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Abstract Background Somatic mutations have been observed to induce aldosterone-producing adenomas (APAs). These may be accelerated during pregnancy. Somatic PRKACA mutations are common in cortisol-producing adenomas (CPAs). However, their role in APAs, particularly aldosterone- and cortisol-producing adenomas (A/CPAs), is not well understood. This study aims to investigate the association between PRKACA mutations and the accelerated development of A/CPAs during pregnancy. Case presentation A patient with primary aldosteronism (PA) associated with severe Cushing’s syndrome (CS) underwent surgical resection of an adrenal tumor one year after delivery. Pathologic examination revealed an adrenocortical adenoma characterized primarily by zona glomerulosa hyperplasia. Somatic mutation analysis revealed the presence of the somatic PRKACA mutation, which was validated as a deleterious mutation by various computational databases. Immunohistochemical results showed positive staining for cytochrome P450 family 11 subfamily B member 1 (CYP11B1), cytochrome P450 family 11 subfamily B member 2 (CYP11B2), and luteinizing hormone/chorionic gonadotropin receptor (LHCGR). Our study included a review of 20 previously documented cases of aldosterone- and cortisol-producing adenomas (A/CPAs), two of which were concurrently positive for both CYP11B1 and CYP11B2, consistent with our findings. Conclusion Somatic mutations in PRKACA may correlate with the upregulation of LHCGR, which synergistically drives the accelerated growth of co-secretion tumors during pregnancy, thereby exacerbating disease progression.

Abstract Background Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder characterized by impaired glucose and galactose utilization as well as proximal renal tubular dysfunction. Methods Clinical, biochemical, genetic, treatment, and follow-up data for 11 pediatric patients with FBS were retrospectively analysed. Results Hepatomegaly (10/11), short stature (10/11) and hypophosphataemic rickets (7/11) were the most common initial symptoms. At diagnosis, all patients had decreased fasting blood glucose (FBG), plasma bicarbonate (HCO3 −) and serum phosphorus, as well as elevated liver transaminases, alkaline phosphatase (AKP) and proximal renal tubular dysfunction. Two infant patients were misdiagnosed with transient neonatal diabetes mellitus. After therapy with uncooked cornstarch and conventional rickets treatment, remission of hepatomegaly was observed in all patients, with significant improvements in pre-prandial blood glucose, liver transaminases, triglyceride, plasma HCO3 − and AKP (p G (p.L406R) (allele frequency: 4/22, 18%). Patients with biallelic missense variants showed milder metabolic acidosis than those with null variants. Two of five patients from nonconsanguineous families with rare homozygous variations showed 5.3 Mb and 36.6 Mb of homozygosity surrounding the variants, respectively; a region of homozygosity (ROH) involving the entire chromosome 3 covering the SLC2A2 gene, suggesting uniparental disomy 3, was detected in one patient. Conclusions Early diagnosis of FBS is difficult due to the heterogeneity of initial symptoms. Although short stature is a major issue of treatment for FBS, rhGH is not recommended in FBS patients who have normal GH stimulation tests. Patients with biallelic null variants may require alkali supplementation since urine bicarbonate loss is genetically related. ROH is a mechanism for rare homozygous variants of FBS in nonconsanguineous families.

Objective To evaluate the effectiveness of oral probiotic supplements in patients undergoing immune checkpoint inhibitors (ICIs) for the treatment of advanced lung cancer. Methods This prospective real-world study enrolled patients with advanced lung cancer who were receiving ICIs as part of their treatment. The patients were divided into 2 groups: Group OPS received oral probiotic supplements along with ICIs, while Group C did not. The primary endpoint was progression-free survival (PFS). The secondary outcome measure was the objective response rate (ORR). Results A total of 253 patients were included in the study, with 71 patients in Group OPS and 182 patients in the control group (Group C). No significant differences were observed in the median PFS between the 2 groups for all patients. However, for small cell lung cancer (SCLC) patients, the median PFS was significantly better in the Group OPS compared to the Group C (11.1 months vs 7.0 months, P = .049). No significant differences were observed in median PFS for the non-small cell lung cancer (NSCLC) cohort between the 2 groups, but a trend towards better median PFS in Group OPS was noticed (16.5 months vs 12.3 months, P = .56). The ORR for the entire cohort was 58.0%. Conclusion Oral probiotics supplements in combination with ICIs included regimen may improve the outcome in patients with advanced SCLC. The above points should be proved by further study.

