[Clinical characteristics of children with severe SARS-CoV-2 infection in Yunnan].

Objective: To investigate the clinical characteristics of 130 children with severe SARS-CoV-2 infection in Yunnan province after the relaxation of non-pharmaceutical interventions, and analyze the risk factors for mortality. Methods: This study is a retrospective case summary that analyzed the demographic data, underlying diseases, clinical diagnoses, disease outcomes, and laboratory results of 130 children with severe COVID-19 infections admitted to nine top-tier hospitals in Yunnan Province from December 2022 to March 2023. According to the prognosis, the patients were divided into survival group and death group. The clinical and laboratory data between the two groups were compared, and the risk factors of death were evaluated. The χ2 test and Mann-Whitney U test were employed to compare between groups, while Spearman correlation test and multiple Logistic regression were used to analyze the risk factors for death. The predictive value of independent risk factors was evaluated by receiver operating characteristic curve. Results: The 130 severe patients included 80 males and 50 females with an onset age of 28.0 (4.5, 79.5) months. There were 97 cases in the survival group and 33 cases in the death group with no significant differences in gender and age between the two groups (P>0.05). Twenty-five cases (19.2%) out of the 130 patients had underlying diseases, and the number with underlying diseases was significantly higher in death group than in survival group (36.4% (12/33) vs. 13.4%(13/97), χ2=8.36, P=0.004). The vaccination rate in the survival group was significantly higher than that in the death group (86.1% (31/36) vs. 7/17, χ2=9.38, P=0.002). A total of 42 cases (32.3%) of the 130 patients were detected to be infected with other pathogens, but there was no significant difference in the incidence of co-infection between the death group and the survival group (39.3%(13/33) vs. 29.9% (29/97), χ2=1.02, P>0.05). Among the 130 cases, severe respiratory cases were the most common 66 cases (50.8%), followed by neurological severe illnesses 34 cases (26.2%) and circulatory severe 13 cases (10%). Compared to the survival group, patients in the death group had a significantly higher levels of neutrophil, ferritin, procalcitonin, alanine aminotransferase, lactate dehydrogenase, creatine kinase isoenzyme, B-type natriuretic peptide, interleukin-6 and 10 (6.7 (4.0, 14.0) vs. 3.0 (1.6, 7.0)×109/L, 479 (298, 594) vs. 268 (124, 424) µg/L, 4.8 (1.7, 10.6) vs. 2.0 (1.1, 3.1) µg/L, 66 (20, 258) vs. 23 (15, 49) U/L, 464 (311, 815) vs. 304 (252, 388) g/L, 71(52, 110) vs. 24(15, 48) U/L, 484 (160, 804) vs. 154 (26, 440) ng/L, 43 (23, 102) vs. 19 (13, 27) ng/L, 216 (114, 318) vs. 86 (45, 128) ng/L, Z=-4.21, -3.67, -3.76, -3.31, -3.75, -5.74, -3.55, -4.65, -5.86, all P<0.05). The correlated indexes were performed by multivariate Logistic regression and the results showed that vaccination was a protective factor from death in severe cases (OR=0.01, 95%CI 0-0.97, P=0.049) while pediatric sequential organ failure assessment (PSOFA) (OR=3.31, 95%CI 1.47-7.47, P=0.004), neutrophil-to-lymphocyte ratio (NLR) (OR=1.56, 95%CI 1.05-2.32, P=0.029) and D dimer (OR=1.49, 95%CI 1.00-1.02, P=0.033) were independent risk factors for death (all P<0.05). The area under the curve of the three independent risk factors for predicting death were 0.86 (95%CI 0.79-0.94), 0.89 (95%CI 0.84-0.95) and 0.87 (95%CI 0.80-0.94), all P<0.001, and the cut-off values were 4.50, 3.66 and 4.69 mg/L, respectively. Conclusions: Severe SARS-CoV-2 infection can occur in children of all ages, primarily affecting the respiratory system, but can also infect the nervous system, circulatory system or other systems. Children who died had more severe inflammation, tissue damage and coagulation disorders. The elevations of PSOFA, NLR and D dimer were independent risk factors for death in severe children.

Molecular mechanisms underlying phenotypic degeneration in Cordyceps militaris: insights from transcriptome reanalysis and osmotic stress studies.

