This paper aims to study the effect of p-cymene on mice with deficiency-cold syndrome induced by hydrocortisone and deficiency-heat syndrome induced by dexamethasone and explore the medicinal properties and mechanism of p-cymene with mild and warm nature based on the dominant characteristics of the two-way applicable conditions of mild drugs. A total of 80 KM mice were randomly divided into blank group, deficiency-cold syndrome model group, deficiency-cold syndrome + ginseng group, and deficiency-cold syndrome + low-dose and high-dose p-cymene groups, as well as blank group, deficiency-heat syndrome model group, deficiency-heat syndrome + American ginseng group, and deficiency-heat syndrome + low-dose and high-dose p-cymene groups. Hydrocortisone and dexamethasone solution were intragastrically administered for 14 consecutive days to prepare deficiency-cold syndrome and deficiency-heat syndrome models. Except for the blank group and the model group intragastrically administered with normal saline, the other groups were intragastrically administrated with drugs for 14 days. The levels of cyclic adenosine monophosphate(cAMP), cyclic guanosine monophosphate(cGMP), triiodothyronine(T3), thyroxine(T4), total cholesterol(TC), triglyceride(TG), immunoglobin G(IgG), and immunoglobin M(IgM) in serum, as well as the activity of Na~+-K~+-ATPase in liver tissue were detected. The expression of transient receptor potential melastatin 8(TRPM8), transient receptor potential vanilloid 1(TRPV1), and uncoupling protein 1(UCP1) in brown adipose tissue of deficiency-cold syndrome model after intervention with p-cymene was studied. The results showed that p-cymene could effectively improve the levels of cAMP, cAMP/cGMP, TC, IgM, and IgG in serum and the activity of Na~+-K~+-ATPase in liver tissue of mice with deficiency-cold syndrome and reduce the content of cGMP. The effects on T3, T4, and TG were not statistically significant. At the same time, p-cymene could reduce the levels of cAMP, cAMP/cGMP, and T4 in serum and the activity of Na~+-K~+-ATPase in liver tissue of mice with deficiency-cold syndrome and increase the levels of cGMP, IgM, and IgG, and it had no effect on T3, TC, and TG. In addition, p-cymene could up-regulate the expression of TRPV1 and UCP1 in brown fat of mice with deficiency-cold syndrome and down-regulate the expression of TRPM8. In summary, p-cymene could significantly regulate the syndrome indexes of mice with deficiency-cold syndrome, and some indexes of mice with deficiency-heat syndrome could be improved, but the effects on lipid metabolism and energy metabolism indexes were not obvious, indicating that the regulation effect of p-cymene on deficiency-cold syndrome model was more prominent and that the medicinal properties of p-cymene were mild and warm. The regulation of TRPV1/TRPM8/UCP1 channel expression may be the molecular biological mechanism of p-cymene with mild and warm nature affecting the energy metabolism of the body.
Animals ; Cymenes ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Disease Models, Animal ; Humans ; Cyclic AMP/metabolism* ; Monoterpenes/administration & dosage* ; Liver/metabolism* ; Cyclic GMP/metabolism* ; TRPV Cation Channels/genetics* ; Uncoupling Protein 1/genetics*

