ObjectiveTo observe the intervention effect of Fufang Kangjiaolv capsules on anxiety-like behaviors in the rat model of chronic restraint stress （CRS） and explore the mechanism underlying the anti-anxiety effect via the microbiota-gut-brain axis. MethodsRats were assigned into blank， model， positive drug （diazepam， 1 mg·kg^-1）， and low-， medium-， and high-dose （0.75， 1.5， 3 g·kg^-1， respectively） Fufang Kangjiaolv capsules groups. After 14 days of administration， the elevated plus maze test， open field test， light and dark box test， and marble burying test were performed. Hematoxylin-eosin staining was employed to observe the pathological changes in the hippocampus and colon of rats， and Nissl staining was conducted to observe the damage of hippocampal neurons. The gut microbiota was analyzed by 16S rRNA gene sequencing. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of zonula occludens-1 （ZO-1） and occludin in the colon of rats. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in the colon， serum， and hippocampus were determined by enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of ZO-1， occludin， nuclear factor-κB p65 （NF-κB p65） in the colon tissue and NF-κB p65 and brain-derived neurotrophic factor （BDNF） in the hippocampal tissue. ResultsCompared with the blank group， the model group showed reductions in the time and frequency ratio of rats entering the elevated plus maze， the time and frequency of rats entering the central area of the open field， the time of entering the open box， the times of passing through the light and dark box， and the number of unburied beads （P<0.05， P<0.01）. Compared with the model group， Fufang Kangjiaolv capsules ameliorated the anxiety of the model rats to varying degrees， and the high-dose group had the best effect， with increases in the proportions of time and frequency of rats entering the open arm in the elevated plus maze （P<0.05）， the number of rats entering the central area in the open field （P<0.05）， the time of entering the open box， the times of passing through the light and dark boxes， and the number of unburied beads （P<0.01）. Moreover， the high-dose group showed alleviated pathological damage of hippocampal neurons and colon. The results of 16S rRNA gene sequencing showed that the model group had increased relative abundance of Firmicutes， Deferribacterota， Romboutsia， and Phascolarctobacterium， while it had decreased relative abundance of Bavcteroidota and Lactobacillus. The drug administration groups showed increased relative abundance of Bavcteroidota， Bacteroides， norank f norank o Clostridia UCG-014， and Blautia and decreased relative abundance of Firmicutes and Deferribacterota. Compared with the blank group， the model group showed down-regulated protein and mRNA levels of ZO-1 and occludin in the colon （P<0.01）， elevated levels of TNF-α， IL-6， and IL-β in the colon， serum， and hippocampus （P<0.01）， up-regulated protein level of NF-κB p65 in the colon and hippocampus （P<0.01）， and down-regulated protein level of BDNF in the hippocampus （P<0.05）. Compared with the model group， high-dose Fufang Kangjiaolv capsules up-regulated the mRNA levels of ZO-1 and occludin in the colon （P<0.01）， lowered the levels of TNF-α， IL-6， and IL-β in the colon， serum， and hippocampus （P<0.01）， up-regulated the protein levels of ZO-1 （P<0.01） and occludin （P<0.05） in the colon， down-regulated the protein level of NF-κB p65 in the colon and hippocampus （P<0.05）， and up-regulated the protein level of BDNF in the hippocampus. ConclusionFufang Kangjiaolv capsules can reduce the anxiety-like behaviors in the rat model of CRS by regulating the gut microbiota disturbance， up-regulating the expression of tight junction proteins in the colon， repairing intestinal mucosal mechanical barrier， and down-regulating NF-κB/BDNF signaling pathway， thereby reducing peripheral and central inflammation. This study proves the hypothesis that Fufang Kangjiaolv capsules play an anti-anxiety role via the microbiota-gut-brain axis， providing a new idea for further research.

