Bone Transplantation/adverse effects* ; Transplantation, Autologous/adverse effects*

Objective To observe the effect and survival benefits of camrelizumab combined with chemotherapy in the treatment of advanced esophageal squamous cell carcinoma(ESCC).Methods Patients with advanced ESCC were divided into control group and treatment group.The control group was given albumin-paclitaxel(260 mg·m-2,qd,intravenous drip on the 1st day)and cisplatin(20 mg·m-2,once a day,intravenous drip on the 1 st-5 th day),while treatment group was given camrelizumab(200 mg,qd,intravenous drip on the 1st day)on basis of control group.All patients were treated for 4 cycles(21 d/cycle).The curative effect(disease control rate,objective response rate),immune function(CD4+,CD8+,CD4+/CD8+),tumor markers(carbohydrate antigen 199,carcinoembryonic antigen,carbohydrate antigen 125),safety and survival benefits in the two groups were compared after treatment.Results There were 48 cases in treatment group and 42 cases in control group.After treatment,disease control rates in treatment group and control group were 79.17％(38 cases/48 cases)and 57.14％(24 cases/42 cases),objective response rates were 62.50％(30 cases/48 cases)and 40.48％(17 cases/42 cases),the differences were statistically significant(all P＜0.05).After treatment,levels of peripheral blood CD4+/CD8+levels were 1.11±0.29 and 1.87±0.38;levels of levels of serum carbohydrate antigen 199 were(50.03±6.21)and(36.41±4.87)ng·mL-1;levels of serum carcinoembryonic antigen were(21.25±3.39)and(14.97±2.85)ng·mL-1;levels of serum carbohydrate antigen 125 were(29.82±4.16)and(20.63±3.34)ng·mL-1,the differences were statistically significant(all P＜0.05).The differences in 6-month survival rate between treatment group and control group were statistically significant[95.83％(46 cases/48 cases)vs 80.95％(34 cases/42 cases),P＜0.05].The adverse drug reactions of the two groups were mainly proteinuria,abnormal liver function,bone marrow suppression,abnormal thyroid function and gastrointestinal reaction,and there was no significant difference in the incidence of adverse drug reactions between the two groups(P＞0.05).Conclusion Camrelizumab combined with chemotherapy can enhance immune function in patients with advanced ESCC,inhibit the expressions of tumor markers and increase survival rate.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Improving the prognosis of patients with colorectal cancer (CRC) holds important clinical and social significance. Immunotherapy is an emerging therapy approach for cancers, which mainly include immune checkpoint inhibitors (ICI), immune vaccine and adoptive cell therapy. ICI have achieved good clinical translation in treatment of metastatic CRC with deficient DNA mismatch repair/high microsatellite instability (dMMR/MSI-H) status. The application of some ICI, such as PD-1 inhibitors pembrolizumab and nivolumab, in this type patients have been approved by the FDA. In addition,numerous positive results are acquired in clinical trials of neoadjuvant therapy for resectable dMMR/MSI-H CRC. These results greatly bolstered the exploration enthusiasm of CRC immunotherapy. However, the proficient DNA mismatch repair/microsatellite stability (pMMR/MSS) CRC, which accounting for the vast majority in related patients, hardly benefit from ICI therapy. Various combination strategies, mainly including ICI combined with traditional chemotherapy, radiotherapy, or targeted therapy, have been attempted to alter the “cold tumors” microenvironment characteristics of pMMR/MSS CRC in clinical trials, whereas no breakthrough results were reached. Theoretically, tumor vaccines are ideal choice to break down the barrier of insufficient immune infiltration in solid tumors. However, the outcomes of related clinical trials in CRC patents are not satisfactory, and partially due to the weak specificity of the applied tumor-associated antigens. Clinical studies of adoptive cell therapy in CRC are also actively underway. The favorable efficacy of tumor-infiltrating lymphocyte, cytokine-induced killer (CIK) and dendritic cell-CIK in CRC have been confirmed, while the CAR-T and TCR-T therapies need more exploration based on screening more suitable antigens and optimizing engineering design. In this review, we made a summary based on the mainline of clinical studies related to diverse immunotherapies, so as to clarify the progress of CRC immunotherapy and provide bases for exploration of better treatment options.

