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.

Stringent Tests of Lorentz Invariance Violation from LHAASO Observations of GRB 221009A.

On 9 October 2022, the Large High Altitude Air Shower Observatory (LHAASO) reported the observation of the very early TeV afterglow of the brightest-of-all-time gamma-ray burst 221009A, recording the highest photon statistics in the TeV band ever obtained from a gamma-ray burst. We use this unique observation to place stringent constraints on the energy dependence of the speed of light in vacuum, a manifestation of Lorentz invariance violation (LIV) predicted by some quantum gravity (QG) theories. Our results show that the 95% confidence level lower limits on the QG energy scales are E_{QG,1}>10 times the Planck energy E_{Pl} for the linear LIV effect, and E_{QG,2}>6×10^{-8}E_{Pl} for the quadratic LIV effect. Our limits on the quadratic LIV case improve previous best bounds by factors of 5-7.

Constraints on Ultraheavy Dark Matter Properties from Dwarf Spheroidal Galaxies with LHAASO Observations.

In this Letter we try to search for signals generated by ultraheavy dark matter at the Large High Altitude Air Shower Observatory (LHAASO) data. We look for possible γ rays by dark matter annihilation or decay from 16 dwarf spheroidal galaxies in the field of view of the LHAASO. Dwarf spheroidal galaxies are among the most promising targets for indirect detection of dark matter that have low fluxes of astrophysical γ-ray background while having large amount of dark matter. By analyzing more than 700 days of observational data at LHAASO, no significant dark matter signal from 1 TeV to 1 EeV is detected. Accordingly we derive the most stringent constraints on the ultraheavy dark matter annihilation cross section up to EeV. The constraints on the lifetime of dark matter in decay mode are also derived.

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.

[Opportunities and challenges in the development of artificial intelligence research in spinal surgery].

Artificial intelligence has emerged as a game-changer in the field of spine surgery, offering transformative diagnostic and therapeutic approaches for spinal conditions. The application of AI in spine research encompasses a diverse range of diseases, with usage scenarios becoming increasingly widespread and technological integration going deeper. AI technology shows immense promise and value in the diagnosis of spinal diseases, the formulation of treatment strategies, surgical navigation, prognostic evaluation, and postoperative rehabilitation. Through deep learning and machine learning, AI can aid doctors in enhancing diagnostic accuracy, creating personalized treatment plans, and executing precise maneuvers during surgery, thus improving operational safety. Moreover, AI can provide intelligent support for patients' postoperative recovery, facilitating the restoration of their functions. However, current research is still in its nascent stage and confronts several challenges, such as the lack of standardized databases, the simplicity of algorithmic learning models, the inadequate fusion of multi-modal clinical information, and the limited clinical applicability. By developing open-source, standardized spine databases, incorporating innovative intelligent core algorithms, and establishing normalized screening, diagnostic, and predictive models for spinal conditions, we trust that we can drive the innovation and refinement of diagnostic and treatment technologies in spine surgery. This will realize an effective conjunction between technological provision and clinical demands, continuously elevating the intelligence level of spine surgery and offering safer, more effective medical services to a vast array of patients.

[Analysis of tumor regression after concurrent radiochemotherapy for locally advanced hypopharyngeal carcinoma].

