). In free-text responses, many women also reported that they wished they had been given more realistic information about IVF and their chance of success. LIMITATIONS, REASONS FOR CAUTION: The dissemination method precludes calculation of response rate, and it is not possible to know if participants are representative of all women undergoing IVF. Additionally, we only surveyed women undergoing IVF, while those who decided not to have IVF were not included. Therefore, women who overestimated their chance may have been overrepresented. There is also inherent imprecision in the way understanding of chance of success was estimated. The potential impact of recall bias could neither be quantified nor excluded. It is difficult to determine to what extent women's lack of understanding of what is possible with IVF is due to poor information-provision by clinicians and the clinic, and how much can be explained by optimism bias. WIDER IMPLICATIONS OF THE FINDINGS: The finding of poor understanding of personal chance of success amongst women undergoing IVF in Australia requires further investigation to determine potential reasons for this. The findings can be used by clinics to develop strategies for improvement in the information-provision process to ensure that women can make informed decisions about their fertility treatment. STUDY FUNDING/COMPETING INTEREST(S): This study received no external funding. S.L. is supported by a NHMRC Investigator Grant (APP1195189). R.W. is supported by a NHMRC Investigator Grant (APP2009767). B.W.M. is supported by a NHMRC Investigator Grant (GNT1176437). B.W.M. reports consultancy for Merck and ObsEva and has received research funding and travel funding from Merck. The other authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Evaluating the Performance of UV Disinfection across the 222-365 nm Spectrum against Aerosolized Bacteria and Viruses.

Bioaerosols play a significant role in the transmission of many infectious diseases, especially in enclosed indoor environments. Ultraviolet (UV) disinfection has demonstrated a high efficacy in inactivating microorganisms suspended in the air. To develop more effective and efficient UV disinfection protocols, it is necessary to evaluate and optimize the effectiveness of UV disinfection against aerosolized bacteria and viruses across the entire UV spectrum. In this study, we evaluated the performance of UV disinfection across the UV spectrum, ranging from 222 to 365 nm, against aerosolized bacteria and viruses, including Escherichia coli, Staphylococcus epidermidis, Salmonella enterica, MS2, P22, and Phi6. Six commonly available UV sources, including gas discharge tubes and light-emitting diodes with different emission spectra, were utilized, and their performance in terms of inactivation efficacy, action spectrum, and energy efficiency was determined. Among these UV sources, the krypton chloride excilamp emitting at a peak wavelength of 222 nm was the most efficient in inactivating viral bioaerosols. A low-pressure mercury lamp emitting at 254 nm performed well on both inactivation efficacy and energy efficiency. A UV light-emitting diode emitting at 268 nm demonstrated the highest bacterial inactivation efficacy, but required approximately 10 times more energy to achieve an equivalent inactivation level compared with that of the krypton chloride excilamp and low-pressure mercury lamp. This study provides insights into UV inactivation on bioaerosols, which can guide the development of effective wavelength-targeted UV air disinfection technologies and may significantly help reduce bioaerosol transmission in public areas.

Quantification of ocean heat uptake from changes in atmospheric O2 and CO2 composition.

The ocean is the main source of thermal inertia in the climate system1. During recent decades, ocean heat uptake has been quantified by using hydrographic temperature measurements and data from the Argo float program, which expanded its coverage after 20072,3. However, these estimates all use the same imperfect ocean dataset and share additional uncertainties resulting from sparse coverage, especially before 20074,5. Here we provide an independent estimate by using measurements of atmospheric oxygen (O2) and carbon dioxide (CO2)-levels of which increase as the ocean warms and releases gases-as a whole-ocean thermometer. We show that the ocean gained 1.33 ± 0.20  × 1022 joules of heat per year between 1991 and 2016, equivalent to a planetary energy imbalance of 0.83 ± 0.11 watts per square metre of Earth's surface. We also find that the ocean-warming effect that led to the outgassing of O2 and CO2 can be isolated from the direct effects of anthropogenic emissions and CO2 sinks. Our result-which relies on high-precision O2 measurements dating back to 19916-suggests that ocean warming is at the high end of previous estimates, with implications for policy-relevant measurements of the Earth response to climate change, such as climate sensitivity to greenhouse gases7 and the thermal component of sea-level rise8.

