OBJECTIVE: To explore clinical characteristics, lesion sites and correlation differences of different types of diabetic foot gangrene, and to provide evidence-based basis for clinical classification of diabetic foot gangrene. METHODS: A retrospective analysis was conducted on 266 patients with newly diagnosed diabetic foot gangrene who were admitted from January 2018 to December 2018, including 183 males and 83 females, aged from 35 to 92 years old with an average of (69.55±10.84) years old, and they were divided into wet gangrene group and dry gangrene group according to the different natures of gangrene. There were 139 patients in wet gangrene group, including 98 males and 41 females, aged from 35 to 90 years old with an average of (68.95±10.93) years old. There were 127 patients in dry gangrene group, including 85 males and 42 females, aged from 38 to 92 years old with an average of (70.21±10.75) years old. Body mass index (BMI), waist-to-hip ratio (WHR), body temperature, skin temperature difference between the affected and healthy sides of the lower extremities, and Wagner grade between two groups were recorded to evaluate symptoms and signs. The white blood cell count (WBC), neutrophil percentage (NEUT%), and C-reactive protein (C-reactive protein), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), and interleukin-6 (IL-6) in peripheral blood between two groups were detected and compared to evaluate the infection status;the severity of diabetic peripheral neuropathy (DPN) was evaluated by using Toronto Clinical Scoring System (TCSS);the degree of pain in patients with diabetic foot gangrene was evaluated by numerical rating scale (NRS); ankle-brachial index (ABI) and popliteal artery blood flow velocity were used to evaluate the degree of arterial lesions. Spearman correlation analysis was used to analyze the correlations between gangrene TCSS, ABI and age, BMI, WHR, body temperature, calf skin temperature difference, WBC, NEUT%, CRP, ESR, PCT, IL-6, NRS, and Wagner classification indicators. RESULTS: The body temperature, skin temperature difference between the affected and healthy sides of the lower extremities, Wagner grade, WBC, NEUT%, CRP, ESR, PCT, IL-6, TCSS score, ABI, and popliteal artery blood flow velocity in wet gangrene group were higher than those in dry gangrene group (P<0.01), and BMI, WHR, and NRS score in dry gangrene group were higher than those in wet gangrene group;the differences were all statistically significant (P<0.01). The results of Spearman correlation analysis showed TCSS score of gangrene patients was correlated with body temperature (r=0.214), calf skin temperature difference (r=0.364), WBC (r=0.240), NEUT% (r=0.291), CRP (r=0.347), ESR (r=0.167), PCT (r=0.241), IL-6 (r=0.316), and popliteal fossa arterial blood flow velocity (r=0.261) and Wagner grade (r=0.273) were positively correlated, and the differences were statistically significant (P<0.01). ABI was negatively correlated with age (r=-0.183), BMI (r=-0.252), WHR (r=-0.288), and NRS score (r=-0.354), and the differences were statistically significant (P<0.01). CONCLUSION Diabetic foot gangrene is an extremely difficult and critical disease. Wet gangrene has a significant synergic effect with infection and neuropathy, while dry gangrene is closely related to vascular occlusion. The main contradiction of gangrene could be revealed through blood vessels, nerves and infection, providing evidence-based basis for the selection of debridement timing, anti-infection strategies and revascularization, with the aim of reducing the risk of amputation.
Humans ; Male ; Female ; Aged ; Middle Aged ; Diabetic Foot/diagnosis* ; Aged, 80 and over ; Adult ; Retrospective Studies ; Gangrene/physiopathology* ; C-Reactive Protein

