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.

ObjectiveTo investigate the efficacy and safety of Babaodan Capsule （BBD） in the treatment of patients with chronic hepatitis B virus （HBV） infection with damp-heat in the liver and gallbladder comorbid with gallbladder polyps. MethodsA randomized， double-blinded， placebo-controlled single-center trial was conducted among 120 patients with chronic HBV infection who were admitted to Beijing YouAn Hospital， Capital Medical University， from August 2020 to April 2023， and they were divided into treatment group （BBD） and control group （placebo）， with 60 patients in each group. The course of treatment was 24 weeks， and follow-up assessments were conducted every 4 weeks. The primary outcome measures were the number and maximum diameter of gallbladder polyps （assessed by ultrasound）， and the secondary outcome measures included traditional Chinese medicine （TCM） syndrome score， blood lipid levels， and liver function parameters. The independent-samples t test or the Wilcoxon rank-sum test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups； the Wilcoxon rank-sum test was used for comparison of ranked data between two groups； the generalized estimating equation was used to analyze repeated measures data. ResultsAfter 8 weeks of treatment， the treatment group had a significantly smaller diameter of polyps and a significantly lower number of polyps than the control group （Z=-1.76 and -1.80， both P<0.05）， and after 24 weeks of treatment， the treatment group had a significantly higher polyp reduction rate than the control group （30.51% vs 10.91%， P<0.05）. The subgroup analysis showed that patients receiving combined antiviral therapy， male patients， patients with a diameter of polyps of <5 mm， and patients with multiple polyps tended to achieve significantly greater benefits. At week 8 of treatment， the treatment group had a significantly better TCM syndrome score than the control group （Z=-2.35， P<0.05）； after treatment， compared with the control group， the treatment group had a significantly greater increase in high-density lipoprotein （Z=-1.85， P<0.05） and significantly lower levels of alanine aminotransferase （Z=-2.06， P <0.05）， aspartate aminotransferase （Z=-2.13， P<0.05）， total bilirubin （Z=-2.12， P<0.05）， and direct bilirubin （Z=-3.09， P<0.05）. No serious adverse events were reported in either group. ConclusionBBD can effectively reduce the size of gallbladder polyps， improve TCM syndrome score， and reduce the level of bilirubin in patients with chronic HBV infection with damp-heat in the liver and gallbladder， with a favorable safety profile， and it may be more suitable for patients receiving combined antiviral therapy and specific subgroups （male patients， patients with a diameter of polyps of <5 mm， and patients with multiple polyps.

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 identify genetic etiology of ischemic stroke(IS)based on pleiotropy of obe-sity related genes.Methods:A discordant sib-pair study was designed based on the Fangshan family co-hort in Beijing.Body mass index(BMI)polygenic risk score(PRS)was first constructed under different P values.Using the polygenic transmission disequilibrium test(pTDT),we then compared the actual BMI genetic risk of siblings with IS to their expected risk,to analyze whether higher BMI was over-trans-mitted to siblings with IS.The single nucleotide polymorphism(SNP)that comprised the PRS over-trans-mitted with IS and that corresponded to the highest heritability of IS were identified as a pleiotropy SNPs set between BMI and IS.This set was then utilized as a candidate set to identify and verify risk SNPs as-so-ciated IS by transmission disequilibrium test.Finally,we identified independent genomic risk loci and mapped to genes,we then explored the biological function of the identified risk loci and genes by func-tional annotation and pathway enrichment.Results:A total of 541 participants were enrolled,with an average age of(58.4±8.1)years,including 326 discordant sib pairs of ischemic stroke.Compared with non-IS participants,IS participants with males,education level below junior high school,hypertension and hyperlipidemia accounted for a higher proportion(P＜0.05).For all the BMI PRS,we found that the actual genetic risk of BMI in siblings with IS was higher than their expectation,suggesting that genetic risk associated with high BMI was over-transmitted with IS.Compared with other SNP sets,the set(P＜5 × 10-4)corresponded to the best analytical statistics of pTDT and the highest heritability of IS and was identified as the pleiotropy SNP set between BMI and IS.Within this set,there were 45 SNPs having linkage and association with IS,which were located in 43 independent genomic risk loci and mapped to 40 genes.These genes were significantly enriched in the lipid metabolism pathway.The rs2232852 cor-rected by multiple tests was mapped to CYB5R1 and ADIPOR1,which were related to lipid metabolism and the ferroptosis pathway.Conclusion:Pleiotropy between BMI-related genes and IS was observed.Forty-five SNPs were found with linkage and association with IS in the pleiotropy gene set and mapped to 40 genes,which were functionally enriched in lipid metabolic pathways.The rs2232852 corrected by multiple tests during association analysis validation was mapped to CYB5R1 and ADIPOR1,which were related to lipid metabolism and the ferroptosis pathway,suggesting that lipid metabolism and ferroptosis played an important role in the development of IS.

