Neurofibromatosis type 1 (NF1) presents with a diverse range of symptoms that can affect the skin, bones, eyes, central nervous system, and other organs. This article reports the diagnosis and treatment process of a patient with NF1 complicated by bilateral severe-to-profound sensorineural hearing loss. Genetic testing revealed a heterozygous variant of NF1 NM_ 000267.3: c.4054_ 4058del(p.Ser1352LeufsTer20, supporting the diagnosis of NF1. After thorough evaluation, a right cochlear implantation was performed, yielding satisfactory postoperative results. This case suggests that NF1 patients may exhibit phenotypic heterogeneity and atypicality, providing a reference for clinicians in the diagnosis and treatment of such patients.

Objective:To evaluate the clinical effectiveness of the reconstruction of multiple digit-tip defects with transfer of polyfoliate perforator flaps of the fibular hallux.Methods:From January 2019 to June 2022, 15 patients had undergone reconstruction surgery for multiple digit-tip defects using polyfoliate perforator flaps of ipsilateral fibular hallux, with the first dorsal metatarsal artery as the pedicle, in the Department of Upper Limb Repair and Reconstruction Surgery, Guizhou Hospital of Beijing Jishuitan Hospital. The patients were 10 males and 5 females and aged 20 to 45 years old. Eight patients had the defects of thumbs and index fingers, 4 of thumbs and middle fingers, 2 of thumb, index and middle fingers and 1 of thumb, index and ring fingers. All the 15 digit injuries had nail bed defects to which reconstructive surgery were required. For the flaps of dorsal artery, flaps were 1.8 cm×2.0 cm-2.0 cm×3.1 cm in size and for those of plantar artery, the flaps sized 1.5 cm×2.0 cm-2.5 cm×3.0 cm. Donor site defects in the hallux were reconstructed with free superficial circumflex iliac perforator flaps. Postoperative follow-up lasted until 30th June 2023 and included visits to the outpatient clinic, WeChat and telephone reviews to assess the appearance, function and sensation recovery of the digits.Results:All the 15 flaps survived. During the 6 to 24 months (16 months in average) of postoperative follow-up, the appearance and texture of all flaps were found close to the healthy digits, with good nail growth and without deformity. TPD were found between 8.0 mm and 12.0 mm. The donor sites on the great toes that reconstructed with superficial circumflex iliac artery flaps were all survived well, and the incisions were satisfactorily healed without the functions of walking, running or jumping being significantly affected.Conclusion:The use of polyfoliate perforator flaps of fibular hallux for reconstruction of multiple digit-tip defects is an ideal surgical method due to the consistency of vascular anatomy, ease with flap harvest, similarity in the normal digital skin texture, and the capability to include a nail bed with the flap. A single donor from the hallux can simultaneously reconstruct two defects of digit-tip, making it an excellent treatment in the reconstruction of small-to medium-sized composite tissue defects in multiple digits.

Kidney deficiency syndrome is a common clinical syndrome in traditional Chinese medicine （TCM）. With the progress of science and technology， clinical and animal experiments on kidney deficiency syndrome have made remarkable progress. Research on kidney deficiency and the nature of "kidney" involves a large number of physiological and pathological bases， which are closely related to physiological and pathological links in the human body， among which the neuroendocrine-immune network shares the closest relationship. However， there are still many challenges in modern research on kidney deficiency syndrome， such as expert consensus on clinical diagnostic criteria and evaluation indexes and optimization of animal experimental models. In the past decade， a large number of clinical and animal experiments have been reported in the literature on kidney deficiency syndrome， among which the literature focusing on the combination of disease and syndrome is predominant， and most of them focus on kidney Yang deficiency and kidney Yin deficiency， involving the exploration of many pathological mechanisms. Research on the mechanisms related to kidney deficiency syndrome encompasses multiple signaling pathways and various biochemical indicators， including the phosphatidylinositol 3-kinase/protein kinase B/nuclear factor-erythroid 2-relatedfactor-2（PI3K/Akt/Nrf2） signaling pathway， the Toll-like receptor 4/myeloid differentiation factor88/nuclear factor-κB（TLR4/MyD88/NF-κB） signaling pathway， the Janus kinase 2/signal transducer and activator of transcription 3（JAK2/STAT3） signaling pathway， Osteoprotectin/nuclear factor-κB receptor activator ligand/receptor activator of nuclear factor-κB （OPG/RANKL/RANK） signaling pathway. The biochemical indicators cover the cyclic adenosine monophosphate/cyclic guanosine monophosphate （cAMP/cGMP） ratio， Na⁺-K⁺-ATPase activity， Ca²⁺-Mg²⁺-ATPase activity， adrenocorticotropic hormone （ACTH）， polycorticosterone （CORT）， 17-OHCS， and other sex hormone indicators， providing crucial reference values for diagnosing kidney Yang deficiency or kidney Yin deficiency. The literature related to kidney deficiency syndrome over the past decade was collated and excavated， with a view to providing a reference for research on kidney deficiency syndrome.

