Ultrahigh-energy photons up to 1.4 petaelectronvolts from 12 γ-ray Galactic sources.

The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 1015 electronvolts) indicates the existence of the so-called PeVatrons-cosmic-ray factories that accelerate particles to PeV energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays1. The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref. 2). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane3-6, unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators.

UniProt and Mass Spectrometry-Based Proteomics-A 2-Way Working Relationship.

The human proteome comprises of all of the proteins produced by the sequences translated from the human genome with additional modifications in both sequence and function caused by nonsynonymous variants and posttranslational modifications including cleavage of the initial transcript into smaller peptides and polypeptides. The UniProtKB database (www.uniprot.org) is the world's leading high-quality, comprehensive and freely accessible resource of protein sequence and functional information and presents a summary of experimentally verified, or computationally predicted, functional information added by our expert biocuration team for each protein in the proteome. Researchers in the field of mass spectrometry-based proteomics both consume and add to the body of data available in UniProtKB, and this review highlights the information we provide to this community and the knowledge we in turn obtain from groups via deposition of large-scale datasets in public domain databases.

Measurements of All-Particle Energy Spectrum and Mean Logarithmic Mass of Cosmic Rays from 0.3 to 30 PeV with LHAASO-KM2A.

We present the measurements of all-particle energy spectrum and mean logarithmic mass of cosmic rays in the energy range of 0.3-30 PeV using data collected from LHAASO-KM2A between September 2021 and December 2022, which is based on a nearly composition-independent energy reconstruction method, achieving unprecedented accuracy. Our analysis reveals the position of the knee at 3.67±0.05±0.15 PeV. Below the knee, the spectral index is found to be -2.7413±0.0004±0.0050, while above the knee, it is -3.128±0.005±0.027, with the sharpness of the transition measured with a statistical error of 2%. The mean logarithmic mass of cosmic rays is almost heavier than helium in the whole measured energy range. It decreases from 1.7 at 0.3 PeV to 1.3 at 3 PeV, representing a 24% decline following a power law with an index of -0.1200±0.0003±0.0341. This is equivalent to an increase in abundance of light components. Above the knee, the mean logarithmic mass exhibits a power law trend towards heavier components, which is reversal to the behavior observed in the all-particle energy spectrum. Additionally, the knee position and the change in power-law index are approximately the same. These findings suggest that the knee observed in the all-particle spectrum corresponds to the knee of the light component, rather than the medium-heavy components.

Chinese family care partners of older adults in Canada have grit: A qualitative study.

AIM: To explain the process taken by Chinese family care partners of older adults in the Greater Toronto Area, Canada, to access health and social services in their communities. The research question was: What mechanisms and structures impact the agency of Chinese family care partners of older adults, in the process of assisting them to access health and social services? DESIGN: This qualitative study was informed by critical realism. METHODS: Chinese family care partners of older adults in the Greater Toronto Area, Canada, were interviewed from August 2020 to June 2021. Transcripts underwent thematic analysis. FINDINGS: Twenty-eight Chinese family care partners expressed a firm commitment to maintain caregiving conditions and to judiciously access health and social services. Their commitment was made up of three parts: (a) legislative and cultural norms of family, work, and society; (b) their perseverance to fill gaps with limited social and financial resources; (c) the quality of their relationship to, and illness trajectory of the older adults. The social structures created tension in how Chinese family care partners made decisions, negotiated resources, and ultimately monitored and coordinated timely access with older adults. CONCLUSION: Participants' commitment and perseverance were conceptualized as "grit," central to their agency to conform to legislative and cultural norms. Moreover, findings support grit's power to motivate and sustain family caregiving, in order for older adults to age in place as long as possible with finite resources. IMPLICATIONS FOR THE PROFESSION: This study highlights the importance of cultural awareness education for nurses, enabling continuity of care at a systems level and for a more resilient healthcare system. IMPACT: Family care partners' grit may be crucial for nurses to harness when together, they face limited access to culturally appropriate health and social services in a system grounded in values of equity and inclusion, as in Canada. REPORTING METHOD: When writing this manuscript, we adhered to relevant EQUATOR guidelines of the Consolidated Criteria for Reporting Qualitative Research (COREQ). PATIENT OR PUBLIC INVOLVEMENT AND ENGAGEMENT: No patient or public involvement.