OBJECTIVES: To investigate the clinical features and gene mutation characteristics of combined oxidative phosphorylation deficiency type 7 (COXPD7) caused by mutations in the C12orf65 gene, and to enhance the awareness of this disease. METHODS: A child diagnosed with COXPD7 in the Department of Neurology, Children's Hospital Affiliated to Zhengzhou University in 2021 was included, along with 10 patients reported in the literature. All subjects were analyzed for their genotypes and clinical phenotypes. RESULTS: A total of 11 patients with COXPD7 were included, comprising 1 reported in this study and 10 from the literature. Among the 11 patients, 9 had homozygous mutations in the C12orf65 gene, while 2 had compound heterozygous mutations, which were identified as frameshift or nonsense mutations. The age of onset ranged from 1 day to 2 years, and clinical manifestations included optic nerve atrophy and delays in intellectual and motor development. Eight patients exhibited external ophthalmoplegia, and five patients displayed spastic paralysis. Cranial magnetic resonance imaging revealed optic nerve atrophy in all 11 patients, abnormal brainstem signals in 10 patients, and a lactate peak on brainstem magnetic resonance spectroscopy scans in 3 patients. CONCLUSIONS COXPD7 associated with the C12orf65 gene results from homozygous or compound heterozygous mutations, with primary clinical manifestations of optic nerve atrophy and delays in intellectual and motor development. Some patients may also present with spastic paralysis or external ophthalmoplegia. Cranial imaging reveals symmetrical abnormal signals in bilateral basal ganglia and brainstem, and a lactate peak is observed on brainstem magnetic resonance spectroscopy scans.
Child, Preschool ; Female ; Humans ; Infant ; Male ; Mitochondrial Diseases/genetics* ; Mitochondrial Proteins/genetics* ; Mutation ; Oxidative Phosphorylation ; Infant, Newborn

OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis

OBJECTIVES: To evaluate the efficacy and safety of avatrombopag in promoting platelet engraftment after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children, compared with recombinant human thrombopoietin (rhTPO). METHODS: A retrospective analysis was conducted on 53 pediatric patients who underwent allo-HSCT at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from April 2023 to August 2024. Based on medications used during the periengraftment period, patients were divided into two groups: the avatrombopag group (n=15) and the rhTPO group (n=38). RESULTS: At days 14, 30, and 60 post-transplant, platelet engraftment was achieved in 20% (3/15), 60% (9/15), and 93% (14/15) of patients in the avatrombopag group, and in 39% (15/38), 82% (31/38), and 97% (37/38) in the rhTPO group, respectively. There were no significant differences between the two groups in platelet engraftment rates at each time point, cumulative incidence of platelet engraftment, overall survival, and relapse-free survival (all P>0.05). Multivariable Cox proportional hazards analysis indicated that acute graft-versus-host disease was an independent risk factor for delayed platelet engraftment (P=0.043). CONCLUSIONS In children undergoing allo-HSCT, avatrombopag effectively promotes platelet engraftment, with efficacy and safety comparable to rhTPO, and represents a viable therapeutic option.
Humans ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child ; Child, Preschool ; Infant ; Adolescent ; Transplantation, Homologous ; Blood Platelets/drug effects* ; Thiazoles/therapeutic use* ; Thrombopoietin/therapeutic use* ; Thiophenes

Objective To evaluate the transition rules of normal body mass index(BMI),overweight and metabolic syndrome(MetS)in patients with major depressive disorder(MDD).Methods Patients with MDD who had multiple admission records between Jan 2016 and Nov 2021 in Beijing Anding Hospital,Capital Medical University were included.Based on the overweight and metabolic syndrome status assessed at each admission,the patients were categorized into three states:normal BMI,overweight and metabolic syndrome.A multi-state Markov model was used to analyze the transition intensity and transition frequency between three states and the influence of covariates on transitions.Results A total of 892 records of 398 subjects were included,with a median age of 56 years old and 31.4% males.The median follow-up period was 40 months.The multi-state model showed that there were 494 transitions between the three states,of which 5.1% moved from normal BMI to overweight and 5.5% moved from overweight to MetS.The intensity of transition was the highest from overweight to MetS,9.52 times greater than overweight to normal BMI.After 48.53 months,MDD patients with normal BMI began to transition to MetS.For overweight MDD patients,the transition to MetS started after 8.77 months.MDD patients with normal BMI or overweight had 31.4% and 50.4% probabilities of developing Mets after 36 months.For MDD patients comorbid with MetS,the probability of staying at MetS was 51.2% after 36 months.Multivariate analysis showed that being unmarried was a risk factor against developing overweight in normal BMI MDD patients,while a higher level of education was a protective factor against developing MetS in overweight MDD patients.Conclusion MDD patients exhibited a higher intensity and risk of developing MetS,and it is not easy to reverse MetS,suggesting that BMI management and MetS intervention should be strengthened in MDD patients.