Objective: To investigate the pathological characteristics of tumor regression and the expression level of chemoradiotherapy resistance-related molecular markers after preoperative concurrent radiochemotherapy in patients with locally advanced hypopharyngeal carcinoma. Methods: The clinical data of 44 patients with locally advanced hypopharyngeal carcinoma who underwent preoperative concurrent radiochemotherapy in the Department of Head and Neck Surgery of Shandong Otolaryngology Hospital from August 2016 to August 2020 were retrospectively analyzed. All patients received preoperative concurrent chemotherapy and radiotherapy. After radiochemotherapy, electronic laryngoscopy and imaging examination were performed to assess the tumor regression status. After 4 weeks, surgical resection was performed, and the specimens of the primary focus were processed as continuous pathological sections. After operation, HE staining and TdT-mediated dUTP nick-end labeling (TUNEL) method were used to detect the distribution characteristics and apoptosis of the remaining cancer focus, and immunohistochemistry was performed to determine the proliferation of the remaining cancer focus and the expression of radiation resistance-related molecular markers [signal transducer and activator of transcription 3 (STAT3), hypoxia-inducible factor-1alpha (HIF-1α), sex determining region Y-box 2 (SOX2), and P53]. Results: A total of 44 patients were included, all of whom were male, with a mean age of (58.3±3.5) years. There were 40 cases of pyriform sinus carcinoma and 4 cases of posterior pharyngeal wall carcinoma. Twenty-nine cases were in stage T3 and 15 cases were in stage T4. There were 6 stage Ⅲ cases and 38 stage Ⅳ cases. According to the response evaluation criteria in solid tumors (RECIST), 13 patients achieved complete response (CR), 22 patients had partial response (PR), and 9 patients achieved stable disease (SD) after concurrent radiochemotherapy. The primary lesion resection methods included 19 cases of hypopharyngeal circumferential resection and 2 cases of total laryngectomy and partial hypopharyngeal resection. Twenty-three cases underwent supracricoid cartilage subtotal laryngectomy cricoid tongue fixation (CHP). Among 22 patients with PR, 10 had large PR (remission rate ≥70%) and 12 had small PR (remission rate <70%). The residual tumor was found in 30 patients (68.2%) after resection of all primary lesions by HE staining of pathological sections, of which 3 patients (3/13) with CR had residual cancer, all of which were focal residues. In large PR patients, residual cancer was detected in 6 cases (6/10), scattered in 4 cases, and focal residual in 2 cases, respectively. Large residual tumors were detected in small PR and SD patients. TUNEL method did not show any sign of apoptosis in 30 specimens with residual cancer focus, and the positive expression rate of Ki-67 was less than 10%. The expression of STAT3 (3.40±2.49 vs 5.23±3.02, t=-2.932, P=0.007) in 19 cases (63.3%) and HIF-1α (3.73±2.66 vs 6.97±3.05, t=-4.45, P<0.001) in 22 cases (73.3%) of residual cancer were significantly higher than those before radiochemotherapy. Other molecular markers showed no significant changes. All patients were followed up for 3 years. The 2-year survival rate was 59.3%, and the 3-year survival rate was 54.1%. Conclusions: Preoperative radiochemotherapy can make some patients with locally advanced hypopharyngeal carcinoma achieve complete or significant remission in clinical evaluation, but pathological detection still shows some residual cancer lesions with enhanced anti-apoptosis ability and decreased proliferation activity.

[Epidemiological characteristics of a local cluster epidemic caused by the BA.2 evolutionary branch of Omicron variant].

Descriptive epidemiological methods were used to analyze the epidemiological characteristics of the local cluster of COVID-19 in the logistic park of Yuhang District in Hangzhou in March 2022. The cluster epidemic was detected by a case who actively visited the fever clinic. The epidemic lasted for 8 days, and a total of 58 cases (53 workers, 2 students, 1 farmer, 1 teacher and 1 unemployed) were found, including 40 males and 18 females. The age was (33.29±12.22) years. There cases were mainly in Yuhang District (48 cases, 82.77%) and Shangcheng District (7 cases, 12.07%) of Hangzhou. The real-time regeneration number peaked at 2.31 on March 10th and decreased to 0.37 on March 15th. The sequencing result of the indicated case was 100% homologous with the sequence uploaded from South Korea on March 4th, 2022.

[The current status and challenges of surgical treatment for chronic Achilles tendon rupture].