Pericoronary adipose tissue attenuation predicts outcome of percutaneous intervention for chronic total occlusion.

AIM: To investigate the association between pericoronary adipose tissue (PCAT) attenuation (PCATA) and outcomes of chronic total occlusion (CTO) after percutaneous coronary intervention (PCI), and to establish a clinical model that can be easily generalised to predict the outcomes of PCI-CTO. MATERIALS AND METHODS: Between September 2015 and September 2019, patients from two centres were enrolled retrospectively. The primary endpoint was a procedural success (defined as achieving residual stenosis of <30% and a grade 3 thrombolysis in myocardial infarction [TIMI] flow). The new predictive model was generated by factors that were determined by multivariate analysis. The PCATA of CTO (PCATA-CTO) score was developed by assigning 1 point for each independent predictor, and then summing all points accrued. In addition, the predictive efficacy and interobserver and intraobserver agreement of PCATA-CTO and other scoring systems based on coronary computed tomography angiography (CCTA) were compared. RESULTS: A total of 201 patients (mean age 58.9 ± 10.8 years, 85% male) were enrolled. The PCI success was achieved in 76% of the lesions. PCAT was higher in the PCI success group (-72.44 ± 10.45HU versus -76.76 ± 10.54 HU, p<0.05). Multivariable analysis yielded severe calcification, lesion length ≥15 mm, and perivascular fat attenuation index (FAI) ≤-69.5HU as independent negative predictors for procedural success. The area under the receiver operating characteristic curves for the PCATA-CTO score was 0.72. Comparing the PCATA-CTO score with other predictive scores, the PCATA-CTO score showed the highest interobserver (kappa = 0.74) and intraobserver agreement (kappa = 0.90, all p<0.01). CONCLUSION: FAI ≤-69.5HU is an independent negative predictor of procedural success. The PCATA-CTO score improved the reliability of the prediction model. Its potential for clinical implementation requires evaluation.

Inter-equipment validation of PET-based radiomics for predicting EGFR mutation statuses in patients with non-small cell lung cancer.

AIM: To validate the inter-equipment generality of the radiomics based on PET images to predict the EGFR mutation status of patients with non-small cell lung cancer. MATERIALS AND METHODS: Patients were retrospectively collected in the departments of nuclear medicine of Heyi branch (Siemens equipment) and East branch (General Electric (GE) equipment) of the first affiliated hospital of Zhengzhou university. 5 predicting logistic regression models were established. The 1st one was trained and tested by the GE dataset; The 2nd one was trained and tested by the Siemens dataset; The 3rd one was trained and tested by the mixed dataset consisting of GE and Siemens. The 4th one was trained by GE and tested by Siemens; The 5th one was trained by Siemens and tested by GE. RESULTS: For the 1st ∼ 5th models, the mean values of AUCs for training/testing datasets were 0.78/0.73, 0.74/0.72, 0.75/0.70, 0.74/0.65 and 0.68/0.63, respectively. CONCLUSION: The AUCs of the models trained and tested on the datasets from the same equipment were higher than those for different equipment. The inter-equipment generality of the radiomics was not good enough in clinical practice.

Mouse model of Graves' orbitopathy induced by the immunization with TSHR A and IGF-1R α subunit gene.

