Objective To analyze the adverse events(AEs)associated with linezolid in tuberculosis treatment reported in the FDA Adverse Event Reporting System(FAERS)database,assess its safety profile,and provide scientific evidence for ra-tional clinical use.Methods Reports of adverse events related to linezolid in tuberculosis treatment from Q1 2016 to Q1 2024 were extracted.The data were cleaned and pre-processed,and signal detection was performed using the Reporting Odds Ratio(ROR)and Information Component(IC)methods.Results A total of 1,135 linezolid-related AEs were identified,with the most common types being hospitalization(18.46％)and death(10.99％).The Results indicated that linezolid AEs primarily involved disorders of the blood and lymphatic system,as well as liver and biliary system diseases.Common adverse reactions in-cluded anemia,peripheral neuropathy,and optic neuropathy.Additionally,some adverse reaction signals not mentioned in the prescribing information were identified,such as polyneuropathy(ROR=75.25,IC025=5.8),toxic optic neuropathy(ROR=776.95,IC025=8.86),and hearing loss(ROR=14.66,IC025=3.26).Conclusion This study suggests that linezolid may be associated with some serious adverse reactions in tuberculosis treatment.It is recommended that patients on long-term linezolid therapy undergo regular neurological,ophthalmological,and auditory assessments to provide a more adequate basis for rational clinical use.

The recurrent neural network architecture improves the processing ability of time-series data. However, issues such as exploding gradients and poor feature extraction limit its application in the automatic diagnosis of mild cognitive impairment (MCI). This paper proposed a research approach for building an MCI diagnostic model using a Bayesian-optimized bidirectional long short-term memory network (BO-BiLSTM) to address this problem. The diagnostic model was based on a Bayesian algorithm and combined prior distribution and posterior probability results to optimize the BO-BiLSTM network hyperparameters. It also used multiple feature quantities that fully reflected the cognitive state of the MCI brain, such as power spectral density, fuzzy entropy, and multifractal spectrum, as the input of the diagnostic model to achieve automatic MCI diagnosis. The results showed that the feature-fused Bayesian-optimized BiLSTM network model achieved an MCI diagnostic accuracy of 98.64% and effectively completed the diagnostic assessment of MCI. In conclusion, based on this optimization, the long short-term neural network model has achieved automatic diagnostic assessment of MCI, providing a new diagnostic model for intelligent diagnosis of MCI.
Humans ; Bayes Theorem ; Neural Networks, Computer ; Algorithms ; Brain ; Cognitive Dysfunction/diagnosis*

Background::Cluster of differentiation 8 (CD8 T) cells play critical roles in eradicating human immunodeficiency virus (HIV)-1 infection, but little is known about the effects of T cells expressing CD8 at low levels (CD8 low) or high levels (CD8 high) on HIV-1 replication inhibition after HIV-1 invasion into individual. Methods::Nineteen patients who had been acutely infected with HIV-1 (AHI) and 20 patients with chronic infection (CHI) for ≥2 years were enrolled in this study to investigate the dynamics of the quantity, activation, and immune responses of CD3 +CD8 low T cells and their counterpart CD3 +CD8 high T cells at different stages of HIV-1 infection. Results::Compared with healthy donors, CD3 +CD8 low T cells expanded in HIV-1-infected individuals at different stages of infection. As HIV-1 infection progressed, CD3 +CD8 low T cells gradually decreased. Simultaneously, CD3 +CD8 high T cells was significantly reduced in the first month of AHI and then increased gradually as HIV-1 infection progressed. The classical activation of CD3 +CD8 low T cells was highest in the first month of AHI and then reduced as HIV-1 infection progressed and entered the chronic stage. Meanwhile, activated CD38 -HLA-DR +CD8 low T cells did not increase in the first month of AHI, and the number of these cells was inversely associated with viral load ( r = -0.664, P = 0.004) but positively associated with the CD4 T-cell count ( r = 0.586, P = 0.014). Increased programmed cell death protein 1 (PD-1) abundance on CD3 +CD8 low T cells was observed from the 1st month of AHI but did not continue to be enhanced, while a significant T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif (ITIM) domains (TIGIT) abundance increase was observed in the 12th month of infection. Furthermore, increased PD-1 and TIGIT abundance on CD3 +CD8 low T cells was associated with a low CD4 T-cell count (PD-1: r = -0.456, P = 0.043; TIGIT: r = -0.488, P = 0.029) in CHI. Nonetheless, the nonincrease in PD-1 expression on classically activated CD3 +CD8 low T cells was inversely associated with HIV-1 viremia in the first month of AHI ( r = -0.578, P = 0.015). Notably, in the first month of AHI, few CD3 +CD8 low T cells, but comparable amounts of CD3 +CD8 high T cells, responded to Gag peptides. Then, weaker HIV-1-specific T-cell responses were induced in CD3 +CD8 low T cells than CD3 +CD8 high T cells at the 3rd and 12th months of AHI and in CHI. Conclusions::Our findings suggest that CD3 +CD8 low T cells play an anti-HIV role in the first month of infection due to their abundance but induce a weak HIV-1-specific immune response. Subsequently, CD3 +CD8 low T-cell number decreased gradually as infection persisted, and their anti-HIV functions were inferior to those of CD3 +CD8 high T cells.