Objective:To explore the clinical characteristics and experiences in diagnosis and treatment of severe hand injuries caused by chaff cutters.Methods:A retrospective analysis was conducted on 60 patients (193 digits) who had mangled hand injuries caused by chaff cutters and admitted to the Department of Upper Limb Repair and Reconstruction, Beijing Jishuitan Hospital Guizhou Hospital between January 2015 and June 2022. The patients were 39 males and 21 females, with 10 to 72 (mean 42.6) years old of age. The injuries involved 41 right hands and 19 left hands. The extent of hand injuries of soft tissue and bones varied from digit-tips to wrist. Among them, 5 digits were completely destroyed in 8 cases, 3 digits including thumb were destroyed in 12 cases, 4 digits including thumb were destroyed in 10 cases, 3 or more fingers without thumb were destroyed in 8 cases, simple hand destroyed in 8 cases, digits and palm destroyed in 8 cases, and total hand destroyed in 6 cases. The sizes of wound ranged from 1.8 cm×2.0 cm to 6.8 cm×15.6 cm. Based on the wound contamination and conditions of tissue damage, surgical treatment included debridement, stump trimming, in-situ replantation, transpositional replantation, venous bridging flap transfer and emergency or phased free second toe and free flap transfers. The flap sizes were 3.0 cm×5.0 cm-7.0 cm×16.0 cm. Both the reconstructed and flap donor sites were primarily closed in one stage. Postoperative follow-ups were conducted through regular visits of outpatient clinic or via WeChat interviews. The survival and functional recovery of flap and finger were observed.Results:Of the 60 patients, emergency orthotopic replantation of 112 digits were performed with survival of 96 digits; 16 digits transposition replantation were carried out with 12 survived; 5 digits received venous bridging flap transfer with 4 survived; all 5 Flow-through anteriolateral thigh perforator flaps (ALTPFs) were survived; all of 12 phase II digit reconstructions with free second toe transfer survived; and all 18 phase II free flap transfers survived [10 ALTPFs and 8 superficial circumflex iliac artery perforator flaps(SCIAPFs)]. Postoperative complications such as wound exudation and fever happened in 8 patients, and all were rectified after debridement and symptomatic anti-infection treatment. The follow-up ranged 6 to 18 months, with 12 months in average. Hand functions were assessed using the Michigan Hand Outcomes Questionnaire (MHQ), and the scores achieved at 20.3 to 72.8 points, with 42.6 points ± 16.6 points in average.Conclusion:Severe hand injuries caused by chaff cutters are severe and complicated. A thorough assessment of wound contamination and residual digits and tissues are required. Successful surgical outcomes can be achieved through emergency and elective surgery with multiple microsurgical techniques and multi-phased surgical reconstructions, although overall functional recovery of the injured hand is often not quite realistic.

BACKGROUND: Previous studies have examined the bulk transcriptome of peripheral blood immune cells in acquired immunodeficiency syndrome patients experiencing immunological non-responsiveness. This study aimed to investigate the characteristics of specific immune cell subtypes in acquired immunodeficiency syndrome patients who exhibit immunological non-responsiveness. METHODS: A single-cell transcriptome sequencing of peripheral blood mononuclear cells obtained from both immunological responders (IRs) (CD4 + T-cell count >500) and immunological non-responders (INRs) (CD4 + T-cell count <300) was conducted. The transcriptomic profiles were used to identify distinct cell subpopulations, marker genes, and differentially expressed genes aiming to uncover potential genetic factors associated with immunological non-responsiveness. RESULTS: Among the cellular subpopulations analyzed, the ratios of monocytes, CD16 + monocytes, and exhausted B cells demonstrated the most substantial differences between INRs and IRs, with fold changes of 39.79, 11.08, and 2.71, respectively. In contrast, the CD4 + T cell ratio was significantly decreased (0.39-fold change) in INRs compared with that in IRs. Similarly, the ratios of natural killer cells and terminal effector CD8 + T cells were also lower (0.37-fold and 0.27-fold, respectively) in the INRs group. In addition to several well-characterized immune cell-specific markers, we identified a set of 181 marker genes that were enriched in biological pathways associated with human immunodeficiency virus (HIV) replication. Notably, ISG15 , IFITM3 , PLSCR1 , HLA-DQB1 , CCL3L1 , and DDX5 , which have been demonstrated to influence HIV replication through their interaction with viral proteins, emerged as significant monocyte marker genes. Furthermore, the differentially expressed genes in natural killer cells were also enriched in biological pathways associated with HIV replication. CONCLUSIONS We generated an atlas of immune cell transcriptomes in HIV-infected IRs and INRs. Host genes associated with HIV replication were identified as markers of, and were found to be differentially expressed in, different types of immune cells.
