Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

OBJECTIVE: To analyze the laboratory detection results of hemolytic disease of the fetus and newborn(HDFN). METHODS: Related test results of 283 newborns and their mothers' blood samples from Kunming Maternal and Child Health Hospital from August 2023 to May 2024 were collected, including mother and child ABO blood group, RhD blood group, as well as 3 tests of HDFN, total bilirubin (TBil) and indirect bilirubin (IBil). RESULTS: 283 were ABO incompatibility, among which 187 were HDFN positive, with a positive rate of 66.08%; the positive rate of HDFN in neonates with antigen-A incompatibility was 74.12%(126/170), the positive rate of HDFN in neonates with antigen-B incompatibility was 53.57%(60/112), which was the highest in neonates with O/A incompatibility ［75.45%(126/167)］, followed by O/B incompatibility［54.55%(60/110)］. Group by age, the positive rates of HDFN in the ≤1 d group, 2 d group, 3 d group, 4 d group, 5 d group and ≥6 d group were 76.03%(111/146), 67.86%(38/56), 57.14%(24/42), 38.46%(5/13), 46.15%(6/13) and 23.08%(3/13), respectively. With the increase of age, the positive rates of HDFN gradually decreased, there was a statistically significant difference between the ≤3 day age group and >3 day age group ( P <0.05). There was no statistically significant difference in TBil and IBil levels between the "direct antibody+indirect antibody+release+" group and the HDFN negative group in newborns. HDFN infants exhibited a rapid increase in bilirubin levels within the first day after birth, with significantly higher TBil and IBil values compared to Non ABO-HDFN infants in the ≤1 day group ( P <0.01). However, the difference of bilirubin levels between the two groups gradually narrowed from 2-6 days after birth, and the difference was not statistically significant (P >0.05). The peak value of TBil and IBil occurred on the 4th day after birth in HDFN infants. CONCLUSION ABO-HDFN is most commonly seen in newborns whose mothers are type-O, and the positive rate was the highest in newborns with O/A incompatibility. The detection rate of HDFN is affected by the age of the newborns, and the two were correlated inversely. ABO-HDFN group developed more rapidly with a higher peak. Therefore, HDFN tests should be carried out as soon as possible for mothers and newborns with incompatible blood types, and appropriate treatment should be provided to prevent complications.
Humans ; Infant, Newborn ; ABO Blood-Group System ; Erythroblastosis, Fetal/epidemiology* ; Female ; China/epidemiology* ; Blood Group Incompatibility ; Male ; Bilirubin/blood*

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Objective To investigate and analyze the current status and challenges of infant and toddler nutritional services in urban and rural medical facilities in Sichuan Province.Methods In 2022,a questionnaire survey was conducted to collect data on infant and toddler nutritional services,including feeding guidance,physical growth assessment,and micronutrient deficiency screening,as well as information on personnel and tools in medical facilities throughout Sichuan Province.The provision of nutritional services was analyzed and the urban-rural disparities were assessed.Results A total of 2206 medical facilities(29.1%from urban areas and 70.9%from rural areas)were investigated.Only 35.8%of medical facilities provided all three types of nutritional services.Specifically,the overall service provision rates were high for feeding guidance(94.6%)and physical growth assessment(85.0%),but lower for micronutrient deficiency screening(37.4%).Rural facilities exhibited significantly lower rates than their urban counterparts for both physical growth assessment and micronutrient deficiency screening(P＜0.05).The provision rates of feeding guidance ranged from 70.6%to 93.2%,with responsive feeding guidance being the least implemented(70.6%),particularly in rural areas compared to urban areas(P＜0.05).Rates for physical growth assessment and micronutrient deficiency screening ranged from 75.3%to 81.8%and 23.6%to 30.8%,respectively,both showing lower rates in rural settings compared to urban ones(P＜0.05).Nutrition service providers were predominantly nurses(52.3%)and clinical practitioners(43.4%).The availability of dietary assessment tools ranged from 7.7%to 15.9%,significantly lower in rural areas compared to urban areas(P＜0.001),while physical measurement tools were widely available at rates of 94.6%to 98.5%.Conclusion At present,the infant and toddler nutritional service provisions of medical facilities in Sichuan Province are incomplete,particularly so in the implementation of feeding guidance,physical growth assessment,and micronutrient deficiency screening.There is a notable shortage of personnel and necessary tools,with rural areas facing more significant challenges.Enhancing the overall capacity of infant and toddler nutritional services in Sichuan Province is essential,with specific attention needed for rural healthcare settings.