PURPOSE: The study aimed to establish a mouse model of Graves' disease (GD) with Graves' orbitopathy (GO; GD + GO) that can represent the clinical disease characteristics. METHODS: A eukaryotic expression plasmid of insulin-like growth factor 1 receptor (IGF-1R) α subunit (pcDNA3.1/IGF-1Rα) and a thyrotropin receptor (TSHR) A subunit plasmid (pcDNA3.1/TSHR-289) were injected in female BALB/c mice followed by immediate electroporation to induce a GD + GO model. Grouping was performed according to the frequency of injection (2- to 4-week intervals) and type of injected plasmids: T: pcDNA3.1/TSHR-289( +), I: pcDNA3.1/IGF-1Rα( +), or co-injection T + I: pcDNA3.1/TSHR-289( +) and pcDNA3.1/IGF-1Rα( +). Serum TSH, T4, TSAb, TSBAb, body weight, and blood glucose levels were evaluated. Thyroid 99mTcO4- imaging and retrobulbar magnetic resonance imaging (MRI) were performed, and bilateral eye muscle volumes were measured. Immunohistochemistry and hematoxylin-eosin staining were performed on the relevant tissues, and semi-quantitative analysis was performed. RESULTS: A total of 60% of mice (3/5, one mouse died) in the T group developed GD + GO. In the T + I group, 83.3% of mice (5/6) developed GD + GO. Mice in the I group did not develop GD. Compared with the control group, serum T4, TSAb, and TSBAb of the mice in the GD + GO model groups were increased to varying degrees (P < 0.05), and serum TSH and body weight were significantly lower compared to the control group (P < 0.05). The thyroid uptake capacity of 99mTcO4- and the volume of eye muscle of mice in the GD + GO group were significantly higher compared to the control group (P < 0.05). The thyroid and retrobulbar muscles of these mice showed varying inflammatory infiltration and interstitial muscle edema. The severity of GD + GO in the co-injection group was not related to injection frequency; however, GD and ocular signs in co-injection mice were more severe compared to the T group. CONCLUSIONS: We successfully induced a GD + GO mouse model by a repeated co-injection of pcDNA3.1/IGF-1Rα and pcDNA3.1/TSHR-289 plasmids. Injection of pcDNA3.1/IGF-1Rα alone failed to induce GD. Co-injection of two plasmids induced more severe GD + GO than pcDNA3.1/TSHR-289( +) alone.

The association between computed tomography-based osteosarcopenia and osteoporotic vertebral fractures: a longitudinal study.

PURPOSE: Osteoporosis and sarcopenia usually coexist in older population. The concept of osteosarcopenia has been proposed in recent years. However, studies on the relationship between osteosarcopenia and the risk of fracture are rare, and the association is unclear at present. This study aimed to investigate the association between osteosarcopenia evaluated based on chest computed tomography (CT) and osteoporotic vertebral fracture (OVF). METHODS: This study recruited 7906 individuals aged 50 years and older who did not have OVFs and underwent chest CT for physical examination between July 2016 and September 2019. Subjects were followed up annually until June 2023. Osteosarcopenia was defined by a low muscle area of the erector spinae (< 25.4 cm2) and the bone attenuation (Hounsfield unit, HU < 135). Genant's grades were used to define OVFs. Control subjects were selected by Propensity Score Matching at a ratio 20:1. Cox proportional hazards models were used to assess the associations between osteosarcopenia and OVFs. RESULTS: Of the 7906 participants included, 95 had a new OVF within a median follow-up of 3 years. A total of 1900 control subjects were matched. Individuals in the osteosarcopenia group had a higher prevalence of spinal fractures than those in normal group (16.4% vs. 0.4%, P < 0.001). Osteosarcopenia was independently associated with OVF (adjusted hazard ratio (aHR): 12.67, 95% confidence interval (CI) 3.79-42.40) and severe OVF (aHR = 14.07, 95% CI 1.84-107.66). Similar trends were observed in males, females and those subjects aged older than 60 years. Osteosarcopenia had good predictive efficacy for OVF (area under the curve = 0.836). A nomogram was also developed for clinical application. CONCLUSION: Osteosarcopenia assessed based on chest CT was associated with OVF, and osteosarcopenia has good performance for vertebral fracture prediction.

Testosterone promotes the migration, invasion and EMT process of papillary thyroid carcinoma by up-regulating Tnnt1.