With the growing demand for physical activity, an increasing number of individuals with chronic Achilles tendon ruptures are opting for surgical intervention. Surgical approaches encompass end-to end anastomosis, tendon flap techniques, tendon transfer procedures, and free tendon grafting, among others. When selecting the appropriate surgical method and determining the surgical indications, it is imperative to consider factors like the length of the Achilles tendon defect, patient age, aesthetic preferences, functional requirements, and local tissue conditions. As medical devices evolve and surgical techniques advance, the criteria for surgical intervention are also evolving. Drawing from existing literature evidence, it becomes crucial to define reasonable parameters for addressing Achilles tendon defects with each surgical technique, aligning more closely with clinical needs. Additionally, auxiliary technologies such as biologic therapy and innovative biomaterials have demonstrated promising results in laboratory or animal models. The focal point of advancing these auxiliary technologies lies in facilitating the translation of pertinent clinical outcomes in the future.

[Comparison of the clinical efficacy of all-inside arthroscopic lateral ligament augmentation procedure and Broström procedure for the treatment of chronic lateral rotational ankle instability].

Objective: To compare the clinical efficacy of patients with chronic lateral rotational ankle instability(CLRAI) after all-inside arthroscopic lateral ligament augmentation procedure and Broström procedure. Methods: This is a retrospective cohort study. The clinical and imaging data of 106 CLRAI patients were collected at the Xuzhou Central Hospital from January 2021 to December 2022. The patients included 55 males and 51 females with an age of (32.6±8.2) years (range: 16 to 50 years). All patients were treated under all-inside arthroscopic, and were divided into Broström-Gould surgery group (n=54) and Broström surgery group (n=52) according to different ligament repair methods. At 3, 6, and 12 months after surgery, ankle inversion stress tests and anterior drawer tests were used to examine the stability of the ankle joint and observe gait. The American Orthopedic Foot and Ankle Society ankle hindfoot scale (AOFAS-AH) and Karlsson ankle function score (KAFS) were used to assess ankle function; Tegner score was used to assess the patient's level of exercise; the foot and ankle outcome score(FAOS)(including score of symptoms,pain,function, daily living,function, sports and recreational activities (sport); quality of life (QOL) was used to assess the patient's daily activity ability. Comparisons of data were made using independent sample t test, repeated measures analysis of variance, LSD-t multiple comparison method, χ2 test or Mann-Whitney U test. Results: All operations were successfully accomplished. All incisions healed by first intention, without evidence of postoperative complications of implant rejection, ligation reaction, and nerve and vessel injury. All patients were followed up at 3, 6, and 12 months after surgery. Ankle varus stress test and anterior drawer test were negative. No evidence supporting lateral ankle instability was obtained. All patients eventually regained normal gait. No patients underwent revision surgery. Repeated measurement analysis of variance showed that AOFAS-AH, Tegner, KAFS and FAOS scores in the Brostrom-Gould group and the Brostrom group were significantly higher than those before surgery (P<0.01). The change trends of Tegner score and FAOS-sport score were significantly different between the two groups (F=18.839, P<0.01; F=8.169, P=0.005). Multiple comparisons revealed that at 3-, 6-and 12-month follow-up, the Tegner scores (3 months: 3.7±0.5 vs. 3.3±0.5, t=-3.980, P<0.01; 6 months: 4.4±0.6 vs. 3.8±0.7, t=-4.792,P<0.01; 12 months: 5.8±0.9 vs. 5.1±1.0, t=-3.889,P<0.01), sport scores (3 months: 82.5±3.7 vs. 79.3±3.8, LSD-t=-4.316, P<0.01; 6 months: 88.5±4.9 vs. 85.7±3.8, LSD-t=-3.312,P=0.001;12 months: 90.1±4.3 vs. 88.2±5.1, LSD-t=-2.112,P=0.037) in the Broström-Gould surgery group were higher than those in the Broström surgery group, with statistical significances. Conclusions: Both Broström-Gould and Broström procedures under all-inside arthroscopic can make ankle stability and improve ankle function in the treatment of CLRAI. However, the former maybe shorten the time to return to exercise and achieve higher motor function.

