A rare case report: multiple intrahepatic masses in a pediatric patient with citrin deficiency.

Deficiency of citrin, the liver-type aspartate-glutamate carrier, arises from biallelic mutations of the gene SLC25A13. Although citrin deficiency (CD) is associated with higher risk of hepatocellular carcinoma (HCC) in adult patients, this association remains inconclusive in pediatric cases. The patient in this paper had been diagnosed to have CD by SLC25A13 analysis at the age 10 months, and then in response to dietary therapy, her prolonged jaundice and marked hepatosplenomegaly resolved gradually. However, she was referred to the hospital once again due to recurrent abdominal distention for 2 weeks at her age 4 years and 9 months, when prominently enlarged liver and spleen were palpated, along with a strikingly elevated serum alpha-fetoprotein (AFP) level of 27605 ng/mL as well as a large mass in the right liver lobe and a suspected tumor thrombus within the portal vein on enhanced computed tomography. After 4 rounds of adjuvant chemotherapy, right hepatic lobectomy and portal venous embolectomy were performed at her age 5 years and 3 months, and metastatic hepatoblastoma was confirmed by histopathological analysis. Afterwards, the patient underwent 5 additional cycles of chemotherapy and her condition remained stable for 7 months after surgery. Unfortunately, hepatoblastoma recurred in the left lobe at the age 5 years and 10 months, which progressed rapidly into liver failure, and led to death at the age 6 years and 1 month. As far as we know, this is the the first case of hepatoblastoma in a patient with CD, raising the possibility of an association between these two conditions.

Covert hepatic encephalopathy is associated with aggressive disease progression and poor survival in patients with cirrhosis.

OBJECTIVES: Covert hepatic encephalopathy (CHE) negatively affects the health-related quality of life and increases the risk of overt HE (OHE) in patients with liver cirrhosis. However, the impact of CHE on long-term patient outcomes remains controversial. This study aimed to explore the association between CHE and disease progression and survival among cirrhotic patients. METHODS: This was a single-center prospective study that enrolled 132 hospitalized patients with cirrhosis, with an average follow-up period of 45.02 ± 23.06 months. CHE was diagnosed using the validated Chinese standardized psychometric hepatic encephalopathy score. RESULTS: CHE was detected in 35.61% cirrhotic patients. During the follow-up, patients with CHE had a higher risk of developing OHE (log-rank 5.840, P = 0.016), exacerbation of ascites (log-rank 4.789, P = 0.029), and portal vein thrombosis (PVT) (log-rank 8.738, P = 0.003). Cox multivariate regression analyses revealed that CHE was independently associated with the occurrence of OHE, exacerbation of ascites, and PVT. Furthermore, patients with progression of cirrhosis were more likely to be diagnosed as CHE (log-rank 4.462, P = 0.035). At the end of the follow-up, patients with CHE had a lower survival rate compared to those without CHE (log-rank 8.151, P = 0.004). CHE diagnosis (hazard ratio 2.530, P = 0.008), together with elder age and higher Child-Pugh score, were risk factors for impaired survival in cirrhotic patients. CONCLUSION: CHE is associated with disease progression and poor survival in patients with cirrhosis, indicating that CHE may serve as an independent predictor of poor prognosis among these patients.

Effects of high- and low-yield moso bamboo (Phyllostachys edulis) forests on bacterial community structure.

To study the characteristics of bacterial community structure in high-yield and low-yield moso bamboo (Phyllostachys edulis) forests, we collected bamboo rhizome, rhizome root, stem, leaf, rhizosphere soil, and non-rhizosphere soil from high- and low-yield forests in Yong'an City and Jiangle County of Fujian Province, China. The genomic DNA of the samples was extracted, sequenced and analyzed. The results show that: the common differences between the high-yield and low-yield P. edulis forest samples in the two regions were mainly in bacterial community compositions in the bamboo rhizome, rhizome root, and soil samples. Differences in the bacterial community compositions in the stem and leaf samples were insignificant. The bacterial species and diversity in rhizome root and rhizosphere soil of high-yield P. edulis forests were less than those of low-yield forests. The relative abundance of Actinobacteria and Acidobacteria in rhizome root samples of high-yield forests was higher than that in low-yield forests. The relative abundance of Rhizobiales and Burkholderiales in bamboo rhizome samples in high-yield forests was higher than that in low-yield forests. The relative abundance of Bradyrhizobium in bamboo rhizome samples in high-yield forests was higher than that in low-yield forests in the two regions. The change of bacterial community composition in P. edulis stems and leaves showed little correlation with high- or low-yields of P. edulis forests. Notably, the bacterial community composition of the rhizome root system was correlated with the high yield of bamboo. This study provides a theoretical basis for using of microbes to enhance the yields of P. edulis forests.