OBJECTIVE: To explore the effectiveness of limb shortening/re-lengthening technique combined with in situ tissue regeneration technique in limb salvage for patients with complex lower limb fractures and soft tissue defects. METHODS: Between January 2021 and December 2024, 12 patients with complex lower limb fractures and soft tissue defects caused by trauma were admitted. There were 10 males and 2 females; the age ranged from 18 to 46 years, with an average of 36 years. Among them, 1 case of open comminuted tibiofibular fracture caused bone necrosis and soft tissue infection; 4 cases of open tibiofibular fractures developed bone and soft tissue infections after being fixed with a combined external fixator, resulting in defects; 7 cases of closed tibial fractures that underwent internal fixation developed soft tissue infections, leading to bone and soft tissue necrosis. The time from injury to the formation of bone and soft tissue defects was 2-9 weeks, with an average of 6 weeks. The length of bone defects was 5.0-10.2 cm, with an average of 6.8 cm; the area of soft tissue defects was 32-54 cm ², with an average of 43.9 cm ². After admission, all patients underwent thorough debridement. The limb shortening treatment was performed after the wound had filled with fresh granulation tissue, and an Ilizarov ring-shaped external fixator was placed or replaced. The limb was shortened at a rate of 1 mm/day to reduce bone defects. At the same time, the soft tissue defects were repaired using the in situ tissue regeneration technique. After the wound healed, osteotomy was performed, and limb lengthening was carried out at a rate of 1 mm/day. The lower limb full-length X-ray films were taken, and the lengthening was stopped when the lower limb alignment was restored. The healing condition of the wound was observed and the healing time was recorded. RESULTS: One patient died due to a traffic accident during limb lengthening. The remaining 11 patients completed limb shortening and re-lengthening treatment and were followed up 18-36 months, with an average of 20 months. All 11 patients successfully preserved their limbs. The wound healing time was 4-12 weeks, with an average of 8 weeks; the limb shortening time was 4-8 weeks, with an average of 6 weeks; and the limb lengthening time was 4-12 weeks, with an average of 8 weeks. One patient experienced delayed bone mineralization during bone lengthening, and one had pin tract infection. Both were treated symptomatically. The lower limb mechanical axis of all 11 patients was restored, and they were able to walk independently. CONCLUSION The application of limb shortening/re-lengthening technique combined with in situ tissue regeneration technique in the treatment of large bone and soft tissue defects not only effectively avoids the occurrence of nonunion at the apposition ends and increases the stability of the lower limb, but also significantly shortens the wound healing time, avoids the risk of soft tissue infection and increases the limb salvage rate. It can be used as a treatment technique for patients with complex lower limb fractures combined with soft tissue defects.
Humans ; Adult ; Male ; Female ; Middle Aged ; Soft Tissue Injuries/surgery* ; Limb Salvage/methods* ; Adolescent ; Young Adult ; Bone Lengthening/methods* ; External Fixators ; Lower Extremity/surgery* ; Fracture Fixation, Internal/methods* ; Fractures, Bone/surgery* ; Tibial Fractures/surgery* ; Treatment Outcome ; Regeneration

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective To investigate the clinical effect of Qiji Zhuyu Zhixue decoction in treatment of previous cesarean scar defect(PCSD)and explore the value of transvaginal two-dimensional ultrasound combined with three-dimensional power Doppler ultrasound(3D-PDUS)in the diagnosis of PCSD.Methods A total of 120 PCSD patients treated and treated in Wenzhou People's Hospital from April to October 2023 were selected as study objects,and they were randomly divided into case group(50 cases)and control group(70 cases).The case group was treated with Qiji Zhuyu Zhixue decoction,and the control group was treated with desogestrel and ethinylestradiol tablets.The clinical effects after 6 months of treatment were compared between two groups.The length,width,depth,lateral muscle thickness and volume of PCSD before and after treatment were evaluated by two-dimensional ultrasound combined with 3D-PDUS.The receiver operating characteristic curve was used to evaluate the efficacy of ultrasonic parameters in diagnosis of PCSD.Results After 6 months of treatment,the total effective rate of case group was significantly higher than that of control group(x2=21.97,P＜0.01).After treatment,the diverticulum depth and volume in case group were significantly lower than before treatment(P＜0.05).The diverticulum depth in case group was significantly lower than that in control group(P＜0.05).The lateral muscle thickness in case group was significantly greater than that before treatment and control group(P＜0.05).The area under the curve of the combined diagnosis of PCSD with diverticular depth,diverticular lateral muscle thickness and diverticular volume was 0.707.Conclusion The clinical effect of Qiji Zhuyu Zhixue decoction on PCSD is remarkable.Transvaginal two-dimensional ultrasound combined with 3D-PDUS is the first choice for the diagnosis of PCSD,and it is worth popularizing and applying.

