National Medical Journal of China
Volume 105 · Issue 27 · 2025
Natl Med J China
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a cluster of life-threating and organ-destructive systemic vasculitis. Although the traditional regimen of glucocorticoid (GC) combined with cyclophosphamide (CTX) has significantly improved the survival rate, it is associated with severe adverse effects such as infections and malignancies. In 2016, the European League Against Rheumatism (EULAR) guideline recommended Rituximab (RTX) as the first-line induction drug for remission in severe AAV. RTX has shown efficacy superior to CTX in patients with PR3-ANCA-positive AAV and relapsed AAV, and also has safety advantages for special AAV patients, including the elderly/frail patients, children, those with fertility needs and those requiring reduced GC doses. Currently in China, the induction therapy for severe AAV is primarily based on GC+CTX, but the use of RTX is gradually increasing. Currently, emphasis should be placed on the first-line induction therapy of RTX for severe AAV, the application of RTX-based intensified immunosuppressive regimens (such as combination with Avacopan or CTX) in refractory and critically ill patients, as well as the unique characteristics of Chinese AAV patients, particularly the risk of RTX-related severe infections. Further exploration is warranted to determine the optimal dosing regimen for Chinese patients.
Growth hormone-related cirrhosis (GHRC) refers to cirrhosis and its complications caused by long-term growth hormone deficiency in patients with anterior hypopituitarism. The primary clinical characteristics include anterior pituitary hypofunction, growth hormone deficiency, and cirrhosis. The main pathogenic mechanism of GHRC is hepatic fat accumulation due to the lack of growth hormone and insulin-like growth factor-1 (IGF-1). The replacement therapy with physiological doses of growth hormone can improve symptoms. GHRC severely impairs patient quality of life and can be life-threatening. Yet current clinical awareness is inadequate, leading to high rates of misdiagnosis and mistreatment. Clinicians should be vigilant for GHRC in patients with cryptogenic cirrhosis. Conducting screenings for anterior pituitary hormones especially growth hormone and IGF-1 to accurately identify GHRC and promptly initiate growth hormone replacement therapy, with the aim of reversing the disease condition, saving lives, and avoiding unnecessary liver transplantation. Enhancing understanding and awareness of GHRC holds significant clinical and theoretical value and could revolutionize the diagnosis, treatment, and prognosis of these patients. This consensus statement was developed by over 50 experts from various fields, including endocrinology, neurosurgery, gastroenterology, respiratory medicine, and hematology, based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system for clinical evidence levels. It addressed key scientific issues such as the diagnosis, risk factors, and risks and benefits of growth hormone replacement therapy. Integrating Delphi method feedback, the consensus ultimately formulated 10 recommendations to guide clinicians in managing GHRC.
Malignant tumors have a high incidence and mortality rate in our country, becoming a significant public health issue that affects the health of residents and the econiomic and social development of China. Currently, relying on a single discipline for diagnosis and treatment can no longer meet the clinical needs of cancer patients. Therefore, leveraging the multidisciplinary capabilities of comprehensive hospitals to establish cancer centers has become an inevitable trend. To this end, Institute of Hospital Management of Tsinghua University has organized a committee of experts in the fields of oncology and hospital management. The expert consensus was formulated, based on the latest research developments both domestically and internationally, and combined with expert discussions. This consensus elaborates on the basic definition, construction models, construction standards, and evaluation and supervision of cancer centers in comprehensive hospitals. Fifteen recommended opinions are formualted, aiming to provide comprehensive and standardized references and recommendations for the establishment of cancer centers in comprehensive hospitals.
To evaluate the impact of perineal post-free traction in the Trendelenburg position on enhanced recovery after hip arthroscopy in patients with femoroacetabular impingement (FAI).
