Sepsis is a lethal condition resulting from the host's dysregulated response, involving complex pathophysiological mechanisms, including the host's biphasic immune response and metabolic disturbances. Diagnosing and treating sepsis remain formidable challenges, with the absence of definitive biomarkers and effective therapeutic interventions to date. Animal models of sepsis are pivotal in unraveling the disease's pathogenesis and identifying potential treatments, playing a crucial role in enhancing our comprehension of its intrinsic nature. However, there is no animal model that can comprehensively and accurately simulate the complex pathophysiological process of human sepsis. This review discusses the widely used sepsis animal models, exploring their advantages and limitations in terms of pathogenesis, inflammatory response, pathophysiological changes, and organ dysfunction. It summarizes the application scenarios and latest research advancements of these models and provides an outlook on potential future improvements.
Sepsis/physiopathology* ; Animals ; Disease Models, Animal ; Humans

Doxorubicin(DOX)is a commonly administered chemotherapy drug for treating hematological malignancies and solid tumors;however,its clinical application is limited by significant cardiotoxicity.Cynaroside(Cyn)is a flavonoid glycoside distributed in honeysuckle,with confirmed potential biological functions in regulating inflammation,pyroptosis,and oxidative stress.Herein,the effects of Cyn were evaluated in a DOX-induced cardiotoxicity(DIC)mouse model,which was established by intraperitoneal injections of DOX(5 mg/kg)once a week for three weeks.The mice in the treatment group received dexrazoxane,MCC950,and Cyn every two days.Blood biochemistry,histopathology,immunohistochemistry,reverse transcription-quantitative polymerase chain reaction(RT-qPCR),and western blotting were conducted to investigate the cardioprotective effects and potential mechanisms of Cyn treatment.The results demonstrated the significant benefits of Cyn treatment in mitigating DIC;it could effectively alleviate oxidative stress to a certain extent,maintain the equilibrium of cell apoptosis,and enhance the cardiac function of mice.These effects were realized via regulating the transcription levels of pyroptosis-related genes,such as nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1,and gasdermin D(GSDMD).Mechanistically,for DOX-induced myocardial injury,Cyn could significantly modulate the expression of pivotal genes,including adenosine monophosphate-activated protein kinase(AMPK),peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α),sirtuin 3(SIRT3),and nuclear factor erythroid 2-related factor 2(Nrf2).We attribute it to the mediation of AMPK/SIRT3/Nrf2 pathway,which plays a central role in preventing DOX-induced cardiomyocyte injury.In conclusion,the present study confirms the therapeutic potential of Cyn in DIC by regulating the AMPK/SIRT3/Nrf2 pathway.

Objective:To scientifically measure and morphologically evaluate the anatomical shape of the skin in the first web space based on cadavers, and to guide the design of flap in this area.Methods:Sixteen human cadavers fixed with 10% formaldehyde without injury or deformity on the hand were selected in the Department of Hand Surgery, the Third Hospital of Suqian. According to the characteristics of the first web area, marker points were selected for measurement and morphological observation. Morphological characteristics of the first web with thumb radial abduction(r) or palmar abduction(p) were measured and compared. The t-test was used for statistical analysis. P<0.05 was considered statistically significant. According to the results of measurement, standardised shapes and parameters of the skin were obtained for flap repair of defect of the first web. Results:When the thumb was in palmar abduction, the maximum distance [a(p)] of the first web of female(F) and male(M) was 5.78/8.42 cm(F/M), and the skin [S(p)] was 17.09/23.63 cm 2(F/M), both were significantly greater than the distance [a(r)] at 4.86/6.28 cm and the area of skin area [S(r)] at 14.39/20.15 cm 2 when thumb was in the radial abduction position( P<0.05). There was no significant difference in the length of [b(r)] and [b(p)] alone the long axis of flap between palmar and radial abductions(7.54/9.38 cm and 7.34/9.74 cm, respectively) of the thumb( P>0.05). It was found that the area of first web was not shaped as a symmetrical spindle, but an irregular quadrilateral inclined to the index finger. Conclusion:Design and measurement of a flap for the first web space should take the maximum palmar abduction of a thumb as a reference. The asymmetric quadrilateral flap design is more in line with the anatomical and characteristics in the region.