Risk Factors of Cardiac Complications in Pregnant Women with Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common inherited genetic cardiac disease during pregnancy. Studies of risk factors are of great significance for maternal and fetal outcomes. AIM: The aim of the study was to identify predictive risk factors for cardiac complications in pregnant women with HCM. METHODS: One hundred patients with HCM who delivered at the Shanghai obstetrical cardiology intensive care center between January 2000 and December 2022 were retrospectively reviewed. A logistic regression model was used to identify independent risk factors for cardiac complications. RESULTS: Twenty-one cases were obstructive HCM (21%), 16 with cardiac function grade I and 5 with grade II; 79 cases were non-obstructive HCM (79%), 67 with cardiac function grade I, 11 with grade II, and 1 with grade III. Ninety-one cases had abnormal electrocardiogram (ECG) (91%), mainly with ST-T changes (77%). The average interventricular septum was 19.39 ± 6.13 mm by echocardiography (21.75 ± 5.86 mm for obstructive HCM and 18.73 ± 6.08 mm for non-obstructive HCM). The main cardiac complications were maternal death (n = 2, 2%), heart failure (n = 7, 7%), and sustained ventricular tachyarrhythmia (n = 1, 1%). Cardiac complications occur commonly during the third trimester and postpartum period. Three independent risk factors to predict cardiac complications in pregnant women with HCM were obstructive HCM (P = 0.036), New York Heart Association (NYHA) class ≥II (P = 0.022), and previous history of syncope (P = 0.037). CONCLUSIONS: HCM increases the risk of maternal death, heart failure, and malignant arrhythmia. More attention should be given to risk assessment and pregnancy management. Early detection of risk factors can reduce the incidence of maternal mortality and cardiac complications.

Prediction of knee pain improvement over two years for knee osteoarthritis using a dynamic nomogram based on MRI-derived radiomics: a proof-of-concept study.

OBJECTIVES: To develop and validate a nomogram to detect improved knee pain in osteoarthritis (OA) by integrating magnetic resonance imaging (MRI) radiomics signature of subchondral bone and clinical characteristics. METHODS: Participants were selected from the Vitamin D Effects on Osteoarthritis (VIDEO) study. The primary outcome was 20% improvement of knee pain score over 2 years in participants administrated either vitamin D or placebo. Radiomics features of subchondral bone and clinical characteristics from 216 participants were extracted and analyzed. The participants were randomly split into the training and validation cohorts at a ratio of 8:2. Least absolute shrinkage and selection operator (LASSO) regression was used to select features and generate radiomics signatures. The optimal radiomics signature and clinical indicators were fitted into a nomogram using multivariable logistic regression model. RESULTS: The nomogram showed favorable discrimination performance [AUCtraining, 0.79 (95% CI: 0.72-0.79), AUCvalidation, 0.83 (95% CI: 0.70-0.96)] as well as a good calibration. Additional contributing value of fusion radiomics signature to the nomogram was statistically significant (NRI, 0.23; IDI, 0.14, P < 0.001 in training cohort and NRI, 0.29; IDI, 0.18, P < 0.05 in validating cohort). Decision curve analysis confirmed the clinical usefulness of nomogram. CONCLUSION: The radiomics-based nomogram comprising the MR radiomics signature and clinical variables achieves a favorable predictive efficacy and accuracy in differentiating improvement in knee pain among OA patients. This proof-of-concept study provides a promising way to predict clinically meaningful outcomes.

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.

[Clinical analysis of retropharyngeal lymph node metastasis in patients with hypopharyngeal squamous cell carcinoma].