Abstract Background X-linked adrenal hypoplasia congenita (AHC) is a rare disorder characterized by primary adrenal insufficiency (PAI) and hypogonadotropic hypogonadism (HH), with limited clinical and genetic characterization. Methods The clinical, biochemical, genetic, therapeutic, and follow-up data of 42 patients diagnosed with X-linked AHC were retrospectively analysed. Results Hyperpigmentation (38/42, 90%), vomiting/diarrhoea (20/42, 48%), failure to thrive (13/42, 31%), and convulsions (7/42, 17%) were the most common symptoms of X-linked AHC at onset. Increased adrenocorticotropic hormone (ACTH) (42/42, 100%) and decreased cortisol (37/42, 88%) were the most common laboratory findings, followed by hyponatremia (32/42, 76%) and hyperkalaemia (29/42, 69%). Thirty-one patients presented with PAI within the first year of life, and 11 presented after three years of age. Three of the thirteen patients over the age of 14 exhibited spontaneous pubertal development, and ten of them experienced delayed puberty due to HH. Six patients receiving human chorionic gonadotropin (hCG) therapy exhibited a slight increase in testicular size and had rising testosterone levels (both P

Abstract Background This study aimed to describe the clinical, biochemical, and molecular characteristics of Chinese patients with holocarboxylase synthetase (HLCS) deficiency, and to investigate the mutation spectrum of HCLS deficiency as well as their potential correlation with phenotype. Methods A total of 28 patients with HLCS deficiency were enrolled between 2006 and 2021. Clinical and laboratory data were reviewed retrospectively from medical records. Results Among the 28 patients, six patients underwent newborn screening, of which only one was missed. Therefore, 23 patients were diagnosed because of disease onset. Among all the patients, 24 showed varying degrees of symptoms such as rash, vomiting, seizures, and drowsiness, while only four cases remained asymptomatic nowadays. The concentration of 3-hydroxyisovalerylcarnitine (C5-OH) in blood and pyruvate, 3-hydroxypropionate, methylcitric acid, 3-hydroxyvaleric acid, 3-methylcrotonylglycine in urine were increased greatly among affected individuals. After prompt supplement of biotin, both the clinical and biochemical symptoms were dramatically resolved and nearly all patients developed normal intelligence and physique on follow-up. DNA sequencing revealed 12 known and 6 novel variants in the HLCS gene of patients. Among them, the variant of c.1522C > T was the most common. Conclusions Our findings expanded the spectrum of phenotypes and genotypes for HLCS deficiency in Chinese populations and suggested that with timely biotin therapy, patients with HLCS deficiency showed low mortality and optimistic prognosis. Newborn screening is crucial for early diagnosis, treatment, and long-term outcomes.

Chicken feathers represent a viable material for producing biochar adsorbents. Traditional slow pyrolysis methods often result in sulfur element losses from chicken feathers, whereas hydrothermal reactions generate substantial amounts of nutrient-rich hydrothermal liquor. Magnesium-modified high-sulfur hydrochar MWF was synthesized through magnesium modification, achieving a S content of 3.68%. The maximum equilibrium adsorption amounts of MWF for Cd2+ and Pb2+ were 25.12 mg·g−1 and 70.41 mg·g−1, respectively, representing 4.00 times and 2.75 times of WF. Magnesium modification elevated the sulfur content, pH, ash content, and electronegativity of MWF. The primary mechanisms behind MWF’s adsorption of Cd2+ and Pb2+ involve magnesium ion exchange and complexation with C=O/O=C–O, quaternary N, and S functional groups. MWF maintains robust stability and antioxidative properties, even with low aromaticity levels. Given the lower energy consumption during hydrochar production, MWF offers notable carbon sequestration benefits. The hydrothermal solution derived from MWF is nutrient-rich. Following supplementation with inorganic fertilizer, the hydrothermal solution of MWF significantly enhanced bok choy growth compared to the control group. In general, adopting magnesium-modified hydrothermal reactions to produce hydrochar and converting the resultant hydrothermal solution into water-soluble fertilizer proves a viable strategy for the eco-friendly utilization of chicken feathers. This approach carries substantial value for heavy metal remediation and agricultural practices.

Intestinal mucositis (IM) is a common adverse effect of chemotherapy, limiting its clinical application. Codonopsis pilosula-derived CP-A (an inulin-type fructan) is an edible Chinese medicine with anti-inflammatory and gastrointestinal protective effects, which may be useful for treating IM. Here, we explored CP-A’s role in ameliorating IM induced by 5-fluorouracil (5-FU) and investigated the underlying mechanism using in vitro experiments and rat models. Western blotting, immunohistochemistry (IHC), and real-time PCR (RT-PCR) analyses were used to assess protein expression related to the extracellular-regulated protein kinases (ERK)/myosin light chain kinase (MLCK)/myosin light chain 2 (MLC2) signaling pathway and tight junction proteins. Inflammatory factors were quantified using enzyme-linked immunosorbent assays (ELISAs), and 16S rRNA amplicon sequencing was employed for cecum content analysis. The results indicated that CP-A restored body weight and food intake and reversed histopathological changes in IM rats. Further, abnormal MLCK activation induced by 5-FU was attenuated by CP-A via the ERK/MLCK/MLC2 pathway. CP-A treatment improved tight junction protein levels and reduced inflammatory factor expression. Moreover, CP-A intervention regulated the intestinal microbiota community structure, increasing the abundance of Lactobacillus and decreasing the abundance of Shigella. In conclusion, CP-A mitigates 5-FU-induced IM by inhibiting the ERK/MLCK/MLC2 pathway, reducing the expression of inflammatory factors, improving the intestinal mucosal barrier, and regulating the intestinal microbial community. This study highlights CP-A’s therapeutic potential in IM treatment and provides insights for future research.