Objective:To explore the teaching effect of the combined use of curriculum ideological and political education and CDIO (connective, design, implement, operate) mode in the cultivation of stomatological top-notch innovative personnel.Methods:The research subjects were undergraduate students from School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, who participated in stomatological top-notch innovative personnel training program in 2018 and 2019. CDIO was applied to control group, the combined use of curriculum ideological and political education and CDIO mode was applied to experimental group. After the training, the students' research and innovation capacity was examined and the teaching efficiency of these two models was reflected by the students' questionnaire. SPSS 20.0 software was used for t test. Results:In terms of research and innovation capacity, students scored significantly better in professional English, concluding report, papers publishing, and field defense in experimental group than in control group [(22.43±0.61) vs. (18.49±0.77), (22.48±0.32) vs. (19.05±0.53), (23.69±0.33) vs. (21.89±0.52), and (22.78±0.48) vs. (20.43±0.56), respectively, P<0.05]. The students in experimental group highly agreed with the teaching efficiency of the combined use of curriculum ideological and political education and CDIO mode. Conclusion:The combined use of curriculum ideological and political education and CDIO mode could enhance subjective initiative, sense of identity, sense of pride, sense of belonging, cultivation of multi-dimensional ability, thus helping to form a novel system of stomatological top-notch innovative personnel training.

Objective:To investigate the clinical effect of the relaying perforator flap for repairing the donor site of the anterolateral thigh flap.Methods:From March 2019 to June 2020, 28 consecutive patients who underwent anterolateral thigh free flap reconstruction for limb soft tissue defects were retrospectively reviewed. A relaying perforator flap was selected from one of the four areas adjacent to the donor site of the anterolateral thigh flap for covering the donor site of the anterolateral thigh flap. The secondary donor site was closed directly. The followed-up contents included the appearance and texture of the flaps. The postoperative followed-up was performed through outpatient visits, telephone, and WeChat interviews.Results:A total of 28 patients were included, with an average age of 37.3 (ranging from 15 to 65). The relaying perforator flap was selected from the anteromedial thigh region ( n=13), the proximal anterolateral thigh region( n=6), the distal anterolateral thigh region ( n=5), and the ilioinguinal region ( n=4). The size of the anterolateral thigh flap ranged from 12.0 cm×10.0 cm to 20.0 cm×13.0 cm, and the size of the relaying perforator flap ranged from 6.0 cm×5.0 cm to 11.0 cm×7.5 cm. The followed-up time ranged from 1 to 6 months (mean 4.8 months). The color, texture, and contour of the flaps were good. Only one linear scar is left in the donor site. Two cases with small necrosis (1.0 cm×2.0 cm and 1.5 cm×1.5 cm, respectively) were found in the distal edge of relaying perforator flaps. Conclusions:The relaying perforator flap is considered as an optimized and reliable method for repairing the donor site of an anterolateral thigh flap and should be recommended.

Objective:To investigate the clinical effect of the relaying perforator flap for repairing the donor site of the anterolateral thigh flap.Methods:From March 2019 to June 2020, 28 consecutive patients who underwent anterolateral thigh free flap reconstruction for limb soft tissue defects were retrospectively reviewed. A relaying perforator flap was selected from one of the four areas adjacent to the donor site of the anterolateral thigh flap for covering the donor site of the anterolateral thigh flap. The secondary donor site was closed directly. The followed-up contents included the appearance and texture of the flaps. The postoperative followed-up was performed through outpatient visits, telephone, and WeChat interviews.Results:A total of 28 patients were included, with an average age of 37.3 (ranging from 15 to 65). The relaying perforator flap was selected from the anteromedial thigh region ( n=13), the proximal anterolateral thigh region( n=6), the distal anterolateral thigh region ( n=5), and the ilioinguinal region ( n=4). The size of the anterolateral thigh flap ranged from 12.0 cm×10.0 cm to 20.0 cm×13.0 cm, and the size of the relaying perforator flap ranged from 6.0 cm×5.0 cm to 11.0 cm×7.5 cm. The followed-up time ranged from 1 to 6 months (mean 4.8 months). The color, texture, and contour of the flaps were good. Only one linear scar is left in the donor site. Two cases with small necrosis (1.0 cm×2.0 cm and 1.5 cm×1.5 cm, respectively) were found in the distal edge of relaying perforator flaps. Conclusions:The relaying perforator flap is considered as an optimized and reliable method for repairing the donor site of an anterolateral thigh flap and should be recommended.