Development and validation of the Sinonasal Endoscopic Score (SiNES) for chronic rhinosinusitis.

BACKGROUND: Although there are several endoscopic grading systems for chronic rhinosinusitis (CRS), they are limited in their range and applicability. We developed a SiNonasal Endoscopic Score (SiNES) that builds upon the strengths of previous systems while addressing their limitations. METHODS: The SiNES system was developed by consensus after multiple rounds of guided discussions. Face, content, and convergent validity were investigated. It was validated using an independent sample of 79 CRS individuals from two referral centres from September 2021 to February 2022. Each patient underwent a sinonasal endoscopy and filled PROM questionnaires. Three independent rhinologists graded endoscopic videos using the SiNES and modified Lund-Kennedy (MLK) scores. Inter-rater and test-retest reliability were assessed via the intraclass correlation coefficient (ICC). SiNES and MLK scores were correlated with PROMs using a Spearman correlation and canonical correlation analysis (CCA). RESULTS: The SiNES system evaluates five anatomical spaces regarding edema, discharge, and scarring. Face, content, and convergent validity were deemed satisfactory by the study authors and an independent panel of Otolaryngologists. Inter-rater reliability was excellent for the SiNES and good for the MLK score. Test-retest reliability was excellent for both systems. Total SiNES was correlated with self-reported smell loss. CONCLUSIONS: The SiNES system is an accurate and reliable grading framework applicable to all CRS subtypes. It can be utilized in clinical and research settings and improves upon previously published systems.

[Analysis of clinical and genetic characteristics of the severe liver disease phenotype in patients with hepatolenticular degeneration].

Objective: To investigate the clinical and genetic characteristics and predictive role of the severe liver disease phenotype in patients with hepatolenticular degeneration (HLD). Methods: Inpatients with HLD confirmed at Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine from January 1989 to December 2022 were selected as the research subjects. Clinical classification was performed according to the affected organs. Patients with liver disease phenotypes were classified into the liver disease group and further divided into the severe liver disease group and the ordinary liver disease group. The clinical characteristics and genetic variations were compared in each group of patients. The predictive indicators of patients with severe liver disease were analyzed by multiple regression. Statistical analysis was performed using the t-test, Mann-Whitney U test, or χ(2) test according to different data. Results: Of the 159 HLD cases, 142 were in the liver disease group (34 in the severe liver disease group and 108 in the ordinary liver disease group), and 17 were in the encephalopathy group. The median age of onset was statistically significantly different between the liver disease group and the encephalopathy group [12.6 (7.0, 13.3) years versus 16.9 (11.0, 21.5) years, P<0.01]. 156 ATP7B gene mutation sites were found in 83 cases with genetic testing results, of which 54 cases carried the p.Arg778Leu gene mutation (allele frequency 46.2%). Compared with patients with other types of gene mutations (n=65), patients with homozygous p.Arg778Leu mutations (n=18) had lower blood ceruloplasmin and albumin levels, a higher prognostic index, Child-Pugh score, an international normalized ratio, and prothrombin time (P<0.05). Hemolytic anemia, corneal K-F ring, homozygous p.Arg778Leu mutation, and multiple laboratory indexes in the severe liver disease group were statistically significantly different from those in the ordinary liver disease group (P<0.05). Multivariate logistic regression analysis showed that the predictive factors for severe liver disease were homozygous p.Arg778Leu mutation, total bilirubin, and bile acids (ORs=16.512, 1.022, 1.021, 95% CI: 1.204-226.425, 1.005-1.039, and 1.006-1.037, respectively, P<0.05). The drawn ROC curve demonstrated a cutoff value of 0.215 3, an AUC of 0.953 2, and sensitivity and specificity of 90.91% and 92.42%, respectively. Conclusion: Liver disease phenotypes are common in HLD patients and have an early onset. Total bilirubin, bile acids, and the homozygous p.Arg778Leu mutation of ATP7B is related to the severity of liver disease in HLD patients, which aids in predicting the occurrence and risk of severe liver disease.