Hip fracture in the elderly is characterized by high incidence, high disability rate, and high mortality and has been recognized as a public health issue threatening their health. Surgery is the preferred choice for the treatment of elderly patients with hip fracture. However, lower extremity deep venous thrombosis (DVT) has an extremely high incidence rate during the perioperative period, and may significantly increase the risk of patients′ death once it progresses to pulmonary embolism. In response to this issue, the clinical guidelines and expert consensuses all emphasize active application of comprehensive preventive measures, including basic prevention, physical prevention, and pharmacological prevention. In this prevention system, basic prevention is the basis of physical and pharmacological prevention. However,there is a lack of unified and definite recommendations for basic preventive measures in clinical practice. To this end, the Orthopedic Nursing Professional Committee of the Chinese Nursing Association and Nursing Department of the Orthopedic Branch of the China International Exchange and Promotive Association for Medical and Health Care organized relevant nursing experts to formulate Expert consensus on perioperative basic prevention for lower extremity deep venous thrombosis in elderly patients with hip fracture ( version 2024) . A total of 10 recommendations were proposed, aiming to standardize the basic preventive measures for lower extremity DVT in elderly patients with hip fractures during the perioperative period and promote their subsequent rehabilitation.

Objective:To compare the therapeutic effects of intramedullary nail fixation, simple tibial plate fixation, and tibial plate + posterior-to-anterior screw fixation in the surgical treatment of lower 1/3 spiral fracture of the tibia combined with posterior malleolar fracture.Methods:A retrospective study was conducted to analyze the clinical data of 78 patients with lower 1/3 spiral fracture of the tibia combined with posterior malleolar fracture who had been treated at Department of Orthopedics, The Hospital Affiliated to Qingdao University from June 2015 to June 2022. There were 46 males and 32 females with an age of (48.9±14.6) years. The patients were divided into 3 groups according to their fixation methods. Group A (18 patients) underwent simple intramedullary nail fixation, group B (40 patients) simple tibial plate fixation, and group C (20 patients) tibial plate fixation for tibial fractures and posterior-to-anterior screw fixation for posterior malleolar fractures. The operation time, intraoperative blood loss, fracture union time, postoperative complications, as well as ankle-hindfoot scores of American Orthopaedic Foot and Ankle Society (AOFAS) and Baird-Jackson scores at pre- and post-operation were compared among the 3 groups.Results:The differences in the preoperative baseline data were not statistically significant among the 3 groups, indicating comparability ( P>0.05). All patients were followed up for (24.9±10.1) months. The fracture union time in Group A was 14.0(13.0, 14.0) weeks, significantly longer than that in groups B and C [13 (13, 14) weeks] ( P<0.05). The AOFAS ankle-hindfoot score and Baird-Jackson score at the last postoperative follow-up in all patients were better than those before surgery ( P<0.05). The AOFAS ankle-hindfoot scores at the last follow-up in groups B and C [95.5 (86.0, 96.0) points and 96.0 (89.5, 98.5) points] were significantly higher than that in group A [86.5 (78.0, 93.0) points] ( P<0.05), and the Baird-Jackson scores at the last follow-up in groups B and C [93.0 (88.8, 95.0) points and 95.0 (91.0, 98.0) points] were also significantly higher than that in group A [86.0 (78.0, 89.5) points] ( P<0.05). All the 7 cases of complications (3 ones of poor fracture union and 4 ones of anterior knee pain) were observed in group A. Conclusion:In the surgical treatment of lower 1/3 spiral fracture of the tibia combined with posterior malleolar fracture, tibial plate fixation and tibial plate + posterior-to-anterior screw fixation can achieved better therapeutic effects than intramedullary nail fixation.

