[Adult-onset immunodeficiency induced by anti-interferon-γ autoantibodies: report of 13 cases].

Objective: To investigate the clinical characteristics of a group of patients with adult-onset immunodeficiency (AOID) induced by anti-interferon-γ autoantibodies (AIGA). Methods: Thirteen cases of AOID in a northern China medical center (Peking Union Medical College Hospital) from October 2020 to April 2022 were included. Data comprising clinical manifestations, laboratory results, infection sites and pathogens were collected. Results: Among the 13 patients, 5 were male. The median age of disease onset was 47 (14 to 71) years. The median time from symptom onset to diagnosis was 4 years (1 to 8 years). Four patients were from northern China, and 9 from southern China. Common symptoms included lymphadenopathy (13/13), fever (12/13), respiratory tract symptoms (12/13), and weight loss (11/13). Laboratory tests showed increased levels of white blood cell count (9/13), neutrophil count and proportion (9/13), erythrocyte sedimentation rate (ESR) (12/13), and C reactive protein (CRP) (11/13). The median plasma titers of AIGA upon diagnosis were 5681(3194, 13246). Sites of infection included lungs (12/13), lymph nodes (9/13), bones and joints (9/13), skin and soft tissue (7/13), blood flow and bone marrow (4/13), and glands (3/13). Most patients had nontuberculous mycobacteria (NTM) (12/13) infection. Seven patients had more than one pathogen. Conclusions: AOID also affects patients visiting northern China hospitals. AIGA screening is recommended among patients with disseminated NTM infections or recurrent infections.

[Hypomethylation of DAPL1 associated with prognosis of lung cancer patients with EGFR Del19 mutation].

Objective: To investigate the effect of apoptosis-associated protein kinase-like 1 (DAPL1) hypomethylation on prognosis of lung cancer patients with epidermal growth factor receptor gene exon 19 deletion (EGFR Del19) mutation. Methods: The clinicopathological data of lung cancer patients in databases of genomic data sharing (GDC) TCGA lung adenocarcinoma, TCGA lung adenocarcinoma, and TCGA lung cancer were collected to analyze the effect of DAPL1 methylation level on the prognosis of patients with EGFR Del19 mutation. Linear regression model was used for correlation analysis, Kaplan-Meier method was used to draw the survival curve, and the difference of survival curve between the two groups was tested by Log rank. Results: In GDC TCGA lung adenocarcinoma, TCGA lung adenocarcinoma and TCGA lung cancer databases, the 5-year survival rates of lung cancer patients with high DAPL1 expression (31.9%, 27.5% and 33.0%, respectively) were higher than those with low DAPL1 expression (11.0%, 11.6% and 13.8%, respectively). The differences were statistically significant (P=0.006, 0.028 and 0.025, respectively). The median expression levels of DAPL1 in patients with EGFR Del19 mutation (12.8, 2.75 and 2.9, respectively) were higher than those in patients with other EGFR mutations (11.6, 1.75 and 1.8, respectively, P<0.05). In TCGA lung adenocarcinoma and TCGA lung cancer database, the 5-year survival rate of lung cancer patients with lower DAPL1 methylation levels (22.4% and 16.4%, respectively) were higher than those of lung cancer patients with higher DAPL1 methylation levels (15.1% and 14.2%, respectively), with statistical significance (P<0.05). The expression level of DAPL1 was positively correlated with the EGFR mutant subtype (r=0.909, P<0.05), and negatively correlated with DNA methylation (r=-0.891, P<0.05). The expression of DAPL1 in lung cancer patients was regulated by DNA methylation, which affected the prognosis of lung cancer patients. Conclusion: High DAPL1 expression, or hypomethylation, is associated with lung cancer EGFR Del19 mutation subtype, and DAPL1 hypomethylated lung cancer patients have longer overall survival.

[Gender differences in cardiovascular risk factors in patients with acute myocardial infarction in China].