PURPOSE: To explore the key genes and molecular pathways in the progression of thyroid papillary carcinoma (PTC) promoted by testosterone using RNA-sequencing technology, and to provide new drug targets for improving the therapeutic effect of PTC. METHODS: Orchiectomy (ORX) was carried out to construct ORX mouse models. TPC-1 cells were subcutaneously injected for PTC formation in mice, and the tumor tissues were collected for RNA-seq. The key genes were screened by bioinformatics technology. Tnnt1 expression in PTC cells was knocked down or overexpressed by transfection. Cell counting kit-8 (CCK-8), colony formation assay, scratch assay and transwell assay were adopted, respectively, for the detection of cell proliferation, colony formation, migration and invasion. Besides, quantification real-time polymerase chain reaction (qRT-PCR) and western blot were utilized to determine the mRNA and protein expression levels of genes in tissues or cells. RESULTS: Both estradiol and testosterone promoted the growth of PTC xenografts. The key gene Tnnt1 was screened and obtained by bioinformatics technology. Functional analysis revealed that overexpression of Tnnt1 could markedly promote the proliferation, colony formation, migration, invasion, and epithelial-to-mesenchymal transition (EMT) process of PTC cells, as well as could activate p38/JNK pathway. In addition, si-Tnt1 was able to inhibit the cancer-promoting effect of testosterone. CONCLUSION: Based on the outcomes of bioinformatics and basic experiments, it is found that testosterone can promote malignant behaviors such as growth, migration, invasion and EMT process of PTC by up-regulating Tnnt1 expression. In addition, the function of testosterone may be achieved by activating p38/JNK signaling pathway.

Sodium fluoride-induced autophagy of ameloblast-like cells via the p-ULk1/ATG13/LC3B pathway in vitro.

OBJECTIVE: To investigate the effects of sodium fluoride on the ameloblast and reveal the mechanism of dental fluorosis. MATERIALS AND METHODS: Mouse ameloblast-like cell line (ALC) cells were treated with various concentrations of NaF, and subjected to Incucyte, fluorescence immunoassay, transmission electron microscopy, reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blot for autophagy examination, alkaline phosphatase and alizarin red staining for mineralization after osteogenic induction. RESULTS: NaF exerts a dose-dependent inhibitory effect on ALC cell growth. TEM and fluorescence immunoassay showed that 1.5 mM or higher concentrations of NaF could induce a fusion of lysosome and mitochondria, finally increasing the number of autophagosome. RT-qPCR and western blot showed that the upregulation of autophagy related gene 13 (ATG13), downregulation of phosphorylated Unc-51-like kinase 1 (p-ULK1) were found in NaF-induced autophagy of ALC cells. The knockdown of ATG13 could rescue it as well as the expression of p-ULK1 and LC3B. Besides, alizarin red staining showed that fluoride under these concentrations could promote the mineralization of ALC. CONCLUSIONS: The data show that fluoride in higher concentration can induce autophagy via the p-ULk1/ATG13/LC3B pathway of ALCs than lower ones promote mineralization in vitro, which provides insight into the function of NaF in the autophagy and mineralization of ameloblast.

Retinoids in the treatment of photoageing: A histological study of topical retinoid efficacy in black skin.

