Objective:To investigate whether dual-energy computed tomography(DECT) measurement of monosodium urate(MSU) crystal loading can predict the risk of gout flares.Methods:A single-center, prospective, observational study included 229 gout patients initially diagnosed at the Gout Clinic of Qingdao University from August 2021 to February 2022. The patients underwent MSU assessment of the bilateral feet using DECT. Following enrolment, all patients commenced uric acid-lowering therapy(ULT) and were followed up at 3 and 6 months. Patients who experienced at least one flare within 6 months were compared with those who did not, and the odds ratio( OR) for the risk of gout flares was calculated. Results:Patients who experienced gout flare had a significantly longer disease duration[(6.69±5.42) vs(4.14±4.86) years, P<0.01], a higher number of flares in the past year(4.80±1.73 vs 2.02±1. 23, P<0.01), a higher proportion of fatty livers(11.0% vs 1.4%, P<0.05), and a greater volume of MSU crystals in the feet[(3.52±9.74) vs(0.29±0.98)cm 3,P<0.05] compared to patients without gout flare. The results of the multifactorial logistic regression analysis indicated that the number of flares in the past year( OR=1.295, 95% CI 1.032-1.613, P<0.05) and feet MSU crystal volume( OR=3.245, 95% CI 1.164-9.064, P<0.05) were independent risk factors for gout flares. The receiver operating characteristic(ROC) curve indicated the integration of the MSU prediction model into the clinical prediction model resulted in a comprehensive prediction model with an area under curve(AUC) value of 0.780(95% CI 0.710-0.840), sensitivity of 0.83, and specificity of 0.62. Internal validation of the comprehensive prediction model using the Bootstrap method yielded a C-index of 0.770(95% CI 0.701-0.833) for predicting flares. The calibration curve of the model demonstrated a good fit between the predicted probability of flares and the actual probability, indicating high calibration accuracy. Conclusion:The volume of MSU crystals in the feet is an independent risk factor for flares following ULT. A larger volume of MSU crystals in the foot increases the likelihood of a flare. This study provides a basis for early prediction of flare and a reference for early preventive treatment.

As a new hypoglycemic drug,Dapagliflozin has attracted much attention because of its unique hypoglycemic mechanism. It has been used in many studies on type 2 diabetes mellitus,but the application of type 1 diabetes mellitus(T1DM)in the eastern population is rare. This article uses Dapagliflozin through a case of obese T1DM to provide new ideas for the treatment of T1DM.

Objective To investigate the levels of serum CC chemokine ligand-11(CCL11)and lipocalin-2(LCN-2)in patients with non-small cell lung cancer(NSCLC)and their diagnostic value for NSCLC.Methods NSCLC pa-tients admitted to the hospital from October 2019 to December 2022 were collected as the NSCLC group(80 cases),and 80 patients with benign lung lesions and 80 healthy volunteers treated in the hospital during the same period were collected as benign control group and health control group.Enzyme linked immunosorbent assay(ELISA)was applied to measure serum levels of CCL11 and LCN-2.The general data and serum levels of CCL11 and LCN-2 were compared among the three groups.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of serum CCL11 and LCN-2 for NSCLC.Logistic regression was applied to analyze the influencing factors of the occurrence of NSCLC.Results The serum levels of CCL11 and LCN-2 in NSCLC group were obviously higher than those in benign control group and health control group(P＜0.05),but there was no statistically significant difference between begin control group and health control group(P＞0.05).There was no statistically significant difference in serum CCL11 and LCN-2 levels among NSCLC patients of different genders,ages,and pathological types(P＞0.05),the serum levels of CCL11 and LCN-2 in NSCLC patients with a history of smoking,engaged in work related oil smoke at dust,medium to low differentiation,tumor diameter＞3 cm,lymph node metastasis,and TNM staging Ⅲ-Ⅳ were obviously higher than those in NSCLC patients without a history of smoking,not engaged in work related oil smoke at dust,high differentiation,tumor diameter ≤3 cm,non lymph node metastasis,and TNM stagingⅠ-Ⅱ(P＜0.05).The results of ROC curve showed that the area under the curve(AUC)of CCL11,LCN-2 alone and their combination in the diagnosis of NSCLC was 0.849,0.841 and 0.926 respectively,the sensitivi-ty was 73.8％,75.0％and 85.0％respectively,and the specificity was 70.1％,70.0％and 75.0％respective-ly.The efficacy of combined detection of the two in diagnosing NSCLC was better than those of single detec-tion(P＜0.05).The results of Logistic regression analysis showed that smoking,engaging in high oil fume,dust related works,and serum levels of CCL11 and LCN-2 were all influencing factors for the occurrence of NSCLC(P＜0.05).Conclusion In NSCLC patients,the levels of serum CCL11 and LCN-2 obviously in-crease,and they are closely related to the clinical pathological characteristics of NSCLC patients.Both have certain clinical value in the diagnosis of NSCLC.