Argillaceous limestone (AL) is comprised of carbonate minerals and clay minerals and is widely distributed throughout the Earth’s crust. However, owing to its low surface area and poorly active sites, AL has been largely neglected. Herein, manganic manganous oxide (Mn3O4) was used to modify AL by an in-situ deposition strategy through manganese chloride and alkali stepwise treatment to improve the surface area of AL and enable its utilization as an efficient adsorbent for heavy metals removal. The surface area and cation exchange capacity (CEC) were enhanced from 3.49 to 24.5 m2/g and 5.87 to 31.5 cmoL(+)/kg with modification, respectively. The maximum adsorption capacities of lead (Pb2+), copper (Cu2+), and nickel (Ni2+) ions on Mn3O4-modified argillaceous limestone (Mn3O4–AL) in mono-metal systems were 148.73, 41.30, and 60.87 mg/g, respectively. In addition, the adsorption selectivity in multi-metal systems was Pb2+ > Cu2+ > Ni2+ in order. The adsorption process conforms to the pseudo-second-order model. In the multi-metal system, the adsorption reaches equilibrium at about 360 min. The adsorption mechanisms may involve ion exchange, precipitation, electrostatic interaction, and complexation by hydroxyl groups. These results demonstrate that Mn3O4 modification realized argillaceous limestone resourcization as an ideal adsorbent. Mn3O4-modified argillaceous limestone was promising for heavy metal-polluted water and soil treatment.

Abstract While self‐driving cars have already been widely investigated and achieved spectacular progress, a major obstacle in applications is the great difficulty in providing formal guarantees about their behaviors. Since the environment of the self‐driving is usually not known beforehand and highly uncertain, classical verification approaches cannot be applied to guarantee safety. To cope with any traffic situation, a novel online verification framework is presented for verifying behavioral safety of self‐driving cars. The framework is based on the proposed five safety considerations: new longitudinal and lateral safe distances, lane changes, overtaking and how to face new traffic participants. Different from the previous verification considerations, this verification framework allows actual behaviors of self‐driving cars to be temporarily inconsistent with the popular strict safe distance. As long as the self‐driving car respects the minimum safe distance calculated by our technique and executes improvement behaviors to restore the safe distance, it is still believed that the predictive behavior is safe. The framework can easily be integrated to existing self‐driving systems and evaluate different indicators involving the steering angle, acceleration and braking. The benefits of the framework in different urban scenarios of the CARLA simulator and real traffic data provided by the NGSIM project are demonstrated. Results show that the technology can successfully detect unsafe behaviors and provide effective measures to avoid potential collisions.

Background: Primary carnitine deficiency (PCD) is an autosomal recessive disease caused by mutations in the SLC22A5 gene, which encodes the organic cation transporter 2 (OCTN2). Patients with PCD may be at risk of skeletal or cardiac myopathy, metabolic decompensation, and even sudden death. This study aimed to analyze the biochemical, clinical, and genetic characteristics of PCD patients identified by newborn screening (NBS) in Shanghai.Methods: Dried blood spot (DBS) samples of newborns were analyzed through tandem mass spectrometry (MS/MS) from January 2003 to December 2021. Newborns with low free carnitine (C0) levels were recalled. Mutation in the SLC22A5 gene was analyzed on suspected positive newborns with low C0 levels after recall.Results: 1,247,274 newborns were screened by MS/MS and 40 newborns were diagnosed with PCD, therefore the incidence of PCD in Shanghai was approximately 1:31,200. The mean C0 level in newborns with PCD was 5.37 ± 1.79 μmol/L before treatment and increased to 24.45 ± 10.87 μmol/L after treatment with L-carnitine. Twenty-three different variants were identified in the SLC22A5 gene, including 8 novel variants, of which c.51C>G (p.F17L) was the most frequent (27.27%, 18/66), followed by c.1400C>G (p.S467C) (25.76%, 17/66). Almost all the screened PCD patients were asymptomatic.Conclusion: NBS via MS/MS was a quick and efficient method for the early diagnosis of PCD. The incidence of PCD in Shanghai was 1:31,200. Eight novel variants were identified, which greatly expanded the variant spectrum of SLC22A5. MS/MS combined with genetic testing could effectively improve the diagnostic accuracy of PCD.