Objective: To understand gender differences of cardiovascular risk factors in patients with acute myocardial infarction (AMI) in China. Methods: A total of 26 592 patients with AMI from 107 hospitals in 31 provinces in China from January 1, 2013 to September 30, 2014 were included. Self-designed questionnaire was used to collect patients' age, gender, height, weight, type of AMI, medical history of cardiovascular and cerebrovascular diseases, medication history, lifestyle and AMI risk factors, including high blood pressure, diabetes, dyslipidemia, overweight and/or obesity, smoking history and family history of early onset coronary artery disease. A total of 24 394 patients with complete clinical data were included in the analysis, and gender differences in cardiovascular risk factors were analyzed in all and subgroups with different characteristics. Results: The patients were (62.2±13.8) years old, including 18 162 (74.5%) males and 18 209 (74.6%) ST-segment elevation myocardial infarction (STEMI). The age of male patients was (60.2±13.7) years, which was younger than that of female patients [(68.2±12.3) years]. The body mass index of male patients was (24.2±3.0) kg/m2, which was higher than that of female patients [(23.8±3.4) kg/m2]. The proportions of patients with overweight and/or obesity, smoking history, dyslipidemia, family history of early onset coronary heart disease, fatty diet and history of AMI were 51.8%, 55.2%, 7.2%, 3.8%, 80.4% and 7.7%, which were higher than those of females (45.9%, 9.9%, 5.8%, 2.3%, 65.0% and 5.9%, respectively]. The proportions of hypertension, diabetes, physical inactivity and stroke history were 46.5%, 17.2%, 77.8% and 8.5%, respectively, which were lower than those in female patients [61.4% (3 829 cases), 24.8%, 81.7% and 11.1%, respectively] (all P values<0.05).The proportions of peripheral vascular diseases history in male and female patients were 0.6% and 0.7%, respectively, with no statistical significance in difference (P>0.05). Subgroup analysis showed inconsistent results comparing to analysis of all patients: there were no statistical significance in gender differences as for the proportion of dyslipidemia in the non-ST-segment elevation MI group, the proportion of family history of early onset coronary heart disease in the young and middle aged groups, the proportion of overweight and/or obesity, and the proportion of physical inactivity in the elderly group (all P values>0.05). Conclusions: There are gender differences in cardiovascular risk factors among Chinese patients with acute myocardial infarction. Hypertension and diabetes are more common in women, and overweight and/or obesity, fatty diet and smoking are more common in men.

[Epidemiological and virus molecular characterization of dengue fever outbreak in Hunan province, 2018].

Objective: To analyze the epidemiological and etiological characteristics of a dengue fever outbreak in Hunan province in 2018. Methods: Real-time PCR assay was performed for the laboratory diagnosis of 8 suspected dengue fever cases. Etiological surveillance was performed in 186 suspected dengue fever cases and fever cases who had close contacts with dengue fever patients. C6/36 cells was used for the virus isolation from acute phase serum. By sequencing the full length of E genes of 15 dengue virus strains, phylogenetic analysis was performed based on the sequences obtained, including reference sequences from the NCBI GenBank database, the serotypes and gene subtypes of the virus were analyzed to trace the possible source of transmission. An emergency monitoring of vector density and a retrospective survey of sero-epidemiology in healthy population were conducted in the epidemic area. Results: In the serum samples of 8 suspected patients, 6 were dengue virus RNA positive, and 4 were NS1 antigen positive. In 186 suspected patients, 96 were dengue virus nucleic acid, NS1 antigen or antibody positive in etiological test. A total of 64 dengue virus strains were isolated. The phylogenetic analysis showed that all the dengue virus strains belonged to type 2, which might be from Guangdong or Zhejiang provinces. The Bretub index was up to 65, indicating an extremely high risk of transmission. The positive rate of the dengue virus IgG antibody was 0.53%(2/377) in retrospective survey of 377 healthy people. Conclusion: The field epidemiologic and the molecular genetics analyses showed the outbreak of dengue fever in Hunan in 2018 was caused by imported cases and dengue virus 2.

[Clinical application of self-made drainage tubes in different layers of soft tissue for negative-pressure wound therapy in 33 patients].