Sustained ameliorating effects and autonomic mechanisms of transcutaneous electrical acustimulation at ST36 in patients with chronic constipation.

Background and aims: The treatment of chronic constipation is still a great challenge in clinical practice. This study aimed to determine the efficacy and sustained effects of transcutaneous electrical acustimulation (TEA) at acupoint ST36 on the treatment of chronic constipation and explore possible underlying mechanisms. Methods: Forty-four patients with chronic constipation were recruited and randomly assigned to a TEA group or sham-TEA group. A bowel diary was recorded by the patients. The Patient Assessment of Constipation Symptom (PAC-SYM) and the Patient Assessment of Constipation Quality of Life (PAC-QoL) questionnaires were administered during each visit. Anal and rectal functions were evaluated with anorectal manometry. Autonomic functions were assessed by the special analysis of heart rate variability derived from the ECG recording. Results: Compared with sham-TEA, 2-week TEA treatment significantly increased the number of spontaneous bowel movements (SBMs) (5.64 ± 0.54 vs. 2.82 ± 0.36, P < 0.001) and lowered the total scores of PAC-SYM (0.90 ± 0.14 vs. 1.35 ± 0.13, P < 0.001) and PAC-QoL (0.89 ± 0.13 vs. 1.32 ± 0.14, P < 0.05). TEA improved symptoms, as reflected by a reduction in the straining (P < 0.001), the incomplete defecation (P < 0.05), the frequency of emergency drug use (P < 0.05), the days of abdominal distension (P < 0.01) and an increase in intestinal satisfaction (P < 0.01). Interestingly, the effects of TEA on the improvement of weekly SBMs sustained four weeks after the cessation of treatment (P < 0.001). Anorectal manometry indicated that 2-week treatment of TEA lowered the threshold of first sensation (P < 0.05), desire of defecation (P < 0.01) and maximum tolerable volume (P < 0.001) compared with sham-TEA group. TEA also significantly enhanced vagal activity, reflected by high-frequency band of heart rate variability, compared with sham-TEA (57.86 ± 1.83 vs. 48.51 ± 2.04, P < 0.01). Conclusion: TEA ameliorates constipation with sustained effects, which may be mediated via improvement of rectal sensitivity and enhancement of vagal activity. Clinical trial registration: [https://clinicaltrials.gov/], identifier [ChiCTR210004267].

Clinical and genetic characterization of pediatric patients with progressive familial intrahepatic cholestasis type 3 (PFIC3): identification of 14 novel ABCB4 variants and review of the literatures.

BACKGROUND: Progressive familial intrahepatic cholestasis type 3 (PFIC3) is an autosomal recessive disease caused by pathogenic variants of the gene ABCB4. This study aimed to investigate the ABCB4 genotypic and the clinical phenotypic features of PFIC3 patients. METHODS: The clinical and molecular genetic data of 13 new pediatric patients with PFIC3 as well as 82 reported ones in the PubMed and CNKI databases were collected and analyzed. RESULTS: The 13 new PFIC3 patients included six females and seven males, and the main presentations were hepatomegaly, splenomegaly, jaundice, and pruritus, as well as increased levels of gamma-glutamyl transpeptidase (GGT). Fourteen new ABCB4 variants were detected, including eight diagnosed to be likely-pathogenic and six, pathogenic. Among all the 95 PFIC3 cases, hepatomegaly was observed in 85.3% (81/95), pruritus in 67.4% (64/95), splenomegaly in 52.6% (50/95), jaundice in 48.4% (46/95), portal hypertension in 34.7% (33/95) and GGT elevation in 100% (88/88) of the patients. Positive responses at varied degrees to oral ursodeoxycholic acid (UDCA) treatment were observed in 66.1% (39/59) of the patients, among whom 38.5% (15/39) fully recovered in terms of the laboratory changes. Although the condition remained stable in 53 patients (58.9%, 53/90), the clinical outcomes were not promising in the rest 37 cases (41.1%, 37/90), including 7 died, 27 having undergone while another 3 waiting for liver transplantation. A total of 96 ABCB4 variants were detected in the 95 patients. PFIC3 patients with biallelic null variants exhibited earlier onset ages [10.5 (2, 18) vs. 19 (8, 60) months, p = 0.007], lower UDCA response rate [18.2% (2/11) vs. 77.1% (37/48), p = 0.001], and more unpromising clinical outcomes [80% (12/15) vs. 33.3% (25/75), p = 0.001], compared with those with non-biallelic null variants. CONCLUSIONS: PFIC3 presented with hepatomegaly, pruritus, splenomegaly and jaundice with increased serum GGT level as a biochemistry hallmark. Although varying degrees of improvement in response to UDCA therapy were observed, 41.1% of PFIC3 patients exhibited unfavorable prognosis. ABCB4 genotypes of biallelic null variants were associated with severer PFIC3 phenotypes. Moreover, the 14 novel variants in this study expanded the ABCB4 mutation spectrum, and provided novel molecular biomarkers for diagnosis of PFIC3 patients.