Objective:To analyze the clinical phenotype and genetic characteristics of a Chinese pedigree affected with Hereditary antithrombin deficiency.Methods:A pedigree diagnosed at the the Second Affiliated Hospital of Wenzhou Medical University, Yuying Children’s Hospital in June, 2020 was selected as the study subject. Plasma prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and thrombin time (TT) of the probands and their pedigree members were determined using a STA-R automatic coagulation analyzer. Antithrombin activity (AT: A) and antithrombin antigen (AT: Ag) in plasma were determined with chromogenic substrate and immunonephelometry assays. All exons and flanking sequences of the anticoagulant protein gene SERPINC1 were amplified by PCR and subjected to Sanger sequencing. Candidate variants were verified with bioinformatic tools (PolyPhen-2, SIFT, Mutation Taster and PYMOL) to explore their effect on the function and structural conformation of the protein. Results:The probands (Ⅱ 2, Ⅱ 10), their brother (Ⅱ 5) and sons (Ⅲ 1, Ⅲ 8) had shown normal PT, APTT, FIB, and TT, but significantly decreased AT: A and AT: Ag, with their levels being 34%, 57%, 56%, 48%, 53% and 13.51 mg/dL, 13.44 mg/dL, 18.39 mg/dL, 17.36 mg/dL, 17.71 mg/dL, respectively. The remaining pedigree members had normal values. Sanger sequencing revealed that the probands and all affected pedigree members had harbored a heterozygous c. 851T>C (p.Met284Thr) missense variant in exon 5 of the SERPINC1 gene. Bioinformatic analysis and simulation suggested that the variant has resulted in alteration of hydrogen bonds at the c. 851 position, which may affect the structure of the protein. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PS1+ PM1+ PM5+ PP1+ PP4). Conclusion:The probands and other affected members were all diagnosed with type I hereditary AT deficiency, for which the c. 851 T>C (p.Met284Thr) variant of the SERPINC1 gene may be accountable.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

ObjectiveTo investigate the effect of Wudan pill on the polarization of macrophages in the rat model of endometriosis （EMT） with cold congeal and blood stasis syndrome based on p38 mitogen-activated protein kinases （p38 MAPK）. MethodFemale SD rats with regular motility cycles were selected and randomly divided into sham-operated group， model group， Wudan pill high， medium， and low-dose groups （2.4， 1.2， and 0.6 g⋅kg^-1）， Chinese patent medicine group， and western medicine group by the random number table method. The method of ice water bath + autologous endometrial transplantation was used to establish the rat model of EMT with cold congeal and blood stasis， and the rats were executed after 4 weeks of continuous drug administration to collect materials. Expression levels of serum tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， IL-4， and transforming growth factor-β （TGF-β） were determined by enzyme-linked immunosorbent assay （ELISA） to assess inflammation. The real-time quantitative polymerase chain reaction （Real-time PCR） was performed to determine the inducible nitric oxide synthase （iNOS）， TNF-α， arginase 1 （Arg1）， and human mannose receptor （CD206） transcriptional levels to evaluate macrophage polarization. Western blot （WB） and immunofluorescence （IF） assays were used to determine the protein expression levels of iNOS and Arg1 to corroborate macrophage polarization. WB and Real-time PCR were used to determine the protein expression levels of the p38 MAPK pathway. ResultAs compared with sham-operated group， the levels of serum TNF-α， IL-1β， TGF-β， and IL-4 of rats in the model group were significantly higher （P<0.05）. In the model group， the protein levels of iNOS， TNF-α， p-p38 MAPK， and phosphorylated-extracellular signal-regulated kinase （p-ERK） in endothelial tissues were significantly higher， the mRNA levels of iNOS， TNF-α， MAPK， and ERK were significantly higher， and the mRNA and protein expression levels of Arg1 and CD206 were significantly lower （P<0.05， P<0.01）. The number of iNOS positive cells in endothelial tissues was significantly increased， and the number of Arg1 positive cells in endothelial tissues in the model group was significantly decreased （P<0.05， P<0.01）. As compared with the model group， the expression of TNF-α， IL-1β， TGF-β， and IL-4 in each administration group was reduced to different degrees， which was especially significant in the Wudan pill high and medium-dose groups and the western medicine group （P<0.05）. The protein expression levels of iNOS， TNF-α， p-p38 MAPK， and p-ERK in endometrial tissues of rats in the Wudan pill high and medium-dose groups， the Chinese patent medicine group， and the western medicine group were significantly lower， the mRNA expression levels of iNOS， TNF-α， MAPK， and ERK were significantly lower， and the protein expression levels of Arg1 and CD206 were significantly higher （P<0.05， P<0.01）. The number of iNOS positive cells in endometrial tissues of rats was significantly decreased in the Wudan pill high and medium-dose groups， the Chinese patent medicine group， and the western medicine group， whereas the number of Arg1 positive cells was increased （P<0.05， P<0.01）. The low， medium， and high doses of Wudan pill were dose-dependent， and the efficacy of the Wudan pill high-dose group was similar to that of the western medicine group. ConclusionWudan pill reduces the inflammatory response in rat model of EMT with cold congeal and blood stasis syndrome and decreases expression levels of TNF-α， IL-1β， IL-4， and TGF-β， thereby prompting polarization of macrophages from M1 to M2 type. The mechanism is presumedly related to p38 MAPK signaling pathway.

