OBJECTIVES: To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL). METHODS: Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed. RESULTS: In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05). CONCLUSIONS Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
Humans ; Methotrexate/toxicity* ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood* ; Male ; Female ; Child ; Child, Preschool ; gamma-Glutamyl Hydrolase/genetics* ; Antimetabolites, Antineoplastic/adverse effects* ; Infant ; Polymorphism, Genetic ; Adolescent ; Genotype ; Polymorphism, Single Nucleotide

OBJECTIVE: To investigate the prognostic value of peripheral blood absolute monocyte count(AMC) in non-severe aplastic anaemia(NSAA) patients. METHODS: 178 patients with NSAA who attended the Affiliated Hospital of Xuzhou Medical University from April 2008 to September 2020 were retrospectively analyzed, and the optimal cut-off value of peripheral blood AMC was determined by the receiver operating characteristic curve of the subjects, and they were divided into low AMC group (48 patients) and normal AMC group (130 patients), and the differences in clinical characteristics between the two groups were compared. Overall survival(OS) and progression-free survival(PFS) were analyzed by Kaplan-Meier. Univariate and multivariate Cox regression analysis were used to determine the independent prognostic value of AMC. RESULTS: Among 178 NSAA patients, 105(59.0%) were male and 73(41.0%) were female, with a median age of 31(18-87) years old, a median follow-up time of 58 months (range: 6 months-175 months), and a median AMC of 0.15×10⁹/L ［range: (0.01-0.59)×10⁹/L)］. The proportion of granulocytes (27.5% vs 36.0%, P < 0.05), and the proportion of mature monocytes (1% vs 2%, P < 0.05) in the low AMC group were lower than that in the normal AMC group; the proportion of mature lymphocytes in the low AMC group was higher than that in the normal AMC group (54% vs 50%, P < 0.05). However, there was no significantly different in the proportion of erythropoietic cells and stages of the erythropoietic cells between the two groups ( P >0.05). CR (27.7% vs 10.4%) and ORR (75.4% vs 56.3%) in the normal AMC group were higher than that in the low AMC group. Compared with patients in the low AMC group, AA patients in the normal AMC had better 5-year OS (98.5% vs 86.9%, P < 0.01), and the 5-year PFS (86.0% vs 58.9%, P < 0.01). Also, the 10-year survival rate of patients in the normal AMC group was higher than that in the low AMC group (98.5% vs 60.5%,P < 0.01). Univariate analysis showed that age, reticulocyte count, AMC<0.1×10⁹/L and the proportion of bone marrow mature monocytes were related with patients survival. Multivariate Cox regression analysis showed that monocyte count reduction was not an independent poor prognostic factor in NSAA patients （HR =4.474，95%CI ：0.508-44.390； P =0.172）. CONCLUSION Low AMC level at initial diagnosis is not an independent prognostic factor for NSAA patients, but still suggest potential prognostic value of AMC.
Humans ; Anemia, Aplastic/diagnosis* ; Female ; Male ; Prognosis ; Monocytes ; Adult ; Middle Aged ; Retrospective Studies ; Adolescent ; Aged ; Young Adult ; Aged, 80 and over ; Leukocyte Count

