Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Objective:To compare the effect of self-radiopaque markers guiding physician-modified fenestration, chimney technique and hybrid Ⅳb technique on reconstruction of left subclavian artery (LSA) in endovascular treatment of aortic dissection (TEVAR).Methods:The clinical and follow-up data of 312 TEVAR patients treated with LSA blood supply reconstruction technology from Jan 2016 to Dec 2019 at Fuwai hospital were retrospectively analyzed.Results:There were 35 patients in the hybrid Ⅳb technique group, 93 in the chimney technique group, and 184 in the in vitro fenestration group. The follow-up period ranged from 12 to 24 months. No artificial blood vessel and stent occlusion occurred in all patients during follow-up, and the LSA blood flow was unobstructed. A total of 19 patients had endoleak by the last follow-up, and there was no statistical difference between the three groups. Eleven patients underwent reintervention surgery, all were from chimney technique group and in vitro fenestration group, with no statistical difference ( P>0.05). Severe complications occurred in 28 patients during hospitalization, and the incidence of complications was the highest in the hybrid Ⅳb technique group ( P<0.01). During follow-up, 4 patients died in the bypass group, 6 died in the external window group, and 8 died in the chimney group, with no significant difference ( P>0.05). Conclusions:The safety and efficacy of the left subclavian artery flow reconstruction by in vitro fenestration and chimney technique were similar. The occurrences of early complications were lower than that of the hybrid Ⅳb technique, but the reintervention rate of endoleak was higher.

BACKGROUND: Clinical trial evidence is limited to identify better topical non-steroidal anti-inflammatory drugs (NSAIDs) for treating knee osteoarthritis (OA). We aimed to compare the clinical efficacy and safety of flurbiprofen cataplasms (FPC) with loxoprofen sodium cataplasms (LSC) in treating patients with knee OA. METHODS: This is an open-label, non-inferiority randomized controlled trial conducted at Peking University Shougang Hospital. Overall, 250 patients with knee OA admitted from October 2021 to April 2022 were randomly assigned to FPC and LSC treatment groups in a 1:1 ratio. Both medications were administered to patients for 28 days. The primary outcome was the change of pain measured by visual analog scale (VAS) score from baseline to day 28 (range, 0-10 points; higher score indicates worse pain; non-inferiority margin: 1 point; superiority margin: 0 point). There were four secondary outcomes, including the extent of pain relief, the change trends of VAS scores, joint function scores measured by the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and adverse events. RESULTS: Among 250 randomized patients (One patient without complete baseline record in the flurbiprofen cataplasms was excluded; age, 62.8 ± 10.5 years; 61.4% [153/249] women), 234 (93.6%) finally completed the trial. In the intention-to-treat analysis, the decline of the VAS score for the 24-h most intense pain in the FPC group was non-inferior, and also superior to that in the LSC group (differences and 95% confidence interval, 0.414 (0.147-0.681); P <0.001 for non-inferiority; P = 0.001 for superiority). Similar results were observed of the VAS scores for the current pain and pain during exercise. WOMAC scores were also lower in the FPC group at week 4 (12.50 [8.00-22.50] vs . 16.00 [11.00-27.00], P = 0.010), mainly driven by the dimension of daily activity difficulty. In addition, the FPC group experienced a significantly lower incidence of adverse events (5.6% [7/124] vs . 33.6% [42/125], P <0.001), including irritation, rash and pain of the skin, and sticky hair uncovering pain. CONCLUSIONS This study suggested that FPC is superior to LSC for treating patients with knee OA in pain relief, joint function improvement, and safety profile.
Humans ; Female ; Middle Aged ; Aged ; Osteoarthritis, Knee/drug therapy* ; Flurbiprofen/therapeutic use* ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use* ; Pain/drug therapy* ; Treatment Outcome ; Double-Blind Method

