BackgroundInvasive vagus nerve stimulation therapy has been approved for the adjunctive treatment of treatment-resistant depression， which may contribute to the anti-inflammatory properties of vagus nerve stimulation （VNS）， whereas the efficacy of non-invasive transcutaneous cervical vagus nerve stimulation （tcVNS） in treating major depressive disorder （MDD） and its impact on plasma inflammatory factors remain unclear. ObjectiveTo observe the effect of escitaloprom combined with tcVNS on the status of depression， anxiety and sleep quality as well as the plasma levels of interleukin-6 （IL-6） and interleukin-10 （IL-10） in MDD patients， in order to provide references for the recovery and treatment of MDD patients. MethodsFrom August 21， 2019 to April 17， 2024， 45 patients who met the diagnostic criteria for MDD in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were recruited from the psychosomatic outpatient clinic of the First Affiliated Hospital of Air Force Military Medical University. Subjects were divided into study group （n=23） and control group （n=22） using random number table method. All patients were treated with escitalopram. On this basis， study group added a 30-minute tcVNS therapy once a day for 4 weeks. While control group was given corresponding sham stimulation， and the duration of each stimulation lasted 30 seconds. Before and after 4 weeks of treatment， Hamilton Depression Scale-17 item （HAMD-17） was used to assess depressive symptoms， and HAMD-17 anxiety/somatization subfactor and insomnia subfactor were used to assess patients' anxiety/somatization symptoms and sleep quality. Levels of plasma IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe generalized estimating equation model yielded a significant time effect for HAMD-17 total score， anxiety/somatization subfactor score and insomnia subfactor score in both groups （Wald χ²=315.226， 495.481， 82.420， P<0.01）. After 4 weeks of treatment， HAMD-17 total score and anxiety/somatization subfactor score of study group were lower than those of control group， with statistically significant differences （Wald χ²=4.967， 32.543， P<0.05 or 0.01）， while no statistically significant difference was found in the insomnia subfactor score between two groups （Wald χ²=0.819， P=0.366）. Significant time effects were reported on plasma IL-6 and IL-10 levels in both groups （Wald χ²=21.792， 5.242， P<0.05 or 0.01）. Compared with baseline data， a reduction in plasma IL-6 levels was detected in both groups （Wald χ²=22.015， 6.803， P<0.01）， and an increase in plasma IL-10 levels was reported in study group （Wald χ²=5.118， P=0.024） after 4 weeks of treatment. ConclusionEscitalopram combined with tcVNS therapy is effective in improving depressive symptoms， anxiety/somatization symptoms and sleep quality in patients with MDD. Additionally， it helps reduce plasma IL-6 levels and increase IL-10 levels. ［Funded by Shaanxi Provincial Key Research and Development Program-General Project （number， 2023-YBSF-185）， www.clinicaltrials.gov number， NCT04037111］

Neutralizing antibodies have been designed to specifically target and bind to the receptor binding domain (RBD) of spike (S) protein to block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from attaching to angiotensin converting enzyme 2 (ACE2). This study reports a distinctive nanobody, designated as VHH21, that directly catalyzes the S-trimer into an irreversible transition state through postfusion conformational changes. Derived from camels immunized with multiple antigens, a set of nanobodies with high affinity for the S1 protein displays abilities to neutralize pseudovirion infections with a broad resistance to variants of concern of SARS-CoV-2, including SARS-CoV and BatRaTG13. Importantly, a super-resolution screening and analysis platform based on visual fluorescence probes was designed and applied to monitor single proteins and protein subunits. A spontaneously occurring dimeric form of VHH21 was obtained to rapidly destroy the S-trimer. Structural analysis via cryogenic electron microscopy revealed that VHH21 targets specific conserved epitopes on the S protein, distinct from the ACE2 binding site on the RBD, which destabilizes the fusion process. This research highlights the potential of VHH21 as an abzyme-like nanobody (nanoabzyme) possessing broad-spectrum binding capabilities and highly effective anti-viral properties and offers a promising strategy for combating coronavirus outbreaks.
Single-Domain Antibodies/immunology* ; Spike Glycoprotein, Coronavirus/metabolism* ; SARS-CoV-2/immunology* ; Animals ; Humans ; Antibodies, Neutralizing/immunology* ; Camelus ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Angiotensin-Converting Enzyme 2