Phenotypic degeneration in Cordyceps militaris poses a significant concern for producers, yet the mechanisms underlying this phenomenon remain elusive. To address this concern, we isolated two strains that differ in their abilities to form fruiting bodies. Our observations revealed that the degenerated strain lost the capacity to develop fruiting bodies, exhibited limited radial expansion, increased spore density, and elevated intracellular glycerol levels. Transcriptome reanalysis uncovered dysregulation of genes involved in the MAPK signaling pathway in the degenerate strain. Our RT-qPCR results demonstrated reduced expression of sexual development genes, along with upregulation of genes involved in asexual sporulation, glycerol synthesis, and MAPK regulation, when compared to the wild-type strain. Additionally, we discovered that osmotic stress reduced radial growth but increased conidia sporulation and glycerol accumulation in all strains. Furthermore, hyperosmotic stress inhibited fruiting body formation in all neutralized strains. These findings indicate dysregulation of the MAPK signaling pathway, the possibility of the activation of the high-osmolarity glycerol and spore formation modules, as well as the downregulation of the pheromone response and filamentous growth cascades in the degenerate strain. Overall, our study sheds light on the mechanisms underlying Cordyceps militaris degeneration and identifies potential targets for improving cultivation practices.

[Zellweger syndrome caused by PEX6 gene variation in 2 cases and literature review].

Objective: To summarize the clinical features and genetic characteristics of Zellweger spectrum disorder caused by PEX6 gene variation. Methods: This was a case series research. Clinical date and genetic results of 2 neonatal cases of Zellweger syndrome caused by PEX6 gene variation in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology and Affiliated Hospital of Guangdong Medical University from July 2021 to July 2022 were retrospectively collected and analyzed. Literature up to August 2023 was searched from electronic databases of China National Knowledge Infrastructure (CNKI), Wanfang Data and PubMed with the combined keywords of "Zellweger syndrome" "Zellweger spectrum disorder", and "PEX6 gene" both in Chinese and English. The main clinical features and genetic characteristics of Zellweger spectrum disorder caused by PEX6 gene variation were summarized. Results: The 2 male neonates both developed clinical manifestations as dyspnea, hypotonia, feeding difficulties, enlarged fontanelle, and high palatine arch after birth. Biochemical parameters indicated elevated bile acids, and the cranial ultrasound showed the enlarged bilateral ventricles and subependymal cyst in both 2 neonates. Zellweger syndrome was confirmed by whole exome sequencing, and the results revealed PEX6 gene variation in the 2 neonates, including compound heterozygous variants c.315G>A and c.2095-3T>G, and homozygous variant c.506_507del. Case 1 was hospitalized for 5 days, and case 2 for 32 days; they both died shortly after being discharged (the specific time is unknown). Literature review found 26 patients, including 2 neonates in this study, with Zellweger spectrum disorder caused by PEX6 gene defect reported in 1 Chinese article and 11 English articles. Clinical features included hearing loss (19 cases), developmental delay (19 cases), vision impairment (19 cases), elevated very long chain fatty acids (17 cases), brain malformations (15 cases), hypotonia (12 cases), hepatic insufficiency (12 cases), distinctive facies (10 cases), and dental impairment (9 cases). Compound heterozygous variations dominated the variation types (15 cases), and the frameshift variations (16 cases) were the main pathogenic variations. Conclusions: Zellweger spectrum disorder should be considered when neonates show hypotonia, feeding difficulty, distinctive facial appearance, brain malformations and failure of hearing screening, or when older children show retinitis pigmentosa, sensorineural hearing loss, amelogenesis imperfecta and developmental delays. Detection of genetic variation in the PEX gene is crucial for definitive diagnosis.

[Detection rate and clinical characteristics of vulvar squamous intraepithelial lesion].