A retrospective analysis was conducted on patients who underwent hip arthroscopy for FAI at the First Medical Center of the PLA General Hospital between September 2023 and September 2024. Patients were divided into two groups: a control group (traditional traction, n=80) and an enhanced recovery group (Trendelenburg position with perineal post-free traction, n=80). Intraoperative data, including operative time, traction time, Trendelenburg angle, and traction force, were recorded. Clinical outcomes were assessed using the modified Harris Hip Score (mHHS), the International Hip Outcome Tool-12 (iHOT-12), and the visual analogue scale (VAS) for pain, administered preoperatively and at 3 days and 4 weeks postoperatively. Postoperative limb numbness was evaluated using the numeric rating scale (NRS), VAS scores, and time to resolution. Additional outcomes included the incidence and resolution time of perineal complications, skin injuries, analgesic consumption, length of hospital stay, and patient satisfaction.
A total of 160 patients were included, comprising 94 males and 66 females with a mean age of (39.9±14.3) years. The control group included 49 males and 31 females with a mean age (40.5±13.3) years, while the enhanced recovery group included 45 males and 35 females with a mean age of (39.3±15.1) years. No significant differences was observed between the control group and the enhanced recovery group in terms of operative time [(78.73±15.45) vs (79.53±13.28) min] or traction time [(35.50±8.36) vs (37.58±10.66) min] (both P>0.05). At both 3 days and 4 weeks postoperatively, mHHS, iHOT-12 and VAS scores exhibited significant improvement when compared to those preoperative values in both groups (all P<0.001), but with no significant differences between groups (all P>0.05). However, the enhanced recovery group demonstrated significantly better outcomes than the control group in terms of postoperative NRS of numbness [(1.32±0.53) vs (3.22±1.14) points], VAS of numbness [(2.52±1.53) vs (5.51±1.52) points], resolution time of numbness [(2.51±1.52) vs (3.51±1.53) days], incidence of perineal complications [0 vs 5.0%(4/80)], incidence of skin injury [3.8%(3/80) vs 8.8%(7/80)], postoperative analgesic use [(50.25±17.75) vs (75.25±12.25) mg], length of hospital stay [(3.23±0.52) vs (4.23±1.52) days], and patient satisfaction scores [(98.23±1.03) vs (90.12±5.16) points] (all P<0.05).
The Trendelenburg position with perineal post-free traction technique provides FAI patients with comparable intraoperative efficacy to traditional traction methods while significantly enhancing postoperative recovery outcomes in patients undergoing hip arthroscopy.
To explore the application effects of the proximal anterior-distal anterolateral accessory (PA-DALA) in hip arthroscopy for treating common hip diseases.
A retrospective analysis was conducted on the clinical data of patients who underwent hip arthroscopic surgery at the Chinese People×s Liberation Army General Hospital from January 2018 to December 2023. The diseases included femoral acetabular impingement syndrome (FAI), ankylosing spondylitis (AS), synovial chondromatosis (SC), and pigmented villonodular synovitis (PVNS). Based on the different surgical approaches, the patients were divided into two groups: the control group underwent the conventional distal anterolateral approach (DALA) commonly used in hip arthroscopy, while the observation group received the PA-DALA approach. The application effects of the PA-DALA in hip arthroscopic surgery for common hip disorders were evaluated, and the incidence of intraoperative complications, postoperative wound healing, and functional scores such as the visual analog scale (VAS) for pain, modified Harris Hip Score (mHHS), and International Hip Outcome Tool-12 (iHOT-12) at various follow-up time points before and after surgery (1, 3, 6 months and 1 year after surgery) were compared between the two groups.
