OBJECTIVES: To analyze the clinical characteristics of diffuse panbronchiolitis (DPB) in children and to enhance the clinical diagnosis and treatment of this disease. METHODS: A retrospective analysis was conducted on the clinical data of 6 children diagnosed with DPB who were hospitalized at The First Affiliated Hospital of Guangzhou Medical University from January 2011 to December 2019. RESULTS: Among the 6 patients, there were 2 males and 4 females; the age at diagnosis ranged from 7 to 12 years. All patients presented with cough, sputum production, and exertional dyspnea, and all had a history of sinusitis. Two cases showed positive serum cold agglutinin tests, and 5 cases exhibited pathological changes consistent with chronic bronchiolitis. High-resolution chest CT in all patients revealed centrilobular nodules diffusely distributed throughout both lungs with a tree-in-bud appearance. Five patients received low-dose azithromycin maintenance therapy, but 3 showed inadequate treatment response. After empirical anti-tuberculosis treatment, non-tuberculous Mycobacteria were found in the bronchoalveolar lavage fluid. Follow-up over 2 years showed 1 case cured, 3 cases significantly improved, and 2 cases partially improved. CONCLUSIONS The clinical presentation of DPB is non-specific and can easily lead to misdiagnosis. In cases where DPB is clinically diagnosed but does not show improvement with low-dose azithromycin treatment, special infections should be considered.
Humans ; Male ; Female ; Bronchiolitis/drug therapy* ; Retrospective Studies ; Child ; Haemophilus Infections/diagnosis*

OBJECTIVES: To investigate the clinical features of children with STAT gene mutations, and to explore corresponding immunotherapy strategies. METHODS: A retrospective analysis was performed for the clinical data of 10 children with STAT gene mutations who were admitted to the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University, from October 2015 to October 2024. Exploratory immunotherapy was implemented in some refractory cases, and the changes in symptoms, imaging manifestations, and cytokine levels were assessed after treatment. RESULTS: For the 10 children, the main clinical manifestations were recurrent rash since birth (7/10), cough (8/10), wheezing (5/10), expectoration (4/10), and purulent nasal discharge (4/10). Genotyping results showed that there was one child with heterozygous loss-of-function (LOF) mutation in the STAT1 gene, four children with heterozygous LOF mutation in the STAT3 gene, and five children with heterozygous gain-of-function (GOF) mutation in the STAT3 gene. Two children with LOF mutation in the STAT3 gene showed decreased interleukin-6 levels and improved clinical symptoms and imaging findings after omalizumab treatment. Three children with GOF mutation in the STAT3 gene achieved effective disease control after treatment with methylprednisolone (0.5 mg/kg per day). Two children with GOF mutation in the STAT3 gene received treatment with JAK inhibitor and then showed some improvement in symptoms. CONCLUSIONS STAT gene mutation screening should be considered for children with recurrent rash and purulent respiratory tract infections. Targeted immunotherapy may improve prognosis in patients with no response to conventional treatment.
Humans ; Male ; Immunotherapy ; Female ; Child, Preschool ; Child ; Gain of Function Mutation ; Retrospective Studies ; Infant ; Loss of Function Mutation ; STAT Transcription Factors/genetics*