Objective:To evaluate the effect of vagus nerve stimulation on the homologous phosphatase and tensin homologue (PTEN)-induced putative kinase 1 (PINK1)/Parkin signaling pathway on myocardial injury induced by hepatic ischemia-reperfusion (I/R) in rats.Methods:Twenty-seven clean-grade healthy male Sprague-Dawley rats, aged 10-12 weeks, weighing 280-320 g, were divided into 3 groups ( n=9 each) using a random number table method: sham operation group (Sham group), hepatic I/R group (HI/R group) and vagus nerve stimulation group (VNS group). The liver I/R injury model was made by clamping the liver pedicle for 1 h followed by 6-h reperfusion. In VNS group, the left cervical vagus nerve was stimulated by a voltage with a frequency of 20 Hz and a wave width of 0.1 ms immediately after liver ischemia, lasting for 1 h. The stimulation voltage was adjusted with the rat heart rate, and the heart rate decreased by more than 10% of the basic value was considered as a successful stimulation. The rats were anesthetized at the end of reperfusion, and carotid blood samples were collected for determination of the serum cardiac troponin I (cTnI) concentration by enzyme-linked immunosorbent assay. Then rats were sacrificed, and left ventricular myocardial tissues were taken for determination of the apoptosis in cardiomyocytes (by TUNEL) and expression of PINK1, Parkin, p62, Bax and Bcl-2 (by Western blot). The apoptosis rate was calculated. Results:Compared with Sham group, the concentrations of serum cTnI and apoptotic rate of cardiomyocytes were significantly increased, the expression of PINK1, Parkin and Bcl-2 in myocardial tissues was down-regulated, and the expression of p62 and Bax was up-regulated in HI/R group and VNS group ( P<0.05). Compared with HI/R group, the concentrations of serum cTnI and apoptotic rate of cardiomyocytes were significantly decreased, the expression of PINK1, Parkin and Bcl-2 in myocardial tissues was up-regulated, and the expression of p62 and Bax was down-regulated in VNS group ( P<0.05). Conclusions:The mechanism by which vagus nerve stimulation alleviates myocardial injury induced by hepatic I/R is related to activation of the PINK1/Parkin signaling pathway in rats.

Objective:To investigate clinical characteristics of and genetic variants in the NF1 gene in children with neurofibromatosis type 1 (NF1) .Methods:Clinical data were collected from 22 children with NF1, who were admitted to the Department of Dermatology, Children's Hospital, Capital Institute of Pediatrics from January 2022 to September 2023, and were analyzed. Next-generation sequencing was performed to detect NF1 mutations in the probands, and the variants were verified in the family members by Sanger sequencing. A homology modeling software was used to predict the three-dimensional protein structure, and analyze the characteristics of gene mutations.Results:Among the 22 children with NF1, there were 14 males and 8 females, and they were aged from 3 months to 12 years at the clinic visit. All the 22 children presented with multiple café-au-lait spots, and their age at onset ranged from birth to 2 years. Nine patients were accompanied by freckles in the axillary or inguinal regions, 2 by cutaneous neurofibromas, 2 by juvenile xanthogranuloma, 2 by learning disabilities, and Lisch nodules of the iris, central precocious puberty and scoliosis occurred in 1 case each; 5 cases showed characteristic manifestations of neurofibroma on brain magnetic resonance imaging. A total of 5 types of NF1 gene variants were identified in the 22 patients, including complete heterozygous deletion of the NF1 gene (1 patient), missense variants (4 patients, one of whom carried 2 types of missense variants), frameshift variants (8 patients), nonsense variants (6 patients), and classical splicing variants (3 patients). Among the 22 variants, 7 were unreported variants, including c.758T>A (p.Val253Glu), c.2360dupC (p.Thr788Asnfs*5), c.5513T>G (p.Leu1838*), c.2774dupT (p.Leu925Phefs*11), c.6894dupT (p.Val2299Cysfs*7), c.6882_6883delCT (p.Phe2295Leufs*10), and c.6448A>T (p.Lys2150*). Of the unreported variants, 6 were frameshift or nonsense variants leading to different degrees of truncated protein expression, and severely affecting protein function; based on the three-dimensional protein structure prediction analysis, it was uncertain if the missense variant c.758T>A (p.Val253Glu) affected protein conformation. In 2 children, the NF1 variants were inherited from their mothers; 1 child carried 2 NF1 missense variants, 1 of which was a spontaneous mutation potentially causing the disease, while the other one with unknown pathogenicity was inherited from the phenotypically normal father; the remaining 19 children all carried spontaneous mutations.Conclusions:Children with NF1 mainly present with multiple café-au-lait spots at the early stage, and some characteristic manifestations such as cutaneous neurofibroma, juvenile xanthogranuloma, and Lisch nodules of the iris can also occur. NF1 gene pathogenic variants are complex and diverse, and 22 variants were identified in this study, enriching the spectrum of NF1 gene variants.