The purpose of this work is to study the effect of charging conditions on hydrogen damage. The effects of electrochemical hydrogen charging current density and time on hydrogen-induced blistering (HIB), cracking behavior, and mechanical properties of Q690 steel are studied by electrochemical hydrogen charging, microstructure observation, and slow strain rate tensile (SSRT) tests. The results show that HIB and internal cracks occur when the Q690 steel is charged at different current densities. The charging conditions have a significant effect on the HIB characteristics of the material and the morphology, number, size, and location of internal cracks. The geometrical parameters of blisters on the surface of Q690 steel are quantitatively evaluated, and deeper cracks are found at higher hydrogen concentrations. At high hydrogen charging current density (50 mA/cm2), due to the accumulation of a large number of hydrogen atoms and the precipitation of hydrogen, the active sites on Q690 steel surface increase dramatically, leading to the initiation of a large number of blisters. At this time, high current density is responsible for the initiation of blisters. The relationship between hydrogen charging current density and mechanical properties of Q690 steel is studied, and the change in the fracture morphology is observed. The Q690 steel was damaged and failed due to an internal crack caused by excessive hydrogen pressure. On the other hand, electrochemical hydrogen charging leads to the degradation of mechanical properties and the transition from ductile fracture to brittle fracture.

Objective: Polyethylene glycol recombinant human growth hormone (PEG-rhGH, Jintrolong®) is the first long-acting rhGH preparation that is approved to treat children with growth hormone deficiency (GHD) in China. Clinical experience with dose selections of PEG-rhGH is scarce. The present study compared the efficacy and safety of a lower dose to increase dosing regimens of PEG-rhGH treatment.Methods: A multicenter, randomized, open-label, dose-comparison clinical study was conducted to compare the improvements in the height standard deviation score (Ht SDS), height velocity (HV), insulin-like growth factor-1 (IGF-1) SDS, and safety profiles of children with GHD who are treated with 0.2 mg/kg/week of PEG-rhGH dose or 0.14 mg/kg/week for 26 weeks.Results: Ht SDS, HV, and IGF-1 SDS increased significantly after PEG-rhGH treatment in the two dose groups (p < 0.05). The improvements of Ht SDS, HV, and IGF-1 SDS were more significant in the high-dose group than in the low-dose group (p < 0.05). Ht SDS improvement in low-dose group was not non-inferiority to that in the high-dose group (p = 0.2987). The incidences of adverse events were comparable between the two groups.Conclusion: The improvements of Ht SDS, HV, and IGF-1 SDS were more significant in the high-dose group than in the low-dose group (p < 0.05). PEG-rhGH at the dose of 0.14 mg/kg/week was effective and safe for children with GHD.Clinical Trial Registration:clinicaltrials.gov, identifier NCT02908958.

Abstract Background The unclear mechanisms and severity of injuries in the injury pyramids for Chinese children and adolescents prevent the prioritization of interventions. This study aimed to describe the injury mechanisms and injury pyramids in this population to provide a priority for injury prevention strategies. Methods Death, hospitalization, and outpatient/emergency department visit data from patients aged 0 ~ 17 years with injuries were obtained from January 1, 2013, to December 31, 2017, in Zhuhai City, China. The injury mechanism ratios were calculated, and the injury pyramid ratios were drawn in proportion using injury mortality and the incidence of both injury hospitalizations and outpatient/emergency department injury visits. Results The top three mechanisms for injuries in children and adolescents treated in outpatient/emergency departments were falls (52.02%), animal bites (14.57%), and blunt injuries (10.60%). The top three mechanisms for injury hospitalizations were falls (37.33%), road traffic injuries (17.87%), and fire/burns (14.29%), while the top three mechanisms for injury deaths were drowning (32.91%), road traffic injuries (20.25%) and falls (13.92%). The incidence rate of outpatient/emergency department injury visits for children and adolescents was 11,210.87/100,000; the incidence rate of injury hospitalization was 627.09/100,000, and the injury death rate was 10.70/100,000. For each injury death, there were 59 injury hospitalizations and 1048 outpatient/emergency injury visits. Conclusions The injury mechanisms were different for injury-related outpatient/emergency department visits, hospitalizations, and deaths among children and adolescents. The injury mechanisms by sex at different stages of child development, and interventions should be formulated based on this finding. The ratios of the injury pyramids varied by age, sex, region, and injury mechanisms; minor nonfatal injuries were more common in children and adolescents. The differences in the severity and extent of the injuries suggested that injury interventions in children and adolescents still have a long way to go.