A total of 102 patients with effective follow-up are included in the study, comprising 71 males and 31 females, aged (37.3±13.1) years. There were 34 cases in the control group, and 68 patients in observation group. In the control group, the preoperative VAS score of pain was (6.2±2.3) points, which decreased to (3.1±1.7) points one year after surgery; the preoperative mHHS score was (36.3±12.9) points, which increased to (77.7±9.3) points one year after surgery; and the preoperative iHOT-12 score was (29.5±15.4) points, which raised to (69.2±16.9) points one year after surgery. In the observation group, the preoperative VAS score of pain was (6.0±1.2) points, which decreased to (1.8±1.6) points one year after surgery; the preoperative mHHS score was (38.8±12.2) points, which increased to (81.0±9.5) points one year after surgery; and the preoperative iHOT-12 score was (32.8±12.6) points, which raised to (74.6±12.6) points one year after surgery. The VAS scores, mHHS scores, and iHOT-12 scores of both groups at all postoperative time points showed significant improvement when compared with those preoperative scores (all P<0.05). The observation group demonstrated a greater advantage in alleviating postoperative pain [VAS at one year after the operation: (1.8±1.6) vs (3.1±1.7) points] (P<0.001). In the control group, 3 patients experienced intraoperative complications, specifically involving perforation of the outer edge of the acetabular cortex during anchor placement, resulting in unstable anchor fixation with a success rate of 91.2%(31/34), but in the observation group, no such complications occurred, and the anchor placement success rate was 100%(68/68), it was significantly higher than that in the control group (P=0.049). Both groups of patients healed well postoperatively and were discharged from the hospital successfully.
The PA-DALA approach can fulfill the requirements for establishing surgical approaches in hip arthroscopy for common hip diseases. Compared with the conventional DALA approach, the PA-DALA approach enhances the safety and success rate of anchor placement.
To explore the mechanism by which homeobox gene A6 (HOXA6) promotes the proliferation of acute myeloid leukemia (AML) cells through the mitogen-activated protein kinase (MAPK) signaling pathway.
The human promyelocytic leukemia cell line (HL-60) and human monocytic leukemia cell line (THP-1) were cultured. The HOXA6 overexpression plasmid and small interfering RNAs (siRNAs) were constructed and synthesized. Three siRNAs targeting HOXA6 (siRNA-1, siRNA-2, siRNA-3, i.e., siRNA group), HOXA6 overexpression plasmid (HOXA6 overexpression group), siRNA negative control (si-NC) group, and empty vector (empty vector group) were transfected into HL-60 and THP-1 cells, respectively. The mRNA expression level and protein expression level of HOXA6 were detected, and the cell proliferation, migration, invasion ability, and apoptosis were also detected. The experiment was repeated three times. The phosphorylation and non-phosphorylation levels of key proteins in the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway were detected. Female BALB/c nude mice were divided into a control group (infected with interference control lentivirus) and a HOXA6 interference group (infected with HOXA6 interference lentivirus group) by a random number table method, with 6 mice in each group. Each nude mouse was inoculated with HL-60 cells. After tumor formation, the tumor volume was measured every 3 days. The nude mice were sacrificed at the end of the 4th week to to measure the tumor weight and compare the effect of HOXA6 interference on the tumorigenic ability of HL-60 cells in nude mice.
The expression level of HOXA6 in the siRNA group (three siRNAs) was all lower than that in the si-NC group, and the interference efficiencys of siRNA-2 and siRNA-3 was the highest (both P<0.001). In HL-60 and THP-1 cells, the protein expression level of HOXA6 in the HOXA6 overexpression group was higher than that in the empty vector group; the expression levels of HOXA6 in the siRNA-2 group and siRNA-3 group were lower than those in the si-NC group (both P<0.001). In HL-60 cells, the cell proliferation, migration and invasion abilities of the siRNA-2 group and siRNA-3 group were lower than those of the si-NC group, and the apoptosis rate was higher than that of the si-NC group (all P<0.001); in THP-1 cells, the proliferation, migration and invasion abilities of the siRNA-2 group and siRNA-3 group were lower than those of the si-NC group (all P<0.001), while the apoptosis rate was higher than that of the si-NC group (all P<0.001). In the HOXA6 overexpression group, the proliferation, migration and invasion abilities of HL-60 cells were higher than those of the empty vector group (all P<0.05); there was no significant difference in the apoptosis rate (all P>0.05); the proliferation, migration and invasion abilities of THP-1 cells were higher than those of the empty vector group (all P<0.05); there was no significant difference in the apoptosis rate (all P>0.05). In HL-60 and THP-1 cells, the phosphorylation levels of phosphorylated extracellular signal-regulated kinase/extracellular signal-regulated kinase (p-ERK/ERK), phosphorylated mitogen-activated protein kinase/mitogen-activated protein kinase (p-MEK/MEK) and phosphorylated rapid acceleration fibrosarcoma kinase/rapid acceleration fibrosarcoma kinase (p-RAF/RAF) in the HOXA6 overexpression group were higher than those in the empty vector group (all P<0.05). Only at the fourth week, the tumor volume of nude mice in the HOXA6 interference group was lower than that in the control group (all P<0.001); and at the fourth week, the weight of tumor was lower than that in the control group [(692.7+151.6) vs (1 327.5+318.0) mg, P=0.001].