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 explore the effects of different concentrations of lidocaine infiltration and analgesia in pleural cavity after lung cancer surgery on rehabilitation of patients.Methods A total of 86 patients with lung cancer were selected and divided into the high concentration group(43 cases)and low concentration group(43 cases)by random number table method.Patients in the high concentration group received injection of 2.0%lidocaine hydrochloride in pleural cavity through the epidural catheter 1st day after surgery,and patients in the low concentration group received injection of 1.5%lidocaine hydrochloride in pleural cavity.In addition,patients in the two groups were treated with patient-controlled intravenous analgesia after surgery.The first time of getting out of bed,first time of exhaustion,first time of defecation and hospital stay after surgery of the two groups were compared.The visual analogue scale(VAS)scores 6 hours,12 hours,24 hours and 48 hours after surgery,the occurrence of agitation during the postoperative awakening period,and the number of analgesic pump compressions and the dosage of analgesic drugs within 24 hours after surgery were compared.The incidence of adverse drug reactions 24 hours after surgery were recorded and the quality of recovery of patients 24 hours after surgery was evaluated by 40-item quality of recovery score(QoR-40).Results The first time of getting out of bed,first time of exhaustion,first time of defecation and hospital stay after operation of patients in the high concentration group were shorter than those in the low concentration group(P<0.05).The VAS scores of the two groups 12 hours and 24 hours after surgery were higher than those 6 hours after surgery(P<0.05),the VAS scores 24 hours and 48 hours after surgery were lower than those 12 hours after surgery(P<0.05),and the VAS scores 48 hours after surgery were lower than those 24 hours after surgery(P<0.05).The VAS scores 6 hours,12 hours,24 hours,and 48 hours after surgery of patients in the high concentration group were lower than those in the low concentration group(P<0.05).The occurrence of agitation during the postoperative awakening period,and the number of analgesic pump compressions and the dosage of analgesic drugs within 24 hours after surgery for patients in the high concentration group were lower/less than those in the low concentration group(P<0.05).There was no significant difference in the total incidence of adverse drug reactions between the two groups(P>0.05).The total QoR-40 score of patients in the high concentration group were higher than those in the low concentration group(P<0.05).Conclusion The use of 2.0%lidocaine infiltration and analgesia in pleural cavity for patients after lung cancer surgery can reduce the agitation during the awakening period,alleviate the postoperative pain,improve the quality of postoperative recovery,and promote the postoperative recovery of the patients,with certain safety.

Objective To investigate the clinical safety of Chinese medicine combined with immune checkpoint inhibitors(ICIs)for the treatment of non-small cell lung cancer(NSCLC)at stage Ⅲ-Ⅳ,and to explore the influencing factors of immune-related adverse events(irAEs)in the treatment of stage Ⅲ-Ⅳ NSCLC with ICIs.Methods A retrospective analysis was carried out for the investigation of the distribution of traditional Chinese medicine(TCM)syndromes,related medication information and the occurrence of irAEs in the hospitalized patients diagnosed as stage Ⅲ-Ⅳ NSCLC and treated with Chinese medicine combined with ICIs in the Oncology Department of Guangdong Provincial Hospital of Chinese Medicine(University-town Branch)from September 1,2019 to August 31,2022.And the levels of adverse reactions and their possible influencing factors were analyzed.Results(1)The treatment for the 90 NSCLC patients involved 4 regimens,namely ICIs monotherapy,ICIs combined with chemotherapy,ICIs combined with anti-angiogenic drugs,and ICIs combined with chemotherapy and anti-angiogenic drugs.Among them,ICIs combined with chemotherapy and anti-angiogenic drugs were used most frequently for 52 cases(49.1%).A total of 8 kinds of ICIs drugs were used,of which Tislelizumab accounted for the highest proportion(43 cases,40.6%).(2)All of the patients were classified into 5 syndrome types,namely qi deficiency and phlegm-stasis syndrome,phlegm-stasis obstructing the collateral syndrome,qi and yin deficiency syndrome,qi and blood deficiency syndrome,and phlegm-heat accumulation syndrome.Among them,qi deficiency and phlegm-stasis syndrome was the most common type(80 cases,88.9%).(3)The overall incidence of irAEs was 38.9%(35/90),and irAEs being or above grade 3(G3)level in the patients only accounted for 5.6%(5/90).The initial irAEs usually occurred at the immunotherapy course 1-3(17 cases,48.6%).The incidence of irAEs being or above G3 level in the patients treated with ICIs monotherapy was higher than that in the patients treated with the combined therapy(33.3%vs 3.6%).(4)The Eastern Cooperative Oncology Group(ECOG)performance status(PS)score of 0-1(OR=8.218,95%CI:1.607-42.023,P = 0.011)and adrenal metastasis(OR=4.497,95%CI:1.237-16.354,P=0.022)were the independent risk factors for irAEs in patients with stageⅢ-Ⅳ NSCLC treated by ICIs(P＜0.05).Conclusion Chinese medicine has the potential to reduce the incidnence of adverse reactions of ICIs in the treatment of stage Ⅲ-Ⅳ NSCLC.PS score of 0-1 and adrenal metastasis may be the independent risk factors for irAEs in patients with stage Ⅲ-Ⅳ NSCLC treated by ICIs.