Objective:To evaluate clinical efficacy and safety of topical compound oleum lithospermi in the treatment of mild to moderate diaper dermatitis.Methods:A multicenter, randomized, positive-drug parallel-controlled clinical trial was conducted in 19 hospitals from July 2019 to August 2020. Children aged 0 - 12 months with mild to moderate diaper dermatitis were enrolled and randomly divided into 2 groups using a random number table: test group topically treated with compound oleum lithospermi, and control group topically treated with zinc oxide cream. The treatment was carried out 6 - 8 times a day for 7 days. Visits were scheduled on days 0 and 7, and total response rate and clinical healing time were evaluated. Changes in the dermatitis family impact (DFI) score were compared between the test group and control group, and adverse events were recorded. Statistical analysis was carried out by using independent-sample t test for normally distributed continuous data, Wilcoxon rank sum test for non-normally distributed continuous data, and chi-square test or Fisher′s exact test for unordered categorical data; survival curves were drawn, and log-rank test was used for comparisons between two groups. Results:A total of 343 children with diaper dermatitis were enrolled in this study. Among them, 31 children violated the protocol, so 312 were included in the per protocol set, including 157 in the test group and 155 in the control group, and all completed the visits on days 0 and 7. The total response rate was significantly higher in the test group (87.26%, 137/157) than in the control group (78.71%, 122/155; χ2 = 4.04, P = 0.044) . The clinical healing time was significantly shorter in the test group (5.33 days) than in the control group (6.13 days; χ2 = 4.67, P = 0.025) . After 7-day treatment, the DFI score significantly decreased in both the 2 groups compared with that before the treatment, but there was no significant difference in the DFI score between the 2 groups (test group: 4.02 ± 6.96, control group: 3.58 ± 5.90, Z = -0.39, P = 0.686) . The incidence of adverse events was 2.92% (5/171) and 5.45% (9/165) in the test group and control group respectively, and there was no significant difference between the 2 groups ( χ2 = 0.03, P = 0.865) . Conclusion:Compound oleum lithospermi can markedly reduce the clinical severity of diaper dermatitis, improve the total response rate, shorten the clinical treatment period, and improve the quality of life of children′s families with a favorable safety profile.

Objective:To analyze the genetic characteristics of Group A Streptococcus (GAS) isolated from the pharynx of children with scarlet fever-like erythema. Methods:Pharyngeal GAS isolates were collected retrospectively from children with scarlet fever-like erythema admitted in the Department of Dermatology, Beijing Children′s Hospital, Capital Medical University from June 2019 to February 2020.PCR and sequencing were used to detect emm genotyping and superantigen genes( speA, speB, speC, speF, speG, speH, speI, speJ, speK, speL, speM, ssa and smeZ) of the isolates.Data were compared by the chi-square test or Fisher′ s exact test between groups. Results:A total of 147 GAS strains were collected.The main emm genotypes were emm1.0 in 76 strains (51.70%) and emm12.0 in 60 strains (40.82%). Other 7 emm genotypes were all found in less than 5 strains.The detection rate of speF, smeZ, speG, speC, speB and ssa were as high as 100.00%(147/147 strains), 100.00%(147/147 strains), 99.32%(146/147 strains), 95.24%(140/147 strains), 94.56%(139/147 strains) and 92.52%(136/147 strains), respectively. speA, speJ, speI, speH and speM had a low detection rate of 51.70%(76/147 strains), 49.66%(73/147 strains), 32.65%(48/147 strains), 23.81%(35/147 strains) and 4.08%(6/147 strains), respectively.No speK and speL were detected.The frequencies of speA and speJ in emm1.0 strains (65/76 strains, 85.53% and 64/76 strains, 84.21%) were significantly higher than those in emm12.0 strains (4/60 strains, 6.67% and 6/60 strains, 10.00%). However, the frequencies of speH and speI in emm1.0 strains (7/76 strains, 9.21% and 2/76 strains, 2.63%) were significantly lower than those in emm12.0 strains (28/60 strains, 46.67% and 45/60 strains, 75.00%) (all P<0.001). Conclusions:At present, emm1.0 and emm12.0 are the main GAS strains isolated from the throat of children with scarlet fever-like erythema in Beijing, and emm1.0 is more common.There is a correlation between emm genotyping and the superantigen gene profile.Type 1 superantigen gene profile is significantly more frequently detected in emm1.0 strains than in emm12.0 strains.Type 2, 3 and 4 superantigen gene profiles are significantly more frequently detected in emm12.0 strains than in emm1.0 strains.

