ObjectiveTo investigate the mechanism by which Notoginsenoside R1 （NGR1） ameliorates hypoxia/reoxygenation （H/R）-induced injury in AC16 human cardiomyocyte cell lines through the regulation of mitophagy. MethodsCommon genes linked to hypoxia/reoxygenation injury and mitophagy were identified by intersecting data from GeneCards and MitoCarta databases. AC16 cell viability was assessed via CCK-8 assay under varying NGR1 concentrations （0， 6.25， 12.5， 25， 50， 100， 200， 300， 400， 500 μmol/L）. AC16 cells were divided into the following groups： control group （Control）， model group （H/R）， and treatment groups （H/R + NGR1 at 100， 200 and 300 μmol/L）. Mitochondrial membrane potential （ΔΨm） was measured using 5，5'，6，6'-tetrachloro-1，1'，3，3'-tetraethylbenzimidazolylcarbocyanine iodide （JC-1） staining. Transcriptional levels of mitophagy-related genes （Parkin， Pink1， P62） were quantified by reverse transcription-quantitative PCR （RT-qPCR）. Protein expression of mitophagy-related markers （Parkin， Pink1， P62， and LC3BⅡ） was evaluated via Western blot analysis. Mitochondrial ultrastructure was visualized by transmission electron microscopy （TEM）. ResultsCompared to the control group， cell viability in the H/R group significantly decreased （P<0.01）. Treatment with NGR1 at concentrations above 100 μmol/L significantly enhanced the cell viability of AC16 cells compared to the H/R group （P<0.01）. H/R induced a significant decrease in mitochondrial membrane potential （P<0.01）， which was restored by NGR1 treatment （P<0.01）. The mRNA levels of Parkin， Pink1， and P62 in the H/R group were upregulated compared to the control group （P<0.05）， while NGR1 intervention downregulated their expression （P<0.05）. Protein expression levels of Parkin， Pink1， and LC3BⅡ in the H/R group significantly increased， while P62 expression decreased compared to the control group （P<0.01）. In contrast， different doses of NGR1 treatment significantly reduced the expression of Parkin， Pink1， and LC3BⅡ while increasing P62 expression （P<0.05）. TEM revealed that the mitochondrial structure in the H/R group was severely disrupted， with fragmented and disorganized cristae， which was alleviated by NGR1. ConclusionNGR1 ameliorates H/R-induced AC16 cell injury， and its mechanism may be associated with modulating the Pink1/Parkin pathway to suppress excessive mitophagy.

Abstract To analyzes the characteristics, problems and enlightenment of physical activity observation tools, so as to provide reference for researchers to quickly and accurately choose appropriate observation tools to evaluate children s and adolescents physical activity. Literature search is conducted in eight databases of Chinese and English, including CNKI, Wanfang, VIP, Web of Science, PubMed, Medline, ERIC, and SPORTDiscus. Ultimately, eight observation tools for assessing physical activity in children and adolescents are included. Through summarization and comparison, it is found that the applications of those tools cover multiple age groups, the observation indicators cover multiple dimensions for each with varying emphases, and the applicable contexts vary in their specific background information, and recording methods tend to be quantitative. However, several issues remain to be addressed in practical applications. First, the observation indicators need to be supplemented and improved; second, physical activity in community environments and academic classrooms requires further attention; third, physical activity intensity needs to be scientifically evaluated; fourth, observation and recording methods need to be integrated and innovated; fifth, the number of observation subjects needs to be expanded. Future research could focus on developing observation tools tailored to the characteristics of Chinese children and adolescents, while drawing on foreign observation tools to comprehensively assess physical activity among children and adolescents.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