From January 2014 to June 2018, 28 patients with different types of deep soft tissue injury or infection were admitted to the Affiliated Jiangyin Hospital of Medical College of Southeast University; 5 patients were admitted to the Zhengzhou First People's Hospital. There were 24 males and 9 females, aged 18-89 (40±20) years. Disposable suction tubes with holes cut on side walls were used as self-made drainage tubes. The authors placed the self-made drainage tubes on different deep soft tissue layers and wound surfaces after debridement. The effective drainage sections of the wound surface drainage tubes were wrapped with silver ion antimicrobial functional active dressings. Bio-permeable membrane was used to close the operative area. The drainage tubes in the deep layer of wound and wound surface were connected in parallel by a tee and connected to wall-hanging medical negative-pressure suction device to conduct negative-pressure wound treatment at -20.0 to -10.6 kPa. The deep drainage tubes were usually removed or changed 4 or 5 days after surgery.The drainage tubes in the wound surface were synchronously replaced when removing or replacing he drainage tubes in the deep layer of wound. On 4 to 15 days after surgery, the deep drainage tubes were removed. On 8 to 25 days after surgery, the wound surface drainage tubes were removed. Then the treatment was changed to a conventional dressing change until the wounds were completely healed or the wound bed was ready for skin grafts or tissue flaps. The indwelling time of deep drainage tubes in this group of patients was (6.2±2.8) days, and the indwelling time of wound surface drainage tubes was (12.0±3.0) days. The wound healing time was (22±5) days, the hospital stay time was (29±7) days, and wound bacteria were reduced from 6 species and 11 strains before treatment to 3 species and 4 strains after treatment. No adverse events such as wound bleeding, irritative pain, and chronic sinus occurred during treatment. Twenty-three patients were followed up for 13 to 28 months, no treatment-related complications were observed.

[Acute respiratory failure due to Pneumocystis pneumonia in connective tissue disease patients: clinical manifestation and prognostic factors related to hospital mortality].

Objective: To investigate the clinical manifestations and prognostic factors of hospital death in connective tissue disease patients with acute respiratory failure caused by pneumocystis pneumonia (PCP) admitted to two medical intensive care units(MICU). Methods: A retrospective review was conducted for all connective tissue disease (CTD) patients with acute respiratory failure from PCP in MICU of 2 academic medical centers between 2010 and 2015. The patients were divided into survivors and non-survivors. Demographic and clinical data, including laboratory, radiological and microbiological findings, as well as therapy, clinical course, mortality and prognostic factors of hospital mortality were included in the analysis. Logistic regression models were used to determine the effect of prognostic factors on hospital death after adjusting for covariates of which the p values were less than 0.1. Results: A total of 41 patients with connective tissue disease were identified. The PaO(2)/FiO(2) ratio (PFR) on ICU admission was 120 mmHg(55-180 mmHg, 1 mmHg=0.133 kPa). Common clinical features included dyspnea (90.2%, 37/41), fever (87.8%, 36/41) and dry cough(65.9%, 30/41). 58.5%(24/41) and 17.1%(7/41) patients were co-infected by CMV and aspergillus, respectively. The overall mortality rate was 75.6%(31/41). Compared with survivors, the age, APACHEⅡ score and incidence of barotrauma in non-survivors were higher (39±17 vs 58±15, t=3.018, P=0.002), (15±6 vs 19±5, t=2.528, P=0.019), (0/10 vs 12/31, χ(2)=5.473, P=0.021), while PFR on ICU admission was lower in non-survivors (172±68 vs 116±49, t=-1.893, P=0.007). Logistic analysis showed that PFR on ICU admission was the independent risk factor for hospital death (OR=1.004, 95%CI: 1.002-1.006, P=0.048). Conclusions: Mortality rate among patients with acute respiratory failure secondary to CTD related PCP is still high, and the poor prognostic factors of hospital mortality included PFR on ICU admission and barotrauma.

Microstructural visual pathway abnormalities in patients with primary glaucoma: 3 T diffusion kurtosis imaging study.