HOXA6 promotes the proliferation of AML cells by phosphorylating and activating the MAPK signaling pathway.
To investigate the feasibility of cement-augmented pedicle screws (CAPS) applied in elderly patients with thoracolumbar infectious spondylitis (IS) and severe osteoporosis. We retrospectively analyzed data of 35 eligible patients between January 2017 and October 2022. The outcomes included regional kyphotic angle (RKA), visual analog scores (VAS), Oswestry disability index (ODI), American Spinal Injury Association (ASIA), erythrocyte sedimentation (ESR), C-reactive protein (CRP), dissemination or recurrence of infection, and bone fusion. For thoracic IS, the RKA was 21.3° (10.5°, 39.2°) preoperatively and 16.9° (8.9°, 30.5°) at the final follow-up (P<0.001).Significant improvement of RKA was also observed in patients with thoracolumbar IS or lumbar IS. The preoperative VAS and ODI were 6.0 (5.0, 6.5) points and 61.1%±6.7%, these values decreased to 0 (0, 1.0) points and 16.4%±4.8% at the final follow-up, respectively (both P<0.001). Regarding ASIA grading, two patients were grade B, nine patients were grade C, 14 patients were grade D, and 10 patients were grade E preoperatively. At the final follow-up, 6 and 29 patients were classified grade D and E, respectively. The preoperative ESR and CRP were 41.7 (30.0, 57.0) mm/1h and 26.1 (9.2, 42.4) mg/L, these values reduced to 7.0 (5.5, 8.0) mm/1h and 1.8 (1.5, 2.5) mg/L at the final follow-up, respectively (both P<0.001). None dissemination or recurrence of infection was observed. Bony fusion occurred in all patients. CAPS fixation is an effective and safe option to achieve solid fixation and favorable clinical outcomes in elderly patients with IS and severe osteoporosis.
The patients with evidence-based diagnosis of bacterial meningitis(BM) who were admitted to Fudan University affiliated Huashan Hospital during October 2023 to June 2024 were retrospectively selected. The cerebrospinal fluid (CSF) and venous blood samples were collected on days 1, 7, 14, and 30 of admission to detect the levels of soluble leukocyte differentiation antigen 14(sCD14), soluble B7 homolog 3(sB7-H3), and inflammatory factors matrix metalloproteinase-9 (MMP-9) and interleukin-6 (IL-6). Its dynamic changes in combination with its clinical data were also analyzed. A total of 4 patients were included, with 1 female and 3 males, aged 50(46, 56) years. After anti-infection treatment, the clinical symptoms improved significantly. The sCD14, sB7-H3, MMP-9 and IL-6 values in the CSF of the 4 patients were greatly decreased than before treatment. Among them, the levels of CSF immune factors sCD14 and sB7-H3 gradually decreased after treatment, while the levels of CSF inflammatory factors MMP-9, particularly IL-6, rapidly decreased upon treatment. Besides, serum sCD14 and sB7-H3 remained approximately constant before and after treatment. Compared to MMP-9 and IL-6, dynamic monitoring of sCD14 and sB7-H3 in CSF may have more reference value for evaluating the efficacy of BM.