OBJECTIVE: To establish foot and ankle models of different lateral collateral ligament injuries of ankle joint, and conduct finite element analysis on, and to explore the force conditions of subtalar articular cartilage during foot inversion movements under different gait stages and under different loads. METHODS: A normal ankle CT scan of a 30-year-old male healthy volunteer (heighted 175 cm and weighted 60 kg) was selected. The CT images were imported into software such as Mimics 21.0, Geomajic 2017, and Solidworks 2017 respectively, extract the normal ankle bone model. Then, the foot and ankle finite element models of different lateral collateral ligament injuries of ankle joint were constructed and divided into anterior talofibular ligament(ATFL) rupture group, ATFL and calcaneo fibular ligament (CFL) rupture group, ATFL, CFL and posterior talofibular ligament (PTFL) rupture group, and control group with intact ligament function by ANSYS 2021. Corresponding horizontal and vertical loads and torques were applied respectively on tibia and talus according to the force conditions of different phases to simulate landing phase, neutral and off-ground phase in walking gait. The changes in stress distribution area and stress peak of subtalar articular cartilage in the loading phase, neutral phase and off-ground phase gaits among four groups were observed. Simulate varus sprain action, apply different loads of 600, 1, 800, and 4, 200 N respectively, and changes in stress distribution area and the stress peak of subtalar articular cartilage among four groups of models were observed. RESULTS: In the gait simulation, the stress results of loading phase in ATFL fracture group, ATFL and CFL fracture groups, ATFL, CFL and PTFL fracture groups, and control group were 0.889 54, 0.960 89, 1.139 20, and 0.722 64 MPa, respectively. The neutral response force results were 1.250 60, 1.358 50, 1.363 70, 1.246 40 MPa respectively;the results of corresponding forces off-ground phase were 1.029 90, 1.138 70, 1.145 90 and 0.832 40 MPa respectively. In the inversion simulation, the stresses of ATFL fracture group, ATFL and CFL fracture groups, ATFL, CFL and PTFL fracture groups, and control group under load of 600 N were 2.191 3, 2.208 5, 2.215 7, and 2.156 6 MPa respectively. The stresses under a load of 1 800 N were 7.134 7, 9.715 2, 10.064 0, and 7.107 0 MPa respectively;the stresses under a load of 4 200 N were 17.435 0, 25.309 0, 26.119 0 and 16.010 0 MPa respectively. CONCLUSION The lateral collateral ligament of ankle joint plays an important role in the stability of the subtalar joint, especially CFL plays an important role in restricting calcaneal varus. If these ligaments are damaged, it will cause instability of the subtalar joint and further lead to lesions in the subtalar articular cartilage. Relevant exercises should be reduced or the ligament injuries should be treated in a timely manner.
Humans ; Finite Element Analysis ; Male ; Adult ; Cartilage, Articular/physiopathology* ; Ankle Injuries/physiopathology* ; Ankle Joint/physiopathology* ; Biomechanical Phenomena ; Subtalar Joint/injuries* ; Tomography, X-Ray Computed

OBJECTIVES: To study the differences in clinical characteristics of term and preterm neonates with necrotizing enterocolitis (NEC) undergoing surgical treatment. METHODS: A retrospective analysis was conducted on the clinical data of 142 NEC neonates who underwent surgery at the Children's Hospital of Chongqing Medical University from June 2017 to August 2023. The neonates were categorized into a preterm group (gestational age <37 weeks; 95 cases) and a term group (gestational age 37-42 weeks; 47 cases) to compare clinical characteristics. RESULTS: The preterm group had a higher postnatal age at both diagnosis and surgery compared to the term group (P<0.05). The preterm group also had a higher incidence of preoperative bloody stools, lower preoperative platelet counts, and higher rates of preoperative respiratory distress, apnea, reduced/absent bowel sounds, and mechanical ventilation compared to the term group (P<0.05). Postoperatively, the preterm group had higher rates of purulent meningitis, sepsis, and coagulation dysfunction, lower postoperative platelet counts, and lower intraoperative minimum body temperature than the term group (P<0.05). CONCLUSIONS There are significant differences in the clinical characteristics of preterm and term neonates with NEC undergoing surgery, suggesting the need for tailored perioperative management strategies based on these characteristics.
Humans ; Enterocolitis, Necrotizing/surgery* ; Infant, Newborn ; Retrospective Studies ; Male ; Female ; Infant, Premature ; Gestational Age