OBJECTIVE To explore the potential mechanism of Yishenqinglihuoxue Formula(YSQLF)in treating chronic kidney disease fibrosis in rats based on UHPLC-Q-TOF-MS technology and network pharmacology.METHODS UHPLC-Q-TOF-MS was used for qualitative analysis of Yishenqinglihuoxue Formula-containing serum.Targets of the plasma constituents and the disease were retrieved from SwissTargetPrediction,OMIM,GeneCards,and other databases.Then the protein-protein interaction(PPI)network was constructed and core targets were screened for GO term enrichment and KEGG pathway enrichment.Cytoscape software was em-ployed to construct the"drug-compound-core target-pathway"network and the targets and signaling pathways of Yishenqinglihuoxue Formula against fibrosis were predicted.A model of renal fibrosis was established to verify the core targets and pathway proteins.RE-SULTS A total of 56 constituents migrating to blood of Yishenqinglihuoxue Formula were identified.97 common targets of the constit-uents and the disease and 33 core targets were screened out.KEGG enrichment and PPI network analysis showed that Yishenqingli-huoxue Formula may play a role in the treatment of fibrosis through PI3K/Akt and other pathways.Furthermore,the results of animal experiments showed that Yishenqinglihuoxue Formula could reduce the levels of Scr and BUN,improve fibrosis areas,inhibit the acti-vation of the PI3K/Akt pathway,and reduce the protein expression of TNF-α.CONCLUSION Yishenqinglihuoxue Formula may play a role in the treatment of fibrosis by inhibiting PI3K/Akt signaling pathway and inhibiting TNF-α expression.

Objective:To explore the characteristics of SMN1 gene variants and carry out functional verification for two children with Spinal muscular atrophy (SMA). Methods:Two male children with complicated SMA diagnosed at the Children′s Hospital Affiliated to Capital Institute of Pediatrics respectively in July 2021 and April 2022 due to delayed or retrograde motor development were selected as the study subjects. Clinical data of the children were collected. Primary culture of skin fibroblasts was carried out, and peripheral blood samples were collected from both children and their parents. Multiplex ligation-dependent probe amplification, combined long-range PCR and nested PCR, and Sanger sequencing were carried out to detect the copy number and variants of the SMN1 gene. Absolute quantitative real-time PCR, Western blotting and immunofluorescence were used to determine the transcriptional level of the SMN gene, expression of the SMN protein, and the number of functional SMN protein complexes (gems body), respectively. This study was approved by Medical Ethics Committee of the Children′s Hospital Affiliated to Capital Institute of Pediatrics (Ethics No. SHERLLM2021009). Results:Child 1, a 1-year-old boy, was clinically diagnosed with type 1 SMA. Child 2, a 2-and-a-half-year-old boy, was clinically diagnosed with type 3 SMA. Both children were found to harbor a paternally derived SMN1 deletion and a maternally derived SMN1 gene variant, namely c. 824G>T (p.Gly275Val) and c. 884A>T (p.*295Leu). Compared with the normal controls and carriers, the levels of full-length SMN1 transcripts in their peripheral blood and skin fibroblast cell lines were significantly decreased ( P<0.05), and the levels of SMN protein normalized to that of β-actin, and the numbers of gems bodies in the primary fibroblast cells were also significantly lower ( P<0.05). Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were classified as likely pathogenic (PS3+ PM3+ PM5+ PP3; PS3+ PM3+ PM4+ PP3). Following the diagnosis, both children had received nusinersen treatment. Although their motor function was improved, child 1 still died at the age of 2 due to severe pulmonary infection. The walking ability of child 2 was significantly improved, and his prognosis appeared to be good. Conclusion:Two cases of clinically complicated SMA have been confirmed by genetic testing and experimental studies, which has provided a reference for their accurate treatment.