Objective:To investigate prognostic factors for acral lentiginous melanoma (ALM) , and to construct a nomogram to verify the predictive value of these factors.Methods:Clinical data on 1 573 patients with ALM were collected from the Surveillance, Epidemiology, and End Results (SEER) database of National Cancer Institute in United States between 2004 and 2015. Data about patients′ age, gender, ulcer status, SEER staging, surgical protocols, T-, N- and M-staging, overall survival rates and disease-specific survival rates were extracted. Chi-square test was used to analyze the correlation of clinical characteristics with overall survival rates and melanoma-specific survival rates, and univariate and multivariate Cox proportional hazards regression models were used to investigate prognostic factors and establish predictive models.Results:Among the 1 537 patients with ALM, 714 were males, 823 were females, 818 were under 64 years of age, and 1 363 were Caucasian. Skin lesions occurred on the lower limbs and buttocks in 1 205 cases, and 974 cases had ulcers; according to the SEER staging, non-spread localized skin lesions were observed in 1 048 cases. There were significant differences in the mortality rate among patients of different ages at diagnosis, different gender, with different ulcer status, surgical status, and at different SEER stages, T-stages, N-stages and M-stages (all P < 0.001) . Univariate and multivariate Cox regression analysis showed that age ≥ 65 years, male, ulcers and distant lymph node metastasis in the SEER staging were associated with increased risk of death in the patients (all P < 0.05) , and the mortality rate was significantly higher in the patients with T2-, T3- or T4-stage ALM than in those with T1-stage ALM (all P < 0.05) , and higher in the patients with N1-, N2- and N3-stage ALM than in those with N0-stage ALM (all P < 0.05) . Conclusion:Age, gender, ulcer status, SEER stage, T-stage and N-stage are independent prognostic factors for overall survival rates and disease-specific survival rates of ALM.