ObjectiveTo explore the association between daily executive function and core symptoms， the symptoms of attention deficit hyperactivity disorder （ADHD） in children with autism spectrum disorder （ASD）， and the moderating effect of theory of mind and other cognitive abilities on this association. MethodsChildren aged 6-12 years with ASD were recruited， and 86 children were identified according to the inclusion and exclusion criteria. Wechsler Intelligence Test for Children， Fourth Edition （WISC-Ⅳ）， Strange Story Test （SST） and Behavior Rating Inventory of Executive Function （BRIEF） were used to evaluate children's cognitive ability. Swanson Nolan and Pelham-Version Ⅳ Scale （SNAP-Ⅳ）， Social Responsiveness Scale （SRS）， and Repetitive Behavior Scale-Revise （RBS-R） were used to assess the severity of ADHD symptoms， social impairment， and repetitive stereotyped behavior. Multiple linear regression was used to explore the association between daily executive function and ADHD symptoms， social impairment， repetitive stereotyped behaviors. ResultsAfter controlling for the score of strange stories， verbal comprehension index （VCI） and other factors， the full scale score and each index of BRIEF were positively correlated with full scale score of SNAP （b = 0.619-0.741， b’ = 0.637-0.755）， SRS （b = 0.928-1.200， b’ = 0.417-0.513） and RBS-R （b = 0.326-0.525， b’ = 0.339-0.520） in children with ASD （P< 0.05）， and the SNAP total score was more strongly correlated with the full scale BRIEF score and each index score （b’ = 0.637-0.755，P< 0.01）. In addition to daily executive function， strange stories score （b = -2.218- -1.839） and age （b = 3.181-4.037） were also the important factors affecting the social function of children with ASD （P< 0.01）. There were no moderating effects of strange stories score and age on the association between BRIEF score and full scale score of SNAP， SRS， and RBS-R（P> 0.05）. ConclusionThe deficits of daily executive function in school-aged ASD children are significantly associated with core symptoms and ADHD symptoms， and the association is independent of other cognitive domains， such as theory of mind and verbal comprehension intelligence quotient.

Objective:To investigate the effects of 40 Hz and 70 Hz frequency flash stimulation on the ability of learning memory and autonomous exploratory in young rats.Methods:Twenty-seven SPF grade male SD rats aged 19-21 days were divided into control group (Ctr group), 40 Hz group and 70 Hz group with 9 in each group according to the random number table.The rats in Ctr group were not given flash stimulation, while rats in the 40 Hz and 70 Hz group were received 40 Hz, 70 Hz flash stimulation (1.5 h/d for 39 days), respectively.The Morris water maze experiment was used to assess the learning and memory ability of rats, and the open field experiment was used to evaluate the ability of autonomous exploratory of rats.Nissl staining was used to assess the morphology of Nissl bodies in the hippocampus CA1 region of the rats.The local field potentials (LFPs) collected from the primary visual cortex (V1 area) region by electrophysiological experiments was used to verify the synchronization of flash evoked neural oscillations.SPSS 23.0 software was used for statistical analysis.The repeated measures ANOVA and one-way ANOVA were used to analyze normal distribution measurement data, and LSD and Tamhane tests were used for further pairwise comparison.The Kruskal-Wallis test was used for non-normal distribution measurement data.Results:(1) The flash stimulation of 40 Hz and 70 Hz both can effectively caused synchronization of neural oscillations in the primary visual cortex of healthy young rats.(2) The results of repeated measures ANOVA analysis showed that there was no interaction effect of grouping and time in the escape latency of young rats in the Morris water maze positioning navigation phase( F=1.326, P>0.05 ). The escape latency had time main effect ( F=40.025, P<0.05), but no grouping main effect ( F=2.039, P>0.05). With the increase of learning days, the escape latency of young rats in each group decreased significantly.There was no interaction effect of grouping and time in the total distance of young rats ( F=2.029, P>0.079). It had time main effect ( F=32.052, P<0.05), but not grouping main effect ( F=2.390, P>0.05) on total distance.With the increase of learning days, the total distance of young rats in each group significantly shortened.On the 6th day of the Morris water maze experiment, there was no statistically significant difference among groups in terms of time in the target quadrant and the number of crossing platforms ( F=2.511, 0.802, both P>0.05). The results of the open field experiment showed that the total distance traveled in the center of young rats in each group was statistically significant ( H=8.935, P<0.05), the total distance traveled in the center in the 70 Hz group (3.80 (2.25, 6.93) m)was significantly longer than that in the 40 Hz group (0.80 (0.72, 1.46) m), P<0.05). The percentage of time spent in the center was statistically significant in the three groups ( H=11.050, P<0.05). Young rats in the 70 Hz group spent significantly higher percentage of time in the center(3.20(2.43, 8.30)) than those in the 40 Hz group (0.95 (0.37, 1.06 ), P<0.05 ). (3) Nissl staining results showed that Nissl bodies in the hippocampal CA1 area of young rats in Ctr, 40 Hz and 70 Hz group were all arranged neatly and tightly, no edema was found in the surrounding stroma, and no obvious inflammatory cell infiltration was found. Conclusion:70 Hz frequency flash stimulation may promote the ability of learning memory and autonomous exploratory of young rats.