Objective: To explore the detection rate, clinical characteristics of vulvar squamous intraepithelial lesion (SIL). Methods: Women diagnosed with vulvar high-grade squamous intraepithelial lesions (HSIL) through colposcopy-guided biopsy from January 1, 2018 to August 31, 2022 in Obstetrics and Gynecology Hospital of Fudan University were included in a 1∶1 ratio with patients diagnosed with vulvar low-grade squamous intraepithelial lesions (LSIL) during the same period. Clinical characteristics including human papillomavirus (HPV) infection rate, genotype, cytology result, colposcopy impression, and lesion location were retrospectively analyzed. Results: (1) The proportion of vulvar SIL detected by colposcopy-guided biopsy increased annually from 2018 to 2022, with rates of 1.64% (740/45 057), 2.34% (1 110/47 402), 2.68% (1 108/41 335), 3.26% (1 536/47 078), 3.31% (667/20 155), with an average rate of 2.57% (5 161/201 027). (2) A total of 1 096 cases of vulvar HSIL and 1 096 cases of vulvar LSIL were included. The overall infection rate of HPV was 92.7% (1 993/2 150), with higher infection rate in vulvar HSIL patients than that in vulvar LSIL patients [96.0% (1 012/1 054) vs 89.5% (981/1 096); χ2=33.62, P<0.001]. Among vulvar HSIL patients, the common HPV genotype from high to low were HPV 16 (66.7%), HPV 52 (14.3%), and HPV 58 (10.0%). For vulvar LSIL patients, the most common HPV genotype were respectively HPV 16 (24.9%), HPV 6 (20.1%) and HPV 52 (17.1%). The overall sensitivity rate of cytology was 53.6%, with no significance difference between vulvar LSIL and HSIL groups (54.3% vs 52.9%; χ2=0.40, P=0.526). The accuracy of colposcopy impression for vulvar HSIL was lower than that for vulvar LSIL [40.2% (163/405) vs 81.7% (380/465); χ2=158.72, P<0.001]. About 57.3% (1 257/2 192) of the patients had concomitant cervical and vaginal lesions, with a higher rate in vulvar HSIL group than that in vulvar LSIL group [62.6% (686/1 096) vs 52.1% (571/1 096); χ2=24.67, P<0.001]. Unifocal lesion was the main type, with no significance difference between vulvar LSIL and HSIL groups [81.4% (381/468) vs 82.5% (386/468); χ2=0.18, P=0.671]. The most common lesion locations were the posterior commissure, followed by labia minora, vaginal vestibule, labia majora, perianal and clitoris. Conclusions: The detection rate of vulvar SIL under colposcopy is about 3%, and the infection rate of HPV is 92.7%. Vulvar SIL, especially vulvar HSIL, is likely to cause concomitant cervical and vaginal lesions. The accuracy of colposcopy in diagnosing vulvar HSIL is low. Therefore a comprehensive and careful examination of the vulva is necessary and suspicious vulvar lesions should be undergone colposcopy-guided biopsy for diagnosis.

[Value of artificial intelligence in the improvement of diagnostic consistency of radiology residents].

OBJECTIVE: To explore the value of artificial intelligence (AI) in improving the detection rate of traumatic rib fractures by radiologist residents and the consistency among different readers. METHODS: Chest CT images of 393 patients with acute trauma from China-Japan Union Hospital of Jilin University (hospital 02) and Shanghai Ninth People' s Hospital (hospital 03) were collected in this research. The consensus achieved by three radiology experts was regarded as the reference standard. All the images assigned to three hospitals: Peking University First Hospital (hospital 01), hospital 02 and hospital 03, and were then randomly divided into two groups (group A and group B: group A included 197 patients, and group B included 196 patients). Each group was read by one radiologist resident from each hospital for rib fracture detection. Each case was read twice by the same radiologist, with and without the assistance of the AI ["radiologist-only" reading and "radiologist + AI" reading]. The detection rates of different types of rib fractures (displaced fractures and occult fractures) were compared between "radiologist-only" reading and "radiologist + AI" reading. The consistencies of different radiologists with different reading methods were evaluated. RESULTS: The detection rates of displaced rib fractures and occult rib fractures by "radiologist + AI" reading were significantly higher than those read by "radiologist-only" reading (94.56% vs. 78.40%, 76.60% vs. 49.42%, P < 0.001). For "radiologist-only reading", the Kappa coefficients of the radiologists between hospital 01 and hospital 03 were slightly greater than 0.4 (indicating moderate consistency), the coefficients of the radiologists between hospital 01/hospital 02 and hospital 02/hospital 03 were less than 0.4 (indicating poor consistency). The Phi coefficients of the radiologists among different hospitals were all less than 0.6 (indicating moderate correlation). With "radiologist + AI" reading, the Kappa and Phi coefficient among the radiologists in dif-ferent hospitals were greater than or equal to 0.6 (indicating good consistency and correlation). CONCLUSION: AI software can be used to automatically detect suspected rib fracture lesions, which helps to improve the detection rate of fracture lesions and the consistency among different readers.

[Comparison of pulmonary vascular tortuosity and fractal dimension in patients with chronic thromboembolic pulmonary disease and chronic thromboembolic pulmonary hypertension].