Humans ; Acquired Immunodeficiency Syndrome ; Transcriptome/genetics* ; HIV ; HIV Infections/genetics* ; Leukocytes, Mononuclear/metabolism* ; CD4-Positive T-Lymphocytes/metabolism* ; Virus Replication ; Membrane Proteins/metabolism* ; RNA-Binding Proteins/metabolism*

Objective:To investigate and compare the regulatory effects of umbilical cord mesenchymal stem cells (MSC) and their conditioned medium (MSC-CM) on gut microbiota of septic mice.Methods:Twenty-eight six-to-eight-week-old female C57BL/6J mice were randomly divided into sham operation group (Sham group), sepsis model group (CLP group), sepsis+MSC treatment group (CLP+MSC group) and sepsis+MSC-CM treatment group (CLP+MSC-CM group), with seven mice in each group. The septic mouse model was established by cecal ligation and puncture (CLP). In Sham group, CLP were not performed, and other operations were the same as CLP group. Mice in the CLP+MSC group and CLP+MSC-CM group received 0.2 mL 1×10 6 MSC or 0.2 mL concentrated MSC-CM via intraperitoneal injection 6 hours after CLP, respectively. Sham group and CLP group were given 0.2 mL sterile phosphate buffer saline (PBS) via intraperitoneal injection. Histopathological changes were evaluated by hematoxylin-eosin (HE) staining and colon length. Levels of inflammatory factors in serum were detected by enzyme-linked immunosorbent assay (ELISA). Phenotype of peritoneal macrophages was analyzed by flow cytometry, and the gut microbiota was analyzed via 16S rRNA sequencing. Results:Compared with Sham group, significant inflammatory injury in lung and colon was observed, and shorter colon was detected in CLP group (cm: 6.00±0.26 vs. 7.11±0.09), the level of inflammatory cytokine interleukin-1β (IL-1β) in serum was significantly increased (ng/L: 432.70±17.68 vs. 353.70±17.01), the proportion of F4/80 + peritoneal macrophages was increased [(68.25±3.41)% vs. (50.84±4.98)%], while the ratio of F4/80 +CD206 + anti-inflammatory peritoneal macrophages was decreased [(45.25±6.75)% vs. (66.66±3.36)%]. The α diversity sobs index of gut microbiota was downregulated significantly (118.50±23.25 vs. 255.70±6.87), the structure of species composition was altered, and the relative abundance of functional gut microbiota related to transcription, secondary metabolites biosynthesis, transport and catabolism, carbohydrate transport and metabolism, and signal transduction were decreased significantly in CLP group (all P < 0.05). Compared with CLP group, upon MSC or MSC-CM treatment, the pathological injury in lung and colon was alleviated to varying extent, the length of colon was increased (cm: 6.53±0.27, 6.87±0.18 vs. 6.00±0.26), the level of IL-1β in serum was downregulated (ng/L: 382.10±16.93, 343.20±23.61 vs. 432.70±17.68), the ratio of F4/80 + peritoneal macrophages was decreased [(47.65±3.93)%, (48.68±2.51)% vs. (68.25±3.41)%], the ratio of F4/80 +CD206 + anti-inflammatory peritoneal macrophages was increased [(52.73±5.02)%, (66.38±4.73)% vs. (45.25±6.75)%], and the α diversity sobs index of gut microbiota was increased (182.50±16.35, 214.00±31.18 vs. 118.50±23.25), and the effects of MSC-CM were more significant (all P < 0.05). At the same time, species composition of gut microbiota was rebuilt, and a tendency of increase in relative abundance of functional gut microbiota was observed upon MSC and MSC-CM treatment. Conclusion:Both MSC and MSC-CM could alleviate inflammatory injury in tissues, and showed regulatory effects on gut microbiota in septic mouse model, moreover, MSC-CM exhibited superior advantages over MSC.