Objective:To evaluate the clinical effect of the modified transfer of the proximal interphalangeal joint (PIPJ) from the second toe in the treatment of a finger PIPJ defect.Methods:A total of 13 patients with finger PIPJ defects caused by traumatic injury were enrolled from May, 2017 to March, 2020. All the PIPJ defects had primary traumatic repairs. The causes of injury: 5 patients were caused by strangulation, 4 by chainsaw, 2 by strangulation and 2 by crushing. Of which, 7 patients had index finger injury, 3 middle fingers and 3 ring fingers. The operations were carried out 3-7 months after the first stage of treatment. The grafting of the PIPJ of the second toe with modified vascular anastomosis were performed. The ipsilateral second toe was taken in 10 patients, and the contralateral second toe in 3 patients. The grafted joints all carried observation skin islands, with an area of 1.0 cm×1.5 cm-1.0 cm×2.0 cm. All the secondary bone defects in the donor site of the toe were reconstructed with iliac bone grafts, and the length of the iliac bone strips was 4.0-6.0 cm. At the same time, the island flap on the fibular side of the great toe was removed and repaired at the donor site, with an area of 1.1 cm×1.6 cm - 1.1 cm×2.1 cm. Early postoperative rehabilitation was performed. The patients were followed-up through outpatient visits, telephone and WeChat interviews.Results:All the 13 finger PIPJ and donor site island flaps survived. Bone healing were observed in all patients with the healing time in 8-12(average 10) weeks. Three patients with severe adhesion of joint and tendon were treated with secondary release. All the patients were followed-up for 10 - 18 months without degeneration of PIPJ. Active range of motion of PIPJ ranged: 45°-90° in flexion and 0°-10° in extension, the average motion activity was 66.3°. Seven patients were in excellent, 4 in good and 2 in fair, according to the function assessment proposed by the Society of Hand Surgery of Chinese Medical Association. The appearance on donor site was good and the walking was normal in the longterm follow-up. Only one linear scar was left in the ilioinguinal donor site without obvious discomfort.Conclusion:It was possible to use the modified transfer of the PIPJ from the second toe in the treatment of a finger PIPJ defect. An iliac bone graft and an island flap of the first toe transfer can preserve the appearance and function of the toes.

Objective:To investigate the therapeutic effect of modified sural neuro-fasciocutaneous perforator flap in reconstruction of foot and ankle soft tissue defects.Methods:Sixteen patients undergoing the modified flap for foot and ankle reconstruction were included in this study between June, 2016 and June, 2018. The 16 patients were 11 males and 5 females with an average age of 32.5 (range 21 to 51) years. Ten defects were in heel and 6 in ankle and dorsal side of foot. A "Z" -shape skin incision was performed to explore the perforator vessels. A peroneal-based perforator, a superficial vein, and the vascular axis of the sural nerve were included in the pedicle. A relaying island perforator flap was used to close the donor site without skin graft. Follow-up was carried out through outpatient service, telephone follow-up and Wechat photo transmission.Results:The patients were followed-up for 12 to 18 months. All flaps survived completely without complications. The colour, texture and apperance of the flaps were good. The area of the flaps ranged from 12 cm×5 cm to 30 cm×15 cm. The diameter of the pedicle ranged from 1 to 2 cm. No complication occurred in the donor sites. A relaying perforator island flaps were used in 10 cases for donor site closure and without a skin graft. All cases were satisfied with appearance and function at the final followed-up.Conclusion:It is possible to use the modified sural neuro-fasciocutaneous perforator flap to repair foot and ankle soft tissue defects. A relaying island perforator flap can be used as a relaying flap to cover the donor site without skin graft.