[Analysis of the effect of all-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening for Achilles tendon contracture].

Objective: To examine the feasibility and clinical effect of all-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening for Achilles tendon contracture. Methods: This is a retrospective case series study. From February 2021 to February 2023, the clinical data of 24 patients (30 feet) with Achilles tendon contracture treated with all-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening were analyzed retrospectively. There were 10 males and 14 females, aged (32.8±16.1) years (range: 9 to 62 years). There were 8 cases of left side only, 10 cases of right side only and 6 cases of bilateral. There were 14 cases (16 feet) of foot varus, 4 cases (6 feet) of foot valgus, and 6 cases (8 feet) without deformity. All patients underwent all-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening. The surgical effects were evaluated using the maximum dorsal extension angle of ankle joint in knee extension position, the visual analogue scale (VAS) of pain, the American Orthopedic Foot and Ankle Society ankle-hindfoot score(AOFAS-AH). Paired sample t test was used to compare the scores before and after operation. Results: All patients successfully completed the operation, and the operation time of Achilles tendon lengthening was (22.0±5.7)minutes (range: 15 to 35 minutes) and the intraoperative blood loss was (6.5±2.7)ml (range: 2 to 15 ml). All patients primarily healing without any complications such as sural nerve injury, Achilles tendon rupture, important blood vessel injury, and obvious decrease of lift heel strength of achilles tendon. All 24 patients were followed up for (17.2±4.5) months (range: 12 to 28 months). One patient suffered from lift heel's weakness in one foot after operation, and recovered after repeated lift heel functional exercises. The ankle dorsiflexion function of two patients with calf triceps spasm were not improved after operation, and it was obviously improved after botulinum toxin injection. At the last follow-up, the maximum dorsal extension angle of ankle joint in knee extension position increased from -9.2°±7.6°(range:-25° to 5°) preoperatively to 14.5°±7.0°(range:0° to 28°)(t=24.83, P<0.01); the VAS score was reduced from (4.5±1.7) points (range:1 to 8 points) preoperatively to (1.5±0.9) points (range:0 to 3 points) (t=9.53, P<0.01), the AOFAS-AH was increased from (60.5±11.4)points (range:38 to 85 points) to (90.8±5.4) points (range:80-100 points)(t=14.21, P<0.01). Conclusions: All-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening for Achilles tendon contracture not only provides Achilles tendon lengthening, but also avoids complications such as Achilles tendon rupture and sural nerve injury. It is an effective method for the treatment of Achilles tendon contracture.

Unintrusive multi-cancer detection by circulating cell-free DNA methylation sequencing (THUNDER): development and independent validation studies.

BACKGROUND: Early detection of cancer offers the opportunity to identify candidates when curative treatments are achievable. The THUNDER study (THe UNintrusive Detection of EaRly-stage cancers, NCT04820868) aimed to evaluate the performance of enhanced linear-splinter amplification sequencing, a previously described cell-free DNA (cfDNA) methylation-based technology, in the early detection and localization of six types of cancers in the colorectum, esophagus, liver, lung, ovary, and pancreas. PATIENTS AND METHODS: A customized panel of 161 984 CpG sites was constructed and validated by public and in-house (cancer: n = 249; non-cancer: n = 288) methylome data, respectively. The cfDNA samples from 1693 participants (cancer: n = 735; non-cancer: n = 958) were retrospectively collected to train and validate two multi-cancer detection blood test (MCDBT-1/2) models for different clinical scenarios. The models were validated on a prospective and independent cohort of age-matched 1010 participants (cancer: n = 505; non-cancer: n = 505). Simulation using the cancer incidence in China was applied to infer stage shift and survival benefits to demonstrate the potential utility of the models in the real world. RESULTS: MCDBT-1 yielded a sensitivity of 69.1% (64.8%-73.3%), a specificity of 98.9% (97.6%-99.7%), and tissue origin accuracy of 83.2% (78.7%-87.1%) in the independent validation set. For early-stage (I-III) patients, the sensitivity of MCDBT-1 was 59.8% (54.4%-65.0%). In the real-world simulation, MCDBT-1 achieved a sensitivity of 70.6% in detecting the six cancers, thus decreasing late-stage incidence by 38.7%-46.4%, and increasing 5-year survival rate by 33.1%-40.4%, respectively. In parallel, MCDBT-2 was generated at a slightly low specificity of 95.1% (92.8%-96.9%) but a higher sensitivity of 75.1% (71.9%-79.8%) than MCDBT-1 for populations at relatively high risk of cancers, and also had ideal performance. CONCLUSION: In this large-scale clinical validation study, MCDBT-1/2 models showed high sensitivity, specificity, and accuracy of predicted origin in detecting six types of cancers.