BACKGROUND: Photoageing describes complex cutaneous changes that occur due to chronic exposure to solar ultraviolet radiation (UVR). The 'gold standard' for the treatment of photoaged white skin is all-trans retinoic acid (ATRA); however, cosmetic retinol (ROL) has also proven efficacious. Recent work has identified that black skin is susceptible to photoageing, characterized by disintegration of fibrillin-rich microfibrils (FRMs) at the dermal-epidermal junction (DEJ). However, the impact of topical retinoids for repair of black skin has not been well investigated. OBJECTIVES: To determine the potential of retinoids to repair photoaged black skin. METHODS: An exploratory intervention study was performed using an in vivo, short-term patch test protocol. Healthy but photoaged black volunteers (>45 years) were recruited to the study, and participant extensor forearms were occluded with either 0.025% ATRA (n = 6; 4-day application due to irritancy) or ROL (12-day treatment protocol for a cosmetic) at concentrations of 0.3% (n = 6) or 1% (n = 6). Punch biopsies from occluded but untreated control sites and retinoid-treated sites were processed for histological analyses of epidermal characteristics, melanin distribution and dermal remodelling. RESULTS: Treatment with ATRA and ROL induced significant acanthosis (all p < 0.001) accompanied by a significant increase in keratinocyte proliferation (Ki67; all p < 0.01), dispersal of epidermal melanin and restoration of the FRMs at the DEJ (all p < 0.01), compared to untreated control. CONCLUSIONS: This study confirms that topical ATRA has utility for the repair of photoaged black skin and that ROL induces comparable effects on epidermal and dermal remodelling, albeit over a longer timeframe. The effects of topical retinoids on black photoaged skin are similar to those reported for white photoaged skin and suggest conserved biology in relation to repair of UVR-induced damage. Further investigation of topical retinoid efficacy in daily use is warranted for black skin.

Community Health Navigators for Cancer Screening Among Deaf, Deafblind, and Hard of Hearing Adults Who Use American Sign Language.

Deaf, deafblind, and hard of hearing (DDBHH) individuals experience barriers to accessing cancer screening, including ineffective patient-physician communication when discussing screening recommendations. For other underserved communities, culturally and linguistically aligned community health navigators (CHNs) have been shown to improve cancer screening and care. A needs assessment study was conducted to identify barriers and gather recommendations for CHN training resources. A community-based participatory needs assessment was conducted from May 2022 to June 2022 using three focus groups. Eight were cancer survivors, six advocates/navigators, and three clinicians. All questions were semi-structured and covered screening barriers, observations or personal experiences, perceived usefulness of having a CHN to promote cancer screening adherence, and training resources that may be useful to American Sign Language (ASL)-proficient CHNs, who are also culturally and linguistically aligned. Out of 20 focus group participants, seven self-identified as persons of color. Data highlighted systemic, attitudinal, communication, and personal-level barriers as recurrent themes. The most frequently cited barrier was access to training that supports the role and competencies of CHNs, followed by cultural considerations, access to cancer guidelines in ASL, dialect diversity in sign language, and the health system itself. Unaddressed barriers can contribute to health disparities, such as lower preventive cancer screening rates amongst DDBHH individuals. The next step is to translate recommendations into actionable tasks for DDBHH CHN training programs. As a result, CHNs will be well-equipped to help DDBHH individuals navigate and overcome their unique barriers to cancer screening and healthcare access.

Genetic analysis of a Kaijiang duck conservation population through genome-wide scan.

1. The Kaijiang duck is a native Chinese breed known for its excellent egg laying performance, killing-out percentage (88.57%), and disease resistance. The assessment of population genetic structure is the basis for understanding the genetics of indigenous breeds and for their protection and management.2. In this study, whole-genome sequencing was performed on 60 Kaijiang ducks to identify genetic variations and investigate the population structure. Homozygosity (ROH) analysis was conducted to assess inbreeding levels in the population.3. The study revealed a moderate level of inbreeding, indicated by an average inbreeding coefficient of 0.1043. This may impact the overall genetic diversity.4. Genomic Regions of Interest identified included 168 genomic regions exhibiting high levels of autozygosity. These regions were associated with processes including muscle growth, pigmentation, neuromodulation, and growth and reproduction.5. The significance of these pathways indicated their potential role in shaping the desirable traits of the Kaijiang duck. These findings provide insights into the genetic basis of the Kaijiang duck's desirable traits and can inform future breeding and conservation efforts.

[Clinical analysis of 10 patients with Fabry disease].