AIM: To explore the feasibility of swept source optical coherence tomography angiography(SS-OCTA)in evaluating early retinal and choroidal microcirculation changes in patients with hypertension.METHODS:Prospective clinical study. A total of 27 patients with grade 2 or 3 essential hypertension(hypertension group)diagnosed in the Department of Cardiology of Xi'an First Hospital from July to November 2022 were included in the study. There were 14 males and 13 females. The mean age was(57.11±3.36)years. During the same period, 27 age- and sex-matched normal people without a history of hypertension were selected as the control group, including 12 males and 15 females. The average age was(55.74±2.95)years old. All patients underwent BCVA(LogMAR), intraocular pressure, axial length, slit lamp examination, fundus color photography and SS-OCTA examination. SS-OCTA was used to scan the macular area of the right eye in the range of 6×6 mm. The retina and choroid were divided into three concentric circles with diameters of 0-1 mm, 1-3 mm and 3-6 mm around the fovea according to ETDRS. Macular vessel density(VD), perfusion area(PA), retinal thickness(CMT), choroidal thickness(CT), choroidal vessel volume(CVV)and choroidal vasculr index(CVI)of the superficial capillary plexus(SCP)and the deep capillary plexus(DCP)in the macular area of 0-1 mm, 1-3 mm and 3-6 mm were analyzed and recorded. The changes in VD, PA, CMT, CT, CVV and CVI were compared between the two groups. Independent sample t-test was used to compare VD, PA, CMT and CVI between the two groups; CT, CVV and LogMAR visual acuity were analyzed by Wilcoxon signed rank test of independent samples.RESULTS:Compared with the control group, the hypertensive group had significantly lower VD in the macular area 0-3 mm(0-1 mm, t=-3.144; 1-3 mm, t=-3.611, P<0.05). VD in the area of 3-6 mm showed a tendency to increase compared with the control group(t=1.715, P>0.05). The CMT in the 0-1mm area of the macular area in the hypertension group was lower than that in the control group(t=-2.624, P<0.05). There was no significant difference in CT, CVV and CVI between the two groups(P>0.05).CONCLUSION:The VD of DCP in the 0-3 mm area and the CMT in the 0-1 mm area are decreased in hypertensive patients. There were no significant differences in CT, CVV and CVI between the two groups. VD and CMT in macular DCP may be used as indicators to evaluate the early changes of retinal and choroidal microcirculation in hypertensive patients.