To analyze the clinical characteristics of patients with mismatch repair deficient (dMMR) colorectal cancer(CRC) and investigate the prevalence of Lynch syndrome (LS). A total of 847 patients (516 males and 331 females) who underwent CRC surgery at Fujian Cancer Hospital between July 2022 and June 2023 were prospectively enrolled. The age was 60.0(52.0, 68.0) years. Patients were divided into dMMR group (n=101) and proficient mismatch repair (pMMR) group (n=746) based on dMMR status. Immunohistochemistry results showed that patients in the dMMR group accounted for 11.9% (101/847). Compared to the pMMR group, the dMMR group had a higher proportion of patients aged≤50 years, tumor diameter≥5 cm, poorly differentiated (signet ring or mucinous), tumor located in the splenic flexure and proximal colon, and stage TNM-Ⅱ tumors. The risk of tumor nerve invasion was lower in the dMMR group (all P<0.05). Among the 101 dMMR patients, 89 underwent high-throughput sequencing (HTGS), including 24 pathogenic variants (7 cases of MLH1, 13 cases of MSH2, 3 cases of MSH6, and 1 case of PMS2) and 5 variants of uncertain significance (1 case of MSH2, 3 cases of MSH6, and 1 case of PMS2). Among the 29 cases, 15 (51.7%) had synchronous or metachronous tumors, 11 (37.9%) met Chinese LS clinical screening criteria, and 4 (13.8%) met LS clinical diagnostic criteria but no pathogenic variants were found. Pathogenic MSH2 variants accounted for 54.2% (13/24). Compared to the pMMR patients, dMMR CRC has clinical features, including younger age, larger tumor size, poorer differentiation, more proximal colon location, and more stage TNM-Ⅱ tumors. The prevalence of LS with confirmed pathogenic variants by HTGS reached 27.0%(24/89).
A 58-year-old male was seen in Peking Union Medical College Hospital on September 22, 2022 due to "repeated erythematous rash for more than 7 months". The patient had repeated erythematous rash and fever, accompanied by muscle soreness and fatigue. Auxiliary examination revealed pancytopenia. Bone marrow acute myeloid leukemia/myelodysplastic syndrome/myeloproliferative tumor (AML/MDS/MPN) -DNA detection revealed the variant allele frequency (VAF) of DNMT3A gene: 44.9%. The diagnosis was clonal cytopenia (CCUS) of unknown significance. High-dose glucocorticoid treatment was effective, but the disease was repeated after glucocorticoid reduction. The treatment effect of combined tripterygium wilfordii, methotrexate, cyclophosphamide and other immunosuppressants was poor. Vacuolar changes were seen after multiple bone marrow smears, and mutations of UBA1 gene and DNMT3A gene were found in peripheral blood gene detection, and VEXAS syndrome was finally diagnosed. After the patient received prednisone combined with tripterygium wilfordii and cyclosporine treatment, the rash decreased, muscle soreness and fatigue decreased. During the treatment, opportunistic infections and complications related to Pneumocystis pneumonia and herpes zoster occurred. Immunosuppressants were suspended, and the symptoms improved after anti-infective treatment. The pain of postherpetic neuralgia was relieved by drug and surgery. Follow-up until June 7, 2025, for a total of 2 years and 8 months, the condition has not been completely controlled, and it is still under follow-up.