Measurement of Ultra-High-Energy Diffuse Gamma-Ray Emission of the Galactic Plane from 10 TeV to 1 PeV with LHAASO-KM2A.

The diffuse Galactic γ-ray emission, mainly produced via interactions between cosmic rays and the interstellar medium and/or radiation field, is a very important probe of the distribution, propagation, and interaction of cosmic rays in the Milky Way. In this Letter, we report the measurements of diffuse γ rays from the Galactic plane between 10 TeV and 1 PeV energies, with the square kilometer array of the Large High Altitude Air Shower Observatory (LHAASO). Diffuse emissions from the inner (15°10 TeV). The energy spectrum in the inner Galaxy regions can be described by a power-law function with an index of -2.99±0.04, which is different from the curved spectrum as expected from hadronic interactions between locally measured cosmic rays and the line-of-sight integrated gas content. Furthermore, the measured flux is higher by a factor of ∼3 than the prediction. A similar spectrum with an index of -2.99±0.07 is found in the outer Galaxy region, and the absolute flux for 10≲E≲60 TeV is again higher than the prediction for hadronic cosmic ray interactions. The latitude distributions of the diffuse emission are consistent with the gas distribution, while the longitude distributions show clear deviation from the gas distribution. The LHAASO measurements imply that either additional emission sources exist or cosmic ray intensities have spatial variations.

Willingness to receive and recommend hypothetical mpox vaccination and associated factors in Chinese adults: a community-based survey in Shenzhen, China.

OBJECTIVES: China may face new threats to public health due to the increased risk of imported mpox (monkeypox) cases. However, research gaps exist in the acceptance of mpox vaccination and potential associated factors in the Chinese population. STUDY DESIGN: We conducted a cross-sectional study targeting community residents in Shenzhen, China, from August 5 to September 7 2022. METHODS: A self-administered questionnaire was used to collect information about demographic and health characteristics, mpox-related perceptions, and attitudes towards mpox vaccination. Multivariable logistic regression models were applied to detect the factors associated with willingness to receive and recommend mpox vaccination. RESULTS: A total of 2293 community residents were included in the analyses (average age: 34.03, female: 72.6%). Among the participants, 76.9% were aware of mpox, 62.1% were aware of the global mpox outbreak, but only 53.6% had a high knowledge level of mpox. Males had a higher proportion of high knowledge (56.9% vs 52.3%, P＜0.05) and a lower proportion of high worry (30.2% vs 45.4%, P＜0.05) than females. Approximately 69.1% of the participants were willing to vaccinate against mpox, and 69.6% were willing to recommend mpox vaccination to people around them, in which no gender difference was found. The obstacle reported most among people hesitant to receive vaccination was concerning the safety and side-effects, whereas it changed to be concerning the suitability due to individual health differences among people hesitant to recommend mpox vaccines. Factors associated with the willingness to receive and recommend mpox vaccination included having a history of influenza vaccination, having a history of COVID-19 vaccination, being aware of the global mpox outbreak, having a high knowledge level of mpox, and having a high level of mpox-related worry. CONCLUSIONS: This study identified a moderate willingness to receive and recommend mpox vaccination among Chinese adults. Without gender differences, willingness to receive and recommend mpox vaccination was significantly associated with mpox-related perceptions, such as awareness, knowledge, and worry. Authoritative and up-to-date information is needed to help the general population improve public confidence in mpox vaccines in China.