Genetic Factors Causing Thyroid Dyshormonogenesis as the Major Etiologies for Primary Congenital Hypothyroidism: Clinical and Genetic Characterization of 33 Patients.

BACKGROUND AND AIMS: Although the significance of primary congenital hypothyroidism (CH) is supported by an increasing amount of evidence, the clinical and genetic characteristics of this condition are still poorly understood. This study aimed to explore the underlying genetic etiologies in a cohort of primary CH patients. SUBJECTS AND METHODS: The clinical data of 33 patients with primary CH were collected and analyzed via a cross-sectional study. Genetic analysis was performed by high-throughput sequencing and Sanger verification, and the pathogenicity of the novel missense variants was predicted using a variety of comprehensive bioinformatic tools. RESULTS: Among the 33 patients, 22 (22/33, 66.7%) harbored pathogenic variants in the causative genes of thyroid dysgenesis or dyshormonogenesis, with DUOX2 (15/33, 45.5%) topping the list, followed by TG, TPO, DUOXA2 and PAX8. Four novel genetic variants were detected, including a pathogenic frameshift and three likely pathogenic missense variants. Positive neonatal screening for TSH, neonatal jaundice and abnormal thyroid morphology were the main positive findings among all cases. Although 31 of the total 33 CH patients exhibited normal anthropometric and social performance, the other 2 had poor prognosis in this study. CONCLUSIONS: This study reported 33 new CH patients bearing four novel genetic variants, which enriched the variant spectrum of CH genes. In this cohort, genetic factors causing thyroid dyshormonogenesis were the main etiologies of CH development. Most patients exhibited a favorable prognosis; however, systematic management remains a challenge in achieving improved clinical outcomes for CH patients.

Effects of Low-dose and High-dose Rifaximin in the Treatment of Covert Hepatic Encephalopathy.

Background and Aims: Rifaximin is effective in preventing and treating hepatic encephalopathy (HE). This study aimed to investigate the efficacy and safety of different dosages of rifaximin in the treatment of cirrhotic patients with covert HE (CHE). Methods: In this single-center, randomized, controlled, open-label study, CHE was diagnosed using a combination of the psychometric HE score and the EncephalApp Stroop test. Cirrhotic patients with CHE were recruited and randomly assigned to low-dose rifaximin 800 mg/day, high-dose rifaximin (1,200 mg/day), and control groups, and were treated for 8 weeks. The sickness impact profile (SIP) scale was used to evaluate the health-related quality of life (HRQOL) of patients. Forty patients were included in the study, 12 were assigned to the low-dose group, 14 to the high-dose group, and 14 patients to the control group. Results: The percentage of patients with CHE reversal was significantly higher in both the low-dose (41.67%, 5/12) and high-dose (57.14%, 8/14) groups than in the control group (7.14%, 1/14) at 8 weeks (p=0.037 and p=0.005, respectively). In addition, both doses of rifaximin resulted in significant improvement of the total SIP score compared with the control group. There were no significant differences in the CHE reversal rate, total SIP score improvement, and incidence of adverse event between the low-dose and high-dose groups (p>0.05). Conclusions: Low-dose rifaximin reverses CHE and improves HRQOL in cirrhotic patients with comparable effects and safety to high-dose rifaximin.

Identification of a novel pathogenic TBCK variant in a Chinese patient with infantile hypotonia with psychomotor retardation and characteristic facies type 3 (IHPRF3): a case report.