Objective:To evaluate the clinical efficacy of Huzhang Polou Decoction combined with acupoint application in the treatment of children with mycoplasma pneumoniae pneumonia (MPP) complicated with atelectasis.Methods:A total of 105 MPP children with atelectasis and phlegm-heat obstructing lung syndrome in our hospital from August 2019 to March 2022, who met the inclusion criteria, were divided into control group (53 cases) and observation group (52 cases), by random number table method. The control group was given azithromycin sequential therapy on the basis of conventional western medicine treatment, and the observation group was given Huzhang Polou Decoction and acupoint application on the basis of the control group. Both groups were treated for 19 days. TCM syndromes were scored before and after treatment. The FEV1 and peak expiratory flow rate (PEF) were measured by pulmonary function measurement instrument. The CRP was measured by immunoturbidimetry and procalcitonin (PCT) was measured by ELISA. The recovery time of fever, disappearance time of cough and sputum, disappearance time of lung rales, lung recruitment time, and adverse reactions during treatment were recorded, and the clinical efficacy was evaluated.Results:The total effective rate was 96.15% (50/52) in the observation group and 84.91% (45/53) in the control group, and the difference between the two groups was statistically significant ( χ2=3.85, P=0.050). After treatment, the TCM syndrome score of the observation group was significantly lower than that of the control group ( t=22.78, P<0.01). FEV1 [(1.87±0.29) L vs. (1.54±0.28) L, t=5.93] and PEF [(79.82±6.29) L/min vs. (74.32±6.30) L/min, t=4.48] were significantly higher than those in the control group ( P<0.01). The levels of serum CRP [(9.18±2.98) mg/L vs. (12.34±3.00) mg/L, t=5.42] and PCT [(0.60±0.15) ng/L vs. (0.96±0.21) ng/L, t=9.93] were significantly lower than those in the control group ( P<0.01). The recovery time of fever, disappearance time of cough and sputum, disappearance time of lung rale and lung recruitment time in the observation group were significantly earlier than those in the control group ( t=7.27, 6.84, 3.76, 5.87, all Ps<0.01). During treatment, the incidence of adverse reactions was 3.77% (2/53) in the control group and 1.92% (1/52) in the observation group, and there was no significant difference between the two groups ( χ2=0.32, P=0.569). Conclusion:The Huzhang Polou Decoction combined with acupoint application can improve the pulmonary function of children with MPP complicated with atelectasis, reduce the level of serum inflammatory cytokines, improve the clinical efficacy safely.

Objective: To analyze the phenotype and genotype of a pedigree affected with congenital dysfibrinogenemia. Methods: Liver and kidney functions of the proband and her relatives were determined. Coagulation tests including prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time(TT), fibrin(ogen) degradation products (FDPs), D-dimer(D-D) and the calibration experiment of protamine sulfate of against plasma TT were detected in the proband and her predigree members. The activity and antigen of fibrinogen (Fg) in plasma were measured by Clauss method and immunonephelometry method, respectively. All of the exons and exons-intron boundaries of the three fibrinogen genes (FGA, FGB and FGG) were subjected to PCR amplification and Sanger sequencing. Potential influence of the suspected mutations were analyzed with bioinformatics software including PolyPhen-2, SIFT and Mutation Taster. Results: The proband had normal PT, APTT, FDPs, D-D and prolonged TT (31.8 s). The activity of fibrinogen (Fg) in plasma was significantly decreased but the antigen was normal. Genetic analysis revealed a heterozygous c. 92G>A (p.Gly31Glu) mutation in exon 2 of the FGA gene. Family studies revealed that the mother carried the same mutation. Bioinformatic analysis suggested that the mutation may affect the function of Fg Protein. Conclusion The dysfibrinogenemia was probably caused by the novel Gly31Glu mutation of the FGA gene.

OBJECTIVE: To analyze the phenotype and genotype of a pedigree affected with congenital dysfibrinogenemia. METHODS: Liver and kidney functions of the proband and her relatives were determined. Coagulation tests including prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time(TT), fibrin(ogen) degradation products (FDPs), D-dimer(D-D) and the calibration experiment of protamine sulfate of against plasma TT were detected in the proband and her predigree members. The activity and antigen of fibrinogen (Fg) in plasma were measured by Clauss method and immunonephelometry method, respectively. All of the exons and exons-intron boundaries of the three fibrinogen genes (FGA, FGB and FGG) were subjected to PCR amplification and Sanger sequencing. Potential influence of the suspected mutations were analyzed with bioinformatics software including PolyPhen-2, SIFT and Mutation Taster. RESULTS: The proband had normal PT, APTT, FDPs, D-D and prolonged TT (31.8 s). The activity of fibrinogen (Fg) in plasma was significantly decreased but the antigen was normal. Genetic analysis revealed a heterozygous c.92G>A (p.Gly31Glu) mutation in exon 2 of the FGA gene. Family studies revealed that the mother carried the same mutation. Bioinformatic analysis suggested that the mutation may affect the function of Fg Protein. CONCLUSION The dysfibrinogenemia was probably caused by the novel Gly31Glu mutation of the FGA gene.
Afibrinogenemia ; congenital ; genetics ; DNA Mutational Analysis ; Female ; Fibrinogen ; genetics ; Humans ; Mutation ; Pedigree ; Phenotype