[Objective]To investigate the chemical compositions,antioxidant and anti-inflammatory activities of Jiangshan Polygonatum sibiricum alcoholic extract(PSAE)in vitro.[Methods]The chemical compositions of PSAE were identified by ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MSE),its antioxidant activity was studied,and in vitro experiments were conducted to determine its effect on lipopolysaccharide(LPS)-induced THP-1 cells.Molecular docking was further used to validate the results.[Results]PSAE contained 17 chemical compositions,including 5 flavonoids,5 saponins,3 lignans,1 phenolic acid,1 steroid and 2 other compositions.In vitro experiments showed that PSAE possessed great antioxidant activity.Besides,PSAE could increase the viability of LPS-induced THP-1 cells,significantly decrease the levels of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in cell supernatants and the expression of NOD-like receptor thermal protein domain associated protein 3(NLRP3),apoptosis-associated speck-like protein containing CARD(ASC)and cysteinyl aspartate specific proteinase-1(Caspase-1).Molecular docking results showed that 16 of the 17 chemical compositions detected in PSAE had good docking activities with the core targets of NLRP3,ASC and Caspase-1.[Conclusion]PSAE has great antioxidant and anti-inflammatory activities,and the main active compositions may be flavonoids and saponins.

Objective:To investigate clinical and histopathological features of adult erythema nodosum (EN) .Methods:Clinical data were collected from 54 adult inpatients with histopathologically confirmed EN in Department of Dermatology and Venereology, the First Affiliated Hospital of Wannan Medical College from November 2019 to July 2022, and analyzed retrospectively.Results:Among the 54 EN patients, there were 6 males and 48 females, their ages were 42.50 ± 11.68 years (range, 18 - 73 years), and their disease course ranged from 1 day to 10 years; 30 patients (55.56%) were diagnosed with idiopathic EN, and 24 (44.44%) with secondary EN. The most common etiological factor in secondary EN was infection (17 cases), including respiratory tract infection (9 cases), tuberculosis infection (6 cases), upper respiratory tract infection comorbid with active hepatitis B virus infection (2 cases) ; the following common etiological factor was connective tissue disease (7 cases), including Behcet′s syndrome (4 cases), Sj?gren′s syndrome (1 case), and undifferentiated connective tissue diseases (2 cases). The patients′ ages were significantly younger in the secondary EN group (38.33 ± 12.15 years) than in the idiopathic EN group (46.17 ± 10.20 years, t = 2.58, P = 0.013). All patients had skin lesions on their lower limbs, lesions were limited to both lower limbs in 24 patients with idiopathic EN and 12 with secondary EN, and the proportion of patients with lesions limited to both lower limbs was significantly lower in the secondary EN group than in the idiopathic EN group ( χ2 = 5.44, P = 0.020). Compared with the idiopathic EN group, the secondary EN group showed significantly increased white blood cell counts ([7.56 ± 2.46] × 10 9/L vs. [6.04 ± 1.60] × 10 9/L, t = 2.62, P < 0.05) and C-reaction protein levels (34.34 ± 46.48 mg/L vs. 11.45 ± 18.13 mg/L, t = 2.28, P < 0.05). In the idiopathic EN group, 23 patients mainly showed histopathological features of septal panniculitis, while 17 patients in the secondary EN group mainly showed histopathological features of mixed panniculitis or lobular panniculitis, and the proportion of patients with histopathological features of mixed panniculitis or lobular panniculitis was significantly higher in the secondary EN group than in the idiopathic EN group ( χ2 = 12.18, P < 0.001) . Conclusion:EN was more common in female adults; idiopathic EN was the most common type, and secondary EN may be a cutaneous sign of systemic diseases; for EN patients at a relatively young age, with lesions involving both lower limbs or more sites, higher white blood cell counts and C-reaction protein levels, and histopathological manifestations of lobular panniculitis, systemic examinations were required to rule out underlying causes.

Objective:To investigate the clinical manifestation, pathological types, treatment and prognosis of primary tracheobronchial tumors in children.Methods:We retrospectively studied the primary tracheobronchial tumors patients who diagnosed from May 2009 to Jan 2021 in Guangzhou Women and Children Medical Center. The clinical manifestations, pathological types, therapeutic methods and prognosis were analyzed.Results:There were 15 patients identified as the primary tracheobronchial tumors, including synovial sarcoma (1 case), pulmonary inflammatory myofibroblastic tumor(IMT 4 cases), mucoepidermoid carcinoma(7 cases), infantile hemangioma (1 case), Ewing's sarcoma (1 case). Respiratory symptoms are the most complaint at the time of diagnosis including 15 patients with cough, 2 with hemoptysis, and 1 with dyspnea. Endoscopic treatment of tracheobronchial tumors was performed under extracorporeal membrane oxygenation (ECMO) support in 1 patient. Sleeve lobectomy was performed in 3 patients, lobectomies in 6, and local tumor resections in 4 patients including 2 patients suffered second surgery due to tumor recurrence.Conclusion:The clinical manifestations of the primary tracheobronchial tumors in children are nonspecific. Complete resection led to excellent outcome.