BACKGROUND: Infantile hypotonia with psychomotor retardation and characteristic facies type 3(IHPRF3) (OMIM #616,900) is an autosomal recessive disorder caused by biallelic pathogenic variants of the TBCK gene, and to date, this disease was reported rather limitedly in number and all described cases were Caucasians. CASE PRESENTATION: This paper reported the clinical and genetic features of a Chinese patient with IHPRF3. The patient was a 15-month-old male with global developmental delay, profound hypotonia, and typical facial dysmorphic features including mildly coarse facial appearance, hypertelorism, tented upper lip, exaggerated Cupid's bow, macroglossia and arched eyebrows. Magnetic Resonance Imaging (MRI) analysis of the brain revealed slightly widened bilateral ventricles and subarachnoid space. On genetic analysis, the patient was homozygous for a novel TBCK variant c.247C > T(p.Arg83Ter). The parents were both carriers without any positive symptoms or signs. With an extremely low frequency (0.0000082) in Exome Aggregation Consortium, the variant has not been reported in any other databases or official literatures, and was diagnosed to be pathogenic according to the American College of Medical Genetics and Genomics(ACMG) standards and guidelines. Neurorehabilitation training did not work well and the long-term prognosis remained to be observed. CONCLUSIONS: This study reported the clinical and molecular features of the first non-Caucasian patient with IHPRF3 arising from a novel homozygous TBCK mutation, which provided a novel molecular marker for the definite diagnosis of IHPRF3 patients and for its genetic counseling and prenatal diagnosis in the affected families.

Molecular Epidemiology of Na+-Taurocholate Cotransporting Polypeptide Deficiency in Guangdong Province, China: A Pilot Study by Screening for Four Prevalent Variants of the Causative Gene SLC10A1.

Na+-taurocholate cotransporting polypeptide deficiency (NTCPD) is an autosomal recessive disorder arising from biallelic SLC10A1 mutations. As a newly-described inborn error of bile acid metabolism, the epidemiology of this condition remains largely unclear in Chinese population so far. In this study, a total of 2,828 peripheral blood samples were collected from 12 cities in Guangdong, a province with the largest population in China, and the four prevalent SLC10A1 variants c.800C > T (p.Ser267Phe), c.263T > C (p.Ile88Thr), c.595A > C (p.Ser199Arg) and c.665T > C (p.Leu222Ser) were screened for by using polymerase chain reaction (PCR)- restriction fragment length polymorphism (RFLP). As a result, 663 mutated SLC10A1 alleles were detected, and the mutated allele frequency was calculated to be 11.72% (663/5,656), with a carrier frequency 20.69% (1/5) and a theoretical morbidity rate 1.37% (1/73) of NTCPD in Guangdong province. The variant c.800C > T (p.Ser267Phe) exhibited highest allele frequency among the four prevalent variants (χ2 = 1501.27, p < 0.0001) as well as higher allele frequency in the peripheral region than that within the Pearl River Delta (χ2 = 4.834, p < 0.05). The results suggested that NTCPD might be a disorder rather common in Guangdong province. The findings depicted the molecular epidemiologic features of NTCPD, providing preliminary but significant laboratory evidences for the subsequent NTCPD diagnosis and management in Guangdong population.

Community structure and diversity characteristics of rhizosphere and root endophytic bacterial community in different Acacia species.

Rhizosphere and endophytic microbiota significantly affect plant growth and development by influencing nutrient uptake and stress tolerance. Herein, root and rhizosphere soil of Acacia species were collected and analyzed to compare the structural differences of the rhizosphere and root endophytic bacterial communities. High-throughput 16S rRNA gene sequencing technology was employed to analyze the rhizosphere and root endophytic bacterial communities. A total of 4249 OTUs were identified following sequence analysis. The rhizosphere soil contained significantly more OTUs than the root soil. Principal component analysis (PCA) and hierarchical cluster analysis indicated that bacterial communities exhibited significant specificity in the rhizosphere and root soil of different Acacia species. The most dominant phylum in the rhizosphere soil was Acidobacteria, followed by Proteobacteria and Actinobacteria, whereas the dominant phylum in the root soil was Proteobacteria, followed by Actinobacteria and Acidobacteria. Among the various Acacia species, specific bacterial communities displayed different abundance. We systematically described the core bacteria in the rhizosphere and root endophytic bacterial communities and predicted their relevant functions. The type and abundance of specific bacteria were correlated with the nutrient absorption and metabolism of the Acacia species. This study addresses the complex host-microbe interactions and explores the rhizosphere and root bacterial community structure of different Acacia species. These results provide new insights into the role of rhizosphere and root endophytic bacterial communities on the growth and reproduction of Acacia, thus informing future efforts towards sustainable development and utilization of Acacia.

Transcutaneous Electrical Acustimulation Ameliorates Motion Sickness Induced by Rotary Chair in Healthy Subjects: A Prospective Randomized Crossover Study.