Objective:To analyze the efficacy of the enhanced recovery after surgery(ERAS)approach in endometrial cancer patients treated with surgical staging and its beneficial effects on the oxidative stress response.Methods:Eight-two endometrial cancer patients treated with surgical staging at our hospital between March 2020 and March 2022 were recruited and divided into different groups using a computer-generated random number table, with 41 in the control group who were given routine intervention and 41 in the observation group receiving ERAS.Results:About perioperative performances, the oxidative stress response, inflammatory factor levels and complications were compared between the two groups.Results in the observation group, the intraoperative body surface temperature was higher than in the control group[(36.71±0.22)℃ vs.(36.20±0.21)℃, t=10.737, P=0.000], and the time from the end of surgery to first water intake[(4.41±1.30)h vs.(6.79±1.28)h, t=8.353, P=0.000], to first food intake[(7.86±1.35)h vs.(12.88±2.57)h, t=11.073, P=0.000], to first ambulation[(12.92±3.11)h vs.(24.24±5.06)h, t=12.204, P=0.000], to first flatus[(24.11±4.96)h vs.(35.13±6.20)h, t=8.887, P=0.000], to first bowel movement[(2.67±0.63)d vs.(4.03±1.15)d, t=6.641, P=0.000]and the length of hospitalization[(3.31±1.25)d vs.(5.77±1.59)d, t=7.788, P=0.000]were shorter than in the control group.On the third day after surgery, the levels of malondialdehyde[(77.96±7.62)μmol/L vs.(90.16±7.88)μmol/L, t=7.126, P=0.000], advanced oxidation protein products[(33.16±4.75)μmol/L vs.(43.55±5.37)μmol/L, t=9.280, P=0.000], CAT[(22.59±3.01)U/ml vs.(25.12±3.3)U/ml, t=3.609, P=0.000]and reactive oxygen species[(74.13±5.02)pmol/L vs.(90.33±5.89)pmol/L, t=13.404, P=0.000]in the two groups were higher than those on the day before surgery, but were lower in the observation group than in the control group at the same time points after surgery.On the 3rd day after surgery, the levels of Tumor Necrosis Factor-α, C-reactive protein and interleukin 6 in the two groups were higher than those on the day before surgery, but were lower in the observation group than in the control group at the same points after surgery(all P<0.05). In the observation group, the incidence of complications was 14.63%, lower than 39.02% in the control group( χ2=6.212, P=0.013). Conclusions:The ERAS approach can achieve significant results in endometrial cancer patients treated with surgical staging.It can not only improve perioperative performance, relieve oxidative stress and lower inflammatory factor levels, but also effectively prevent complications.

OBJECTIVE: To investigate whether Omicron BA.1 breakthrough infection after receiving the SARS-CoV-2 vaccine could create a strong immunity barrier. METHODS: Blood samples were collected at two different time points from 124 Omicron BA.1 breakthrough infected patients and 124 controls matched for age, gender, and vaccination profile. Live virus-neutralizing antibodies against five SARS-CoV-2 variants, including WT, Gamma, Beta, Delta, and Omicron BA.1, and T-lymphocyte lymphocyte counts in both groups were measured and statistically analyzed. RESULTS: The neutralizing antibody titers against five different variants of SARS-CoV-2 were significantly increased in the vaccinated population infected with the Omicron BA.1 variant at 3 months after infection, but mainly increased the antibody level against the WT strain, and the antibody against the Omicron strain was the lowest. The neutralizing antibody level decreased rapidly 6 months after infection. The T-lymphocyte cell counts of patients with mild and moderate disease recovered at 3 months and completely returned to the normal state at 6 months. CONCLUSION Omicron BA.1 breakthrough infection mainly evoked humoral immune memory in the original strain after vaccination and hardly produced neutralizing antibodies specific to Omicron BA.1. Neutralizing antibodies against the different strains declined rapidly and showed features similar to those of influenza. Thus, T-lymphocytes may play an important role in recovery.
Humans ; Antibodies, Neutralizing ; Prospective Studies ; SARS-CoV-2 ; Breakthrough Infections ; COVID-19 Vaccines ; COVID-19 ; T-Lymphocytes ; China/epidemiology* ; Antibodies, Viral

Objective:To analyze the surveillance data of Kashin-Beck disease (KBD) in Shandong Province, master the changes of KBD, and provide scientific basis for formulating prevention and control strategies of KBD and adjustment of the prevention and control focus of KBD.Methods:According to the requirements of the "National KBD Monitoring Plan" and the "Shandong KBD Monitoring Plan", from 2016 to 2020, the disease monitoring was carried out in the villages of KBD areas in Shandong Province, including the number of clinical positive cases, the number of X-ray positive cases, and the number of metaphyseal positive cases. The detection rate was calculated, and the dynamic changes of the disease was analyzed macroscopically.Results:From 2016 to 2020, a total of 1 816 children aged 7 - 12 years were clinically examined in Shandong Province, and no child with KBD was found. A total of 1 224 children were examined by X-ray, among which 1 positive patient was found in 2016 and 2017, respectively, both of whom were metaphyseal changes, with a total detection rate of 0.16%. There were 367 adult patients with KBD in Shandong Province, including 304 patients with grade Ⅰ, 47 patients with grade Ⅱ and 16 patients with grade Ⅲ. All villages in the KBD areas in Shandong Province had reached the elimination standard, with the elimination rate of 100%.Conclusion:No clinical case of KBD is detected in children aged 7 - 12 years in Shandong Province from 2016 to 2020, which has reached the elimination standard and is in a continuous elimination state.