Objective:To explore the risks of cardiovascular disease (CVD) and influencing factors in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients with long-term combination anti-retroviral therapy (cART).Methods:The baseline data from the multi-center prospective cohort of HIV/AIDS patients who received long-term cART from 2018 to 2020 were collected. cART-naive HIV/AIDS patients were matched by age and gender using the propensity score matching (PSM) as controls. Data collection adverse events of anti-human immunodeficiency virus drugs reduced model (D: A: D[R]) score, Framingham risk score (FRS) and atherosclerotic cardiovascular disease (ASCVD) risk score were used to assess the 10-year CVD risk in patients with long-term cART treatment and in cART-naive patients. Logistic regression analysis was used to assess the risk factors related to high 10-year CVD risk.Results:A total of 301 HIV/AIDS patients received long-term cART and 300 cART-naive HIV/AIDS patients were included, with an average age of 39.8 years old. There were 490 male accounting for 81.5%. Based on the D: A: D [R] score, 4.3%(13/301) of patients in the long-term cART group had a 10-year CVD risk assessment of ≥10%, and 6.3%(19/300) of patients in the cART-naive group. Based on the FRS, 13.4%(36/269) of patients in the long-term cART group had a 10-year CVD risk assessment of ≥10%, and 10.6%(28/264) in the cART-naive group. Based on the ASCVD risk score, 10.4%(14/135) of patients in the long-term cART group had a 10-year CVD risk assessment of ≥7.5%, and 13.8%(17/123) in the cART-naive group. There was no significant difference in the prevalence of high 10-years CVD risk between the long-term cART group and the cART-naive group assessed by any of risk equations (all P>0.050). By multivariate logistic regression analysis, the risk factors associated with 10-year CVD risk ≥10% assessed by D: A: D[R] model were age≥50 years, smoking, hypertension, diabetes, dyslipidemia and CD4 + T lymphocyte count <200×10 6 cells/L (adjusted odds ratio ( AOR)=697.48, 4 622.28, 23.11, 25.95, 27.72 and 18.25, respectively, all P<0.010). The risk factors associated with 10-year CVD risk ≥10% assessed by FRS were age≥50 years, male, smoking, hypertension, diabetes and dyslipidemia ( AOR=53.51, 4.52, 36.93, 36.77, 6.15 and 3.84, respectively, all P<0.050). The risk factors associated with 10-year CVD risk ≥7.5% assessed by ASCVD risk score were age≥50 years, male, smoking, hypertension, diabetes ( AOR=18.48, 14.11, 14.81, 13.42 and 12.41, respectively, all P<0.050). Conclusions:Long-term cART has no significant effect on the 10-year CVD risk in HIV/AIDS patients. Higher CVD risk in HIV/AIDS patients are mainly associated with CD4 + T lymphocyte counts<200×10 6 cells/L and traditional CVD risk factors, including age≥50 years old, smoking, hypertension, diabetes and dyslipidemia.

Objective:To investigate the role of LncRNA-TUG1 in the injury of intestinal epithelial cells induced by lipopolysaccharide (LPS).Methods:LPS was used to treat HIEC-6 human intestinal epithelial cells for 24 h to construct a sepsis injury model. Whole transcriptome RNA sequencing was used to analyze the expression changes of mRNA, microRNA and lncRNA in HIEC-6 cells after LPS treatment. Real-time fluorescence quantitative (qRT-PCR) and Western blot was performed to detect the expression changes of lncRNA-TUG1, microRNA-132-3p (miR-132-3p), SIRT1 mRNA and SIRT1 protein in HIEC-6 cells after LPS treatment. The expression levels of LncRNA-TUG1, miR-132-3p and SIRT1 were artificially changed by in vitro transfection. qRT-PCR and Western blot were used to confirm the regulatory effect of lncRNA-TUG1 on microRNA-132-3p and SIRT1. CCK-8 and flow cytometry were used to analyze the effects of LncRNA-TUG1, miR-132-3p and SIRT1 on the proliferation and apoptosis of HIEC-6 cells. The dual luciferase report analysis was used to verify the targeting relationship between LncRNA-TUG1, miR-132-3p and SIRT1. Statistical analysis was performed using SPSS 17.0, and differences between the two groups were compared using independent sample t test. Results:RNA sequencing results showed that the expressions of lncRNA-TUG1 and SIRT1 were decreased in HIEC-6 cells after LPS treatment ( t=3.26, P<0.05 and t=2.55, P<0.05), but the expression of miR-132-3p was increased ( t=4.12, P<0.05). In vitro cell experiments, the expression of lncRNA-TUG1 and SIRT1 were decreased in HIEC-6 cells treated with LPS ( t=5.69, P<0.05 and t=5.712, P<0.05), while the expression of miR-132-3p was increased ( t=3.88, P<0.05). Overexpression of lncRNA-TUG1 increased the proliferation rate ( t=6.55, P<0.05) and decreased the apoptosis rate ( t=3.94, P<0.05) of LPS-treated cells. Upregulation of lncRNA-TUG1 decreased the expression of miR-132-3p ( t=4.66, P<0.05), and increased the mRNA and protein levels of SIRT1 ( t=3.91, P<0.05). Transfection of miR-132-3P mimic could inhibit the mRNA ( t=4.08, P<0.05) and protein levels of SIRT1. In LPS-treated cells, the cells co-transfected with miR-132-3pmimic and siRNA-SIRT1 had a lower proliferation rate ( t=4.55, P<0.05 and t=5.67, P<0.05) and a higher apoptosis rate ( t=3.90, P<0.05 and t=4.22, P<0.05) than those transfected with only pcDNA3.1-lncRNA-TUG. Conclusions:lncRNA-TUG1 may act as a ceRNA to regulate miR-132-3p/SIRT1, therefore alleviating HIEC-6 cell injury caused by LPS. Intervention of lncRNA-TUG1/miR-132-3p/SIRT1 regulatory pathway may become a potential strategy to prevent sepsis-induced intestinal mucosal damage.