Objective: To analyze the incidence and the related risk factors of retropharyngeal lymph node metastasis in patients with hypopharyngeal squamous cell carcinoma, evaluate the accuracy of preoperative enhanced CT in judging retropharyngeal lymph node metastasis, and investigate the impact of retropharyngeal lymph node metastasis on the prognosis. Methods: Retrospective analyses were made on 398 patients with hypopharyngeal squamous cell carcinoma who underwent surgery as the primary therapy and accepted retropharyngeal lymph node exploration and clearance during surgery in Shandong Provincial ENT Hospital from January 2014 to December 2019. Multivariate logistic regression analysis was used to clarify the related risk factors of retropharyngeal lymph node metastasis. Multivariate Cox regression analysis was used to investigate the impact of retropharyngeal lymph node metastasis on prognosis. The retropharyngeal lymph nodes of 218 cases with available preoperative enhanced CT images were evaluated by two experienced radiologists and compared with postoperative pathological results. Results: Retropharyngeal lymph node metastasis were confirmed in 54 of 398 (13.6%) cases according to postoperative pathology. The sensitivity and specificity of preoperative enhanced CT in the diagnosis of retropharyngeal lymph node metastasis were 34.6% and 91.1%, respectively, and the overall accuracy was 84.4%. Multivariate logistic regression analysis showed that the site of the primary lesion and pathological N stage were independent risk factors for retropharyngeal lymph node metastasis in hypopharyngeal squamous cell carcinoma. Patients with primary lesion located in the posterior wall of hypopharynx (OR=4.83, 95% CI: 1.27-18.40), N2 stage (OR=6.30, 95% CI: 2.25-17.67), and N3 stage (OR=26.89, 95% CI: 5.76-125.58) were prone to retropharyngeal lymph node metastasis. The 5-year overall survival rate of the 398 patients was 50.4%, and the 5-year disease-free survival rate was 48.3%. Multivariate Cox regression analysis showed that T stage, N stage, retropharyngeal lymph node metastasis, and radiotherapy were independent influencing factors for overall survival (T stage: HR=1.28, 95% CI: 1.06-1.54; N stage: HR=1.26, 95% CI: 1.14-1.40; retropharyngeal lymph node metastasis: HR=2.13, 95% CI: 1.47-3.08; radiotherapy: HR=0.54, 95% CI: 0.38-0.76) and disease-free survival of patients with hypopharyngeal squamous cell carcinoma (T stage: HR=1.26, 95% CI: 1.06-1.51; N stage: HR=1.25, 95% CI: 1.13-1.37; retropharyngeal lymph node metastasis: HR=2.24, 95% CI: 1.56-3.21; radiotherapy: HR=0.55, 95% CI: 0.40-0.77). Conclusions: Metastasis of retropharyngeal lymph nodes in hypopharyngeal squamous cell carcinoma is not rare. Enhanced CT is of low accuracy and limited value in diagnosing retropharyngeal lymph node metastasis. Primary lesions located in the posterior wall of the hypopharyngx, N2 stage, and N3 stage are independent high-risk factors for retropharyngeal lymph node metastasis. The prognosis of hypopharyngeal cancer patients with retropharyngeal lymph node metastasis is worse, and active surgical exploration and clearance can effectively reduce the mortality caused by retropharyngeal lymph node metastasis.

[Follow-up analysis of sex hormone levels and prognosis in women after hematopoietic stem cell transplantation].