Objective:To observe the effects of different repair methods in the defects after Mohs surgical excision of malignant nasal tumors. Methods:Twenty-two cases of external nasal malignant tumor surgery from January 2021 to May 2024 were selected as the research. The tumors were resected using Mohs surgical technique, and the defects were repaired using forehead axial flap, bipedicle flap, nasolabial flap, free full-thickness skin graft from the groin, forehead axial flap, facial kite flap, and composite flap of earlobe cartilage and perichond. The postoperative flap survival, external nasal morphology, and tumor recurrence were observed. Results:Among the 22 cases, there were 1 case of Kaposis sarcoma（KS）, 2 cases of squ cell carcinoma, and 19 cases of basal cell carcinoma. Tumors were located at the nasal root in 3 cases, the nasal dorsum in5 cases, the nasal tip in 2 cases, the ala in 8 cases, both the ala and the nasal dorsum in 2 cases, nasal columella, the nasal tip, and the ala in 1 case, the nasal tip, the nasal dorsum, the ala, and paranasal area in 1 case. The size of the defects ranged from 1.2 cm×1.4 cm to 3.7 cm×4.8 cm. Three cases were repaired with forehead axial flaps, four cases with bilobed flaps, thirteen cases with nasolabial groove flaps, one case with free full-thickness skin grafts from the inguinal region, and one case with a combination of forehead axial flaps and facial kite flaps plus a composite of earlobe cartilage and perichondrium. All flaps survived well after surgery. Patients were followed up for 6 months to 3 years after surgery, during which no tumor recurrence was observed, and most patients were satisfied with appearance of their nose. Conclusion:Mohs surgery is used to excise the malignant tumor of the external nose, and satisfactory surgical results can be obtained by using different repair methods based the location and size of the postoperative defect.
Humans ; Mohs Surgery/methods* ; Nose Neoplasms/surgery* ; Surgical Flaps ; Skin Transplantation ; Male ; Carcinoma, Basal Cell/surgery* ; Skin Neoplasms/surgery* ; Female ; Middle Aged ; Plastic Surgery Procedures/methods* ; Nose/surgery* ; Aged ; Adult ; Carcinoma, Squamous Cell/surgery*

Objective : To investigate the effects of astragalus mongholicus extract ( AME) on lung injury and the myeloid differentiation factor 88 ( MyD88 ) / Toll-like receptor 4 ( TLR4 ) / nuclear factor kappa B ( NF-κB) p65 pathway in rheumatoid arthritis induced interstitial lung disease (RA-ILD) rats． Methods : SD rats were randomly divided into a control group，RA-ILD group，low-dose AME group (5 g / L) ，high-dose AME group ( 10 g / L) ，and high-dose AME + lipopolysaccharide (LPS) group ( 10 g / L AME + 1 mg / L TLR4 activator LPS) ．Except for the control group，rats in all other groups were injected with bovine type Ⅱ collagen，Freund ’s complete adjuvant， and bleomycin to establish the RA-ILD model．The arthritis index and lung tissue wet-dry weight ratio of rats were tested．ELISA was applied to detect the levels of inflammatory factors interleukin (IL) -1 β , IL-6 and tumor necrosis factor-α ( TNF-α) in bronchoalveolar lavage fluid． Hematoxylin eosin staining was used to observe pathological changes of rat knee joint tissue and lung tissue．Western blot was applied to detect the expression of autophagy fac- tors Beclin 1，microtubule-associated protein 1A /1B-light chain 3 (LC3) Ⅱ / Ⅰ , and MyD88 /TLR4 /NF-κB p65 pathway related proteins in lung tissue． Results : Compared with control group，knee joint tissue and lung tissue of rats in RA-ILD group were damaged，the arthritis index，lung tissue wet-dry weight ratio，levels of IL-1 β , IL-6， and TNF-α , the expression levels of MyD88 and TLR4 proteins ，and p-NF-κB p65 /NF-κB p65 ratio increased (P＜0. 01) ，the expression of Beclin 1 and LC3 Ⅱ / Ⅰ proteins decreased (P＜0. 01) ．Compared with RA-ILD group，the low-dose and high-dose AME groups showed reduced tissue damage in rats，the arthritis index，lung tis- sue wet-dry weight ratio，levels of IL-1 β , IL-6，and TNF-α , the expression levels of MyD88 and TLR4 proteins， and p-NF-κB p65 /NF-κB p65 ratio showed a dose-dependent decrease (P＜0. 05 or P＜0. 01) ，the expression of Beclin 1 and LC3 Ⅱ / Ⅰ proteins showed a dose-dependent increase (P＜0. 05 or P＜0. 01) ．Compared with high- dose AME group，the tissue damage of rats in the high-dose AME + LPS group was worsened，the arthritis index， lung tissue wet-dry weight ratio，levels of IL-1 β , IL-6，and TNF-α , the expression levels of MyD88 and TLR4 pro- teins，and p-NF-κB p65 /NF-κB p65 ratio were higher (P＜0. 01) ，the expression of Beclin 1 and LC3 Ⅱ / Ⅰ pro- teins was lower (P ＜0. 01 ) ． Conclusion AME inhibits the MyD88 /TLR4 /NF-κB p65 pathway and alleviates lung injury in RA-ILD rats．