AIM: To evaluate microstructural visual pathway damage in patients with primary glaucoma (PG) by using 3 T diffusion kurtosis imaging (DKI). MATERIALS AND METHODS: The study was approved by the ethics committee, and all participants provided written informed consent. Ten patients with PG were examined. Twenty healthy individuals served as control subjects. DKI was performed with a GE Silent 3 T magnetic resonance imaging (MRI) unit. Mean diffusivity (MD), fractional anisotropy (FA), and mean kurtosis (MK) maps were automatically created. Mean MK, MD, and FA values were calculated for each part of the visual pathway. RESULTS: No abnormalities in the shape and signal intensity were observed along the entire visual pathway in patients and the control group on the conventional MRI. Higher MD, and lower MK and FA were observed in the optic nerves (ON), lateral geniculate nucleus (LGN), optic radiations (OR), and visual cortex (VCx) of PG patients, as compared with control subjects. A significantly higher MD was observed in the ON (p<0.01), and significantly lower FA was observed in OR (p<0.05). Additionally, significantly lower MK was observed in the ON, LGN, and VCx, except for OR (p<0.01). Changes of DKI parameters in the ON were the most distinct. CONCLUSION: Glaucoma is a complex neurological disease that affects the entire visual pathway. MK derived from DKI would be a better biomarkers than FA and MD in detecting microstructural damage.

Transparent Tiger barb Puntius tetrazona, a fish model for in vivo analysis of nocardial infection.

Nocardiosis afflicts multiple species of cultured fish, resulting in substantial economic losses to the aquaculture industry, however, lack of detailed knowledge on disease pathogenesis has hampered the development of effective prevention and control strategies. In this study, we injected a green fluorescent protein (GFP)-labeled Nocardia seriolae strain into a transparent mutant strain of Tiger barb (Puntius tetrazona) to monitor tissue pathogen accumulation and tissue damage in vivo, and to clarify the relationship between pathogenic processes and overt symptoms. GFP-labeled bacteria were phagocytized by leukocytes and could proliferate within these cells, which in turn led to leukocyte aggregation, leukocyte death, and granuloma formation. In addition, intracellular bacteria could permanently colonize various tissues via leukocyte circulation, causing multi-organ infection as revealed by changes of tissue transparency. Histology revealed granulomatous lesions in organs such as muscle, kidney, and spleen that was corresponded to the tissue opacities in vivo. Confocal microscopy confirmed massive accumulations of GFP-labeled bacteria within these granulomas, which often contained a necrotic core. Tiger barb transparency allows for real-time observation of in vivo pathological changes within the same animal, and the pathogenic process can be evaluated based on the shape and size of body opacities. Thus, transparent Tiger barb is a promising model to study the pathogenesis of nocardiosis.

[Clinical features of acute respiratory failure due to pneumocystis pneumonia in non-HIV immunocompromised patients].

Objective: To examine the clinical features of patients with acute respiratory failure (ARF) caused by pneumocystis pneumonia (PCP) admitted into two medical intensive care units (ICU) in non- human immunodeficiency virus (HIV) infected immunocompromised patients. Methods: A retrospective review was conducted among 92 non-HIV patients with ARF caused by PCP in medical ICU of Peking Union Medical College Hospital and China-Japan Friendship Hospital between Jan 2010 and Dec 2015. Patient characteristics, clinical presentation, laboratory and radiological findings, complications, as well as therapy and mortality were included in the analysis. Results: All patients were immunocompromised before PCP, among which 69.6% (64/92) patients were suffered from autoimmune disease. The diagnosis of PCP was made by the identification of P. jiroveci organisms with Giemsa or polymerase chain reaction in specimens of bronchoalveolar lavage, sputum or tracheal aspiration. The Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ was high (19±5) and the partial pressure of oxygen/ fraction of inspiration oxygen(PaO2/FiO2) ratio was low[(139.6±65.4) mmHg]on ICU admission, with all patients diagnosed as acute respiratory failure during ICU stay. Radiologic findings showed bilateral diffused ground glass opacity (94.6%, 87/92). All patients received Compound Sulfamethoxazole (SMZ/TMP) and only 3.3% (3/92) patients were not given conjunctive corticosteroid. 57.6% (53/92) and 21.7% (20/92) patients were coinfected by cytomegalovirus (CMV) and aspergillos. Invasive ventilatory support was required in 90% (81/90) patients. 22% (18/82) patients used non-invasive positive pressure ventilation (NPPV) on ICU admission but most of them (83.3%, 15/18) failed and switched to invasive positive pressure ventilation (IPPV). Median ICU and hospital length of stay were 11 and 17 days, respectively. The overall hospital mortality rate was 76.1% (70/92). Conclusions: Among patients with ARF secondary to non-HIV related PCP, autoimmune system diseases are the most common primary diagnosis. The clinical manifestations were severe and coinfections are common, with poor prognosis.