Objective: To investigate the levels of sex hormone and fertility in female patients after hematopoietic stem cell transplantation (HSCT), as well as their correlation with conditioning regimens, and analyse the effect of hormone replacement therapy (HRT) in young women after HSCT. Methods: Retrospective case series study. The clinical data of 147 women who underwent HSCT in the First Affiliated Hospital of Soochow University from January 2010 to January 2021 were retrospectively analyzed. The sex hormone levels were measured and followed-up, and the survival, menstrual fertility and the use of HRT of the patients were also followed-up. The sex hormone levels were measured after transplantation, and the ovarian function was evaluated. Independent sample t test and χ2 test were used for comparison between the two groups. Results: The median age of the 147 patients was 26 (range, 10-45) years. Of them, 135 patients received allogeneic HSCT and 12 patients received autologous HSCT. Furthermore, 129 patients received myeloablative conditioning, and 18 patients received reduced conditioning dose. The median follow-up time was 50 months (range, 18-134 months). Five patients died of disease recurrence during follow-up. Of the 54 patients with subcutaneous injection of zoladex, three recovered menstruation spontaneously after transplantation, and all of them were myeloablative conditioning patients, one patient gave birth to twins through assisted reproductive technology. Ninety-three patients did not use zoladex before conditioning, two patients with aplastic anemia with non-myeloablative transplantation resumed menstruation spontaneously, and conceived naturally. The level of follicle stimulating hormone after transplantation in patients receiving myeloablative conditioning regimen was significantly higher than that in patients receiving reduced-dose conditioning regimen [(95.28±3.94) U/L vs. (71.85±10.72) U/L, P=0.039]. Among 147 patients, 122 patients developed premature ovarian failure, 83 patients received sex hormone replacement therapy after transplantation, and 76 patients recovered menstruation and improved endocrine function. Conclusions: The incidence of premature ovarian failure is high in female patients after HSCT, and patients have a chance at natural conception. Reducing the dose of conditioning regimen and the application of zoladex before transplantation can reduce ovarian of conditioning drugs. HRT after transplantation can partially improve the endocrine function of patients.

[Effect of hollow compression screw internal fixation in treating McCrory-Bladin type â ¡ lateral process fracture of the talus: open versus arthroscopy surgery].

In order to explore the clinical efficacy of hollow compression screw internal fixation in the treatment of lateral process fracture of the talus under open surgery versus arthroscopy procedure, a retrospective cohort study was conducted to analyze the clinical data of 33 patients with lateral process fracture of the talus admitted to Xuzhou Central Hospital from January 2019 to December 2021. There were 19 males (19 feet) and 14 females (14 feet), aged 18 to 50 years, with an average age of (32.2±9.3) years. According to the modified McCrory-Bladin classification, all patients were classified as type Ⅱ. Based on the different surgical methods, the patients were divided into the arthroscopy group (21 cases, treated with double-tunnel subtalar arthroscopy combined with hollow compression screw internal fixation) and the open group (12 cases, treated with open reduction and internal fixation with hollow compression screw). The operation time was observed and the surgical effects were evaluated using the visual analogue scale (VAS) of pain, the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, the Foot Function Index (FFI), and the Foot and Ankle Ability Measure (FAAM), which includes the FAAM-ADL (activity of daily living subscale) and the FAAM-S (sport subscale). All the patients of the two groups achieved stage Ⅰ wound healing. On the first day after the operation, the mean VAS score of the arthroscopy group was 2.4±0.7, which was significantly lower than that of the open group (3.4±1.6) (P=0.020). No significant difference was observed in terms of the follow-up time, operation time and AOFAS score between the two groups (all P>0.05). The FFI score of the arthroscopy group was significantly lower than that of the open group, and the FAAM-ADL and FAAM-S scores were significantly higher than those in the open group (all P<0.05). Two cases of dorsal foot numbness occurred in the open group after the operation, and the incidence of complications was not significantly different from that of the arthroscopy group (P=0.054). For McCrory-Bladin type Ⅱ lateral process fracture of the talus, the use of compression screw internal fixation could achieve reliable results, however, compared to open surgery, arthroscopy procedure obtained mini trauma and better functions.

[Efficacy and safety of allogeneic hematopoietic stem cell transplantation for the treatment of primary myelofibrosis].