OBJECTIVE: To study the effects and mechanisms of juglone on the proliferation and apoptosis of acute myeloid leukemia (AML) cells. METHODS: Juglone and AML targets were collected from public databases, and the intersecting target clusters were taken for functional enrichment analysis to explore the potential mechanism of juglone in the treatment of AML. Then wet experiments were performed to verify. AML cell lines including KG-1a, MV-411, THP-1 and MOLM-13 were treated with different concentrations of juglone for 24 h. MTT assay was used to detect cell viability and determine the IC₅₀, and the most sensitive cell line was screened for subsequent experiments. Flow cytometry was used to detect the apoptosis of cells treated with different concentrations of juglone. Western blot was performed to check the expression of relevant proteins. RESULTS: Eleven targets were obtained as potential targets for juglone in the treatment of AML, and the top ten significantly enriched pathways were intrinsic pathway of apoptosis, programmed cell death, cytochrome c-mediated apoptotic response, apoptosis, apoptotic factor-mediated response, regulated necrosis, cytokine signaling in immune system, signaling by interleukins, oncogene induced senescence, and signal transduction. The cell viability of KG-1a, MV-411, THP-1 and MOLM-13 was decreased with increasing juglone concentration after 24 h of juglone treatment (r =-0.992, -0.886, -0.956, -0.910). Among them, MOLM-13 was the most sensitive to juglone. The results of flow cytometry showed that the apoptosis rate of MOLM-13 tended to significantly increase with the increasing concentration of juglone (r =0.99). At the same time point, p-RIPK1/RIPK1, p-RIPK3/RIPK3, and p-MLKL/MLK were decreased in each juglone concentration group compared with control group. CONCLUSION Juglone inhibits the viability of KG-1a, MV-411, THP-1 and MOLM-13 cells, and induces apoptosis of MOLM-13 cells, the mechanism of which may be related to the inhibition of RIPK1/RIPK3/MLKL signaling pathway.
Humans ; Naphthoquinones/pharmacology* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Leukemia, Myeloid, Acute/pathology* ; Cell Line, Tumor ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Protein Kinases/metabolism* ; Signal Transduction ; Cell Survival/drug effects*

Objective To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder(IMD)among neonates in Gansu Province of China.Methods A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021.A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.Results A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates,and the overall prevalence rate of IMD was 0.63‰(1/1 593),among which phenylketonuria showed the highest prevalence rate of 0.32‰(1/3 083),followed by methylmalonic acidemia(0.11‰,1/8 959)and tetrahydrobiopterin deficiency(0.06‰,1/15 927).In this study,166 variants were identified in the 28 pathogenic genes,with 13 novel variants found in 9 genes.According to American College of Medical Genetics and Genomics guidelines,5 novel variants were classified as pathogenic variants,7 were classified as likely pathogenic variants,and 1 was classified as the variant of uncertain significance.Conclusions This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Objective To investigate whether or not the infusion of anti-SARS-CoV-2 antibody-positive stock plasma inducing the antibody-dependent enhancement(ADE)effect in the patients with COVID-19 complicating liver dysfunction.Methods The clinical data of 26 patients with COVID-19 complicating liver dysfunction infused with SARS-CoV-2 antibody-positive stock plasma in this hospital from December 15,2022 to January 20,2023 were analyzed retrospectively.The changes of peripheral blood mononuclear cells(MONO)count and cytokines IL-2,IL-4,IL-6,IL-10,TNF-α and IFN-γ levels were compared and analyzed before and after plasma infusion.Thirty-seven patients with COVID-19 without plasma infusion during the same period served as the control group.The situation such as peripheral blood MONO count,cytokines lev-els,throat swab SARS-CoV-2 nucleic acid test,pulmonary infection lesion absorption on 5 d of treatment were compared between the two groups.Results The proportions of peripheral blood MONO count increase in the observation group and control group were 69.23％and 59.56％respectively,the proportions of cytokines in-crease were 66.67％vs.76.92％for IL-2,22.22％vs.46.15％for IL-4,33.33％vs.38.46％for IL-6,33.33％vs.30.27％for IL-10,33.33％vs.46.15％for TNF-α and 44.44％vs.61.54％for IFN-γ,the throat swab SARS-CoV-2 nucleic acid detection negative ratio was 46.67％vs.59.09％.The proportion of the pa-tients with lesion absorption beginning was 87.50％vs.84.85％,and the differences were not statistically sig-nificant(P＞0.05).Conclusion Infusion of stock plasma containing anti-SARS-CoV-2 polyclonal antibodies in the patients with COVID-19 complicating liver dysfunction does not induce significant ADE.