Objective: To compare the differences in pulmonary vascular morphological parameters between patients with chronic thromboembolic pulmonary disease (CTEPD) and chronic thromboembolic pulmonary hypertension(CTEPH), and to explore the value of pulmonary artery morphology in the differential diagnosis of CTEPD and CTEPH. Methods: Thirty-nine patients with CTEPH [14 males, 25 females, mean age: (54.1±12.4) years] and 29 patients with CTEPD [10 males, 19 females, mean age: (51.4±18.0) years] from January 2018 to December 2020 were retrospectively included. The pulmonary artery and vein tree was segmented from the computed tomography pulmonary angiography (CTPA) images, and the morphological parameters of pulmonary vessels including the number of pulmonary arteries, pulmonary arterial tortuosity(distance metric, DM) and fractal dimension (FD), were calculated. The differences in pulmonary vascular morphological parameters between the two groups were compared, and the correlation between morphological parameters and hemodynamics was analyzed. Results: There was no significant difference in gender and age between CTEPH and CTEPD groups (χ2=0.015,P=0.904 & t=-0.729, P=0.469). The number of pulmonary arteries in CTEPH group (n=249.43±76.27) was significantly lower than that in CTEPF group (n=298.79±78.11, t=2.612, P=0.011). The pulmonary arterial tortuosity in CTEPH group (DM=1.26±0.17) was significantly higher than that in CTEPD group (DM=1.17±0.10, t=3.516, P=0.002). There was no significant difference in FD between CTEPH and CTEPD (FD=3.01±0.21 & 3.08±0.22, t=1.359, P=0.179). The number of pulmonary arteries was negatively correlated with pulmonary vascular resistance (r=-0.325, P=0.026). Pulmonary arterial tortuosity was positively correlated with mean pulmonary artery pressure (r=0.387,P=0.017), and was positively correlated with pulmonary vascular resistance (r=0.647, P<0.001). Conclusion: Pulmonary artery curvature is an important morphological parameter in differentiating CTEPH from CTEPD, and is related to mean pulmonary artery pressure and pulmonary vascular resistance.

[Comparative study of next generation sequencing and immunohistochemistry on molecular classification of endometrial carcinoma].

Objective: To investigate the differences in molecular classification of endometrial carcinoma (EC) between various technical methods and to explore molecular classification schemes suitable for Chinese population. Methods: The study used a comprehensive scheme of next generation sequencing (NGS) and immunohistochemistry for molecular classification of 254 EC cases that were obtained at Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China from April 2021 to March 2022. According to the recommended threshold of Sanger sequencing which was approximate-20% variant allele fraction (VAF), NGS data were extracted to simulate the results of Sanger sequencing. Results: The 254 EC patients had a mean age of 51 years (range, 24 to 89 years). Combination of POLE (9-14 exons), TP53 total exons and microsatellite instability (MSI) detection was a better single scheme than NGS alone, while combination of MSI fragment analysis and conventional immunohistochemistry was the best solution and seemed best aligned with TCGA data and recent studies. POLE ultramuted type, mismatch repair defect type, TP53 mutant type and non-specific molecular characteristic type accounted for 11.4% (29/254), 31.5% (80/254), 22.4% (57/254) and 34.6% (88/254) of the cases, respectively. If Sanger sequencing was adopted for POLE and TP53 detection, the frequencies of these EC types were 9.1% (23/254), 31.5% (80/254), 12.9% (33/254) and 46.6% (118/254), respectively, with greatly increasing non-specific molecular characteristics cases. If POLE was detected by Sanger sequencing and others by immunohistochemistry, they were 9.1% (23/254), 42.2% (92/218), 13.8% (35/254) and 40.9% (105/254), respectively, with increasing the false positive rates of the mismatch repair defect group. Conclusions: Small and medium-sized NGS panels with MSI detection is a better solution than NGS alone. Sanger sequencing is currently available for POLE mutation detection, which is not sensitive enough for TP53 mutation detection, and seems equivalent to the efficiency of TP53 by immunohistochemistry. Further optimization of small and medium-sized NGS panels covering MSI detection and POLE and TP53 full exons may be the best choice for the future to meet national conditions.

Current status and research progress of nanoparticle application in superficial fungal infection.

Superficial fungal infections (SFIs) are characterized by diverse etiologies, complex pathogenesis, and marked geographical differences in patient symptoms. Conventional management of SFIs is associated with complications such as hepatotoxicity, skin problems, severe headaches, and clinical difficulties including intractable relapses and drug-drug interactions in patients with chronic diseases remain to be addressed. Moreover, in topical treatment, low penetration of antifungal drugs in hard tissues such as finger (toe) nails and drug-resistant fungi are emerging concerns in current antifungal therapy. Nanotechnology has been a leading research topic in recent years for new dosing forms of antifungal drugs, chemical modification of traditional drugs, and pharmacokinetic improvement, providing potential opportunities for the effective treatment of SFIs. The present study reviewed the direct use of nanoparticles in SFIs and the use of nanoparticles as carriers in SFIs and discussed their future medicinal applications. Graphical Abstract: https://www.europeanreview.org/wp/wp-content/uploads/01-12915-PM-29863.jpg.