OBJECTIVES: Motion sickness (MS) is a common physiological response to real or virtual motion. The purpose of this study was to investigate the effects of transcutaneous electrical acustimulation (TEA) on MS and the underlying mechanisms in healthy subjects. MATERIALS AND METHODS: A total of 50 healthy participants were recruited and randomly assigned into two groups to complete two separate sessions in a crossover study. A Coriolis rotary chair was used as a model to provoke severe MS. The total tolerable rotation time and Graybiel scoring scale were recorded. Gastric slow waves were detected by electrogastrogram. The autonomic nervous function, including the vagal activity, was evaluated by the analysis of heart rate variability derived from the electrocardiogram recording. The serum levels of arginine vasopressin (AVP) and norepinephrine (NE) were examined. RESULTS: Of note, 22 participants in TEA and only 11 participants in the sham-TEA session completed the entire five-rotation MS stimuli (p = 0.019). TEA significantly prolonged the total tolerable rotation time of MS stimuli (220.4 ± 11.59 vs 173.6 ± 12.3 seconds, p < 0.001) and lowered MS symptom scores (12.56 ± 2.03 vs 22.06 ± 3.0, p < 0.001). TEA improved the percentage of normal gastric slow waves, compared with sham-TEA (56.0 ± 2.1% vs 51.6 ± 2.0%, p = 0.033). TEA also significantly enhanced vagal activity compared with sham-TEA (0.41 ± 0.02 vs 0.31 ± 0.02, p < 0.001). In addition, the increased serum levels of AVP and NE on MS stimulation were markedly suppressed by TEA treatment, compared with sham-TEA (AVP, 56.791 ± 4.057 vs 79.312 ± 10.036 ng/mL, p = 0.033; NE, 0.388 ± 0.037 vs 0.501 ± 0.055 ng/mL, p = 0.021). CONCLUSIONS: Needleless TEA is a potent therapeutic approach for severe MS, as it increases participants' tolerance and ameliorates MS symptoms, which may be attributed to the integrative effects of TEA on autonomic functions and neuroendocrine balance.

Treatment of patients with Covid-19 with a high dose of ulinastatin.

Currently, there are no specific therapeutic agents available for the treatment of coronavirus disease 2019 (Covid-19). The present study aimed to assess the efficacy of high-dose ulinastatin for the treatment of patients with Covid-19. A total of 12 patients hospitalized with confirmed severe acute respiratory syndrome coronavirus 2 infection were treated with a high dose of ulinastatin alongside standard care. Changes in clinical manifestations, laboratory examinations and chest images were retrospectively analyzed. A total of 10 patients with severe Covid-19 and two patients with moderate Covid-19 received ulinastatin treatment. The average age of the patients was 68.0±11.9 years (age range, 48-87 years). In total, nine of the 12 patients (75.0%) had one or more comorbidities. The most common symptoms on admission were fever (8/12, 66.7%), cough (5/12, 41.7%) and dyspnea (5/12, 41.7%). The percentage of lymphocytes was decreased in 41.7% of patients (5/12) and 58.3% of patients (7/12) had elevated hypersensitive C-reactive protein (CRP) levels (mean, 49.70±77.70 mg/l). The white blood cell levels and the percentage of lymphocytes returned to normal in all of the patients, and CRP was significantly decreased and returned to normal in 83.3% of patients (10/12; mean, 6.87±6.63 mg/l) on day 7 after ulinastatin treatment. Clinical symptoms were relieved synchronously. The peripheral oxygen saturation improved and 66.7% of the patients (8/12) did not require further oxygen therapy 7 days after ulinastatin treatment. No patients required intensive care unit admission or mechanical ventilation. All patients revealed different degrees of absorption of pulmonary lesions after treatment. Compared with the standard care group, ulinastatin treatment significantly prevented illness deterioration. In conclusion, these preliminary data revealed that high-dose ulinastatin treatment was safe and exhibited a potential beneficial effect for patients with Covid-19.