OBJECTIVE: Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery. METHODS: We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated. RESULTS: A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery. CONCLUSION These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.
Female ; Humans ; Male ; Middle Aged ; Brucellosis ; COVID-19 ; Retrospective Studies ; SARS-CoV-2 ; Treatment Outcome ; Case Reports as Topic

The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.
Rats ; Mice ; Animals ; Chronic Pain/metabolism* ; Rats, Sprague-Dawley ; Ganglia, Spinal/metabolism* ; Ligands ; Signal Transduction ; Hyperalgesia/metabolism* ; Drugs, Chinese Herbal

Objective: To investigate the application value of computed tomography (CT) examination of lymph node short diameter in evaluating cardia-left gastric lymph node metastasis in thoracic esophageal squamous cell carcinoma (ESCC). Methods: A total of 477 patients with primary thoracic ESCC who underwent surgical treatment in the Affiliated Cancer Hospital of Zhengzhou University from January 2013 to December 2017 were collected. All of them underwent McKeown esophagectomy plus complete two-field or three-field lymph node dissection. Picture archiving and communication system were used to measure the largest cardia-left gastric lymph node short diameter in preoperative CT images. The postoperative pathological diagnosis results of cardia-left gastric lymph node were used as the gold standard. Receiver operating characteristic (ROC) curve was used to evaluate the efficacy of CT lymph node short diameter in detecting the metastasis of cardia-left gastric lymph node in thoracic ESCC, and determine the optimal cut-off value. Results: The median short diameter of the largest cardia-left gastric lymph node was 4.1 mm in 477 patients, and the largest cardia-left gastric lymph node short diameter was less than 3 mm in 155 cases (32.5%). Sixty-eight patients had cardia-left gastric lymph node metastases, of which 38 had paracardial node metastases and 41 had left gastric node metastases. The lymph node ratios of paracardial node and left gastric node were 4.0% (60/1 511) and 3.3% (62/1 887), respectively. ROC curve analysis showed that the area under the curve of CT lymph node short diameter for evaluating cardia-left gastric lymph node metastasis was 0.941 (95% CI: 0.904-0.977; P<0.05). The optimal cut-off value of CT examination of the cardia-left gastric lymph node short diameter was 6 mm, and the corresponding sensitivity, specificity and accuracy were 85.3%, 91.7%, and 90.8%, respectively. Conclusion: CT examination of lymph node short diameter can be a good evaluation of cardia-left gastric lymph node metastasis in thoracic ESCC, and the optimal cut-off value is 6 mm.
Humans ; Esophageal Squamous Cell Carcinoma/pathology* ; Cardia/surgery* ; Esophageal Neoplasms/pathology* ; Lymphatic Metastasis/pathology* ; Lymph Nodes/pathology* ; Lymph Node Excision ; Tomography, X-Ray Computed/methods* ; Esophagectomy/methods* ; Retrospective Studies

Objective: To investigate the application value of computed tomography (CT) examination of lymph node short diameter in evaluating cardia-left gastric lymph node metastasis in thoracic esophageal squamous cell carcinoma (ESCC). Methods: A total of 477 patients with primary thoracic ESCC who underwent surgical treatment in the Affiliated Cancer Hospital of Zhengzhou University from January 2013 to December 2017 were collected. All of them underwent McKeown esophagectomy plus complete two-field or three-field lymph node dissection. Picture archiving and communication system were used to measure the largest cardia-left gastric lymph node short diameter in preoperative CT images. The postoperative pathological diagnosis results of cardia-left gastric lymph node were used as the gold standard. Receiver operating characteristic (ROC) curve was used to evaluate the efficacy of CT lymph node short diameter in detecting the metastasis of cardia-left gastric lymph node in thoracic ESCC, and determine the optimal cut-off value. Results: The median short diameter of the largest cardia-left gastric lymph node was 4.1 mm in 477 patients, and the largest cardia-left gastric lymph node short diameter was less than 3 mm in 155 cases (32.5%). Sixty-eight patients had cardia-left gastric lymph node metastases, of which 38 had paracardial node metastases and 41 had left gastric node metastases. The lymph node ratios of paracardial node and left gastric node were 4.0% (60/1 511) and 3.3% (62/1 887), respectively. ROC curve analysis showed that the area under the curve of CT lymph node short diameter for evaluating cardia-left gastric lymph node metastasis was 0.941 (95% CI: 0.904-0.977; P<0.05). The optimal cut-off value of CT examination of the cardia-left gastric lymph node short diameter was 6 mm, and the corresponding sensitivity, specificity and accuracy were 85.3%, 91.7%, and 90.8%, respectively. Conclusion: CT examination of lymph node short diameter can be a good evaluation of cardia-left gastric lymph node metastasis in thoracic ESCC, and the optimal cut-off value is 6 mm.
Humans ; Esophageal Squamous Cell Carcinoma/pathology* ; Cardia/surgery* ; Esophageal Neoplasms/pathology* ; Lymphatic Metastasis/pathology* ; Lymph Nodes/pathology* ; Lymph Node Excision ; Tomography, X-Ray Computed/methods* ; Esophagectomy/methods* ; Retrospective Studies