Objective: To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of primary myelofibrosis (PMF) patients. Methods: A total of 14 cases of PMF who underwent allo-HSCT from December 2008 to December 2022 were analyzed retrospectively, including 8 males and 6 females with a median age [M(Q1, Q3)]of 36 (24, 42) years. Three-year overall survival (OS), disease free survival (DFS), cumulative incidence of relapse (CIR), transplantation-related mortality (TRM) were analyzed. Meanwhile, the complications were followed up by telephone and outpatient appointments for 49.6 (9.0,93.1) months. Results: All patients received myeloablative conditioning regimens (MAC). All patients had successful engraftment, and the median time of neutrophils and platelet engraftment were 13.5 (11.8, 18.0) days and 19.5 (13.5, 24.5) days, respectively. Ⅱ-Ⅳ acute graft versus host disease (GVHD) occurred in 3 cases, while chronic GVHD in 8 cases. The rate of 3-year OS,DFS,CIR and TRM were (92.9±6.9)%, (76.0±12.2)%, (38.6±2.7)% and (7.1±0.5)% respectively after a median follow-up time of 1 489.0 (270.3,2 794.8) days. Two patients died from treatment-related complications, one of which died 39 days after transplantation due to heart failure caused by severe anemia, the other patient died 6 years after relapse due to pulmonary infection. Conclusion: Allo-HSCT can be used as a safe and effective approach to treat PMF.

[Effect of HCMV infection on immune reconstitution of CD8+T cells in children with allogeneic hematopoietic stem cell transplantation].

Objective: To investigate the risk factors for human cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation in children and the impact of human cytomegalovirus infection on post-transplant immune reconstitution. Methods: A Retrospective Co-Hort study design was used to include 81 children treated with allo-HSCT from January 2020 to March 2022 at the Department of Hematology, Capital Institute of Pediatrics, Beijing, China, and followed up for 1 year. Real-time quantitative PCR was used to detect positive detection of HCMV in children after allo-HSCT, multifactorial logistic regression modeling was used to analyze the risk factors leading to HCMV infection, and generalized estimating equation modeling was used to analyze the effect of HCMV infection on the T-cells of the children who received allo-HSCT. Results: The age M(Q1, Q3) of 81 children was 5.1 years (10 months, 13.8 years), and 50 (61.7%) were male. By the endpoint of follow-up, a total of 50 HCMV-positive cases were detected, with an HCMV detection rate of 61.7%; The results of multifactorial logistic regression modeling showed that children with grade 2-4 aGVHD had a higher risk of HCMV infection compared with grade 0-1 after transplantation [OR (95%CI) value: 2.735 (1.027-7.286)]. The results of generalized estimating equation modeling analysis showed that the number of CD3+T cells in HCMV-positive children after transplantation was higher than that in the HCMV-negative group [RR (95%CI) value: 1.34 (1.008-1.795)]; the ratio of CD4+T/CD8+T cells was smaller than that in the HCMV-negative group [RR (95%CI) value: 0.377 (0.202-0.704)]; the number of CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.435 (1.025-2.061)]; the number of effector memory CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.877 (1.089-3.236)]. Conclusion: Acute graft-versus-host disease may be a risk factor for HCMV infection in children after allo-HSCT; post-transplant HCMV infection promotes proliferation of memory CD8+T-cell populations and affects immune cell reconstitution.

[Impact of orthotopic liver transplantation on serum lipid level and growing development in patients with homozygous or compound heterozygous familial hypercholesterolemia].