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

Objective:To explore the clinical effects of early rehabilitation treatment after repair surgery of skin and soft tissue defects accompanied by extensor tendon injury on the back of hand.Methods:This study was a retrospective non-randomized controlled study. From February 2015 to February 2023, 24 patients (15 males and 9 females, aged 12-55 years) with skin and soft tissue defects accompanied by extensor tendon injury on the back of hand, who met the inclusion criteria and were repaired with flap transplantation and tendon grafting or tendon anastomosis, were admitted to the First Affiliated Hospital of Air Force Medical University. According to different intervention time for postoperative rehabilitation treatment of patients, the patients were divided into conventional rehabilitation group and early rehabilitation group, with 12 cases in each group. Patients in early rehabilitation group received rehabilitation treatment immediately after surgery under the rehabilitation guidance of specialized rehabilitation physicians based on the characteristics of different postoperative periods. Patients in conventional rehabilitation group began rehabilitation treatment from the third week after surgery, and their rehabilitation treatment was the same as that of patients in early rehabilitation group from the second week after surgery. The patients in 2 groups were treated in the hospital until the sixth week after surgery. The occurrence of flap vascular crisis and tendon rupture were observed within 6 weeks after surgery. After 6 weeks of surgery, the manual muscle test was used to measure the pinching force between the index finger and thumb, lateral pinching force, three-point pinching force, and grip force of the affected hand; the total action motion method was used to evaluate the finger joint range of motion of the affected hand, and the excellent and good ratio was calculated; the Carroll upper extremity function test was used to score and rate the function of the affected hand.Results:Within 6 weeks after surgery, only 1 patient in conventional rehabilitation group suffered from venous crisis, and the flap survived after the second surgical exploration and anastomosis of blood vessels; there was no occurrence of tendon rupture in patients of 2 groups. After 6 weeks of surgery, there were no statistically significant differences in pinching force between the index finger and thumb, lateral pinching force, three-point pinching force, or grip force of the affected hand between the two groups of patients ( P>0.05); the excellent and good ratio of the finger joint range of motion of the affected hand of patients in early rehabilitation group was 11/12, which was higher than 7/12 in conventional rehabilitation group, but there was no statistically significant difference ( P>0.05); the affected hand function score of patients in early rehabilitation group was 90±6, which was significantly higher than 83±8 in conventional rehabilitation group ( t=2.41, P<0.05); the function rating of the affected hand of patients in early rehabilitation group was obviously better than that in conventional rehabilitation group ( Z=2.04, P<0.05). Conclusions:Early rehabilitation treatment for patients with skin and soft tissue defects accompanied by extensor tendon injury on the back of hand after repair surgery can improve hand function, but it would not increase surgery related complications, which is worthy of clinical promotion and application.

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates.Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity.This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes.The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes,and corresponding reference ranges will be established.The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance,with altitude gradients divided into 4 categories:800 m,1 900 m,2 400 m,and 3 500 m,with an anticipated sample size of 170 neonates per altitude gradient.This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.[Chinese Journal of Contemporary Pediatrics,2024,26(4):403-409]

Confirmed cases of Lyme disease(LD)in Ji'an City,Jiangxi Province and the clinical manifestations and region-al distribution were assessed to provide a basis for timely diagnosis and treatment.In total,133 serum samples were collected from patients with suspected LD in Ji'an Central People's Hospital from December 2021 to August 2022.Serum antibodies a-gainst Borrelia burgdorferi were detected with a two-step testing process.In addition,a specific gene of B.burgdorferi in samples was identified by nested PCR.Sequencing analysis was conducted to confirm the positive samples.Overall,25(18.80％)serum samples were positive for B.burgdorferi nucleic acid and antibodies,which included 20(15.04％)positive for antibodies and 6(4.51％)positive for nucleic acids.The sequences of the 5S-23S rRNA gene spacer of 6 samples were con-sistent with the corresponding sequences of Borrelia yangtzensis and one of the six samples was also positive for antibodies.The 25 positive samples were collected from 9 counties in Ji'an City,with the majority in Jizhou District(44％).All positive patients may experience symptoms related to LD,including joint disorders,neurological disorders,infectious fever,der-matitis,and/or chest pain.The most common symptom was joint disorders(72％).Six cases positive for B.yangtzensis nucleic acids were mainly collected in the Jizhou District,of which four had joint lesions and two had infectious fever.This study confirms the existence of LD in Jiangxi Province,which may be the first confirmation of human infection with B.yan-gtzensis in southern China.Hence,doctors in this region should consider the possibility of LD for cases presenting with related symptoms.Although LD may occur in this region,further investigations and monitoring are warranted.

Mytilus is one of bivalves with great economic and ecological values.The innate immune de-fense of Mytilus shows great significance in the study of marine biological immunology.Hemolymph is the main immune tissue for Mytilus.The Nanopore full-length transcriptome of Mytilus coruscus hemocytes,and the serum differential proteomics based on SDS-PAGE analysis were performed to identify key pro-teins involving in the immune response of Mytilus hemolymph in response of different bacteria and fungi stresses.A total of 44 proteins were identified in the serum induced by different microorganisms.Among them,26 proteins showed significant differential expression level in response to different microbial stres-ses,and their functions were involved in protein folding protection,cell autophagy and apoptosis regula-tion,reactive oxygen species production,energy metabolism regulation,cell detoxification,and immune regulation.The changes in expression levels of these proteins varied in response to different bacterial and fungal stresses,suggesting that Mytilus has different immune response strategies to different bacterial and fungal stresses.The results provide a new scientific basis for understanding the differential immune mech-anism of Mytilus innate immune system in response to different types of microbial invasion,as well as the screening of specific biomarker proteins for microbial infection,and provide ideas for the healthy develop-ment and disease prevention of shellfish aquaculture.