Abstract Background Methylmalonic acidemia is an inherited organic acid metabolic disease. It involves multiple physiological systems and has variable manifestations. The primary causative gene MMUT carries wide range of mutations, and one of them, c.1663G > A (p.A555T), is considered to be a rare type, which is seen more frequently in Asian than other populations. So far, little is known about the clinical features of patients carrying this mutation. In the present study, we aimed to define the clinical and biochemical features of the patients with this genotype. Methods Among 328 mut type methylmalonic acidemia patients from multiple hospitals in China, we collected 30 compound heterozygous patients sharing the mutation c.1663G > A (p.A555T) in the MMUT gene. Their clinical characteristics and biochemical index were described in detail and compared with methylmalonic acidemia patients without this variant. Results Most of these patients were diagnosed via newborn screening (26/30), treated in a timely manner, and kept healthy (24/30). Disease onset occurred in 7 patients. Developmental delay or intellectual impairment occurred in 4 patients. 100% of these patients (29/29) were responsive to Vitamin B12 administration. The blood propionylcarnitine, blood propionylcarnitine/acetylcarnitine ratio, urinary methylmalonic acid, urinary methylcitric acid before and after treatment in c.1663G > A (p.A555T) carrying patients were much lower than those in non-c.1663G > A (p.A555T) carrying patients. Conclusion Compared to patients with other mutations in the MMUT gene, patients with the c.1663G > A (p.A555T) mutation showed later onset, milder clinical phenotype, lighter biochemical abnormalities, better vitamin B12 responsiveness, lower morbidity, easier metabolic control, and thereby better prognosis. Newborn screening project plays an important role in early diagnosis, treatment, and prognosis of these patients.

Abstract Background This study aimed to describe the clinical and biochemical features of Chinese patients with ornithine transcarbamylase deficiency (OTCD), and to investigate the mutation spectrum of OTC gene and their potential correlation with phenotype. Methods Sixty-nine patients with OTCD were enrolled between 2004 and 2019. Clinical and laboratory data were reviewed retrospectively from medical records. Results Fifteen cases (13 males, 2 females) presented with early onset; 53 cases (21 males, 32 females) had late onset, and one female was asymptomatic. The median onset age was 1.5 years (range 1 day–56 years). Urine orotic acid levels were increased in all patients tested, while only 47.6% of patients showed decreased serum levels of citrulline. The peak plasma ammonia levels were higher in early-onset patients than in late-onset patients (P

Background: The patterns and risk factors of intentional injuries compared to unintentional injuries among Chinese children and adolescents have not been examined in depth. This work comprehensively describes patterns of intentional injuries in China, for which little information has been previously published. Methods: All cases involving individuals 0–17 years old registered at emergency rooms and outpatient clinics were examined using data submitted to the National Injury Surveillance System from 2006 through 2017. A logistic regression model was performed to explore the risk factors related to intentional injuries compared to unintentional injuries. Results: A total of 81,459 (95.1%) unintentional injuries, 4,218 (4.9%) intentional injuries (4,013 violent attacks and 205 self-mutilation/suicide) cases were identified. Blunt injuries accounted for 59.4% of violent attacks, while cuts and poisoning accounted for 37.1% and 23.4% of injuries involving self-mutilation/suicide, respectively. For unintentional injuries, falls (50.4%) ranked first. Additional risk factors for intentional injuries included being male (odds ratio [OR] 1.6), coming from rural areas (OR 1.9), being staff or workers (OR 2.2), and being a student (OR 1.8). As the age of the patients increased, so did the risk of intentional injuries (OR 5.0 in the 15–17 age group). Intentional injuries were more likely to occur at 00:00–03:00 am (OR 2.0). Conclusions: Intentional injuries affected more males, rural and older children, school students, and staff or workers. The mechanisms and occurrence times differed according to age group. Preventive measures should be taken to reduce the dropout of rural students, strengthen the school’s violence prevention plan, and reduce self-harm.

Mucopolysaccharidosis is a rare disease and can be divided into seven different subtypes, according to the affected enzyme. Mucopolysaccharidosis type I, the first subtype discovered and reported, mainly affects the in vivo storage of degraded sugar. The current treatment methods are symptomatic therapy, enzyme replacement therapy, and allogeneic hematopoietic stem cell transplantation. In China, the enzyme for the treatment of mucopolysaccharidosis type I was approved in June 2020. We report a case of an 18-month-old Chinese boy with mucopolysaccharidosis type I who received enzyme replacement therapy with concentrated laronidase solution. This is the second case of the disease in China, and the first case of a child under 2 years of age. Following the therapy, urine mucopolysaccharide particle levels were significantly lower, and the patient's symptoms improved. The medical records of Chinese patients who have been treated with enzyme replacement therapy for mucopolysaccharidosis type I also showed similar results. This case demonstrated that enzyme replacement therapy is a safe and effective treatment for patients with mucopolysaccharidosis type I.