Bladder cancer is one of the most prevalent cancers worldwide, with a high rate of recurrence and mortality, which is the ninth most common malignancy globally. Cystoscopy remains the gold standard for clinical bladder cancer diagnosis, but its invasive nature can lead to bacterial infection and inflammation. Urine cytology is a non-invasive and simple diagnostic method, but it has lower sensitivity in detecting low-grade bladder cancer and may yield false negative results. Therefore, identifying ideal diagnostic and prognostic biomarkers is crucial for accurate diagnosis and effective treatment of bladder cancer. Aptamers, characterized as single-stranded DNA or RNA with unique three-dimensional conformations, exhibit the ability to identify various targets, ranging from small molecules to tumor cells. Aptamers, also known as chemical antibodies, are generated by systematic evolution of ligands by exponential enrichment (SELEX) process and can function similarly to traditional antibodies. They hold numerous advantages over antibodies, such as ease of modification, low immunogenicity, and rapid tissue penetration and cell internalization due to their nucleic acid molecule structure. Since their discovery in the 1990s, aptamers have been widely used in biochemical analysis, disease detection, new drug research and other fields. This article provides an overview of aptamer selection and characterization for bladder cancer, discussing the research advancements involving aptamers in diagnosing and treating this disease. It covers aptamers obtained through different SELEX methods, including protein-SELEX, cell-SELEX, tissue-SELEX, and aptamers from other cancer SELEX; the detection in blood samples and urine samples; and application in targeted therapy and immunotherapy for bladder cancer. Currently, several aptamers capable of identifying bladder cancer have been generated, serving as molecular probes that have played a pivotal role in the early detection and treatment of bladder cancer. Bladder cancer perfusion therapy is well-suited for aptamer drug therapy because it does not require internal circulation, making it a suitable clinical indication for aptamer drug development. In addition, bladder cancer can be detected and monitored by collecting urine samples from patients, making it a preferred disease for clinical conversion of aptamers. While aptamers show promise, there is still much room for development compared with antibodies. There are still many clinically applied cancer biomarkers without corresponding aptamers, and more aptamers targeting different biomarkers should be selected and optimized to improve the sensitivity and accuracy for cancer detection and therapy. The field of aptamers urgently needs successful commercial products to promote its development, and home rapid detection/monitoring, imaging and targeted therapy of bladder cancer by infusion may be the breakthrough point for future application of aptamers.

To evaluate the effectiveness and safety of implantable D-shant atrial shunt device in patients with severe pulmonary arterial hypertension(PAH)and right heart failure.A 53-year-old female patient diagnosed with severe idiopathic PAH and right heart failure,her WHO FC grade was Ⅳ.The right heart catheter and implantation of D-shant atrial shunt device were performed under local anesthesia on November 30,2021.A 6 mm×4 cm peripheral artery balloon was selected to dilate the atrial septum and a D-shant atrial shunt device with a fixed 4 mm diameter orifice was implanted into the heart.The clinical symptoms and hemodynamics of the patient was improved after the intervention.Implantation of atrial shunt device as a palliative therapy to established a right to left shunt is another strategy for treating patients with severe PAH in late period,which has good effectiveness and safety.It could be the last replacement therapy to improve symptoms and prolonged lives to drug resistant and severe PAH patients.