We aimed to analyze the clinical data of 10 patients (6 male and 4 female) with Fabry disease (FD). The mean age of the patients was (28.80±9.27) years. Seven patients had classical FD and three had delayed onset FD. Among the 10 patients, six had skin involvement and cutaneous angiokeratoma; five had hypohidrosis or anhidrosis; nine had intermittent neuralgia; and three had supraorbital ridge protrusion, forehead bulge, and lip thickening. Five patients had proteinuria, including one with chronic kidney disease stage 3 and one with chronic kidney disease stage 5. Cardiac involvement occurred in three patients, two had myocardial hypertrophy and one had valvular insufficiency. The activity of galactosidase decreased in seven patients (2.80-1.55 µmol·L-1·h-1). Plasma deacetyl-GL-3 was elevated in all 10 patients(3.12-120.00 ng/ml). Three patients underwent renal biopsy, wherein two cases of focal segmental glomerulosclerosis and one of mesangial proliferative glomerulonephritis was found. A large number of myeloid and zebra bodies were found in the podocytes in three patients, including a small number of myeloid and zebra bodies in the renal tubular epithelial cells in one patient with occasional zebra bodies in the renal interstitium. Nine patients had GLA gene mutations. One patient was c.102T>A, a de novo mutation. Four patients were treated with agalsidase α injection (0.2 mg/kg, intravenous infusion every 2 weeks), and their prognosis was good. FD has various clinical manifestations and multi-system involvement, which requires multidisciplinary cooperation. Detection of galactosidase activity, plasma globotriaosylsphingosine, and GLA gene mutation can help for accurate diagnosis.

[Analysis of the efficacy and safety of pulsed radiofrequency for the treatment of thoracic postherpetic neuralgia in elderly patients with different pain phenotypes].

Objective: To analyze the efficacy and safety of pulsed radiofrequency (PRF) for the treatment of thoracic postherpetic neuralgia (PHN) in elderly patients with different pain phenotypes. Methods: A total of 201 elderly thoracic PHN patients, including 110 males and 91 females aged (72.2±6.9) years who received high-voltage, long-duration PRF at the dorsal root ganglion at Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine from January 2020 to December 2022, were retrospectively included. The neuropathic pain symptom inventory (NPSI) was used to evaluate the five different pain phenotypes, which included superficial spontaneous pain, deep spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dysesthesia, and to analyze the distribution of the five pain phenotypes. The numerical rating scale (NRS) and NPSI scores of all patients were compared before treatment and three months after treatment to evaluate the efficacy and safety of PRF for different pain phenotypes and pain phenotype combinations. Results: All patients had two or more pain phenotypes, and 50.2% (101/201) of the patients had five pain phenotypes at the same time. Compared with those before treatment, three months after treatment, the NPSI scores for superficial spontaneous pain, deep spontaneous pain, paroxysmal pain, evoked pain and paresthesia/dysesthesia decreased (all P<0.05), and the scores decreased byï¼»M（Q1，Q3）］3.0 (2.0, 4.0), 1.5 (0.5, 2.5), 3.0 (2.5, 4.0), 2.3 (1.0, 4.0), and 1.0 (0.5, 2.0) points, respectively, the differences were statistically significant (P<0.001). The decrease in the NPSI score in patients with paroxysmal pain was greater than that in patients with the other 4 pain phenotypes (all P<0.05). After treatment, the NRS score decreased by 4.0 (3.0, 5.0), 4.0 (3.0, 5.0), 4.0 (3.0, 5.0) and 5.0 (4.0, 6.0) points in patients with 2, 3, 4 and 5 pain phenotypes, respectively, and the difference was statistically significant (P<0.001). The decrease in the NRS score was greater in patients with a combination of 5 pain phenotypes than that in patients with a combination of 3 and 4 pain phenotypes (all P<0.05). No complications, such as pneumothorax, haematoma or infection, occurred in any of the patients during treatment. Conclusion: PRF has different therapeutic effects on PHN patients with different pain phenotypes, it has the best effect on paroxysmal pain, and the treatment is safe.

[Multiple primary tumors in children: a clinicopathological analysis of four cases].