Hemodynamic monitoring can reflect cardiac function and blood perfusion and is an indispensable monitoring method in clinical practice. Invasive hemodynamic monitoring methods represented by the thermodilution method are limited in their clinical application scope because they require vascular cannulation. Non-invasive hemodynamic monitoring has attracted extensive attention from medical companies and clinicians at home and abroad in recent years due to its advantages such as safety, non-invasiveness, continuous monitoring, simple operation, and low cost. This paper designs a non-invasive hemodynamic monitoring system based on the impedance cardiography, including hardware, algorithm, software design, and performance parameter evaluation. Among them, the hardware part mainly includes a differential high-frequency constant current source stimulation circuit, impedance cardiogram signal acquisition, and ECG signal acquisition circuit. Signal processing includes wave filtering, impedance cardiogram signal calibration, and ECG signal and impedance cardiogram signal feature point recognition. According to the collected impedance cardiogram and ECG signals, hemodynamic parameters such as heart rate (HR), stroke volume (SV), cardiac output (CO), stroke index (SI), cardiac index (CI), and cardiac contractility index (ICON) are calculated based on the Nyboer thoracic cylinder model. After testing, the key technical indicators of the system hardware are better than that of the relevant medical device standards. The system was used to collect impedance cardiogram and ECG signal data from 40 volunteers. The calculated HR, SV, and CO, three important hemodynamic indicators, were compared with the ICONCore non-invasive cardiac output monitor of OSYPKA Medical in Germany. Their Pearson correlation coefficients were 0.992 ( P<0.001), 0.948 ( P<0.001), and 0.933 ( P<0.001), respectively, verifying that the designed system has high accuracy and reliability.
Cardiography, Impedance/methods* ; Humans ; Hemodynamic Monitoring/methods* ; Equipment Design ; Signal Processing, Computer-Assisted ; Hemodynamics ; Algorithms ; Monitoring, Physiologic/methods* ; Electrocardiography

In order to improve the effect of transcranial electrical stimulation treatment and realize personalized treatment for patients with varying severity levels, this paper designed an integrated four-channel EEG recording multimodal transcranial electrical stimulation system. This system can conduct real-time monitoring on EEG and related characteristic analysis before stimulation, in stimulation, and after stimulation. This enables physicians and researchers to resolve real-time brain states, evaluate transcranial electrical stimulation effect, and then artificially adjust the stimulation parameters. After relevant testing and verification, the system can select four stimulation modes: TACS, TDCS, TPCS and TRNS, which can output the constant stimulation current of 0.03 mA accuracy in the range of ±2 mA and the stimulation frequency of low frequency of 0~4 kHz (precision of 0.01 Hz) and high frequency 50~100 kHz, which can obtain more accurate EEG signals under stimulation interference, demonstrating a good market application prospect.
Electroencephalography/methods* ; Transcranial Direct Current Stimulation/instrumentation* ; Humans ; Equipment Design

This paper introduces a 16-channel multimodal high-precision transcranial electrical stimulation system specifically for non-invasive brain stimulation. This system added TMCS mixed four traditional stimulation modes with TACS, TDCS, TPCS and TRNS. By designing a compensated high-precision constant current source, the constant stimulation current with an accuracy of 0.03 mA in the range of ±2 mA and the stimulation frequency of 50~200 kHz with low frequency of 0~4 kHz (high frequency of 0.1 Hz) are realized. In TACS stimulation mode, there are five adjustable wave forms: triangular wave, sine wave, sawtooth wave, square wave and mixed wave. The system has dual closed-loop control overcurrent detection and simultaneous real-time electrode contact impedance detection. After relevant tests and verification, the system has good stimulation accuracy, high safety and reliability. Compared with the existing products at home and abroad, it features lower cost, richer stimulation mode and waveforms, demonstrating a certain market application value.
Transcranial Direct Current Stimulation/instrumentation* ; Equipment Design ; Humans