A self-sustaining atomic magnetometer with τ(-1) averaging property.

Quantum measurement using coherent superposition of intrinsic atomic states has the advantage of being absolute measurement and can form metrological standards. One example is the absolute measurement of magnetic field by monitoring the Larmor precession of atomic spins whilst another being the Ramsey type atomic clock. Yet, in almost all coherent quantum measurement, the precision is limited by the coherence time beyond which, the uncertainty decreases only as τ(-1/2). Here we show that by non-destructively measuring the phase of the Larmor precession and regenerating the coherence via optical pumping, the self-sustaining Larmor precession signal can persist indefinitely. Consequently, the precision of the magnetometer increases with time following a much faster τ(-1) rule. A mean sensitivity of 240 from 1 Hz to 10 Hz is realized, being close to the shot noise level. This method of coherence regeneration may also find important applications in improving the performance of atomic clocks.

Caffeine inhibits the growth of glioblastomas through activating the caspase-3 signaling pathway in vitro.

OBJECTIVE: To study the effects and associated mechanisms of caffeine on cell viability, cycle dynamics, proliferation and apoptosis both in glioblastoma C6 and U87MG cells. MATERIALS AND METHODS: Cell livability in presence or absence of caffeine was detected by the methyl thiazolyl tetrazolium (MTT) colorimetric assay. Flow cytometric analysis was conducted to investigate the cell cycle dynamics and Cell Counting Kit-8 (CCK-8) was used to further study the proliferation of C6 and U87MG glioblastoma cells after treated with caffeine or DMSO. To study the influence of caffeine on apoptosis of glioblastoma C6 and U87MG cells, the value of apoptosis ratio (AR) was calculated by flow cytometry detection. Western blot analysis was used to detect the expression of apoptosis-related factors, including Caspase-3, Cyt-C, Bax and Bcl-2. RESULTS: Caffeine at 1 mM reduced the cell viability of the both rat C6 and human U87MG glioblastoma cells to less than 70%. Flow cytometry detection found that caffeine remarkably arrested the C6 and U87MG cells in G0/G1 phase (C6, U87MG: p<0.01, p<0.05). Nevertheless, the percentage of cells in S phase obviously decreased in the caffeine-treated group, when comparing to that of the normal control (C6, U87MG: p<0.01, p<0.01). CCK-8 assay demonstrated that significant decreases in the number of glioblastoma cells were observed in caffeine treatment group, when comparing to that of the normal control (C6, U87MG: p<0.01, p<0.05). Flow cytometric analysis also found that the application of caffeine induced much higher apoptosis of glioblastoma cells, compared with the normal control (C6, U87MG: p<0.01, p<0.05). Furthermore, caffeine markedly reduced the expression of Bcl-2 (C6, U87MG: p<0.01, p<0.01), and promoted the expression of Cyt-C (C6, U87MG: p<0.05, p<0.01) and Caspase-3 (C6, U87MG: p<0.01, p<0.01), comparing to the normal control. CONCLUSIONS: Caffeine inhibits proliferation and induces apoptosis of C6 and U87MG cells, leading to an imbalance in the ratio of proliferation and apoptosis. The apoptosis might be promoted by the motivation of the caspase-3 signaling pathway, which is induced by the release of Cyt-C as well as the elevated rate of Bax/Bcl-2.

Impact of three-dimensional endoanal ultrasound on the outcome of anal fistula surgery: a prospective cohort study.