Objective: To investigate the clinicopathological features of children with metachronous or synchronous primary tumors and to identify related genetic tumor syndromes. Methods: The clinicopathological data of 4 children with multiple primary tumors diagnosed in the Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China from 2011 to 2023 were collected. The histological, immunophenotypic and molecular characteristics were examined using H&E staining, immunohistochemical staining, PCR, Sanger sequencing and next-generation sequencing (NGS). The patients were followed up. Results: Case 1 was an 8-year-old boy with the adrenal cortical carcinoma, and 5 years later a poorly differentiated gastric adenocarcinoma was detected. Case 2 was a 2-year-old boy, presented with a left ventricular choroid plexus carcinoma, and a hepatoblastoma was detected 8 months later. Case 3 was a 9-month-old girl, diagnosed with renal rhabdoid tumor first and intracranial atypical teratoid/rhabdoid tumor (AT/RT) 3 months later. Case 4 was a 7-year-old boy and had a sigmoid colon adenocarcinoma 3 years after the diagnosis of a glioblastoma. The morphology and immunohistochemical features of the metachronous or synchronous primary tumors in the 4 cases were similar to the corresponding symptom-presenting/first-diagnosed tumors. No characteristic germ line mutations were detected in cases 1 and 2 by relevant molecular detection, and the rhabdoid tumor predisposition syndrome was confirmed in case 3 using NGS. Case 4 was clearly related to constitutional mismatch repair deficiency as shown by the molecular testing and clinical features. Conclusions: Childhood multiple primary tumors are a rare disease with histological morphology and immunophenotype similar to the symptom-presenting tumors. They are either sporadic or associated with a genetic (tumor) syndrome. The development of both tumors can occur simultaneously (synchronously) or at different times (metachronously). Early identification of the children associated with genetic tumor syndromes can facilitate routine tumor screening and early treatment.

[Adrenal cortical carcinoma in children: a clinicopathological analysis of 25 cases].

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of adrenal cortical carcinoma (ACC) in children. Methods: Twenty-five children with ACC diagnosed in the Department of Pathology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from March 2014 to August 2022 were retrospectively analyzed. The related literature was reviewed. Results: A total of 25 children with ACC were collected, including 11 males and 14 females, with a male to female ratio of 1.0∶1.3. The patient ages ranged from 8 months to 14 years (median, 4 years). Eighteen cases with clinical data had functional tumors (18/22, 81.8%) presenting with virilization or precocious puberty (15/18), symptoms related to hypercortisolism (8/18) or endocrine symptoms mixed with both (5/18), while 3 cases (3/22, 13.6%) had unknown clinical data. The clinical manifestations of four patients with nonfunctional tumors were an abdominal mass and/or abdominal pain, walking instability and others. Grossly, the average maximum diameter of the tumor was 9.4 cm. Most of the tumors were nodular and partially encapsuled. The cut surfaces were gray or gray brown, soft with hemorrhage. Histologically, the tumor cells were diffusely distributed, separated by a vascular-rich network. The tumor cells were large, with distinct nucleoli, abundant eosinophilic or clear cytoplasm, and round or oval nuclei. The mitotic index was high, and atypical mitoses were common. Necrosis, calcification, capsule invasion or/and venous invasion were present. In some cases, the tumor invaded the surrounding soft tissues or kidneys. Immunohistochemically, the tumor cells were diffusely positive for syn and SF1 and focally positive for α-inhibin, Melan A and Calretinin, but negative for CgA. Ki-67 proliferation index ranged from 2%-90%. TP53 gene status was examined in 7 cases, in which mutations were detected in 4 cases. Follow-up data was obtained in 21 patients, among whom 18 received chemotherapy and 3 received radiotherapy. Distant metastasis occurred in 13 patients. Median progression-free survival (PFS) was 11.2 months and median overall survival (OS) was 54.7 months. Patients aged less than 5 years had a better prognosis for OS (P<0.05) than the older ones (≥5 years), but a similar PFS (P>0.05). Male patients and Ki-67 proliferation index <15% had a better prognosis tendency for OS, but there was no statistically significant difference (P>0.05). Conclusions: ACC in children is a rare, often functional tumor associated with Li-Fraumeni genetic syndrome and has a poor prognosis. Diagnosis and differential diagnosis require a combination of morphological, phenotypic and clinical analysis.