Objective:To investigate the influencing factors of hyperuricemia(HUA) and explore early intervention of metabolic diseases.Methods:A total of 70 523 participants were selected from the database of check-ups in 2016. Univariate analysis and logistic regression analysis were used to identify related factors of HUA. Correspondence analysis was performed for the aggregation of different levels of uric acid(UA) and related factors. The mediating effect of mean blood pressure(MBP) between abnormal metabolic indicators and abnormal renal function was tested.Results:The age, sex, occupation, body mass index(BMI), systolic blood pressure, diastolic blood pressure, blood urea nitrogen(BUN), creatinine(Cr), estimated glomerular filtration rate(eGFR), fasting plasma glucose(FPG), total cholesterol(TC), triacylglycerol(TG), high density lipoprotein-cholesterol(HDL-C), low density lipoprotein-cholesterol, plasma viscosity were significantly related to HUA( P<0.001). Logistic regression analysis showed that youth, male, hypertension, TC, TG, and Cr were risk factors for HUA, while HDL-C was a protective factor for HUA( P<0.001). Correspondence analysis showed that during the gradual increase of UA, TC was the first to appear abnormal, followed by hypertension and TG, and the increase of Cr appeared last. Mediating effect showed that in changes of UA, the mediating effects of MBP on TC, TG, and HDL-C were 36.35%, 12.63%, and 9.41%, respectively. In changes of eGFR, the mediating effects of MBP on TC, TG and HDL-C were 30.20%, 27.70%, and 6.13%, respectively. Conclusions:UA is positively correlated with blood pressure, TC, and TG, and inversely with HDL-C. TC and TG have an impact on renal impairment, in which MBP plays a mediating role.

Objective To evaluate the predictive role of TEL/AML1 fusion gene in protocol CCLG-ALL-2008 and to identify relevant factors influencing the outcome of ALL with TEL/AML1 fusion gene. Methods Ninety-nine patients with ALL harboring TEL/AML1 fusion gene (positive) and 329 cases without any specific fusion genes (negative) at diagnosis of B-lineage ALL from June 2008 to December 2014 were enrolled and their clinical and biological features were analyzed. Following-up ended in October 2015, the survival status was calculated by K-M curve and prognostic factors were analyzed by COX model. Results There were no differences between the two groups in age, white blood cell at the diagnostic stage, and treatment responses at 4 time points, namely, prednisone good response on day 8, M3 status of BM on D15, and the minimal residual disease (MRD) more than 1.0×10-3 on day 33 and 12th week. During the follow-up period, the relapse rate was lower in the positive group than that in the negative group (14/99 vs 69/329), the mortality rate of the negative group was twice of that in the positive group (55/329 vs 8/99). The five-year overall survival (OS) rate, relapse-free survival (RFS) rate and event-free survival (EFS) rate of the positive group were (86.1 ± 4.9)%, (80.7 ± 5.1)% and (78.9 ± 5.1)%, respectively, and (79 ±2.8)%, (72± 3.1)%, and (69.6+ 3.1)% for the negative group as well. COX regression analysis indicated that relapse and MRD level at the 12th week were independent prognostic factors on OS, RFS, and EFS (P<0.05) for the two groups. Conclusions TEL/AML1 fusion gene could be regarded as a relatively good indicator of risks in ALL children treated by CCLG-ALL-2008 protocol. ALL patients with TEL/AML1 are recommended to receive more intensive therapy including hematopoietic stem cell transplantation when the patients were high level of MRD on the 12th week after treatment.