[Efficacy of Hintermann calcaneal lengthening osteotomy for flexible flatfoot].

Objective: To investigate the clinical efficacy of Hintermann osteotomy (H-LCL) for flexible flatfoot. Methods: A follow-up study. Clinical data of 30 patients with flexible flatfoot treated with H-LCL operation from January 2020 to December 2021 in Sports Medical Center of the First Affiliated Hospital of Army Medical University were retrospectively analyzed. There were 8 males and 22 females, with a mean age of (39.0±15.2) years. The mean time from symptom onset to the diagnosisï¼»M（Q1，Q3）］was 24.0 (5.5, 102.0) months. The functional and imaging scores of the patients before and after the last follow-up were compared to evaluate the clinical efficacy of the operation. The functional scores included American Orthopedic Foot and Ankle Society (AOFAS) score, visual analogue scale (VAS) of pain, pain interference (PI) and physical function (PF) index in Patient-Reported Outcomes Measurement Information System (PROMIS). And the imaging scores included Meary's angle, calcaneal pitch angle, calcaneal valgus angle and talonavicular coverage angle. Results: The mean operation time was (82.3±24.4) min, and the follow-up periods was (17.9±6.9) months. At the last follow-up, VAS of pain [M(Q1, Q3)] decreased from 5 (4, 6) to 2 (1, 2); PI decreased from 59.8±5.0 to 44.6±5.7; AOFAS increased from 65.2±10.0 to 85.8±3.3; PF increased from 50 (48.5,51.0) to 58.5 (54.0, 66.0); Meary's angle (antero-posterior image) decreased from 15.7° (10.1°, 29.2°) to 3.9° (2.6°, 5.3°); Meary's angle (lateral image) decreased from 13.5°±6.8° to 4.4°±2.6°; calcaneal pitch angle increased from 14.0°±3.3° to 18.6°±4.2°; calcaneal valgus angle decreased from 12.6°±7.3° to 4.3°±2.5°; and talonavicular coverage angle decreased from 20.9°±10.7° to 7.7°±5.2°. The up-mentioned parameters were all improved statistically significant at the last follow-up when compared with those before the operation (all P<0.05). Conclusion: H-LCL brings a significant improvement of clinical outcome scores and good radiological correction of flatfoot deformities in correcting flexible flatfoot, it conforms to the anatomical characteristics of the subtalar joint.

[Rescue balloon pulmonary angioplasty for a patient with acute exacerbation of chronic thromboembolic pulmonary hypertension supported by extracorporeal membrane oxygenation: a case report].

A 33-year-old male patient was admitted to hospital because of "dyspnea after activity for 3 years and aggravation for 15 days". With a history of membranous nephropathy, irregular anticoagulation led to acute exacerbation of Chronic thromboembolic pulmonary hypertension(CTEPH) and acute respiratory failure, and endotracheal intubation and mechanical ventilation was given. Although treated with thrombolysis and adequate anticoagulation, the condition worsened and hemodynamics deteriorated, and then VA-ECMO was performed. Due to severe pulmonary hypertension and right heart failure,ECMO could not be weaned off, and the patient subsequently developed pulmonary infection, right lung hemorrhage, hyperbilirubinemia, coagulation dysfunction and other complications. Then the patient was transferred to our hospital by airplane, and multidisciplinary discussions were quickly arranged after admission. Considering that the patient was critically ill and complicated with multiple organ failure, pulmonary endarterectomy (PEA) could not be tolerated, rescue balloon pulmonary angioplasty (BPA) was recommended and performed on the second day after admission. The mean pulmonary artery pressure was 59 mmHg(1 mmHg=0.133 kPa) measured by right heart catheterization, and pulmonary angiography showed that the main pulmonary artery was dilated, while the right lower pulmonary artery was completely occluded, and there were multiple stenoses in the branches of the right upper lobe, middle lobe pulmonary artery and the left pulmonary artery. BPA was performed on a total of 9 pulmonary arteries. VA-ECMO was weaned off on day 6 after admission, and the mechanical ventilation was weaned off on day 41 after admission. The patient was successfully discharged on day 72 after admission. Rescue BPA was an effective treatment for severe CTEPH patients who could not be treated with PEA.

[Genetic variations in four geographical isolates of Gohieria fusca based on cytochrome b and internal transcribed spacer genes].