This study aimed to observe the effect of terpinen-4-ol(T4O) on the proliferation of vascular smooth muscle cells(VSMCs) exposed to high glucose(HG) and reveal the mechanism via the Krüppel-like factor 4(KLF4)/nuclear factor kappaB(NF-κB) signaling pathway. The VSMCs were first incubated with T4O for 2 h and then cultured with HG for 48 h to establish the model of inflammatory injury. The proliferation, cell cycle, and migration rate of VSMCs were examined by MTT method, flow cytometry, and wound healing assay, respectively. The content of inflammatory cytokines including interleukin(IL)-6 and tumor necrosis factor-alpha(TNF-α) in the supernatant of VSMCs was measured by enzyme-linked immunosorbent assay(ELISA). Western blot was employed to determine the protein levels of proliferating cell nuclear antigen(PCNA), Cyclin D1, KLF4, NF-κB p-p65/NF-κB p65, IL-1β, and IL-18. The KLF4 expression in VSMCs was silenced by the siRNA technology, and then the effects of T4O on the cell cycle and protein expression of the HG-induced VSMCs were observed. The results showed that different doses of T4O inhibited the HG-induced proliferation and migration of VSMCs, increased the percentage of cells in G_1 phase, and decreased the percentage of cells in S phase, and down-regulated the protein levels of PCNA and Cyclin D1. In addition, T4O reduced the HG-induced secretion and release of the inflammatory cytokines IL-6 and TNF-α and down-regulated the expression of KLF4, NF-κB p-p65/NF-κB p65, IL-1β, and IL-18. Compared with si-NC+HG, siKLF4+HG increased the percentage of cells in G_1 phase, decreased the percentage of cells in S phase, down-regulated the expression of PCNA, Cyclin D1, and KLF4, and inhibited the activation of NF-κB signaling pathway. Notably, the combination of silencing KLF4 with T4O treatment further promoted the changes in the above indicators. The results indicate that T4O may inhibit the HG-induced proliferation and migration of VSMCs by down-regulating the level of KLF4 and inhibiting the activation of NF-κB signaling pathway.
NF-kappa B/metabolism* ; Interleukin-18/metabolism* ; Proliferating Cell Nuclear Antigen/genetics* ; Cyclin D1/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Muscle, Smooth, Vascular ; Cell Proliferation ; Signal Transduction ; Cytokines/metabolism* ; Glucose/metabolism*

Intestinal flora is the largest microbial community in human body， which consists of more than 1 000 species. Its structure and metabolites change dynamically with the age， diet and intestinal environment of the host. Study shows that the intestinal microbes play a pivotal role in regulating human physiological and pathological processes， and intestinal flora imbalance may be the key factors affecting the occurrence and development of bone and joint diseases， including osteoporosis， osteoarthritis， rheumatoid arthritis and gouty arthritis. At present， calcitonin， estrogen， nonsteroidal anti-inflammatory drugs， immunosuppressants， xanthine oxidase inhibitors and other western drugs are mostly used to treat the above diseases. However， long-term use of western drugs leads to poor compliance and obvious gastrointestinal adverse reactions among patients. Traditional Chinese medicine （TCM） predominates in the treatment of bone and joint diseases due to its low price， high efficacy and slight side effects， with the advantages of multi-targets， multi-mechanism and multi-levels. In recent years， many scholars have carried out experiments and clinical studies on the treatment of bone and joint diseases by TCMs on the basis of the liver and kidney theory such as "tonifying liver and kidney and strengthening muscles and bones". Gratifying results have been achieved. However， the mechanism of action has not been fully clarified. Intestinal flora becomes a hot spot in medical research， and a close relationship between intestinal flora and bone and joint diseases has been unveiled. Relevant literature in China and abroad showed that TCM has a significant effect on the treatment of bone and joint diseases by regulating intestinal flora. In this paper， the relationship between intestinal flora and bone and joint diseases was summarized and the intervention of TCM active ingredients and compounds on intestinal flora was reviewed to facilitate the prevention and treatment of bone and joint diseases by TCM.