A recombinant adenovirus(rAd)for expression of Mycobacterium tuberculosis(M.tb)c-di-AMP phosphodiesterase CnpB was constructed,and its induced humoral immune response was detected.The codon-optimized gene of M.tb CnpB was cloned into the adenoviral plasmid pcADV.The recombinant plasmid pcADV-CnpB was transfected into HEK293T cells,and expression was detected with Western blot.The recombinant plasmid pcADV-CnpB and the backbone plasmid were co-transfected into HEK293T cells to obtain the recombinant adenovirus rAd-CnpB.rAd-CnpB was amplified in HEK293T cells,and the target protein expression of rAd-CnpB was detected with Western blot and immunofluorescence.Mice were immunized with rAd-CnpB intranasally,and their sera and bronchoalveolar lavage fluid(BALF)were collected.ELISA was used to detect levels of antigen-specific antibodies.Restriction enzyme digestion and sequencing indicated that the recombinant plasmid pcADV-CnpB was successfully constructed and led to protein expression in eukaryotic cells.rAd-CnpB was packaged and produced in HEK293T cells.After amplification and purification,rAd-CnpB with a titer of 5.53×1010 PFU/mL was obtained.rAd-CnpB led to CnpB expression in HEK293T cells.Intranasal immunization with rAd-CnpB increased levels of IgG and secretory IgA in BALF and led to high levels of IgG in sera.rAd-CnpB,the recombinant adenovirus for expression of c-di-AMP phosphodiesterase CnpB was successfully constructed,and was found to induce antigen-specific humoral and mucosal immune responses through mucosal immunization.Thus,rAd-CnpB may be used in further research on new TB vaccine strategies.

Objective:To investigate the application effect of curved incision surgery in the treatment of hammock finger tendon.Methods:45 patients with hammock finger tendon who were admitted to Pingle Orthopedics and Traumatology Hospital in Shenzhen were selected from May 2022 to May 2023,all of whom were treated with curved incision surgery.Wound healing,functional recovery and complication rate were observed after surgery.Results:In this study,45 patients with hammock finger tendon were successfully followed up for 3 to 18 months,with an average follow-up of 1 year.The results of follow-up showed that all the incisions healed in one stage,and there were no complications such as skin infection and necrosis,exposed knots and skin irritation.X-ray reexamination before and after the operation showed,no complications such as loosening of the Kirkner needle,redisplacement of bone mass and nonunion of bone.During the follow-up period,there was no significant recurrence of vertical deformity.Crawford grading showed that,35 cases were excellent,9 were good,and 1 was fair.Conclusion:Using curved incision surgery to treat hammock finger tendon,which has the advantages of less trauma,faster recovery and fewer complications,and the effect is good.