[Response characteristics of tislelizumab combined with chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer].

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.

[Combinational Overexpression of Foxa3 and Hnf4α Enhance the Proliferation and Prolong the Functional Maintenance of Primary Hepatocytes].

In an in vitro culture system, primary hepatocytes usually display a low proliferation capacity, accompanied with a decrease of viability and a loss of hepatocyte-specific functions. Previous studies have demonstrated that the combination introductions of certain hepatocyte-specific transcription factors are able to convert fibroblasts into functional hepatocyte-like cells. However, such combinational usage of transcription factors in primary hepatocytes culture has not yet sufficiently studied. The forkhead box protein A3 (FoxA3) and hepatocyte nuclear factor 4α (Hnf4α) are liver-enriched transcription factors that play vital roles in the differentiation, and maintenance of hepatocytes. Thus, we simultaneously overexpressed the two genes, Foxa3 and Hnf4α, in rat hepatocytes and observed that the combinational augmentation of these two transcription factors have enhanced the proliferation and stabilized the hepatocyte-specific functions of primary hepatocytes over a long-term culture period.

[Validation of calculation method for dose distribution around radioactive iodine-125 particles based on AAPM TG43 report].

Objective: According to the formula provided by the TG43 report [AAPM TG43 (2004)] proposed by the American Association of Physicists in Medicine (AAPM) in 2004, we calculated the dose distribution around the radioactive iodine-125 particles, and verified the calculation accuracy of the radioactive iodine-125 particles treatment planning system. Methods: AAPM TG43 (2004) report provides two calculation methods when calculating the dose around a single radioactive source. The calculation method that does not consider the geometric structure of the radioactive source is called point source calculation method, and the calculation method that considers the geometric structure of the radioactive source is called line source calculation method. Assuming a single Amersham 6711 radioactive iodine-125 particle with an activity of 100 U, the following point doses were calculated according to the two calculation methods provided by AAPM TG43 (2004) report, at 0°, 90° directions, distances 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5 and 6 cm; In the direction of 45°, the doses at 0.71, 1.41, 2.12, 2.83, 3.54, 4.24, 4.95, 5.66, 6.36, 7.07, 7.78 and 8.49 cm. On the clinically used brachytherapy planning system variseeds 8.0, the above two calculation methods are used to calculate the corresponding activity and the dose around the corresponding type of radioactive iodine-125 particles, and the function of capturing points to templates built in the planning system is used to accurately find the above corresponding point position, using a single measurement of the above corresponding point dose; and comparation of the results were performed to see if there is a statistical difference. Results: The AAPM TG43 report uses point source calculation method to calculate the dose of single Amersham 6711 radioactive iodine-125 particles with activity of 100 U at 0° and 90° directions. The points with the same distance and the same dose are 8 082.18, 1 870.08, 756.58, 381.47, 217.11, 131.91, 86.55, 58.32, 39.97, 27.42, 19.74, 14.13 Gy, respectively, at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5 and 6 cm away from them. In the 45° direction, the doses at the distances of 0.71, 1.41, 2.12, 2.83, 3.54, 4.24, 4.95, 5.66, 6.36, 7.07, 7.78 and 8.49 cm are 3 957.37, 865.83, 329.99, 155.69, 84.10, 48.50, 28.49, 17.80, 11.37, 7.38, 4.98 and 3.39 Gy, respectively; For line source calculation method, radioactive particles are at the same distance as above. The doses at each point in the direction of 0° are 3 128.71, 755.44, 330.30, 180.53, 107.74, 68.56, 46.40, 32.22, 22.70, 16.00, 11.51, 8.24 Gy, respectively. The doses at each point in the direction of 90° are 8 306.46, 1 981.01, 802.74, 405.38, 230.60, 140.03, 91.83, 61.84, 42.36, 29.05, 20.91, 14.97 Gy; In the 45° direction, the dose at the corresponding distance as above is 4 020.78, 877.43, 333.49, 156.93, 84.69, 48.81, 28.65, 17.89, 11.42, 7.41, 4.99 and 3.40 Gy, respectively. The maximum dose difference (0.3%) between the two methods is 7.78 cm in the 45° direction, the maximum difference (-0.3%) between the two methods is 8.49 cm in the 45° direction, and the value of other sampling points is less than 0.3%. The closer the Amersham 6711 iodine-125 particles are to the source in the directions of 0°, 45°, and 90°, the faster the dose will drop, and the dose will drop gradually as the distance increases. Conclusion: The brachytherapy planning system variseeds 8.0 and the AAPM TG43 report calculate a maximum dose difference of 0.3%, which can accurately calculate the dose distribution around radioactive iodine-125 seeds, and provide a reliable tool for the clinical implementation of radioactive iodine-125 particles implantation for tumor treatment.