AIM: The aim of the study was to evaluate the impact of three-dimensional endoanal ultrasound (3D-EAUS) on postoperative outcome in patients with anal fistula. METHOD: This prospective study compared clinical and functional outcomes of patients with and without preoperative 3D-EAUS examination 1 year after anal fistula surgery. Patients were prospectively followed and evaluated by a standardized protocol including physical examination, the Wexner Incontinence Score (WIS) and anorectal manometry, at baseline and 1 year after surgery. RESULTS: A total of 196 patients were enrolled. There were no significant differences in demographic and operative parameters, except for operation time, between the two groups. At 1 year follow-up, the overall recurrence rates were 8.8% (9/102) in the 3D-EAUS group and 13.8% (13/94) in the examination under anaesthesia (EUA) group. In the subgroup of patients with complex fistulae, the recurrence rate was numerically lower in the 3D-EAUS group (12.8% vs 22.5%; P = 0.26). The WIS in the EUA group significantly worsened (0.35 ± 0.94 vs 1.07 ± 1.59; P = 0.003) with a decreased the number of fully continent patients (82.5% vs 55%; P = 0.008) while neither the WIS nor the proportion of fully continent patients changed in the 3D-EAUS group. Fewer patients in the 3D-EAUS group developed incontinence postoperatively (6.7% vs 33.3%; P = 0.012) and they had better maximum resting pressure and maximum squeeze pressure than the EUA group. CONCLUSIONS: Preoperative use of 3D-EAUS had a favourable impact on the outcome of surgical treatment for anal fistulae, especially in those with complex anal fistula. It should be routinely used in the clinical setting.

Loop-locked coherent population trapping magnetometer based on a fiber electro-optic modulator.

We have set up a coherent population trapping (CPT)-based magnetometer prototype with the D1 line of 87Rb atoms. The dichromatic light field is derived from a fiber electro-optic modulator (FEOM) connected to an external cavity laser diode. A CPT resonance signal with a 516 Hz linewidth is observed. By feeding back the derivative of the resonance curve to the FEOM with a proportional integral controller, of which the voltage output is directly converted to the measured magnetic field intensity, the resonance peak is locked to the environmental magnetic field. The measurement data we have achieved are well matched with the data measured by a commercial fluxgate magnetometer within 2 nT, and the sensitivity is better than 8 pT/√Hz in a parallel B field.

The effective method for investigation meridian tropism theory in rats.

This present work describes an effective new method for study traditional Chinese medicine (TCM) on meridian tropism (MT) theory, which plays an essential role in clinical selection of TCM according to syndromes and strengthens the therapeutic effects. The new thread included material basis foundation and its tissue distribution study. Xiheliu, the most popular TCM on heart tropism, was investigated by simple and accurate high performance liquid chromatography (HPLC) method. The analysis of plasma after oral administration the total flavonoid of Xiheliu (TFX) exhibited that tamarixetin and kaempferide had the highest concentration and approximately the highest level within 25 min. The mixture of them could last accelerating the urine excretion more than 7 h after a single dose and could not cause the disorder of ion in rats, which was observed in diuretic activity experiment. In view of the reported biological activities was consistent with the effects of Xiheliu, tamarixetin and kaempferide were likely to be the material basis of it. Tissue distribution study showed that the highest level of analytes was in heart, lung, kidney and liver, and most tissues reached maximum level at 30 min post-dose. Since liver was the most important blood-supply tissue, the result of this experiment was in accordance with the MT record of Xiheliu and confirmed that tamarixetin and kaempferide was the material bases of it on MT. This is the first report for the illumination of material basis and the mechanism of Xiheliu on MT by analysis the record of Xiheliu in Compendium of Materia Medica and experimental study.

Note: Generation of Raman laser beams based on a sideband injection-locking technique using a fiber electro-optical modulator.

Two phase-coherent Raman laser beams with a frequency offset of 6.835 GHz were generated by sideband injection-locking technique. A master diode laser was phase-modulated at 6.835 GHz by a fiber electro-optic modulator. A slave diode was injection-locked to the -1 sideband of the phase-modulated beam, and another diode was locked to the master laser carrier. This method produced stable and spatially separated Raman lasers with a large frequency shift range (>180 MHz). The relative linewidth of these two beams was ∼1 Hz, and the unwanted carrier mode was suppressed down to -24 dB. Stimulated Raman transitions and Ramsey fringes were driven by Raman lasers in a cold atomic beam.