Objective To investigate the curative effect of mesalamine combined with trimebutine maleate in the treatment of diarrhea predominant irritable bowel syndrome .Methods According to the digital table ,112 patients with diarrhea predominant irritable bowel syndrome were randomly divided into control group and observation group , 56 cases in each group .The two groups were given conventional symptomatic treatment ,on this basis ,the control group recieved mesalamine treatment ,the observation group recieved mesalamine combined with trimebutine maleate treat -ment.The two groups were treated for 4 consecutive weeks.The main indicators,clinical efficacy and adverse reaction of the two groups were compared .Results The total effective rate of the observation group was 94.6％,which was significatnly higher than 78.6％of the control group (χ2 =3.925,P<0.05).The antidiarrheal time,stool recovery time between the two groups had statistically significant differences (t=19.337,18.068,all P<0.05).The mental status,emotional status,diet and sleep status in the two groups were all improved ,the differences were statistically significant(all P<0.05),which in the observation group improved more significantly than that in the control group , the differences were statistically significant(all P<0.05).The two groups had no other serious adverse reactions . Conclusion On the basis of conventional treatment ,mesalamine combined with trimebutine maleate in the treatment of diarrhea predominant irritable bowel syndrome can significantly improve clinical symptoms ,improve clinical curative effect,and it has good safety and great clinical significance .

Combined radiation-trauma injury is mainly observed in radiation treatment of cancer and radiation injury with traumatic patients. The prominent problem of combined radiation-trauma injury is delayed or prolonged wound healing. The mechanism of the impaired wound healing is complicated, and the current effective treatment method are limited. This paper reviews the mechanism and treatment of this impaired wound healing, including the cellular depletion, stromal cell dysfunction, aberrant collagen deposition, microvascular damage, as well as the targeted therapies for the impaired wound healing such as stem cell repletion, antioxidant therapy, transforming growth factor beta-1 ( TGF-β1 ) modulation, and implantable biomaterials. This paper is designed to provide a reference for further deep research on the mechanism and treatment of radiation-trauma injury.

Objective To investigate the correlation of endoscopic and pathological diagnosis of chronic atrophic gastritis( CAG) . Methods 108 patients diagnosed as CAG by gastroscopy were selected. Whether the results were consistent with the diagnosis between gastroscope and pathology were observed, and the diagnosis relationship between gastroscopic and histopathological features,and the relationship between CAG and Hp were observed,and the coincidence rates of the diagnostic results by using these two methods were calculated. Results 19 cases of chronic superficial gastritis( CSG) and 89 cases of CAG were diagnosed by pathologic biopsy,and 42 cases of CAG with intes-tinal metaplasia,13 cases with dysplasia. The coincidence rate of CAG between gastroscopic and pathological diagnosis was 82. 41%. 9 cases showed the gastric mucosa in rough and showed granular or nodular changes,meanwhile,7 cases of them with CAG were confirmed by histopathology , following 3 cases of them with intestinal metaplasia ( 33 . 33% ) and 1 case of them with heterosexual hyperplasia(11. 11%). 18 cases showed the change of the color of the gastric mucosa with red and white,and mainly in white,following vascular exposure tested by gastroscope. 13 cases of them (72. 22%) with CAG were confirmed by histopathology,4 cases of them with intestinal metaplasia(22. 22%) and 1 case of them with heterosexual hyperplasia(5. 56%). 14 cases showed gastric mucosal folds flat,thinning or even disappear tested by gastroscope. 10 cases of them(71. 43%) with CAG were confirmed by histopathology,following 4 cases of them with intestinal metaplasia(28. 57%) and 2 cases of them with heterosexual hyperplasia(14. 29%). When the three manifestations of gastroscope were presented,the CAG coincidence rate was more than 70. 00%,and the highest was the rough gastric mucosa with the rate of 77. 78%. When the any two of the manifestations of gastroscope were simultaneously presented,the CAG coincidence rate was more than 80. 00%,and the highest was the rough gastric mucosa and the color of red and white combination with the rate of 88. 00%. When the three of the manifestations of gastroscope were simultaneously presented,the CAG coincidence rate was more than 80. 00%. Hp was positive in 55 cases(50. 93%). 89 cases were diagnosed by pathology,48 cases of them(53. 93%) were Hp positive. In the 42 cases with intestinal metaplasia,24 cases of them(57. 14%) were Hp positive. In 13 cases with dysplasia,9 cases of them(69. 23%) were Hp positive. Conclusion It should be combined with gastroscopy and pathological examination in clinic,and should pay more attention to the typical site biopsy and strengthen the identify of endoscopic morphology, and also standardize the endoscopic operation. It can ultimately improve the diagnostic coincidence rate of the two methods.