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.

Objective:To compare the impacts of external fixation of different durations on rehabilitation outcomes after open repair of acute Achilles tendon rupture.Methods:A prospective cohort study was conducted to analyze the clinical data of patients with unilateral acute closed Achilles tendon rupture admitted to Peking University Third Hospital from August 2020 to August 2023. Patients were divided into Group A ( n=96), Group B ( n=347), Group C ( n=346), and Group D ( n=105) based on different postoperative immobilization durations (0, 2, 4 and 6 weeks, respectively). After all the patients received identical open repair procedure, Group A was rehabilitated immediately but the other groups were rehabilitated with the same protocol after removal of the external fixation. Four groups were compared in terms of recovery time of one-leg heel-rise height (OHRH), recovery time of light exercise (LE) in brisk walking and jogging and recovery time of range of motion (ROM). Visual analogue scale (VAS) scores were also compared at 2, 4, 6 and 8 weeks postoperatively. Achilles tendon total rupture score (ATRS) and American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot scores were evaluated at 6, 8, 10, 12, 14 and 16 weeks postoperatively. Complications were recorded. Results:A total of 894 patients including 869 males and 25 females were included, aged 18-60 years [(35.0±6.3)years]. All the patients were followed up for 14-25 months [(19.0±3.0)months]. The recovery time of OHRH in Group A and B was 12.0(12.0, 12.0)weeks and 12.0(10.0, 12.0)weeks, shorter than those in Group C [14.0(14.0, 16.0)weeks] and D [14.0(14.0, 14.0)weeks] ( P<0.05), with no significant difference between Group A and B ( P>0.05) and between Group C and D ( P>0.05). The recovery time of LE in Group A and B was 18.0(18.0, 18.0)weeks and 18.0(16.0, 18.0)weeks, shorter than those in Group C [20.0(20.0, 20.0)weeks] and D [20.0(20.0, 20.0)weeks] ( P<0.05), with no significant difference between Group A and B ( P>0.05) and between Group C and D ( P>0.05). The recovery time of ROM in Group A and B was 6.0(6.0, 6.0)weeks and 6.0(6.0, 6.0)weeks, shorter than those in Group C [8.0(8.0, 10.0)weeks] and D [10.0(10.0, 10.0)weeks)] ( P<0.05), with no significant difference between Group A and B, and between Group C and D ( P>0.05). At 2 weeks postoperatively, the VAS scores were 2.0(1.0, 2.0)points, 2.0(1.0, 2.0)points, and 2.0(1.5, 2.0)points in Group B, C and D, lower than 5.0(5.0, 5.0)points in Group A ( P<0.05), with no significant difference among Group B, C, and D ( P>0.05). At 4 weeks postoperatively, the VAS scores were 1.0(0, 1.0)points, 1.0(0, 1.0)points, and 1.0(0.5, 1.0)points in Group B, C and D, lower than 2.0(1.0, 2.0)points in Group A ( P<0.05), with no significant difference among Group B, C, and D ( P>0.05). At 6 weeks postoperatively, the VAS score was 0(0, 0)points in all the 4 groups, with no significant difference among them ( P>0.05). At 8 weeks postoperatively, the VAS score was 0(0, 0)points, with lower scores in Group A and B than those in Group C and D ( P<0.05) but with no significant difference between Group A and B and between Group C and D ( P>0.05). At 6 weeks postoperatively, the ATRS scores were 52.0(52.0, 53.8)points and 52.0(50.0, 53.0)points in Group A and B, higher than 41.0(38.0, 43.0)points and 19.0(18.0, 20.0)points in Group C and D ( P<0.05), with a higher score in Group C than that in Group D ( P<0.05) but with no significant difference between Group A and B ( P>0.05). At 8 weeks postoperatively, the ATRS scores were 66.0(66.0, 68.0)points in Group A, higher than 63.0(62.0, 