Objective:To detect whether Toll-like receptor 4 ( TLR4) polymorphisms contributed to primary open angle glaucoma (POAG) in a Chinese population. Methods:A Chinese cohort, including 799 unrelated POAG patients and 799 unrelated controls, was enrolled in our case-control association study. The data was collected at Sichuan Provincial People's Hospital from May 2014 to March 2018. TLR4 functional single nucleotide polymorphisms (SNPs), including rs4986790 and rs4986791, were genotyped by SNaPshot method. Genotype and allele frequencies of the two SNPs were evaluated. This study was approved by the Institutional Review Boards of the Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (No.2016-58), and complied with the guidelines of the Declaration of Helsinki. Written informed consents were obtained from all subjects prior to the study. Results:Allelic association analysis revealed that there were no significant association detected in the allelic distributions between the POAG cases and controls for SNPs rs4986790 ( P=0.317) and rs4986791 ( OR=1.000, 95% CI =0.062 5-16.002 2, P=1.000) in the TLR4 gene. Conditional analysis of the two SNPs did not show any significant difference in genotype and allele frequency between the case and the control groups. No association of the two SNPs with POAG was detected under four different genetic models, including homozygote, heterozygote, dominant and recessive models. Conclusions:Polymorphisms rs4986790 and rs4986791 in the TLR4 gene are not related to POAG in the Chinese cohort.

Objective:To investigate the association between choroidal neovascularization (CNV) and the LIPC gene single nucleotide polymorphism (SNP) in a Chinese Han population from Shantou. Methods:A case-control study was designed.Two hundred and twenty-one patients with CNV who visited Shantou International Eye Center from January 2010 to December 2016 were enrolled and served as the CNV group, and 430 healthy volunteers matched in age and gender were enrolled and served as the normal control group.Each of 5 ml fasting peripheral blood of the subjects was extracted, and peripheral blood DNA was extracted after anticoagulation.PCR amplification was conducted on SNP loci of LIPC gene including rs10468017, rs920915 and rs2070895.After purification, genotyping was performed on the above SNP loci using the single base extension (SNaPshot) method.Hardy-weinberg equilibrium (HWE) test was used to determine the genotype frequency of the three SNPs of LIPC gene.The gene frequency and genotype frequency of the 3 loci between the CNV group and normal control group were compared.This study followed the Declaration of Helsinki.Written informed consent was obtained from each subject prior to entering the study cohort.The study protocol was approved by the Ethics Committee of Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong (No.11-004). Results:The genotype frequency distribution of rs10468017, rs920915 and rs2070895 of the three SNPs of LIPC gene reached genetic balance in the total samples ( P>0.05). The genotype frequencies of rs10468017 TT genotype, rs920915 CC genotype and rs2070895 AA genotype in CNV group were 3.62%, 5.43% and 12.22%, respectively, while those of normal control group were 2.56%, 5.58% and 14.19%, respectively, with no statistically significant difference (all at P>0.05). The minimum allele (T) frequency of rs10468017 was 18.1% and 17.2%, the minimum allele (C) frequency of rs920915 was 21.7% and 23.1%, and the minimum allele (A) frequency of rs2070895 was 33.7% and 38.7% in the CNV group and the normal control group, respectively (all at P>0.05). The odd ratio ( OR) values (95%confidence interval [ CI]) of rs10468017, rs920915 and rs2070895 in the CNV group and the normal control group were 1.06 (0.79-1.44), 0.92 (0.70-1.21) and 0.80 (0.63-1.02), respectively. Conclusions:The results from the present study do not indicate the association of LIPC SNPs (rsl0468017, rs920915 and rs2070895) with CNV in the Shantou Han population.