Five cases of corneal suture-associated infectious endophthalmitis / 中华眼底病杂志

Objective:To observe the clinical features and prognosis of eyes with corneal suture-related infective endophthalmitis.Methods:A retrospective interventional case series. From January 2020 to December 2021, 5 patients (5 eyes) with corneal suture-related infectious endophthalmitis diagnosed by ophthalmic examination at Department of Ophthalmology of the Eye-ENT Hospital of Fudan University were included in the study. Among them, there were 3 males and 2 females; all had unilateral disease; the mean age was 30.80±21.98 years. Sutures of 4 cases were secondary to lens related surgery and of 1 case was secondary to penetrating keratoplasty. Average retention time of corneal suture was 20.00±7.41 months. Of the 5 eyes, corneal sutures were removed in 1 eye due to redness and eye pain in another hospital; 3 eyes were loosened of the sutures in the remaining 4 eyes. The patients were given standard treatment for infectious endophthalmitis, including systemic and local anti-infective therapy; corneal suture removal, intraocular injection, and vitrectomy (PPV). In PPV, it was decided whether to give silicone oil filling according to the situation. The follow-up time after treatment was 11.00±7.38 months. The best corrected visual acuity (BCVA), B-mode ultrasound and microbial culture results of the affected eye before and after surgery were observed and analyzed.Results:Infiltrates, ulcers, or abscesses surrounding the suture may be seen on the cornea of the affected eye. B-mode ultrasonography showed vitreous opacity, preretinal cords, and spherical wall edema in the entire segment of the affected eye. The results of vitreous humor culture were positive in 3 eyes, which were Streptococcus viridis, Staphylococcus hominis subspecies, Staphylococcus epidermidis. After treatment, all the intraocular infections in the affected eyes were successfully controlled, and there were no cases of enucleation of ocular contents or enucleation. Before treatment, the BCVA of the affected eye was from no light perception to counting fingers; after treatment, 2 eyes had BCVA> 0.3.Conclusions:Infiltration, ulcers or abscesses around the sutures can be seen in the cornea of corneal suture-related infective endophthalmitis patients, which are related to the long-term retention of the sutures in the eye. Most of the affected eyes have loose sutures when they go to the doctor; timely treatment can effectively control the infection, and some eyes have good visual prognosis.

Preliminary study of clinical application of magnetic resonance linear accelerator in liver malignancies / 中华放射肿瘤学杂志

Objective:To investigate the workflow, efficacy and safety of MR-Linac in liver malignancies.Methods:Clinical data of 15 patients with hepatocellular carcinomas (HCC) or liver metastases treated with MR-Linac between November 2019 and July 2021 were retrospectively analyzed. The workflow of MR-Linac was investigated and image identification rate was analyzed. Patients were followed up for response and toxicity assessment.Results:Fifteen patients (6 HCC, 8 liver metastases from colorectal cancer, 1 liver metastasis from breast cancer) were enrolled. A total of 21 lesions were treated, consisting of 10 patients with single lesion, 4 patients with double lesions and 1 patient with triple lesions. The median tumor size was 2.4 cm (0.8-9.8 cm). The identification rate for gross tumor volume (GTV) in MR-Linac was 13/15. Although GTV of two patients were unclearly displayed in MR-Linac images, the presence of adjacent blood vessel and bile duct assisted the precise registration. All the patients were treated with stereotactic body radiation therapy (SBRT). For HCC, the median fraction dose for GTV or planning gross tumor volume (PGTV) was 6 Gy (5-10 Gy) and the median number of fractions was 9(5-10). The median total dose was 52 Gy (50-54 Gy) and the median equivalent dose in 2 Gy fraction (EQD 2Gy) at α/ β= 10 was 72 Gy (62.5-83.3 Gy). For liver metastases, the median fraction dose for GTV or PGTV was 5 Gy (5-10 Gy) and the median number of fractions was 10(5-10). The median total dose was 50 Gy (40-50 Gy) and the median EQD 2Gy at α/ β=5 was 71.4 Gy (71.4-107.1 Gy). At 1 month after SBRT, the in-field objective response rate (ORR) was 8/13 and the disease control rate was 13/13. At 3-6 months after SBRT, the in-filed ORR was increased to 6/6. During the median follow-up of 4.0 months (0.3-11.6), 4-month local progression-free survival, progression-free survival and overall survival were 15/15, 11/15 and 15/15, respectively. Toxicities were mild and no grade 3 or higher toxicities were observed. Conclusions:MR-Linac provides a platform with high identification rates of liver lesions. Besides, the presence of adjacent blood vessel and bile duct also assists the precise registration. It is especially suitable for liver malignancies with promising local control and well tolerance.

Analysis of silicone oil emulsification and related factors in eyes filled with silicone oil for rhegmatogenous retinal detachment / 中华眼底病杂志