Abstract Background To evaluate the prognostic value of pretreatment lymphocyte counts with respect to clinical outcomes in patients with solid tumors. Methods Systematic literature search of electronic databases (Pubmed, Embase and Web of Science) up to May 1, 2018 was carried out by two independent reviewers. We included Eligible studies assessed the prognostic impact of pretreatment lymphocytes and had reported hazard ratios (HR) with 95% confidence intervals (CIs) for endpoints including overall survival (OS) and progression-free survival (PFS). Only English publications were included. Results A total of 42 studies comprising 13,272 patients were included in this systematic review and meta-analysis. Low pretreatment lymphocyte count was associated with poor OS (HR = 1.27, 95% CI 1.16–1.39, P

Small celestial bodies contain abundant scientific information to understand the origin and evolution of the solar system. The acquisition and analysis of regolith sample is the most direct and effective way to explore the geological construction of poorly known asteroids as remnants of earlier existed planetesimals. China is gradually promoting extraterrestrial regolith sampling technology from asteroids or comets nowadays. To obtain surface regolith from ultralow-gravity asteroids, a novel gas-driven regolith-sampling strategy is proposed, and a prototype was designed and fabricated for experimental validation. In this method, an ultrasonic percussive drill with low-reaction force is designed to break surface regolith to fine particles, and sample mobilization and collection is implemented through highly pressurized gas. Fluid-solid coupling simulation was conducted to evaluate regolith-sampling performance under normal- and micro- gravity conditions. Preliminary experiments, both in room and vacuum conditions, showed that the proposed strategy has good geological adaptability and sample-acquiring ability. This method can provide important technical supports for China's forthcoming asteroid-comet regolith-sampling exploration.

Objective: The cblC type of combined methylmalonic acidemia and homocystinuria, an inherited disorder with variable phenotypes, is included in newborn screening (NBS) programs at multiple newborn screening centers in China. The present study aimed to investigate the long-term clinical benefits of screening individual.Methods: A national, retrospective multi-center study of infants with confirmed cblC defect identified by NBS between 2004 and 2020 was conducted. We collected a large cohort of 538 patients and investigated their clinical data in detail, including disease onset, biochemical metabolites, and gene variation, and explored different factors on the prognosis.Results: The long-term outcomes of all patients were evaluated, representing 44.6% for poor outcomes. In our comparison of patients with already occurring clinical signs before treatment to asymptomatic ones, the incidence of intellectual impairment, movement disorders, ocular complications, hydrocephalus, and death were significantly different (p < 0.01). The presence of disease onset [Odd ratio (OR) 12.39, 95% CI 5.15–29.81; p = 0.000], variants of c.609G>A (OR 2.55, 95% CI 1.49–4.35; p = 0.001), and c.567dupT (OR 2.28, 95% CI 1.03–5.05; p = 0.042) were independently associated with poor outcomes, especially for neurodevelopmental deterioration.Conclusion: NBS, avoiding major disease-related events and allowing an earlier treatment initiation, appeared to have protective effects on the prognosis of infants with cblC defect.

Abstract Background To summarize the relationship between different MMUT gene mutations and the response to vitamin B12 in MMA. Methods This was a retrospective study of patients diagnosed with mut‐type MMA. All patients with mut‐type MMA were tested for responsiveness to vitamin B12. Results There were 81, 27, and 158 patients in the completely responsive, partially responsive, and nonresponsive groups, respectively, and the proportions of symptom occurrence were 30/81 (37.0%), 21/27 (77.8%), and 131/158 (82.9%), respectively (p A, c.2080C>T, c.1880A>G, c.1208G>A, etc. were completely responsive and with the mutations of c.1741C>T, c.1630_1631GG>TA, c.599T>C, etc. were partially responsive. The proportions of healthy/developmental delay outcomes in the three groups were 63.0%/23.5%, 33.3%/40.7%, and 13.3%/60.1%, respectively (p

BackgroundRenal cell carcinoma (RCC) is the most common type of kidney cancer. Studying the pathogenesis of RCC is particularly important, because it could provide a direct guide for clinical treatment. Given that tumor heterogeneity is probably reflected at the mRNA level, the study of mRNA in RCC may reveal some potential tumor-specific markers, especially single-cell RNA sequencing (scRNA-seq).MethodsWe performed an exploratory study on three pathological types of RCC with a small sample size. This study presented clear-cell RCC (ccRCC), type 2 pRCC, and chRCC in a total of 30,263 high-quality single-cell transcriptome information from three pathological types of RCC. In addition, scRNA-seq was performed on normal kidneys. Tumor characteristics were well identified by the comparison between different pathological types of RCC and normal kidneys at the scRNA level.ResultsSome new tumor-specific markers for different pathologic types of RCC, such as SPOCK1, PTGIS, REG1A, CP and SPAG4 were identified and validated. We also discovered that NDUFA4L2 both highly expressed in tumor cells of ccRCC and type 2 pRCC. The presence of two different types of endothelial cells in ccRCC and type 2 pRCC was also identified and verified. An endothelial cell in ccRCC may be associated with fibroblasts and significantly expressed fibroblast markers, such as POSTN and COL3A1. At last, by applying scRNA-seq results, the activation of drug target pathways and sensitivity to drug responses was predicted in different pathological types of RCC.ConclusionsTaken together, these findings considerably enriched the single-cell transcriptomic information for RCC, thereby providing new insights into the diagnosis and treatment of RCC.