Objective To analyse the mediating effect of the pain beliefs on pain and fear of disease progression in patients with trigeminal neuralgia.Methods A convenience sampling method was employed to select hospitalised 220 patients with trigeminal neuralgia as research objects from 3 Grade IIIA hospitals.The selected study subjects were surveyed with a general information questionnaire,the numeric pain rating scale,pain beliefs and perceptions scale,and fear of disease progression short form.Structural equation model was used to verify the pathways that affected the pain and pain beliefs on fear of disease progression in patients with trigeminal neuralgia.Results A total of 214 patients with trigeminal neuralgia completed the survey.The mean score of fear of disease progression was 33.38±8.47,the mean score of pain was 8.25±1.44,and the mean score of pain beliefs was-2(-9,8).Spearman correlation analysis showed that fear of disease progression was positively correlated with the pain beliefs(r=0.746,P<0.01)and pain(r=0.838,P<0.01),and the pain beliefs were positively correlated with pain intensity(r=0.704,P<0.01).Pain beliefs partially mediated between the pain and fear of disease progression in patients with trigeminal neuralgia,with a mediating effect of 0.442,a direct effect of 0.482,and a total effect of 0.924.The mediating effect accounted for 47.84%of the total effect.Conclusion Patients with trigeminal neuralgia generally have a critical state of psychologicol disfunction of fear of disease progression,with a moderate to severe pain,and moderate pain beliefs.Pain intensity in patients with trigeminal neuralgia not only directly affects fear of disease progression but also indirectly affects it through pain beliefs.

Objective:To investigate the effects of Yisui Shengxue Decoction on the regulation of Notch signaling pathway on bone marrow hematopoiesis in mice with aplastic anemia(AA).Methods:A total of 60 CByB6F1 mice were randomly divided into blank group,model group,positive control cyclosporine(CsA)group,low-dose(YSSX-L)group and high-dose(YSSX-H)group of Chinese herbal compound Yisui Shengxue Decoction,with 12 mice in each group.Except for the blank group,the mice in each group were given 5 Gy X-ray irradiation combined with tail vein infusion of lymphocytes to establish the immune-mediated AA mouse model.The low and high dose groups were given 8.6 and 17.2 g/(kg?d)of Yisui Shengxue Decoction by gavage,the model group and the blank group were given equal volume of saline by gavage,and the positive control group was given 25 mg/(kg?d)of cyclosporine by ga-vage for 14 days.The mice were tested for white blood cell count(WBC),red blood cell count(RBC),hemoglobin(Hb),platelet count(PLT)and bone marrow nucleated cell count in peripheral blood,bone marrow pathological changes and the levels of IFN-γ,IL-4 and IL-5 in peripheral serum,and T-lymphocyte transcription factors T-bet,GATA3,RORγt,FOXP3 mRNA and protein in spleen tissues,as well as the expression levels of Notch signaling pathway-related genes and protein in spleen tissues.Results:Compared with the blank group,the peripheral blood WBC,RBC,Hb,PLT,bone marrow nucleated cell count,expressions of serum IL-4,IL-5 and spleen tissue GATA3,FOXP3 mRNA and protein were significantly lower in the model group(P<0.01),and the expressions of serum IFN-γ,spleen tissue T-bet,RORγt mRNA and protein,and Notch1,Jagged1,DLL4 mRNA and protein were significantly in-creased(P<0.05).Compared with the model group,peripheral blood WBC,RBC,Hb,PLT,bone marrow nucleated cell count,ex-pressions of serum IL-4,IL-5 and spleen tissue GATA3,FOXP3 mRNA and protein were significantly higher in each intervention group(P<0.05),and the expression of serum IFN-γ and spleen tissue T-bet,RORγt mRNA and protein as well as Notch1,Jagged1,DLL4 mRNA and protein were significantly reduced(P<0.05).Conclusion:Yisui Shengxue Decoction can improve bone marrow he-matopoietic function and regulate immune disorders in AA mice,and its mechanism of action may be related to the regulation of Notch signaling pathway.