Objective To analyze the stresses in implanted titanium solid and bone trabecular prosthesis hip replacements.Methods A femur model was built inversely based on Mimics software,and optimized using Geomagic software,and then materialized by SolidWorks software.The osteotomized femur was assembled with the metal femoral stem to form a model,and then the model was imported into ABAQUS for finite element calculation.The upper femur was divided into four regions in different states of integration:medial proximal point(small trochanter region),lateral proximal region(large trochanter region),proximal point of the femoral stem(region around the mid-portion of the styloid process)and distal region(around the end of the styloid process and distal portion).Calculations were carried out over the femoral stresses before and after implantation of titanium solid and trabecular prostheses under gait and stair-climbing loads and the interfacial stresses when the region was unintegrated.The type of deformation at the bone interface was analyzed by means of a stress ellipsoid.Results At the small trochanter region,the stress shielding rates of the trabecular prosthesis under gait and stair climbing loads were reduced by 20.5％and 14.7％compared to the titanium solid prosthesis,respectively.In case of different integration states of the titanium solid prosthesis,the interface tensile stresses under the gait and stair climbing loads were up to 10.842 MPa and 12.900 MPa,and the shear stresses reached 7.050 MPa and 6.805 MPa,respectively;in case of different integration states of the trabecular prosthesis,the interface tensile stresses under the gait and stair climbing loads were up to 3.858 MPa and 4.389 MPa,and the shear stresses reached 4.156 MPa and 3.854 MPa,respectively.Under the 2 different loads,the inboard shear stress ellipsoid of the interface opened toward the sides and the bone interface showed tensile deformation;the outboard shear stress ellipsoid of the interface opened up and down and had compressive deformation.Conclusion After total hip arthroplasty,the overall performance of the trabecular prosthesis is better than that of the titanium solid prosthesis.The unintegrated edges of the prosthesis-bone interface are susceptible to stress concentrations and distortion which may result in occurrence of failures.[Chinese Medical Equipment Journal,2024,45(3):29-35]

Aim To determine the effect of histamine H

OBJECTIVE: To evaluate whether electroacupuncture (EA) would improve gastrointestinal function and clinical prognosis in patients with severe traumatic brain injury (TBI) complicocted by acute gastrointestinal injury (AGI). METHODS: This multicenter, single-blind trial included patients with TBI and AGI admitted to 5 Chinese hospitals from September 2018 to December 2019. A total of 500 patients were randomized to the control or acupuncture groups using a random number table, 250 cases in each group. Patients in the control group received conventional treatment, including mannitol, nutritional support, epilepsy and infection prevention, and maintenance of water, electrolytes, and acid-base balance. While patients in the acupuncture group received EA intervention at bilateral Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Tianshu (ST 25), and Zhongwan (RN 12) acupoints in addition to the conventional treatment, 30 min per time, twice daily, for 7 d. The primary endpoint was 28-d mortality. The secondary endpoints were serum levels of D-lactic acid (D-lac), diamine oxidase (DAO), lipopolysaccharide (LPS), motilin (MTL) and gastrin (GAS), intra-abdominal pressure (IAP), bowel sounds, abdominal circumference, AGI grade, scores of gastrointestinal failure (GIF), Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation (APACHE II), Sequential Organ Failure Assessment (SOFA), and Multiple Organ Dysfunction Syndrome (MODS), mechanical ventilation time, intense care unit (ICU) stay, and the incidence of hospital-acquired pneumonia. RESULTS: The 28-d mortality in the acupuncture group was lower than that in the control group (22.80% vs. 33.20%, P<0.05). Compared with the control group, the acupuncture group at 7 d showed lower GIF, APACHE II, SOFA, MODS scores, D-lac, DAO, LPS, IAP, and abdominal circumference and higher GCS score, MTL, GAS, and bowel sound frequency (all P<0.05). In addition, the above indices showed simillar changes at 7 d compared with days 1 and 3 (all P<0.05) in the EA group. CONCLUSION Early EA can improve gastrointestinal function and clinical prognosis in patients with severe TBI complicated by AGI. (Registration No. ChiCTR2000032276).
Humans ; Electroacupuncture ; Lipopolysaccharides ; Single-Blind Method ; Acupuncture Therapy ; Brain Injuries, Traumatic/therapy*