Objective: To investigate the impact of orthotopic liver transplantation on serum lipid and growing development in patients with homozygous (HoFH) or compound heterozygotes (cHeFH) familial hypercholesterolemia. Methods: Patients who were treated in Peking Union Medical College Hospital from August 2019 to August 2021, entered the rare disease database and underwent liver transplantation, were included in this single center retrospective cohort study. The height for age Z score (HAZ) and length for age Z score (WAZ) at birth, at the time of transplantation and one year after transplantation were calculated respectively by collecting demographic characteristics, clinical manifestations, echocardiography, lipid-lowering treatment, blood lipid level data and donor characteristics data of liver transplantation. The serum cholesterol level and growing development changes before and after liver transplantation were evaluated. Results: A total of five patients with HoFH or cHeFH, including two females, were included in this study. The median age was 10 years (6-22 years). The median follow up duration was 28 months (24-33 months). All HoFH or cHeFH patients in this study received the maximum daily dosage of the lipid-lowering drug combined with low salt and low-fat diet control treatment for at least 3 months before orthotopic liver transplantation. The average level of total cholesterol (TC) decreased by 27% compared with that before treatment, the level of low-density lipoprotein cholesterol (LDL-C) decreased by 21% after 3 months treatment. There was no intervention of lipid-lowering therapy after operation. One month after liver transplantation, the average levels of TC and LDL-C further decreased rapidly by 68% and 76% respectively. One year after liver transplantation, the level of LDL-C decreased from (17.1±1.6)mmol/L without any intervention before transplantation to (3.0±0.7)mmol/L, and remained stable thereafter. In addition, compared with no intervention before liver transplantation, the serum triglyceride (TG) level decreased after the maximum daily dosage of the lipid-lowering drug and low salt and low-fat diet control for 3 months ((1.88±0.27) mmol/L vs. (1.12±0.55)mmol/L, P=0.031), and the HDL-C level also decreased significantly ((1.95±0.49)mmol/L vs. (0.95±0.30)mmol/L, P=0.006) at the same time period. TG and HDL-C remained stable after liver transplantation during the 24-month follow-up period (P>0.05). One and two years after liver transplantation, there was no significant difference in height and weight, malnutrition and growth retardation between the patients in this cohort and Chinese children of the same age. Conclusion: Early liver transplantation is a feasible and effective treatment option for HoFH or cHeFH patients with extremely high serum low-density lipoprotein cholesterol levels.

Group B Streptococcus (GBS) colonization is dynamic over time, whilst GBS capsular polysaccharides-specific antibody remains stable.

Group B Streptococcus (GBS) is a leading cause of adverse pregnancy outcomes due to invasive infection. This study investigated longitudinal variation in GBS rectovaginal colonization, serum and vaginal GBS capsular polysaccharide (CPS)-specific antibody levels. Non-pregnant women were recruited in the UK and were sampled every 2 weeks over a 12-week period. GBS isolates were taken from recto-vaginal swabs and serotyped by polymerase chain reaction. Serum and vaginal immunoglobulin G (IgG) and nasal immunoglobulin A (IgA) specific to CPS were measured by Luminex, and total IgG/A by ELISA. Seventy women were enrolled, of median age 26. Out of the 66 participants who completed at least three visits: 14/47 (29.8%) women that were GBS negative at screening became positive in follow-up visits and 16/19 (84.2%) women who were GBS positive at screening became negative. There was 50% probability of becoming negative 36 days after the first positive swab. The rate of detectable GBS carriage fluctuated over time, although serum, vaginal, and nasal CPS-specific antibody levels remained constant. Levels of CPS-specific antibodies were higher in the serum of individuals colonized with GBS than in non-colonized, but similar in the vaginal and nasal mucosa. We found correlations between antibody levels in serum and the vaginal and nasal mucosa. Our study demonstrates the feasibility of elution methods to retrieve vaginal and nasal antibodies, and the optimization of immunoassays to measure GBS-CPS-specific antibodies. The difference between the dynamics of colonization and antibody response is interesting and further investigation is required for vaccine development.

Constraints on Heavy Decaying Dark Matter from 570 Days of LHAASO Observations.

The kilometer square array (KM2A) of the large high altitude air shower observatory (LHAASO) aims at surveying the northern γ-ray sky at energies above 10 TeV with unprecedented sensitivity. γ-ray observations have long been one of the most powerful tools for dark matter searches, as, e.g., high-energy γ rays could be produced by the decays of heavy dark matter particles. In this Letter, we present the first dark matter analysis with LHAASO-KM2A, using the first 340 days of data from 1/2-KM2A and 230 days of data from 3/4-KM2A. Several regions of interest are used to search for a signal and account for the residual cosmic-ray background after γ/hadron separation. We find no excess of dark matter signals, and thus place some of the strongest γ-ray constraints on the lifetime of heavy dark matter particles with mass between 10^{5} and 10^{9} GeV. Our results with LHAASO are robust, and have important implications for dark matter interpretations of the diffuse astrophysical high-energy neutrino emission.