[NAFLD renaming to MAFLD, MASLD: background, similarities, differences, and countermeasures].

Nonalcoholic fatty liver disease (NAFLD) is a chronic metabolic stress liver injury due to chronic malnutrition in genetically susceptible individuals. With the prevalence of obesity, diabetes, and metabolic syndrome, NAFLD has become the world's number one chronic liver disease, and the flaws of forty years of exclusive disease diagnostic criteria and stigmatized disease terminology are becoming increasingly prominent. To this end, in the past three years, the international consensus group and the three major hepatology societies have suggested that NAFLD be renamed metabolism-associated fatty liver disease (MAFLD) and metabolism-associated steatosis liver disease (MASLD). Here is a description of the background of naming NAFLD, MAFLD, and MASLD, the similarities and differences of the three terms, the existing disputes, and our country's coping strategies.

[Factors influencing the clinical phenotype of hepatolenticular degeneration].

Hepatolenticular degeneration is an autosomal recessive genetic disease caused by mutations in the ATP7B gene. More than 800 mutations have been identified in the ATP7B gene so far, with significant differences in clinical phenotypes among different mutation sites. Totally different clinical phenotypic mutations can even exist in the same gene. Although copper accumulation due to gene mutation is the basis of the pathogenesis of hepatolenticular degeneration, more and more evidence demonstrates that it is difficult to explain the diversity of clinical manifestations solely from the perspective of gene mutation. Therefore, this article reviews the research progress on the factors influencing genotype, modifier genes, epigenetics, age, gender, diet, and other factors on the phenotype of patients with hepatolenticular degeneration.

[Long-term trend analysis of liver cancer survival rate in Qidong region, Jiangsu Province, 1972-2019].

Objective: To analyze the incidence and survival rate of liver cancer cases in the entire population in the Qidong region from 1972 to 2019, so as to provide a basis for prognosis evaluation, prevention, and treatment. Methods: The observed survival rate (OSR) and relative survival rate (RSR) of 34 805 cases of liver cancer in the entire Qidong region population from 1972 to 2019 were calculated using Hakulinen's method with SURV3.01 software. Hakulinen's likelihood ratio test was used for statistical analysis. Age-standardized relative survival (ARS) was calculated using the International Cancer Survival Standard. The Joinpoint regression analysis was performed with Joinpoint 4.7.0.0 software to calculate the average annual percentage change (AAPC) of the liver cancer survival rate. Results: 1-ASR increased from 13.80% in 1972-1977 to 50.20% in 2014-2019, while 5-ASR increased from 1.27% in 1972-1977 to 27.64% in 2014-2019. The upward trend of RSR over eight periods was statistically significant (χ (2) = 3045.29, P < 0.001). Among them, male 5-ASR was 0.90%, 1.80%, 2.33%, 4.92%, 5.43%, 7.05%, 10.78%, and 27.78%, and female 5-ASR was 2.33%, 1.51%, 3.35%, 3.92%, 3.84%, 7.18%, 11.45%, and 29.84%, respectively. There was a statistically significant difference in RSR between males and females (χ (2) = 45.68, P < 0.001). The 5-RSR for each age group of 25-34 years old, 35-44 years old, 45-54 years old, 55-64 years old, 65-74 years old, and 75 years old were 4.92%, 5.29%, 8.17%, 11.70%, 11.63%, and 9.60%, respectively. There were statistically significant differences in RSR among different age groups (χ (2) = 501.29, P < 0.001). The AAPC in Qidong region from 1972 to 2019 for 1-ARS, 3-ASR, and 5-ARS were 5.26% (t = 12.35, P < 0.001), 8.10% (t = 15.99, P < 0.001), and 8.96 % (t = 16.06, P < 0.001), respectively. The upward trend was statistically significant in all cases. The AAPC of 5-ARS was 9.82% in males (t = 14.14, P < 0.001), and 8.79% in females (t = 11.48, P < 0.001), and the upward trend was statistically significant in both. The AAPC of 25-34 years old, 35-44 years old, 45-54 years old, 55-64 years old, 65-74 years old, and 75 years old were 5.37% (t = 5.26, P = 0.002), 5.22% (t = 5.66, P = 0.001), 7.20% (t = 6.88, P < 0.001), 10.00% (t = 12.58, P < 0.001), 9.96% (t = 7.34, P < 0.001) and 8.83% (t = 3.51, P = 0.013), and the upward trend was statistically significant. Conclusion: The overall survival rate of registered cases of liver cancer in the Qidong region's entire population has greatly improved, but there is still much room for improvement. Hence, constant attention should be paid to the study on preventing and treating liver cancer.