Bilateral renal cell carcinoma (RCC) is a rare disease that can be classified as either familial or sporadic. Studying the cellular molecular characteristics of sporadic bilateral RCC is important to provide guidance for clinical treatment. Cellular molecular characteristics can be expressed at the RNA level, especially at the single-cell degree. Single-cell RNA sequencing (scRNA-seq) was performed on bilateral clear cell RCC (ccRCC). A total of 3,575 and 3,568 high-quality single-cell transcriptome data were captured from the left and right tumour tissues, respectively. Gene characteristics were identified by comparing left and right tumours at the scRNA level. The complex cellular environment of bilateral ccRCC was presented by using scRNA-seq. Single-cell transcriptomic analysis revealed high similarity in gene expression among most of the cell types of bilateral RCCs but significant differences in gene expression among different site tumour cells. Additionally, the potential biological function of different tumour cell types was determined by gene ontology (GO) analysis. The transcriptome characteristics of tumour tissues in different locations at the single-cell transcriptome level were revealed through the scRNA-seq of bilateral sporadic ccRCC. This work provides new insights into the diagnosis and treatment of bilateral RCC.

BackgroundCompared to other studies, the injury monitoring of Chinese children and adolescents has captured a low level of intentional injuries on account of self-harm/suicide and violent attacks. Intentional injuries in children and adolescents have not been apparent from the data. It is possible that there has been a misclassification of existing intentional injuries, and there is a lack of research literature on the misclassification of intentional injuries. This study aimed to discuss the feasibility of discriminating the intention of injury based on Machine Learning (ML) modelling and provided ideas for understanding whether there was a misclassification of intentional injuries.MethodsInformation entropy was used to determine the correlation between variables and the intention of injury, and Naive Bayes (NB), Decision Tree (DT), Random Forest (RF), Adaboost algorithms and Deep Neural Networks (DNN) were used to create an intention of injury discrimination model. The models were compared by comprehensively testing the discrimination effect to determine stability and consistency.ResultsFor the area under the ROC curve with different intentions of injuries, the NB model was 0.891, 0.880, and 0.897, respectively; the DT model was 0.870, 0.803, and 0.871, respectively; the RF model was 0.850, 0.809, and 0.845, respectively; the Adaboost model was 0.914, 0.846, and 0.914, respectively; the DNN model was 0.927, 0.835, and 0.934, respectively. In a comprehensive comparison of the five models, DNN and Adaboost models had higher values for the determination of the intention of injury. A discrimination of cases with unclear intentions of injury showed that on average, unintentional injuries, violent attacks, and self-harm/suicides accounted for 86.57%, 6.81%, and 6.62%, respectively.ConclusionIt was feasible to use the ML algorithm to determine the injury intention of children and adolescents. The research suggested that the DNN and Adaboost models had higher values for the determination of the intention of injury. This study could build a foundation for transforming the model into a tool for rapid diagnosis and excavating potential intentional injuries of children and adolescents by widely collecting the influencing factors, extracting the influence variables characteristically, reducing the complexity and improving the performance of the models in the future.

There are a variety of applications for asteroid simulants in asteroid studies for science advances as well as technology maturation. For specific purpose, it usually requires purpose-specialized simulant. In this study, we designed and developed a set of prototype simulants as S-type asteroid surface materials analogue based on H, L, and LL ordinary chondrites’ mineralogy and terrestrial observations of near-earth asteroid 2016 HO3, which is the Chinese sample return mission target. These simulants are able to simulate morphology and reflectance characteristics of asteroid (469219) 2016 HO3 and, thus, to be used for engineering evaluation of the optical navigation system and the sampling device of the spacecraft during the mission phase. Meanwhile, these prototype simulants are easily to modify to reflect new findings on the asteroid surface when the spacecraft makes proximate observations.

Abstract Background Aromatic L‐amino acid decarboxylase deficiency (AADCD) is a rare, autosomal recessive inherited disorder which is characterized by neurological and vegetative symptoms. To date, only 130 patients with AADCD have been reported worldwide. Methods We demonstrated 14 previously undescribed patients together with three reportedly patients in Mainland China. Full clinical information was collected, and disease‐causing variants in the DDC gene were detected. Results The common clinical manifestation of patients, including intermittent oculogyric crises, retarded movement development, and autonomic symptoms. Notably, a patient showed bone‐density loss which have not been reported and two mildly phenotype patients improved psychomotor function after being prescribed medication. The most common genotype of Mainland Chinese AADCD is the splice‐site variant (IVS6+4A> T; c.714+4A> T), which accounts for 58.8%, followed by c.1234C>T variant. Three novel compound heterozygous variants, c. 565G>T, c.170T>C, and c.1021+1G>A, were firstly reported. It is important to recognize the milder phenotypes of the disease as these patients might respond well to therapy. Besides, we discovered that patients may presented with milder if found to be compound heterozygote or homozygote for one of the following variants c.478C>G, c.853C>T, c.1123C>T, c.387G>A, and c.665T>C. Discussion The clinical data of the cohort of 17 patients in Mainland China broaden the clinical, molecular, and treatment spectrum of aromatic L‐amino acid decarboxylase deficiency.