OBJECTIVE: To investigate the genetic diversity and genetic differentiation of different geographical isolates of Gohieria fusca. METHODS: G. fusca isolates were sampled from Wuhu (WH), Bengbu (BB) and Bozhou cities (BZ) of Anhui Province and Jiaxing City of Zhejiang Province (JX). Mitochondrial cytochrome b (Cytb) and ribosomal internal transcribed spacer (ITS) genes were amplified in WH, BB, BZ and JX isolates of G. fusca using PCR assay. The gene sequences were edited and aligned using the software Chromas 2 and DNASTAR 1.00, and the haplotype, haplotype diversity (Hd) and nucleotide polymorphism (Pi) of each isolate were calculated using the software DnaSP 5.10.00. The genetic differentiation among isolates (Fst) and gene flow value (Nm) were estimated using the software MEGA 10.2, and a phylogenetic tree was built. Tests of neutrality and analysis of molecular variance (AMOVA) were performed using the software Arlequin 3.1 and a haplotype network was built based on the Median-Joining network using the software Network 10.2. RESULTS: PCR assay showed that the sizes of the Cytb and ITS genes were 372 bp and 1 301 to 1 320 bp, respectively. All four isolates of G. fusca presented high genetic diversity based on mitochondrial Cytb and ITS genes (Hd = 0.804, Pi = 0.006 91). AMOVA showed genetic differentiation among geographical isolates of G. fusca (Fst = 0.202 40, P < 0.05), and the genetic variation was mainly caused by intra-population variations (79.76%). Gene flow analysis showed a high level of gene flow among G. fusca isolates (Nm > 1). Tests of neutrality based on Cytb gene measured a Tajima's D value of -1.796 31 (P < 0.05) and a Fu's FS value of -3.293 98 (P < 0.05) in WH isolate of G. fusca, indicating population expansion in WH isolate of G. fusca. Haplotype network analysis and phylogenetic analysis revealed no remarkable geographical distribution pattern among different geographical isolates of G. fusca. All four isolates of G. fusca presented high genetic diversity (Hd = 0.985, Pi = 0.011 97). AMOVA showed moderate level of genetic differentiation between four isolates (Fst = 0.104 62, P < 0.05). The tests of neutrality based on ITS genes measured a Tajima's D value of -6.088 20 and a Fu's FS value of -1.935 99 (both P > 0.05) in the whole isolate of G. fusca, indicating no obviously population expansion. CONCLUSIONS: The four geographical isolates of G. fusca have high genetic diversity and remarkable genetic differentiation. Since a high level of gene flow is detected among different geographical isolates of G. fusca, no obvious geographical distribution pattern of G. fusca is found.

[Clinical and chest CT features of immune checkpoint inhibitor-related pneumonitis].

Objective: To explore the clinical and chest computed tomography (CT) features and the outcome of immune checkpoint inhibitor-related pneumonitis (CIP). Methods: Clinical and chest CT data of 38 CIP patients with malignant tumors from the Cancer Hospital, Chinese Academy of Medical Sciences between August 2017 and April 2021 were retrospectively reviewed, and the outcomes of pneumonitis were followed up. Results: The median time from the administration of immune checkpoint inhibitors (ICIs) to the onset of CIP was 72.5 days in 38 patients with CIP, and 22 patients developed CIP within 3 months after the administration of ICIs. The median occurrence time of CIP in 24 lung cancer patients was 54.5 days, earlier than 119.0 days of non-lung cancer patients (P=0.138), with no significant statistical difference. 34 patients (89.5%) were accompanied by symptoms when CIP occurred. The common clinical symptoms were cough (29 cases) and dyspnea (27 cases). The distribution of CIP on chest CT was asymmetric in 31 cases and symmetrical in 7 cases. Among the 24 lung cancer patients, inflammation was mainly distributed ipsilateral to the primary lung cancer site in 16 cases and diffusely distributed throughout the lung in 8 cases. Ground glass opacities (37 cases) and consolidation (30 cases) were the common imaging manifestations, and organizing pneumonia (OP) pattern (15 cases) was the most common pattern. In 30 CIP patients who were followed up for longer than one month, 17 cases had complete absorption (complete absorption group), and 13 cases had partial absorption or kept stable (incomplete absorption group). The median occurrence time of CIP in the complete absorption group was 55 days, shorter than 128 days of the incomplete absorption group (P=0.022). Compared with the incomplete absorption group, there were less consolidation(P=0.010) and CIP were all classified as hypersensitivity pneumonitis (HP) pattern (P=0.004) in the complete absorption group. Conclusions: CIP often occurs within 3 months after ICIs treatment, and the clinical and CT findings are lack of specificity. Radiologic features may have a profound value in predicting the outcome of CIP.