[Adult-onset immunodeficiency induced by anti-interferon-γ autoantibodies: report of 13 cases].

Objective: To investigate the clinical characteristics of a group of patients with adult-onset immunodeficiency (AOID) induced by anti-interferon-γ autoantibodies (AIGA). Methods: Thirteen cases of AOID in a northern China medical center (Peking Union Medical College Hospital) from October 2020 to April 2022 were included. Data comprising clinical manifestations, laboratory results, infection sites and pathogens were collected. Results: Among the 13 patients, 5 were male. The median age of disease onset was 47 (14 to 71) years. The median time from symptom onset to diagnosis was 4 years (1 to 8 years). Four patients were from northern China, and 9 from southern China. Common symptoms included lymphadenopathy (13/13), fever (12/13), respiratory tract symptoms (12/13), and weight loss (11/13). Laboratory tests showed increased levels of white blood cell count (9/13), neutrophil count and proportion (9/13), erythrocyte sedimentation rate (ESR) (12/13), and C reactive protein (CRP) (11/13). The median plasma titers of AIGA upon diagnosis were 5681(3194, 13246). Sites of infection included lungs (12/13), lymph nodes (9/13), bones and joints (9/13), skin and soft tissue (7/13), blood flow and bone marrow (4/13), and glands (3/13). Most patients had nontuberculous mycobacteria (NTM) (12/13) infection. Seven patients had more than one pathogen. Conclusions: AOID also affects patients visiting northern China hospitals. AIGA screening is recommended among patients with disseminated NTM infections or recurrent infections.

[Chinese expert guidance on overall application of lenvatinib in hepatocellular carcinoma].

Lenvatinib mesylate is an oral receptor tyrosine kinase inhibitor against targets of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor α, stem cell growth factor receptor, and rearranged during transfection, et al. Lenvatinib has been approved by the National Medical Products Administration of China on September 4, 2018, for the first-line treatment of patients with unresectable hepatocellular carcinoma who have not received systematic treatment before. Up to February 2023, Lenvatinib has been listed in China for more than 4 years, accumulating a series of post-marketing clinical research evidences. Based on the clinical practice before and after the launch of lenvatinib and referring to the clinical experience of other anti-angiogenesis inhibitors, domestic multidisciplinary experts and scholars adopt the Delphi method to formulate the Chinese Expert Guidance on Overall Application of Lenvatinib in Hepatocellular Carcinoma after repeated discussions and revisions, in order to provide reference for reasonable and effective clinical application of lenvatinib for clinicians.

[Posterior arthroscopic subtalar arthrodesis for symptomatic adult talocalcaneal coalition].