Objective:To investigate the effect of Superfine Cordyceps militarisv Powder on the immune functions of the mice,and to provide basis for improving the utilizable ratio of Cordyceps militaris.Methods:A total of 40 mice were randomly divided into negative control group,low dose (0.166 5 g·kg-1),middle dose (0.333 3 g·kg-1),and high dose (0.999 9 g·kg-1) of Superfine Cordyceps militaris Powder groups,and there were 10 mice in each group.The mice in different doses of Superfine Cordyceps militaris Powder groups were administered with the Superfine Cordyceps militaris Powder for 30 d by intragastric infusion respectively,whereas,the mice in negative control group were administered with the same volume of water for 30 d by intragastric infusion.The body weights,the spleen indexes and thymus indexes of the mice in various groups were measured;the lymphocyte transformation abilities of the mice in various groups were observed by lymphocyte transformation experiment;the levels of delayed-type hypersensitivity reaction of the mice were examined with toe incrassation;the number of antibody forming cells,phagocytic rate and phagocytic index of chicken erythrocytes phagocytized by peritoneal macrophages of the mice were detected.Results:Compared with negative control group,the body weights,the spleen indexes a nd thymus indexes of the mice in different doses of Superfine Cordyceps militaris Powder groups had no significant differences (P>0.05).The lymphocyte transformation abilities of the mice in middle and high doses of Superfine Cordyceps militarisPowder groups were higher than that in negative control group(P<0.05).The levels of delayed-type hypersensitivity reaction of the mice in middle and high doses of Superfine Cordyceps militaris Powder groups were higher than those in low dose of Superfine Cordyceps militaris powder group and negative control group(P<0.05).The numbers of antibody forming cells of the mice in low,middle and high doses of Superfine Cordyceps militaris Powder groups were higher than that in negative control group(P<0.05).The phagocytic rates and phagocytic indexes of chicken erythrocytes phagocytized by peritoneal macrophage of the mice in low,middle and high doses of Superfine Cordyceps militaris Powder groups were higher than that in negative control group(P<0.05).Conclusion:Superfine Cordyceps militaris Powder can strengthen the immune functions of the mice,and the recommended doses are 0.333 3 and 0.999 9 g·kg-1.

OBJECTIVETo investigate the function of repair gene LIG4 in radiosensitivity enhancement of rectal cancer cells by curcumin.

METHODSHuman rectal cancer cells HT-29 were cultured in normal. LIG4-overexpression HT-29 cells and blank control plasmid HT-29 cells were established by gene transfection. Both kind of HF-29 cells were further randomly divided into curcumin group, radiotherapy group, curcumin plus radiotherapy group (combined group) and control group. The growth inhibition and apoptosis of cells were detected by MTT and Annexin V/PI respectively. Change of tumor volume was observed in nude mouse xenograft model, and the apoptosis of tumor cells was analyzed by TUNEL.

RESULTSRegarding blank control plasmid HT-29 cells, the growth inhibition rate and apoptosis rate in combined group were significantly higher than those in radiotherapy group(all P<0.05); tumor volume of nude mouse in combined group was significantly smaller than that in radiotherapy group, and the apoptotic index in combined group was significantly higher than that in radiotherapy group (all P<0.05). However, regarding LIG4-overexpression HT-29 cells, the growth inhibition rate and apoptosis rate were not significantly different between combined group and radiotherapy group(all P>0.05); the tumor volume of nude mouse and the apoptotic index were also not significantly different between combined group and radiotherapy group (all P>0.05).

CONCLUSIONDown-regulation of LIG4 is an important mechanism of radiosensitivity enhancement of rectal cancer cells by curcumin.

Objective To evaluate the prognostic factors in predicting relapse of childhood acute lymphoblastic leukemia (ALL) treated with CCLG-2008 protocol. Methods From December 1st 2008 and December 31st 2012, 358 patients diagnosed with ALL and treated with the CCLG-ALL 2008 protocol were enrolled in this study. All patients were followed up until September 1st, 2015. Prognostic impact of clinical features, response to treatment, biological features were analyzed and multivariate analysis of predicted value was performed by Cox-regression analysis. Results After treatment of CCLG-ALL 2008 protocol, 79 patients suffered from relapse. The relapse rate in the standard-risk, intermediate-risk and the high-risk groups were 13.3%, 17.6%, and 41.3%, respectively (P?100×109/L, non-remission in 15th day of induction (M3), the level of minimal residual disease (MRD) on 12w (12w-MRD)?>10-4 were signiifcantly higher, their corresponding hazard ratio were 3.17 (1.58?~?6.36), 1.87 (1.07?~?3.30), and 1.90 (1.12?~?3.20), respectively (P?10-4 were the independent prognostic factors for childhood B-ALL.