64.0)points, 52.0(50.0, 53.0)points, and 39.0(37.0, 40.0)points in Group B, C and D ( P<0.05), with a higher score in Group B than those in Group C and D ( P<0.05) and a higher score in Group C than that in Group D ( P<0.05). At 10 weeks postoperatively, the ATRS score was 75.0(74.0, 76.0)points in Group B, higher than 69.0(69.0, 70.0)points, 72.0(66.0, 74.0)points, and 62.0(58.5, 63.0)points in Group A, C and D ( P<0.05), with higher scores in Group A and C than that in Group D ( P<0.05) but with no significant difference between Group A and C ( P>0.05). At 12 weeks postoperatively, the ATRS score was 84.0(82.0, 85.0)points in Group B, higher than 75.0(75.0, 77.0)points, 79.0(72.0, 81.0)points, and 72.0(71.0, 73.0)points in Group A, C and D ( P<0.05), with higher scores in Group A and C than that in Group D ( P<0.05) but with no significant difference between Group A and C ( P>0.05). At 14 weeks postoperatively, the ATRS score was 87.0(86.0, 87.0)points in Group B, higher than 82.0(82.0, 84.0)points, 83.0(80.0, 85.0)points, and 79.0(77.5, 80.0)points in Group A, C and D ( P<0.05), with higher scores in Group A and C than that in Group D ( P<0.05) but with no significant difference between Group A and C ( P>0.05). At 16 weeks postoperatively, the ATRS scores were 87.0(87.0, 88.0)points and 88.0(87.0, 88.0)points in Group A and B, higher than 86.0(85.0, 87.0)points and 84.0(83.0, 85.0)points in Group C and D ( P<0.05), with a higher score in Group C than that in Group D ( P<0.05) but with no significant difference between Group A and B ( P>0.05). At 6 weeks postoperatively, the AOFAS ankle-hindfoot scores were 94.0(94.0, 95.0)points and 95.0(94.0, 96.0)points in Group A and B, higher than 85.0(83.0, 86.0)points and 74.0(72.0, 75.0)points in Group C and D ( P<0.05), with a higher score in Group C than that in Group D ( P<0.05) but with no significant difference between Group A and B ( P>0.05). At 8 weeks postoperatively, the AOFAS ankle-hindfoot scores were 100.0(99.0, 100.0)points in Group B, higher than 94.0(94.0, 95.0)points, 92.0(90.0, 93.0)points, and 83.0(82.0, 84.0)points in Group A, C and D ( P<0.05), with a higher score in Group A than those in Group C and D ( P<0.05) and a higher score in Group C than that in Group D ( P<0.05). At 10 weeks postoperatively, the AOFAS ankle-hindfoot score was 100.0(100.0, 100.0)points in Group B, higher than 98.0(98.0, 98.0)points, 98.0(96.8, 99.0)points, and 96.0(95.0, 97.0)points in Group A, C and D, with higher scores in Group A and C than that in Group D ( P<0.05) but with no significant difference between Group A and C ( P>0.05). At 12 weeks postoperatively, the AOFAS ankle-hindfoot score was 100.0(100.0, 100.0)points in both Group A and B, with no significant difference between them ( P>0.05), which was higher than 100.0(98.0, 100.0)points and 99.0(98.0, 99.0)points in Group C and D ( P<0.05), with a higher score in Group C than that in Group D ( P<0.05). At 14 and 16 weeks postoperatively, AOFAS ankle-hindfoot score was 100.0(100.0, 100.0)points, with no significant difference among all the groups ( P>0.05). Superficial wound infection occurred in 12 patients [5.2%(5/96) in Group A, 0.6%(2/347) in Group B, 0.6%(2/346) in Group C and 2.9%(3/105) in Group D] ( P<0.01) while rerupture occurred in 16 [9.4%(9/96) in Group A, 1.2% (4/347) in Group B, 0.9%(3/105) in Group C, and 0 patient in Group D] ( P<0.01). Conclusion:For patients with unilateral acute Achilles tendon rupture, two weeks of postoperative external fixation after open repair can shorten the time of returning sports, alleviate pain, and promote functional recovery, without increasing the risk of complications.