Objective: To investigate the functional outcomes of posterior arthroscopic subtalar arthrodesis (PASTA) for adult patients presenting with symptomatic talocalcaneal coalition. Methods: The study was a retrospective case-series research.The data of 17 adult patients (17 feet) with symptomatic talocalcaneal coalitions,treated with PASTA from March 2018 to February 2022 in Xuzhou Central Hospital were collected.This procedure involved 10 males and 7 females,aged (42.4±7.5) years(range:31 to 58 years).There were 9 cases on the right side and 7 cases on the left side.According to the Rozansky classification,there were 4 cases of type Ⅰ,7 cases of type Ⅱ, 3 cases of type Ⅲ,3 cases of type Ⅳ.The following items such as wound healing and bony union of the subtalar joint were observed.Clinical assessment was performed using pain visual analogue scale (VAS),American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot scores and 36-item short form health survey (SF-36) scores.The paired t test was used for data comparison. Results: The follow-up time was (24.8±6.9) months(range:12 to 40 months).There were no complications such as wound infection,deep vein thrombosis,nonunion,or screw breakage.One patient with preoperative spasm,relieved after the second surgical procedure (peroneal brevis tendon lengthening).The union time of the subtalar joint was (8.8±2.2) weeks(range:6 to 12 weeks).At the final follow-up,the VAS decreased from (6.4±1.3) to (1.3±0.9)(t=14.114,P<0.01), the AOFAS ankle-hindfoot score increased from (49.0±8.1) to (90.0±5.1)(t=38.782,P<0.01),and the SF-36 score increased from (50.8±9.5) to (91.0±4.9)(t=20.468,P<0.01). Conclusion: PASTA for adult patients presenting with symptomatic talocalcaneal coalition offers advantages of minimal trauma,fast recovery,and few complications,which is an effective method.

[Health economic evaluation of telemedicine diabetic retinopathy examination using a non-mydriatic fundus camera in China].

Objective: To perform a health economic evaluation of telemedicine diabetic retinopathy (DR) examination with a non-mydriatic fundus camera in China and to investigate the optimal examination interval. Methods: Based on 18 peer-reviewed articles related to epidemiology, clinical trial, and health economic evaluation of DR, surveys from 9 ophthalmologists in 3 tertiary hospitals in China, price lists for medical services in each province, and the negotiated price in 2021, a Markov model was conducted to evaluate the cost utility of telemedicine eye examination for diabetes mellitus patients aged 45 and older from the health system perspective. Separate analyses were performed for no examination and for examination intervals of every 1 to 5 years to predict the lifetime health gain, including cumulative days of blindness, cumulative life years, and quality-adjusted life years (QALYs), and costs for unilateral and bilateral direct medication with a 3.5% discount rate. Results: The cumulative days of blindness in the absence of a DR screening were 2 375.00 days, and ranged from 701.00 to 738.00 days for five different DR screening interval programs. The cumulative life years for no screening and five DR screening programs ranged from 27.120 34 to 28.005 00 years, with QALYs ranging from 9.502 96 to 9.875 02. The direct medication costs in the absence of a DR screening program were 72 785.00 yuan for both unilateral and bilateral scenarios. For the five DR screening intervals, the direct medication costs ranged from 52 065.00 to 52 408.00 yuan for unilateral and 79 100.00 to 79 603.00 yuan for bilateral. Comparing the incremental cost-effectiveness ratios between the DR screening intervals and no screening, the 1-to 5-year intervals were dominant in the unilateral scenario (between -56 368.54 and -55 523.75 yuan/QALY). In the bilateral scenario, the ratios ranged from 17 469.07 to 18 325.15 yuan/QALY. Using a willingness-to-pay threshold equal to the per capita GDP (80 976 yuan/QALY), the 1-year DR screening interval had an 85.9% probability of being cost-effective and a 55.2% probability of being dominant in the unilateral scenario. In the bilateral scenario, the 2-year interval held a 61.4% probability of being cost-effective. Conclusions: Analyses on the remote fundus consultation in diabetic patients and health economics based on the Markov model indicate that telemedicine DR examination through a non-mydriatic fundus camera can be effectively employed for diabetes mellitus patients in China. DR examination every two years is recommended for general diabetic patients, and DR examination every year may be chosen in developed areas.