Objective:To examine the ultrasound images, clinical features, intraoperative conditions, and pathological features of ovarian clear cell carcinoma(OCCC)during perimenopause, in order to improve the early diagnosis of OCCC via ultrasound examination.Methods:A retrospective analysis of 29 patients, aged 42-72(56.8±7.4)years, who were surgically treated and pathologically diagnosed with OCCC at our hospital between 1 September 2015 and 31 December 2022, including 10 in the non-menopausal phase, 3(10.3%)in early menopausal transition, 7(24.1%)in late menopausal transition, and 19(65.5%)in the post-menopausal phase.The number of pregnancies(1.86±1.04)and the number of births(0.97±0.56)were also recorded.Results:In 29 cases, the masses contained solid components, and the ultrasound manifestations were as follows: (1)single-compartment cystic masses(solid components accounted for <50% of the total volume)were found in 11 cases, with clear borders, regular morphology, ground-glass echoes inside the cystic cavity, multiple solid protrusions inside the cystic cavity, and blood flow signals inside the solid components on color Doppler flow imaging(CDFI); (2)multi-compartment cystic masses(solid components accounted for <50% of the total volume)occurred in 8 cases, with largely clear borders, ground-glass echoes inside the cystic cavity, multiple solid protrusions inside the cavity, thick walls where the protrusions were attached, varying thickness of walls separating the cystic cavities, and blood flow signals inside the solid components, walls where there were solid attachments and thicker parts of the separating walls on CDFI; (3)there were 7 cases with predominantly solid cystic masses(the solid components accounted for >50% of the total volume), unclear borders, poor translucency, irregular morphology of the solid components, uneven internal echoes, and blood flow signals in the solid component on CDFI; (4)solid masses(the solid components accounted for >95%of the total volume)were seen in 3 cases with unclear borders, irregular morphology, uneven internal echoes, and a small number of cystic cavities(cystic portion <5%), with poor translucency in the cystic cavities and blood flow signals in the solid components on CDFI.Intraoperative exploration of ascites was performed in 17 cases, and adhesion between the mass and surrounding organs was found in 27 cases.Postoperative pathological results revealed 26 cases with high grade tumors and 3 cases with intermediate grade tumors.There were 3 cases with bilateral OCCC, 13 with left side OCCC and 13 with right side OCCC.According to the FIGO pathological staging system, 12 cases were in stage Ⅰ, 10 in stage Ⅱ, 5 in stage Ⅲ and 2 in stage Ⅳ.Comparison of different pathological stages(early stages Ⅰ and Ⅱ versus late stages Ⅲ and Ⅳ)showed statistically significant differences in the ratio of pathological stages between patients with different ultrasonographic manifestations( χ2=11.163, P<0.05), and the results of two-by-two comparisons showed that OCCC patients with ultrasonographic manifestations of solid masses(solid component accounting for >95%of the total volume)were more often in the late stage at the time of onset, while OCCC patients with a high number of cystic components within the lesions were more likely to be in the early stage at the time of onset.OCCC patients with more cystic components in the lesions tended to have an earlier onset and a better prognosis. Conclusions:When ultrasound imaging shows primarily a single chamber cystic solid mass in a patient in the perimenopausal phase with an endometriosis history, together with signs of specialized examination and pelvic adhesion during transvaginal sonography, a diagnosis of OCCC should be suspected.It is of great significance to pay attention to transvaginal sonography examination, ultrasound image features and clinical symptoms in perimenopausal women for the early diagnosis of OCCC.

Objective To assess the association of metabolic syndrome (MetS) and low-level high density lipoprotein-cholesterol (HDL-C) with the invasion of prostate cancer (PCa) in the patients after radical prostatectomy (RP). Methods We collected and analyzed the data of 232 PCa patients treated with RP for prospective multicenter clinical study.The MetS was assessed according to NCEP-ATP Ⅲ.Patients were divided into MetS group and non-MetS group.Locally advanced PCa was defined as a pT-stage≥3.ISUP Gleason grading system (GS) were used for pathological grading.Logistic regression analyses assessed the association of MetS and its components with pathological data. Results MetS was an independent risk factor for GS≥8 after RP.Low HDL-C level was associated with locally advanced PCa.The risks of adverse pathological features increased with the number of MetS components. Conclusion Low HDL-C level and 4 or more MetS components are associated with higher risk of adverse pathological features of PCa.