The 61-year-old male patient went to the Department of Nephrology, Chengdu First People's Hospital on January 3, 2025 because of "proteinuria discovered for more than 8 years and edema for 1 month". The patient had massive proteinuria, microscopic hematuria and hypoalbuminemia, and renal function continued to deteriorate. Immunofixation electrophoresis revealed blood IgG-κ M protein (+). Repeated renal biopsy showed proliferative changes of glomerular membrane accompanied by high-intensity deposition of IgG-κ, and immunohistochemistry showed that small lymphocytes of phenotype CD5+ and CD20+ infiltrated the renal interstitium. Combined with bone marrow smear, biopsy, flow cytology and immunophenotypic analysis (proliferation of mature B lymphocytes with positive expression of CD5 and CD23), chronic lymphocytic leukemia (CLL) with renal infiltration and membranoproliferative glomerulonephritis (PGNMID) with monoclonal immunoglobulin deposition was diagnosed. After treatment with prednisone and cyclophosphamide, urine protein, plasma albumin and renal function were improved. The patient was followed up until June 7, 2025 for a total of 5 months. At present, the patient's condition is stable and there is no edema.
Ferroptosis, a form of programmed cell death driven by iron ion-dependent lipid peroxidation, plays an important role in chemoresistance in colorectal cancer. Its core mechanism involves the dysregulation of glutathione, glutathione peroxidase 4, and ferroptosis inhibitor protein 1-coenzyme Q systems. Colorectal cancer cells gain chemoresistance through mechanisms such as regulation of antioxidant system, iron ion metabolism and lipid peroxidation. Targeted intervention of ferroptosis-related molecules and signaling pathways can effectively reverse drug resistance and enhance chemotherapy drug sensitivity, thereby improving the anti-tumor effect. This paper systematically discusses the regulatory mechanism of ferroptosis in chemoresistance of colorectal cancer and its potential therapeutic strategies, emphasizes the importance of targeted ferroptosis to improve the prognosis of colorectal cancer patients, and provides a theoretical basis for individualized therapy.
Iron plays an important role in children's allergic diseases because of its important metabolic regulatory function and immune regulatory function. Children with anemia are more likely to suffer from allergic diseases. The imbalance of lung iron metabolism is related to the pathophysiological mechanism of asthma. Serum iron status is closely related to the levels of allergic markers such as IgE and eosinophils. Iron deficiency may be involved in the occurrence and development of allergic diseases by promoting Th2 cell expansion, B cell antibody class switching, and inducing macrophage conversion to the M1 pro-inflammatory phenotype. Based on the basic characteristics of iron metabolism balance and its regulation, this review systematically summarized the relationship between iron metabolism imbalance and childhood allergic diseases and the immune regulation mechanism, aiming to provide new ideas for prevention, treatment and scientific management of childhood allergic diseases.
A 56-year-old male was seen in Qingdao Municipal Hospital for "fever for more than 1 month, aggravated with left middle and upper abdominal pain for 3 days". Perfect blood routine showed: white blood cells 5.63×109/L, lymphocytes (LYM) 1.08×109/L, platelets 55×109/L; Chest CT showed diffuse ground glass density shadows in both lungs with blurred boundaries and uneven density (Figure 1); Abdominal CT showed hepatosplenomegaly with wedge-shaped infarction (Figure 2, shown by arrows). After admission, he was given levofloxacin, piperasela/tazobactam, compound sulfamethoxazole tablets for anti-infection, peramivir for anti-virus, methylprednisolone for anti-inflammation and symptomatic supportive treatment, but his condition did not improve. PET-CT examination 10 days later showed diffuse hypermetabolism in both lungs; Hepatosplenomegaly with diffuse hypermetabolism, wedge-shaped infarction in the spleen (Figure 3, shown by arrows). Percutaneous liver biopsy was performed, and pathology showed that a large number of atypical lymphoid cells were seen in the hepatic sinus (Figure 4, hematoxylin-eosin staining ×400, indicated by arrows); Immunohistochemical results: CD3 (-), CD56 (-), CD4 (-), CDB (-), TIA-1 (-), CD5 (-), CD20 (+), LCA (+), Ki67 (80% +), PAX-5 (+), MUM1 (-), BCL2 (+), BCL6 (-), c-Myc (-), CD10 (-), CD30 (-), combined with immunohistochemical and clinical manifestations, the patient's lesions were consistent with intravascular large B-cell lymphoma (IVLBCL).
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