[An analysis of breast cancer patients with ultrasound BI-RADS 3 lesions after minimally invasive excision in clinicopathological features and influencing factors of residual tumor].

Objectives: To examine the clinicopathological characteristics and the influencing factors of the residual tumor of patients with Breast Image Report and Data System (BI-RADS) grade 3 lesions diagnosed with malignancy after minimally invasive excision. Methods: In this retrospective case-control study, clinicopathological data of 69 cases, which had been evaluated as BI-RADS 3 lesions by ultrasound (4 151 cases) diagnosed with breast cancer by minimally invasive excision pathology, were analyzed between May 2012 and June 2016 at the Department of Breast Surgery of the Second Hospital of Shandong University and Linyi People's Hospital. All patients were female, aged (43.4±8.2) years (range: 22 to 70 years). Based on residual tumor after minimally invasive excision, patients were classified into two subgroups: tumor residual group (n=39) and non-tumor residual group (n=30). The clinicopathological features between the two groups were compared. The differences in clinicopathological characteristics were compared in different groups using the χ2 test and the t test. Potential variables identified in the univariate analysis and other relevant variables will be analyzed multivarially using Logistic regression models. The Kaplan-Meier method was applied for survival analysis and survival curves. Results: The breast cancer detection rate of ultrasound BI-RADS 3 lesions was 1.66% (69/4 151), and their maximum diameter of the masses was (1.27±0.45) cm (range: 0.5 to 2.3 cm). Among them, the maximum diameter were ≤1 cm in 28 cases and >1 cm in 41 cases. Histopathological results showed carcinoma in situ in 24 cases and invasive carcinoma in 41 cases, positive expression of the estrogen receptor in 47 cases, positive expression of the progesterone receptor in 43 cases, Ki-67 proliferation index elevated in 26 cases. Axillary metastasis positive rate was 10.1% (7/69). Residual tumor after minimally invasive surgery was found in 39 cases (56.5%). Univariate analysis showed that the tumour residual group showed a significantly increased rate of positive expression of the estrogen receptor (91.9%(34/37) vs. 61.9%(13/21), χ2=7.838, P=0.012). In multivariate analysis, the only variable found to significantly affect the residual tumor was the positive expression of the estrogen receptor (OR=16.852, 95%CI: 1.819 to 156.130, P=0.013). The 5-year disease-free survival rate of breast cancer patients with breast ultrasound BI-RADS 3 lesions was 97.1% and the overall survival rate was 98.6%. Conclusions: BI-RADS 3 lesions diagnosed by ultrasound undergoing ultrasound-guided minimally invasive excision have a certain risk of detected malignancy, approximately 1.66%. Patients with positive expression of the estrogen receptor are more likely to develop residual tumor. A secondary operation should be considered to ensure that no tumor residues remain in the cavity.

[Wolfram-like syndrome: a case report].

Different from classical autosomal recessive Wolfram syndrome, Wolfram-like syndrome is an autosomal dominant disorder caused by a heterozygous mutation in the WFS1 gene. In this case, a 7-year-old male child presented to the eye clinic due to vision loss that could not be corrected, discovered during a routine examination. The child had experienced hearing impairment since early childhood, leading to cochlear implantation. Ophthalmic examination revealed optic disc atrophy in both eyes. Optical coherence tomography imaging demonstrated a distinctive thickening of the outer plexiform layer with abnormal layering, characteristic of a single mutation in the WFS1 gene. Subsequent genetic testing identified a de novo heterozygous missense mutation c.2051C>T (p.A684V) in the WFS1 gene, which ultimately led to the diagnosis of Wolfram-like syndrome.