Objective:To observe the emulsification of silicone oil in eyes with rhegmatogenous retinal detachment (RRD) after silicone oil filling surgery, and to preliminarily analyze the possible clinical factors related to it.Methods:A cross-sectional clinical study. From January 2019 to April 2022, 50 eyes of 50 patients with RRD who underwent pans plana vitrectomy (PPV) combined with silicone oil filling surgery in Eye and ENT Hospital of Fudan University were included in the study. Among them, there were 25 males with 25 eyes and 25 females with 25 eyes; the age was 54.86±11.79 years old. The retina was in place 3 months after surgery. Before silicone oil removal surgery, intraocular pressure >21 mm Hg (1 mm Hg=0.133 kPa) or treated with≥1 anti-glaucoma drug (high intraocular pressure) in 20 eyes; intraocular pressure ≤21 mm Hg and no anti-glaucoma drug treatment in 30 eyes (normal intraocular pressure). During follow-up after surgery, silicone oil emulsification was found and those who met the indications for silicone oil removal were subjected to silicone oil removal surgery. The first 2 ml of lavage fluid was collected immediately after removal of the silicone oil, and the particle diameter and number of emulsified silicone oil were measured using a Multisizer ? 3 particle/cell counter and particle size analyzer. The measuring range was 0.4-12.0 μm, and the diameter is accordingly divided into 0.4-<1.0, 1.0-<3.0, 3.0-<5.0, 5.0-<7.0, 7.0-12.0 μm. Each sample was measured 3 times and the average value was taken. Spearman correlation analysis and multiple linear regression analysis were used to analyze the correlation between the number of emulsified silicone oil particles and clinical factors. Results:The number of emulsified silicone oil particles was (1.74±2.94)×10 7/ml (0.96×10 7-14.11×10 7/ml), of which the diameter of 0.4-<1.0 μm emulsified silicone oil particle was (1.25±2.41)×10 7/ml, accounted for (64.26±12.70)% [(1.25±2.41)×10 7/(1.74±2.94)×10 7]. The results of correlation analysis showed that there was no correlation between the total particle number of emulsified silicone oil and various clinical factors ( P>0.05). The number of emulsified silicone oil particles with a diameter of 7.0-12.0 μm was negatively correlated with age ( r=-0.298, P=0.036), and positively correlated with axial length ( r=0.325, P=0.021). There was no correlation between the previous ocular trauma, choroidal detachment and different lens states and the number of emulsified silicone oil particles ( P>0.05). Multiple linear regression analysis showed that eye axis ( β=1 570.868, P=0.023) and age ( β=-316.128, P=0.039) were the risk predictors of silicone oil emulsification into large diameter particles (7-<12 μm). The number of emulsified silicone oil particles with a diameter of 7-12 μm in the patients with high intraocular pressure was significantly higher than that in the patients with normal intraocular pressure, and the difference was statistically significant ( U=195.00, P=0.037). Conclusions:Most of the emulsified silicone oil particles in the eyes of RRD patients after silicone oil filling surgery are small-diameter particles; the silicone oil emulsification is more serious in young patients and patients with long ocular axis, and young patients are more prone to high intraocular pressure.

Clinical characterization of NTCP deficiency in paediatric patients : A case-control study based on SLC10A1 genotyping analysis.

Na+ -taurocholate cotransporting polypeptide deficiency (NTCPD) is a newly described disorder arising from biallelic mutations of the SLC10A1 gene. As a result of a lack of compelling evidence from case-control studies, its genotypic and phenotypic features remain open for in-depth investigation. This study aimed to explore the genotypic and clinical phenotypic characteristics of paediatric patients with NTCPD. The SLC10A1 genotypes of all NTCPD patients were confirmed by screening for the prevalent variant c.800C>T and Sanger sequencing when necessary. The clinical presentations and laboratory changes were collected, reviewed and analysed, and then qualitatively and quantitatively compared with the relevant controls. A total of 113 paediatric NTCPD patients were diagnosed while c.374dupG and c.682_683delCT were detected as two novel pathogenic mutations. Hypercholanemia was observed in 99.12% of the patients. Indirect hyperbilirubinemia in affected neonates exhibited higher positive rates in comparison to controls. Moreover, transient cholestatic jaundice, elevated liver enzymes and 25-hydroxyvitamin D (Vit D) deficiency during early infancy were more commonly observed in patients than in controls. All NTCPD patients exhibited favourable clinical outcomes as a result of symptomatic and supportive treatment. The findings enriched the SLC10A1 mutation spectrum and provided comprehensive insights into the phenotypic characteristics of NTCPD. NTCPD should be considered and SLC10A1 gene should be analysed in patients with above age-dependent clinical features. Furthermore, over investigation and intervention should be avoided in the management of NTCPD patients.

Molecular epidemiologic study of citrin deficiency by screening for four reported pathogenic SLC25A13 variants in the Shaanxi and Guangdong provinces, China.