Acute and Repeated Administration of NLX-101, a Selective Serotonin-1A Receptor Biased Agonist, Reduces Audiogenic Seizures in Developing Fmr1 Knockout Mice.

Fragile XSyndrome (FXS) is a leading known genetic cause of Autism Spectrum Disorders (ASD) and intellectual disability. A consistent and debilitating phenotype of FXS is sensory hypersensitivity that manifests strongly in the auditory domain and may lead to delayed language and high anxiety. The mouse model of FXS, the Fmr1 KO mouse, also shows auditory hypersensitivity, an extreme form of which is seen as audiogenic seizures (AGS). The midbrain inferior colliculus (IC) is critically involved in generating audiogenic seizures and IC neurons are hyper-responsive to sounds in developing Fmr1 KO mice. Serotonin-1A receptor (5-HT1A) activation reduces IC activity. Therefore, we tested whether 5-HT1A activation is sufficient to reduce audiogenic seizures in Fmr1 KO mice. A selective and post-synaptic 5-HT1A receptor biased agonist, 3-Chloro-4-fluorophenyl-[4-fluoro-4-[[(5-methylpyrimidin-2-ylmethyl)amino]methyl]piperidin-1-yl] methanone (NLX-101, 0.6, 1.2, 1.8 or 2.4 mg/kg, i.p.) was administered to Fmr1 KO mice 15 min before seizure induction. Whereas the 0.6 mg/kg dose was ineffective in reducing seizures, the 1.2, 1.8 and 2.4 mg/kg doses of NLX-101 dramatically reduced seizures and increased mouse survival. Treatment with a combination of NLX-101 and 5-HT1A receptor antagonists prevented the protective effects of NLX-101, indicating that NLX-101 acts selectively through 5-HT1A receptors to reduce audiogenic seizures. NLX-101 (1.8 mg/kg) was still strongly effective in reducing seizures even after repeated administration over 5 days, suggesting an absence of tachyphylaxis to the effects of the compound. Together, these studies point to a promising treatment option targeting post-synaptic 5-HT1A receptors to reduce auditory hypersensitivity in FXS, and potentially across autism spectrum disorders.

[Survival and prognosis analysis of patients with Hodgkin lymphoma treated with standard treatment paradigm].

Objective: To analyze the survival and prognosis of Hodgkin lymphoma (HL) patients receiving standard first-line therapy. Methods: Data of clinical characteristics and treatment outcomes of patients with HL diagnosed in Cancer Hospital Chinese Academy of Medical Sciences (CHCAMS) from January 1st, 2000 to December 31st, 2018 who received standard first-line treatment were retrospectively analyzed and compared with that of HL patients who received treatment in the Surveillance, Epidemiology and End Results (SEER) database in the United States during the same period. Factors associated with freedom from progression (FFP) of patients in CHCAMS were analyzed. Treatment and survival data of patients with relapsed/refractory HL (r/rHL) who had failed the standard first-line treatment during the corresponding period in CHCAMS were collected to analyze the outcomes of salvage therapy. Results: A total of 764 HL patients in CHCAMS were included in this study. The median age was 30 years (range, 14-83 years), with 424 males and 340 females. By February 26th, 2022, the patients were followed-up for a median time of 111 months(range, 0.3-262.0 months). Lymphoma-specific survival (LSS) rate and overall survival (OS) rate at 10 years for HL patients in CHCAMS was 91.7% (95%CI: 89.5%-93.9%) and 87.1% (95%CI: 84.5%-89.8%), respectively. LSS and OS rate at 10 years for HL patients from SEER database was 86.8% (95%CI: 86.3%-87.2%) and 79.0% (95%CI: 78.5%-79.5%), respectively. The unadjusted LSS and OS rate for patients in CHCAMS were higher than those for patients from SEER database (both P<0.001). No significant difference was observed in LSS and OS rate (both P>0.05) between the two groups after adjustment. European Organization for Research and Treatment of Cancer staging system (early-stage unfavorable: HR=2.35, 95%CI: 1.13-4.89, P=0.023; advanced stage: HR=5.44, 95%CI: 2.62-11.30, P<0.001) and serum ß2 microglobulin (HR=1.67, 95%CI: 1.08-2.58, P=0.021) were influencing factors of FFP for patients in CHCAMS. The complete remission rate, median progression-free survival (PFS), 5-year PFS rate and 5-year OS rate for the 116 patients with r/rHL was 37.9% (95%CI: 29.6%-47.0%), 15.0 months (95%CI: 9.9-20.1 months), 29.9% (95%CI: 20.9%-38.9%) and 62.9% (95%CI: 54.1%-71.7%), respectively. Conclusions: The outcomes of HL patients receiving standard first-line treatment are excellent. However, the therapeutic effect of HL patients who incurrs disease progression or relapse after standard first-line treatment is not satisfying.