Thoracolumbar spine fracture often leads to severe pain, functional impairments, and neurological deficits, for which open reduction and internal fixation can effectively restore the spinal structural stability. Open decompression and reduction with internal fixation can help relieve spinal cord compression and improve spinal function in cases of concomitant cord injury. Although spinal stability can be restored through surgery, patients often face chronic pain and functional impairments postoperatively. A postoperative rehabilitation program is critical in optimizing therapeutic outcomes, reducing complications, and minimizing the risk of secondary injuries. However, current rehabilitation methods, such as physical therapy, functional training, and pain management, are confronted with problems in clinical practice, including significant variation in efficacy, poor patient adherence, and prolonged rehabilitation period. There is an urgent need for a unified rehabilitation strategy to address these problems. To this end, the Spinal Trauma Group of the Orthopedic Physicians Branch of the Chinese Medical Association and the Spine Health Professional Committee of the Chinese Human Health Technology Promotion Association organized experts from relevant fields to formulate Evidence-based guidelines for rehabilitation treatment after internal fixation of thoracolumbar spine fracture in adults ( version 2025) by integrating evidences from clinical researches and advanced rehabilitation concepts at home and abroad. A total number of 14 recommendations concerning the rehabilitation treatment with multimodal analgesia, psychological intervention, deep vein thrombosis prevention, core muscle and extremity exercise, appropriate use of braces, early weight-bearing, device-aided rehabilitation exercise, neuroregulatory therapy, rehabilitation team were put forward, aiming to standardize the post-operative rehabilitation process following internal fixation, promote the functional recovery, and enhance patients′ quality of life.

Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.

Objective To assess the global and Chinese disease burden of early-onset lung cancer(di-agnosed in patients aged 15-49 years)and its major risk factors.Methods Based on the GLOBOCAN 2022 and Global Burden of Disease(GBD)2021 datasets,we evaluated the disease burden and associated risk fac-tors of early-onset lung cancer globally and in China,stratified by age,sex,geographic location,and human development index(HDI).Key indicators included age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),and disability adjusted life years(DALYs)attributable to risk factors.Results In 2022,there were 137 705 new cases and 72 646 deaths from early-onset lung cancer globally,with ASIR and ASMR of 3.43 per 100 000 and 1.82 per 100 000 population,respectively.The disease burden was higher in males than in females(ASIR:3.72 per 100 000 vs.3.14 per 100 000;ASMR:2.31 per 100 000 vs.1.33 per 100 000).High-HDI regions exhibited the highest ASIR(5.51 per 100 000)and ASMR(2.57 per 100 000),with health inequality analysis revealing a concentration of disease burden in higher-HDI areas.China bore the heaviest burden,accounting for 48.69%of global new cases and 35.77%of deaths.China's ASIR(8.21 per 100 000)and ASMR(3.17 per 100 000)exceeded global averages,with incidence higher in fe-males(8.78 per 100 000 vs.7.67 per 100 000)but mortality higher in males(4.01 per 100 000 vs.2.29 per 100 000).Smoking and ambient particulate matter pollution were the leading risk factors globally(DALYs contribution:42.01%and15.62%)and in China(DALYs contribution:46.78%and 20.84%).Globally,household air pollution ranked third,whereas in China,secondhand smoke replaced it as the third leading risk factor,with household air pollution dropping to fifth.Risk factor profiles varied significantly across age groups,with modifiable risks contributing less to disease burden in the 15-24 age group.Conclusions The burden of early-onset lung cancer varies markedly by sex,region,and HDI,with China facing a disproportionately high burden.Policymakers should prioritize equitable resource allocation and targeted interventions,particularly in tobacco control and air pollution mitigation,to enhance cancer prevention and control efforts.