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective:To comprehensively understand the basic situation of critical care medicine in Xinjiang Production and Construction Corps in order to promote the standardization, specialization, and systematization of quality control in critical care medicine.Methods:A survey was conducted from January 1, 2019, to December 31, 2021, using a questionnaire to investigate the human resources and basic allocation of comprehensive intensive care medicine departments in Xinjiang Production and Construction Corps division level hospitals and surrounding second-class hospitals. The survey content includes: basic situation of medical units, intensive care unit (ICU) basic information, ICU personnel situation, ICU equipment configuration situation, ICU performance situation, etc. The survey questionnaire was distributed in March 2022, with dedicated ICU attending physicians or above designated by each ICU as the contact person for the survey.Results:Sixteen questionnaires were distributed and returned, all of which were included from 16 comprehensive intensive care medicine departments in the Corps and surrounding areas, including 5 second class first class hospitals and 11 third class first class hospitals. There were 196 beds in 16 ICU units, and the ICU bed ratio (1.99% overall, 1.77% in third class first class hospitals) was lower than the 2%-8% stipulated in the Guidelines for the Construction and Management of Critical Care Medicine (Trial) issued by the National Health Commission. Only ICU beds in second class first class hospitals accounted for 2.65%, meeting this standard. The comprehensive ICU doctor-bed ratio in 16 hospitals was 0.55∶1, third class first class hospitals was 0.60∶1, and second class first class hospitals was 0.44∶1, compared with 0.8∶1 stipulated in the ministerial guidelines, there was a certain gap. Among the 108 doctors in 16 ICUs, only four have a master's degree or above. Associate senior and above professional and technical titles accounted for 27.78%, less than one third. Among the 334 nursing staff, there were no personnel with a master's degree or above, and only 10 personnel with associate senior or above professional and technical titles. From 2019 to 2021, there was 1 new master's degree personnel, 2 new senior professional and technical personnel, and 12 deputy senior professional and technical personnel. It indicating that the proportion of highly educated and experienced physicians and nurses were lower, team building lags behind, talent introduction were lower, and highly educated talents were scarce. The statistical analysis results of the absolute growth of core technology showed that the growth of core technology was slow, the progressiveness was insufficient, and the professional technical ability was insufficient. Conclusions:The construction of critical care majors and talent echelons in the Xinjiang Production and Construction Corps region is lagging behind, the overall professional level of the discipline is not high, and there is a lack of specialized personnel. Further improvement is needed in talent cultivation, technical development and training, medical quality management, and other aspects to ensure medical quality and safety.

Objective:To investigate the role of group 3 innate lymphoid cells (ILC3) in skin wound healing, and to explore the underlying mechanisms.Methods:Twenty-four 5-week-old male C57BL/6 mice were randomly and equally allocated into 3 groups: the skin wound + ILC3 inhibitor group (referred to as ILC3 inhibitor group), the skin wound group, and the control group, with 8 mice in each group. Four days before the establishment of the wound model, mice in the ILC3 inhibitor group were intraperitoneally injected with 1 μg of ILC3 inhibitor every 2 days for a total of 2 doses, mice in the skin wound group were injected with an equal volume of physiological saline solution, and mice in the control group were fed normally. To establish a mouse skin wound model, a full-thickness circular incision with a diameter of 0.6 cm was made around the midpoint of the dorsal midline using a biopsy punch after the intraperitoneal injection of anesthetics, which was histologically confirmed to be a full-thickness injury. The size of the wounds was observed and recorded, photographs of the wounds were taken on days 0, 1, 3, 5, 7, and 9 after wounding, and corresponding wound healing rates were calculated. On day 9 after wounding, tissue samples were collected from the wound edges, and subjected to flow cytometry analysis to quantify ILC3 infiltrating around the skin wound, and hematoxylin and eosin (HE) staining was performed to assess the healing status of the skin wounds. Real-time quantitative polymerase chain reaction (qRT-PCR) was conducted to determine the mRNA expression of vitamin D receptor (VDR), Notch1, tumor necrosis factor-alpha (TNF-α), interleukin (IL) -17A, IL-17F, and IL-22 in the wound-edge tissues, and Western blot analysis to determine their protein expression. Statistical analysis was carried out by using one-way analysis of variance and t test. Results:On day 9 after wounding, the skin wound group showed an increased number of ILC3 in the wound-edge tissues (5.31% ± 1.47% vs. 3.10% ± 0.54%, P < 0.01), increased mRNA and protein expression of TNF-α, IL-22, IL-17A, and IL-17F (all P < 0.05), but decreased mRNA and protein expression of VDR (both P < 0.05) compared with the control group; the protein expression of Notch1 was significantly higher in the skin wound group than in the control group ( P < 0.05), but there was no significant difference in its mRNA expression between the two groups ( P > 0.05). On days 1, 3 and 5, the wound healing rates were significantly higher in the ILC3 inhibitor group (45.17% ± 9.90%, 61.58% ± 11.61%, 75.61% ± 9.12%, respectively) than in the skin wound group (25.87% ± 10.96%, 47.78% ± 13.81%, 64.55% ± 10.29%, respectively, all P < 0.05). On day 9, the ILC3 inhibitor group showed a decreased number of ILC3 around the wound (2.69% ± 0.95%, P < 0.01), decreased mRNA and protein expression of TNF-α, IL-22, IL-17A, and IL-17F in the wound-edge tissues (all P < 0.05), but increased mRNA and protein expression of Notch1 and VDR in the wound-edge tissues (all P < 0.05) compared with the skin wound group. On day 9 after wounding, histopathological examination with HE staining revealed continuous and intact epithelial structure, as well as dense and neatly arranged collagen fibers in the ILC3 inhibitor group, and the structures of hair follicles, blood vessels, and sebaceous glands were similar to those in the control group. Conclusions:Skin ILC3 infiltrated local wounds and were involved in the skin wound healing process through inflammatory factors such as TNF-α, IL-17A, IL-17F, and IL-22. Downregulating the number of ILC3 may promote skin wound healing by activating VDR and Notch1, as well as inhibiting the TNF-α signaling pathway and the expression of downstream inflammatory factors.