OBJECTIVE To analyze the types and control measures of major microorganisms in pharmaceutical water systems, so as to provide guidance for effective control of pharmaceutical water systems. METHODS The main microbial species, abundance and harmfulness of drinking water, purified water and water for injection were reviewed, and the control measures on microorganisms in pharmaceutical water were discussed. RESULTS There were differences in the main microbial types in pharmaceutical water. Burkholderia cepacia complex and Ralstonia pickettii were conditioned pathogens in pharmaceutical water, thus causing certain biological safety hazards. CONCLUSION Pharmaceutical companies can strengthen the control of microorganisms in the water system by establishing microbial databases and common microbial strain banks at all levels. Trend analysis should to be conducted based on alert limits and action limits, so as to strengthen the control of microorganisms in the water system.

OBJECTIVE To establish a rapid and accurate PCR method for detecting 24 strains of Burkholderia cepacia complex(Bcc) by comparing three detection methods of loop-mediated isothermal amplification(LAMP), SYTO 9 dye method based on polymerase chain reaction(PCR) and TaqMan probe real-time fluorescent quantitative PCR method( TaqMan probe method). METHODS According to the molecular biological information of 24 strains of Bcc in the NCBI database, multiple candidate sequence fragments unique to Bcc were screened out, and specific primer and probe that could simultaneously detect 24 strains of Bcc were designed. At the same time, the detection methods of LAMP, SYTO 9 dye method based on PCR and Taqman probe were explored, and the optimal annealing temperature was optimized and screened. The 39 experimental strains were used to verify the Bcc detection method. RESULTS LAMP method could not effectively detect Bcc, SYTO 9 dye method and TaqMan probe method could effectively detect more than 20 strains of Bcc, while TaqMan probe method had higher amplification effect, better detection sensitivity, repeatability and stability, which could meet the requirements of this study. CONCLUSION In this study, a TaqMan probe method for rapid detection of Bcc was established. Compared with LAMP method and SYTO 9 dye method, this method has the advantages of fast, simple and high sensitivity, and provides technical support for the rapid detectionof Bcc.

Objective To investigate the screening and prevalence of tuberculosis among freshmen in different schools in Baoding City,and provide reference for tuberculosis control in schools.Methods Screening data of tu-berculosis and tuberculin test(PPD)of freshmen from 156 schools in different regions of Baoding City from Septem-ber 2021 to March 2022 were collected.PPD screening results of students from different regions and different school stages were analyzed and compared.Results A total of 68 177 freshmen from 156 schools were investigated for suspected symptoms and close contact history of pulmonary tuberculosis.PPD screening was conducted on 63 939 students.13 821 students were PPD positive,with a positive rate of 21.62％.3 083 students were strongly posi-tive,with a strong positive rate of 4.82％.15 cases of tuberculosis were found,and the reported incidence was 23.46/100 000.PPD positive rate and strong positive rate as well as incidence of tuberculosis in students in different school stages presented statistically significant differences(all P＜0.01).Positive rate and strong positive rate in students in different school stages showed upward trends(all P＜0.01).PPD positive rate and strong positive rate of students from schools in plain and mountainous areas presented statistically significant differences([22.28％vs 17.89％];[4.85％vs 3.62％],both P＜0.01).PPD positive rate and strong positive rate between students from boarding junior school and non-boarding junior school were significantly different,respectively([23.94％vs 21.60％];[5.07％vs 3.56％],both P＜0.01).Conclusion It is necessary to strengthen tuberculosis screening and health education for freshmen,especially those from boarding schools in plain areas,screening latent Mycobac-terium tuberculosis infection as early as possible,take corresponding measures to prevent and control the spread of tuberculosis,and reduce the risk of tuberculosis.