Objective To investigate the diversity and composition of microflora in laboratory-reared Aedes albopictus at different developmental stages and larval habitat waters. Methods The larval habitat waters and different developmental stages of laboratory-reared A. albopictus were collected, and the V3 and V4 regions of the bacterial 16S rRNA gene were sequenced using Illumina Miseq next-generation sequencing. The abundance and diversity of the microflora were examined using alpha diversity index in A. albopictus at different developmental stages, and the difference in the microflora compositions was compared in A. albopictus at different developmental stages using principal component analysis (PCA). In addition, the species composition and relative abundance of microflora in A. albopictus at different developmental stages were described using histograms and Venn diagrams. Results A total of 16 phyla, 30 classes, 72 orders, 129 families and 224 genera of bacteria were detected in larval habitat waters and different developmental stages of A. albopictus. The highest bacterial diversity was seen in larval A. albopictus, with Chao index of 125.20 ± 30.48 and Shannon diversity index of 2.04 ± 0.39, which were comparable to those (Chao index of 118.52 ± 15.07 and Shannon diversity index of 2.15 ± 0.30) in larval habitat waters (t = 0.35 and -0.41, both P values > 0.05). The bacterial abundance and evenness were significantly greater in female adults than in male adults (Chao index: 42.50 ± 3.54 vs. 18.50 ± 2.13, t = 8.23, P < 0.05; Shannon diversity index: 1.25 ± 1.67 vs. 0.50 ± 0.05, t = 6.00, P < 0.05). Proteobacteria, Bacteroidota, Actinobacteriota and Finnicutes were four common phyla of bacteria at each developmental stage of A. albopictus, with Proteobacteria dominated at the pupal stage (90.36%), Bacteroidota dominated at the adult stage (46.01% in female adults and 86.11% in male adults), and Actinobacteriota dominated at the larval stage (32.10%). Elizabethkingia and Rahnella 1 were common dominant genera of bacteria at each developmental stage of A. albopictus, with Rahnellal as the major component at the pupal stage (87.56%), Elizabethkingia as the main component at the adult stage (46.01% in female adults and 86.11% in male adults, respectively), and Microbacteria as the dominant bacterial genus at the larval stage (12.11%). In addition, Delftia, Elizabethkingia, Romboutsia, Serratia, Rahnella 1, Enterococcus and Microbacterium were common genera of bacteria at each developmental stage of A. albopictus, with Edaphobaculum dominated at the larval stage (17.54%) and Sphingobacterium dominated in larval habitat waters (13.93%). Conclusions There are differences in the composition of symbiotic bacteria at different developmental stages of A. albopictus; however, similar microflora diversity is maintained at the phylum level. The microflora diversity is comparable in larvae and larval habitat waters of A. albopictus.

Klebsiella pneumoniae(K.pneumoniae)is an important pathogen that can cause severe hospital-and community-acquired infections.To systematically investigate its methylation features,we determined the whole-genome sequences of 14 K.pneumoniae strains covering varying serotypes,multilocus sequence types,clonal groups,viscosity/virulence,and drug resistance.Their methy-lomes were further characterized using Pacific Biosciences single-molecule real-time and bisulfite technologies.We identified 15 methylation motifs[13 N6-methyladenine(6mA)and two 5-methylcytosine(5mC)motifs],among which eight were novel.Their corresponding DNA methyl-transferases were also validated.Additionally,we analyzed the genomic distribution of GATC and CCWGG methylation motifs shared by all strains,and identified differential distribution pat-terns of some hemi-/un-methylated GATC motifs,which tend to be located within intergenic regions(IGRs).Specifically,we characterized the in vivo methylation kinetics at single-base resolu-tion on a genome-wide scale by simulating the dynamic processes of replication-mediated passive demethylation and MTase-catalyzed re-methylation.The slow methylation of the GATC motifs in the replication origin(oriC)regions and IGRs implicates the epigenetic regulation of replication initiation and transcription.Our findings illustrate the first comprehensive dynamic methylome map of K.pneumoniae at single-base resolution,and provide a useful reference to better understand epigenetic regulation in this and other bacterial species.

Diabetic nephropathy (DN) is considered the primary causes of end-stage renal disease (ESRD) and is related to abnormal glycolipid metabolism, hemodynamic abnormalities, oxidative stress and chronic inflammation. Antagonism of vascular endothelial growth factor B (VEGF-B) could efficiently ameliorate DN by reducing renal lipotoxicity. However, this pharmacological strategy is far from satisfactory, as it ignores numerous pathogenic factors, including anomalous reactive oxygen species (ROS) generation and inflammatory responses. We found that the upregulation of VEGF-B and downregulation of interleukin-22 (IL-22) among DN patients were significantly associated with the progression of DN. Thus, we hypothesized that a combination of a VEGF-B antibody and IL-22 could protect against DN not only by regulating glycolipid metabolism but also by reducing the accumulation of inflammation and ROS. To meet these challenges, a novel anti-VEGFB/IL22 fusion protein was developed, and its therapeutic effects on DN were further studied. We found that the anti-VEGFB/IL22 fusion protein reduced renal lipid accumulation by inhibiting the expression of fatty acid transport proteins and ameliorated inflammatory responses