Objective To investigate the cytotoxicity of γδ T cells to HIV-1 latency cells in patients with early HIV-1 infection.Methods Sixteen early HIV-1-infected patients were enrolled in this study.Peripheral blood mononuclear cells (PBMCs) of patients were isolated and γδ T cells were expanded using zoledronate (5 μmol/L) and interleukin (IL)-2 (1 000 IU/mL) ex vivo.Lactic dehydrogenase (LDH) was used to detect the cytotoxic role of γδ T cells to HIV-1 latency cells(J-Lat Full Length Clonel0.6).The phenotype of γδ T cells before and after expansion and the intensity of GFP in HIV-1 latency cells were detected by flow cytometry.Results Zoledronate plus IL-2 stimulated rapid and large γδ T cells proliferation ex vivo (P＜0.001).γδ T cells showed high cytotoxici ty to latency cells,and the intensity of GFP in latency cells was decreased significantly (P＜0.05).Moreover,expanded γδ T cells displayed cytotoxic NK-like phenotype,the frequency of CD56+ Vδ2 T cells in patients with early HIV-1 infection was significantly higher than that of healthy controls.Conclusions γδ T cell has an ability to eradicate HIV-1 latency,and γδ T cell-based autologous or xenogenous adoptive immunotherapy will have promise prospects to cure HIV-1 infection.

OBJECTIVE To observe the effect of natrin from Naja naja atra(Chinese cobra)on intracellular free calcium overload,and to discuss the protective effect and the possible mechanism of natrin on myocardium calcium(Ca2+)and potassium(K+)ion channels in the primary cardiomyocytes of SD neonatal rats. METHODS The primary cardiomyocytes of SD neonatal rats were used,which were respectively pretreated with natrin 5,25 and 125 mg · L-1 for 24 h before injury was induced by H2O2 0.3 mmol · L- 1. The dynamic variation of intracellular calcium was monitored by laser confocal microscopy using Fluo-3 as Ca2+fluorescence probe. Additionally,the cardio myocytes of neonatal rats were pretreated for 24 h using different concentrations of natrin 5,25,125 mg · L-1 and verapamil 5 nmol · L-1,followed by exposure to H2O2 0.3 mmol · L-1 for 15 min. Then,the mRNA expressions of calcium channels subunits Cav1.2,Calm,RyR2 and potassium channel Kir6.2 were analyzed by FQ-PCR method. RESULTS Laser confocal microscopy revealed that H2O2 obviously caused calcium overload in cardiomyocytes, giving rise to 49.37% fluorescence increase in intracellular calcium compared with the control group(P<0.01). However,natrin 5,25 and 125 mg·L-1 resulted in 27.52%, 12.71% and 5.15% fluorescence increase in intracellular calcium,respectively,compared with the control group(P<0.01). Moreover, the PCR results showed that the mRNA expressions of Cav1.2, Calm and RyR2 in the myocardial cells treated with H2O2 were increased 2.78,2.26,and 5.34 times as compared with the control group,while Kir6.2 displayed a 1.79-fold expression level(P<0.01). By contrast, the combination of natrin and verapamil significantly decreased the mRNA expression of Cav1.2,Calm and RyR2,compared to the H2O2-treated group(P<0.01). Meanwhile,the expression of Kir6.2 was considerably higher than that of the H2O2-treated group(P<0.05). CONCLUSION Natrin can reduce the intracellular calcium overload of cardiomyocytes induced by H2O2 and shows a protective effect against oxidative damage for cardiomyocytes. The possible mechanism is that natrin can decrease the mRNA expression of Cav1.2,Calm,RyR2 and increase the expression of Kir6.2 of the H2O2-induced cardiomyocytes.