Objective To investigate the correlation between the level of N-terminal pro-Brain natriuretic peptide(NT-proBNP)and cardiorespiratory fitness following acute exposure to high altitude.Methods Forty-six subjects were recruited from the Second Affiliated Hospital of Army Medical University in June 2022,including 19 males and 27 females.After completing cardiopulmonary exercise test(CPET),serological detection of myocardial cell-related markers,and multiple metabolites at a plain altitude(300 meters above sea level),all subjects flew to a high-altitude location(3900 meters above sea level).Biomarker testing and CPET were repeated on the second and third days after arrival at high altitude.Changes in serum biomarker and key CPET indicators before and after rapid ascent to high altitude were compared,and the correlation between serum levels of various myocardial cell-related markers and metabolites and high altitude cardiorespiratory fitness was analyzed.Results Compared with the plain altitude,there was a significant decrease in maximal oxygen uptake after rapid ascent to high altitude[(25.41±6.20)ml/(kg.min)vs.(30.17±5.01)ml/(kg.min),P<0.001].Serum levels of NT-proBNP,Epinephrine(E),plasma renin activity(PRA),angiotensin Ⅱ(Ang Ⅱ),angiotensin-converting enzyme 2(ACE2)and leptin(LEP)significantly increased,with all differences being statistically significant(P<0.05)after acute high altitude exposure.In contrast,no statistically significant differences were observed for creatine kinase MB(CK-MB),cardiac troponin I(cTnI),myoglobin(Myo)and norepinephrine(NE)(P>0.05).Correlation analysis showed a significant negative correlation between NT-proBNP at plain altitude(r=-0.768,P<0.001)and at high altitude(r=-0.791,P<0.001)with maximal oxygen uptake at high altitude.Multivariate linear regression analysis indicated that maximal oxygen uptake at plain altitude(t=2.069,P=0.045),NT-proBNP at plain altitude(t=-2.436,P=0.020)and at high altitude(t=-3.578,P=0.001)were independent influencing factors of cardiorespiratory fitness at high altitude.Conclusion Cardiorespiratory fitness significantly decreases after rapid ascent to high altitude,and the baseline NT-proBNP level at plain altitude is closely related to cardiorespiratory fitness at high altitude,making it a potential predictor indicator for high altitude cardiorespiratory fitness.