Silver–Russell syndrome (SRS) is a rare, but well-recognized disease characterized by growth disorder. To date, there are two reports arguing IGF2 mutation for the onset of SRS. Herein, we present another sporadic case harboring IGF2 mutation. The male proband was the first and only child of a non-consanguineous Chinese couple. He was small for gestational age, with relative macrocephaly at birth. Severe feeding difficulties, low feeding, and growth retardation were revealed during neonatal period. At 4.5 years old, obvious body asymmetry was noted. Whole exome sequencing identified a novel de novo c.101G > A (p.Gly34Asp, NM_000612) variant in IGF2 and Sanger sequencing validated the variant. Amplification refractory mutation system polymerase chain reaction demonstrated that the IGF2 variant was on the paternal allele. Alignment shows the variant is evolutionarily conserved. Structural modeling argues that the variant site might be important for the binding of IGF2 to its receptor. Our study provides further evidence that IGF2 mutation may be another mechanism of SRS, and we consider that IGF2 should be included in a disease specific gene panel in case it is designed for SRS routine diagnostics.

Background and Objective Rho family is closely related with the growth , differentiation and metastasis of tumer cells. The objective of this work is to investigate the expression of RhoE in lung and breast carcinoma and their corresponding adjacent tissues, as well as its relationship between the expression and clinical pathological grades. The results of this study provide evidences for exploring the biological functions and clinical significance of RhoE. Methods The expression of RhoE was detected by immunohistochemistry in 62 lung carcinoma samples and 34 breast carcinoma samples, and their corresponding adjacent tissues were taken as control.Results RhoE was generally expressed in normal tissues, but the expression level of RhoE in carcerous tissueswas decreased or absent. The stained value of breast carcinoma was 3.65+/-0.62, but the adjacent cancerous tissueswas 10.53+/-0.44, significantly higher than that of the adjacent cancerous tissues (t=12.402, P

In the title molecule, C22H22O3, the central cyclohexanone ring adopts an envelope conformation. The two outer aromatic rings form a dihedral angle of 19.3 (2)°. The crystal packing exhibits weak intermolecular C—H...O hydrogen bonds.

In the title molecule, C20H16Cl2O, the central cyclohexanone ring adopts an envelope conformation. The two aromatic rings form a dihedral angle of 30.0 (1)°. The crystal packing exhibits weak intermolecular C—H...O hydrogen bonds and short Cl...O contacts [3.213 (3) Å].

In the title molecule, C13H16N2O2, the cyclohexylidene ring adopts a chair conformation. The intramolecular N—H...O hydrogen bond influences the molecular conformation: the benzene ring and the mean plane of the central C(O)NHN fragment form a dihedral angle of 4.9 (1) Å. In the crystal, intermolecular O—H...O hydrogen bonds link the molecules into chains propagated along [001].

Pyrroline-5-carboxylate reductase 1 (PYCR1) is an enzyme involved in cell metabolism and is upregulated in cancer. However, the correlations of PYCR1 expression with the clinicopathological features and prognosis of renal cell carcinoma (RCC) remain unclear. The purpose of this study was to identify the expression of PYCR1 and its clinical relevance in RCC patients.PYCR1 mRNA expression differences between RCC and the adjacent normal renal tissues were assessed using the Cancer Genome Atlas database (TCGA). Subsequently, the expression of PYCR1 mRNA and protein were evaluated by quantitative real-time polymerase chain reaction, Western blot, and immunochemistry using 30 paired frozen samples of RCC and the adjacent normal renal tissues. The protein expression of PYCR1 was evaluated by immunostaining formalin-fixed, paraffin-embedded sections of RCC samples from 96 patients who underwent radical nephrectomy, and its relationship with clinical features were analyzed. Nonpaired t tests were used to statistically analyze the differences between the 2 groups. Cox univariable and multivariable analyses of overall survival (OS) among RCC patients were performed.The expression of PYCR1 mRNA was significantly upregulated in RCC tissues compared to adjacent normal renal tissues in the TCGA database (P < .01). The area under the receiver operating characteristic curve value was 0.748. The expression of PYCR1 mRNA and protein was significantly upregulated in RCC compared with that in paired normal renal tissues (P < .01). Higher PYCR1 levels were associated with metastasis (P < .01). Kaplan-Meier survival curves indicated that higher PYCR1 expression was correlated with poorer OS. Therefore, PYCR1 may act as a novel prognostic marker and therapeutic target in the diagnosis and treatment of RCC.