BACKGROUND: Citrin deficiency (CD) is an autosomal recessive disease resulting from biallelic mutations of the SLC25A13 gene. This study aimed to investigate the molecular epidemiological features of CD in the Guangdong and Shaanxi provinces of China. METHODS: A total of 3,409 peripheral blood samples from Guangdong and 2,746 such samples from Shaanxi province were collected. Four prevalent SLC25A13 mutations NG_012247.2 (NM_014251.3): c.852_855del, c.1638_1660dup, c.615+5G>A, and c.1751-5_1751-4ins(2684) were screened by using the conventional polymerase chain reaction (PCR)/PCR-restriction fragment length polymorphism and newly-developed multiplex PCR methods, respectively. The mutated SLC25A13 allele frequencies, carrier frequencies, and CD morbidity rates were calculated and then compared with the Chi-square and Fisher's exact tests. RESULTS: The mutations were detected in 68 out of 6,818 SLC25A13 alleles in Guangdong and 29 out of 5,492 alleles in the Shaanxi population. The carrier frequencies were subsequently calculated to be 1/51 and 1/95, while the CD morbidity rates were 1/10,053 and 1/35,865, in the 2 populations, respectively. When compared with the Shaanxi population, Guangdong exhibited a higher frequency of mutated SLC25A13 allele (68/6,818 vs. 29/5,492, χ2=8.570, P=0.003) in general, with higher c.852_855del (54/6,818 vs. 13/5,492, χ2=17.328, P=0.000) but lower c.1751-5_1751 -4ins(2684) (2/6,818 vs. 9/5,492, P=0.015) allele frequencies. The distribution of c.615+5G>A and c.1638_1660dup between the 2 provinces, as well as all 4 prevalent mutations among different geographic regions within the 2 provinces, did not differed significantly. CONCLUSIONS: Our findings depicted the CD molecular epidemiological features in Guangdong and Shaanxi populations, providing preliminary but significant laboratory evidences for the subsequent CD diagnosis and management in the 2 provinces of mainland China.

Simulation-based training following a theoretical lecture enhances the performance of medical students in the interpretation and short-term retention of 20 cross-sectional transesophageal echocardiographic views: a prospective, randomized, controlled trial.

BACKGROUND: Both simulation-based training and video-based training serve as educational adjuncts for learning TEE among medical students. In the present study, we hypothesized that simulation-based training would better enhance the performance of medical students in the interpretation of 20 cross-sectional views compared to video-based training. METHODS: A total of 120 4th-year undergraduate medical students were enrolled in the present study. The study began with a pre-test of all the participants, followed by a 90-min theoretical lecture and a post-test. Subsequently, the participants were randomly divided into the video-based group (Group V) and simulation-based group (Group S). Next, Group V received 60 min of TEE video learning, while Group S received 60 min of TEE simulator training. After the respective training, both the groups undertook the retention-test 1 and retention-test 2, 1 week and 1 month later, respectively. The performance for each test was evaluated by five views, which were selected randomly and, respectively, from a set of 20 cross-sectional views. The primary outcome was the performance of the retention-test 1. Secondary outcomes included: (1) comparison the performances of the pre-test, post-test, and retention-test 2 between two groups; (2) comparison the performances of pre-test and post-test in the same group; (3) comparison the performances of retention-test 1, and retention-test 2 in the same group. RESULTS: Better performances were observed in Group S in both retention-test 1 (Group V: 63.2 [52.6, 77.6] vs. Group S: 89.5 [68.4, 100.0], P < 0.001) and retention-test 2 (Group V: 58.0 [48.0, 72.0] vs. Group S: 74.0 [64.0, 80.0], P < 0.001) compared to Group V. No statistically significant differences were observed in the performances of pre-test (Group V: 8.3 [4.2, 12.5] vs. Group S: 8.3 [4.2, 12.5], P = 0.825) or post-test (Group V: 46.2 [38.5, 57.7] vs. Group S: 44.2 [38.5, 56.7], P = 0.694) between the two groups. The improvement had been observed in the post-test, compared with pre-test in the same group, respectively (Group V in post-test: 46.2 [38.5, 57.7] vs. Group V in pre-test: 8.3 [4.2, 12.5], P < 0.001; Group S in post-test: 44.2 [38.5, 56.7] vs. Group S in pre-test: 8.3 [4.2, 12.5], P < 0.001). However, the performance in retention-test 2 was significantly reduced, compared with retention-test 1 in the same group, respectively (Group V in retention-test 2: 58.0 [48.0, 72.0] vs. Group V in retention-test 1: 63.2 [52.6, 77.6] P = 0.005; Group S in retention-test 2: 74.0 [64.0, 80.0] vs. Group S in retention-test 1: 89.5 [68.4, 100.0], P < 0.001). CONCLUSIONS: Following a 90-min theoretical lecture, simulation-based training better enhanced the performance of medical students in the interpretation and short-term retention of 20 cross-sectional views compared to video-based training. TRIAL REGISTRATION: http://www.chictr.org.cn ( ChiCTR2000033519 , 3/June/2020).