Application value of Qisexingtai hand diagnostic method in diagnosis of coronary artery disease.

OBJECTIVE: To evaluate the diagnostic efficacy of Qisexingtai hand diagnostic method in the diagnosis of coronary artery disease (CAD). METHODS: This was an investigator-initiated, prospective, multi-center, cross-sectional study. All the participants from three hospitals in China had been diagnosed by both Qisexingtai hand diagnostic method and coronary angiography. We compared the two diagnostic methods to calculate the sensitivity, the specificity, the omission diagnostic rate, the mistaken diagnostic rate and accuracy in order to evaluate the diagnostic efficacy of Qisexingtai hand diagnostic method for CAD. RESULTS: A total of 326 subjects were enrolled, diagnosed by both Qisexingtai hand diagnostic method and coronary angiography. As a result, there were 166 positive cases according to Qisexingtai hand diagnostic method, and 131 positive cases according to coronary angiography. Compared with the results of coronary angiography, the sensitivity of Qisexingtai hand dia-gnostic method was 80.2%, the specificity was 68.7%, the omission diagnostic rate was 19.8%, the mistaken diagnostic rate was 31.3%, and the accuracy was 73.3%. Area under the receiver operating characteristic curve was estimated as 0.735 for all, and 0.718, 0.735, 0.783 for the three sub-centers. CONCLUSION: Qisexingtai hand diagnostic method with high accuracy and sensitivity has certain application value in the diagnosis of CAD.

[Characteristics analysis of oral clinical trials registered in Chinese Clinical Trial Registry].

Objective: To investigate the project characteristics of oral clinical trials registered in Chinese Clinical Trial Registry (ChiCTR), and to provide reference for medical institutions to improve the quality of oral clinical trials and formulate management systems. Methods: The ChiCTR database was retrieved to collect all the oral-related clinical trials from the time of database establishment to July 25, 2021. Those clinical trials were analyzed statistically in respect of name of registered project, registration time, registration status, regional distribution of research institutions, approval status by ethics committee, sample size, source of funds, involved disease, research type and design, randomization method, and whether blind method was adopted. Results: A total of 778 oral clinical trials, which studied mainly in the oral and maxillofacial diseases, periodontal tissue diseases, oral implant diseases, oral mucosal diseases, and oral prosthetic diseases, were retrieved in the database. Beijing, Sichuan, Shanghai, Guangdong and Hubei were major regions where oral clinical trials were carried out, accounting for 69.68% (772/1 108) of the total. The top four funding sources were hospital finance [24.93% (186/746)], local government finance [22.39% (167/746)], self-financing [17.69% (132/746)], and national finance [12.47% (93/746)]. For the types of researches, 520 interventional studies and 244 observational studies were identified (accounting for 66.84% and 31.36%, respectively). The research designs were dominated by ways of randomized control (381, 48.97%), of which 240 (62.99%) trials were with missing or unspecified blinding methods. Conclusions: Oral clinical trials are increasing year by year, but they are regionally imbalanced, and still need to be further improved in registration information and research design. Administrative departments should pay more attention to strengthen the publicity and education on the registration and publication mechanism of clinical trials, and enhance researchers' cognitions in clinical trials registration and clinical trials design.

[An adaptive CT metal artifact reduction algorithm that combines projection interpolation and physical correction].

OBJECTIVE: To propose an adaptive weighted CT metal artifact reduce algorithm that combines projection interpolation and physical correction. METHODS: A normalized metal projection interpolation algorithm was used to obtain the initial corrected projection data. A metal physical correction model was then introduced to obtain the physically corrected projection data. To verify the effectiveness of the method, we conducted experiments using simulation data and clinical data. For the simulation data, the quantitative indicators PSNR and SSIM were used for evaluation, while for the clinical data, the resultant images were evaluated by imaging experts to compare the artifact-reducing performance of different methods. RESULTS: For the simulation data, the proposed method improved the PSNR value by at least 0.2 dB and resulted in the highest SSIM value among the methods for comparison. The experiment with the clinical data showed that the imaging experts gave the highest scores of 3.616±0.338 (in a 5-point scale) to the images processed using the proposed method, which had significant better artifact-reducing performance than the other methods (P < 0.001). CONCLUSION: The metal artifact reduction algorithm proposed herein can effectively reduce metal artifacts while preserving the tissue structure information and reducing the generation of new artifacts.