Objective:To explore the action mechanism of suppressing expression of mitogen- activated protein kinase 14（MAPK14）to alleviate glutamate excitatory toxicity and its neuronal protection effect.Methods:Lentivirus-mediated MAPK14 interference vector was synthetized by Shanghai Jikai Gene Chemical Technology Co.，Ltd. Astrocytes were obtained from SD rats 48 hours after birth，which were cultured in vitro and transfected by lentivirus-mediated transfection. According to the random number table，the cells were divided into three groups：（1）un-transfected group（normal group）with normal astrocytes and the cells were cultured in regular medium composed of Dulbecco's?modified Eagle's?medium（DMEM）；（2）negative control group with astrocytes transfected by MAPK14 no-loaded interference vector；（3）lentivirus transfected group with astrocytes transfected by MAPK14 interference vector. Seventy-two hours after transfection，astrocytes were co-cultured with neurons for 48 hours，and then they were cultured in a medium containing glutamate for 2 hours. The detection indexes included the optimal multiplicity of infection（MOI）value for astrocytes transfected by lentivirus vector，mRNA levels of MAPK14 and glial glutamate transporter 1（GLT-1）detected by rPCR 72 hours after transfection，protein levels of MAPK14 and GLT-1 detected by Western blot 72 hours after transfection，level of lactate dehydrogenase（LDH）and mortality of neurons measured by spectrophotometry and flow cytometry 2 hours after culturing in the medium with glutamate. Results:（1）The optimal MOI value for lentivirus transfecting astrocytes was 30，and astrocytes grew well after transfection.（2）Seventy-two after transfection，the mRNA level of MAPK14 in lentivirus transfected group（0.005 7±0.000 6）was significantly decreased as compared with un-transfected group（0.013 1±0.001 1）and negative control group（0.013 9±0.001 0）（ P<0.01），the mRNA level of GLT-1 in lentivirus transfected group（0.009 1±0.001 2）was not significantly changed as compared with un-transfected group（0.008 7±0.000 3）and negative control group（0.008 9±0.001 1）（ P>0.05）.（3）Seventy-two hours after transfection，the protein level of MAPK14 in lentivirus transfected group（0.29±0.04）was significantly decreased as compared with non-transfected group（0.61±0.05）and negative control group（0.63±0.01）（ P<0.01），the protein level of GLT-1 in lentivirus transfected group（0.73±0.06）was significantly increased as compared with un-transfected group（0.20±0.03）and negative control group（0.23±0.09）（ P<0.01）.（4）After astrocytes were co-cultured with neurons and subsequently cultured in the medium containing glutamate for 2 hours，the level of LDH in lentivirus transfected group［（109.67±2.40）U/L］was significantly lower than that in un-transfected group［（141.52±3.88）U/L］and negative control group［（141.29±3.61）U/L］（ P<0.01）. The mortality of neurons in lentivirus transfected group［（38.72±0.26）%］was significantly lower than that in un-transfected group［（52.94±1.36）%］and negative control group［（54.30±1.23）%］（ P<0.01）. Conclusions:The transfection with lentivirus-mediated MAPK14 interference vector can increase expression of GLT-1 in astrocytes to increase glutamate re-uptake and relieve the glutamate excitatory toxicity in neurons，which may provide a new experimental basis for future use of astrocyte gene regulation to alleviate neuronal injury caused by glutamate excitatory toxicity after traumatic brain injury.