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

Objective:This work aims to assess the distribution of peripheral blood monocyte subsets, the expression level of the functional markers in rheumatoid arthritis (RA) patients, and analyze the correlation between the above indexes and the onset of RA.Methods:Peripheral blood mononuclear cells were collected and isolated from 62 RA patients, 52 healthy control (HC) and 12 disease control group′s patients via density centrifugation. The enrolled patients were attended or underwent physical examination in East Hospital, Tongji University from June 2020 to December 2021. Monocytes could be classified into classical (CM), intermediate (IM) and non-classical (NCM). Then, the flow cytometry was performed to examine the distribution of monocyte subsets and the measure the expression level of human leukocyte antigen DR (HLA-DR), intracellular tumor necrosis factor α (TNF-α) in peripheral blood monocytes. The statistical methods in this study mainly include: Kruskal-Wallis H test, Chi-Square test, Mann-Whitney U test, Wilcoxon matched-pairs signed ranks test, Spearman correlation coefficient test and Logistic regression analysis. The diagnostic value of IM proportion in RA was analyzed by ROC curve. Results:The monocytes number and monocytes proportion in white blood cells were much higher in RA [0.40 (0.40, 0.50), 7.60% (5.97%, 8.53%)] and disease control [0.40 (0.40, 0.68), 8.20% (5.85%, 10.28%)] compared with HC [0.30 (0.30, 0.40), 5.80% (5.03%, 6.38%)] ( H=24.733, P<0.001; H=27.469, P<0.001). A statistic-significant difference was detected among the proportion of CM[85.49%(76.91%,89.21%),88.94%(86.36%,91.72%),90.26%(80.25%, 92.56%)],IM[11.65%(8.47%,17.89%),7.89%(5.36%,10.75%), 5.56%(4.17%, 8.27%)], NCM[2.22%(1.39%, 3.74%), 2.49%(1.74%, 4.66%), 5.13%(3.39%, 9.85%)] in RA group, HC group and disease control group ( H=11.389, P=0.003; H=20.815, P<0.001; H=10.640, P=0.005). The proportion of CM was lower in RA and the IM proportion was increased in RA( P=0.003; P=0.003). The intracellular TNF-α level of monocytes in all three groups revealed the trend that IM>NCM>CM. The intracellular TNF-α in IM of RA was positively associated with serum TNF-α ( r=0.376, P=0.041). The HLA-DR expression in IM subsets were higher than CM and NCM subsets in all RA,HC and disease control groups. The expression of HLA-DR of IM in RA group and disease control was higher than HC group [8 611.50 (6201.3, 9890.8), 10 295.0 (7 899.0, 13632.0), 6 278.00(4 057.8, 9522.0), H=10.495, P=0.005]. There were no correlations between the proportion of peripheral blood IM and clinical characteristics CRP ( r=0.119, P=0.359), RF ( r=0.204, P=0.112) and ESR ( r=0.153, P=0.236). Logistic regression analysis showed that the proportion of IM ( OR=1.169, 95% CI 1.003-1.363, P=0.046), CRP ( OR=1.277, 95% CI 1.000-1.631, P=0.050), RF ( OR=1.179, 95% CI 1.080-1.287, P<0.001) are positively correlated with RA onset. The area under ROC curve for diagnosis of RA with IM proportion was 0.687, and the 95% confidence interval was 0.590-0.784, P<0.001. Conclusions:The distribution of monocyte subsets in peripheral blood of RA patients is abnormal. The increase in the proportion of IM, the enhanced antigen-presenting ability, and the increased level of TNF-α secretion in RA patients may play an important role in the pathogenesis of RA.