ObjectiveTo investigate the mechanisms of Runmu Dihuang decoction （RMDHD） in treating perimenopausal dry eye with liver-kidney Yin deficiency syndrome based on the silent information regulator 3 （SIRT3）/hypoxia-inducible factor-1α （HIF-1α）/nuclear factor-κB （NF-κB） signaling pathway. MethodsSixty female Sprague-Dawley rats were randomly divided into six groups （n=10 per group）： Sham operation group， model group， sodium hyaluronate eye drop group， and low-， medium-， and high-dose RMDHD groups （5.625， 11.25， 22.50 g·kg^-1）. Except for the sham operation group， all rats underwent bilateral ovariectomy and were administered 0.1% benzalkonium chloride eye drops combined with long-term chronic irritation to establish a perimenopausal dry eye model with liver-kidney Yin deficiency syndrome. Drug administration began in the 11th week after modeling and continued for 21 days. General conditions， screen-grip test scores， tear secretion volume， tear film breakup time （TFBUT）， and corneal fluorescein staining were recorded. Serum levels of reactive oxygen species （ROS）， follicle-stimulating hormone （FSH）， estradiol （E₂）， and progesterone （PROG） were measured by enzyme-linked immunosorbent assay （ELISA）. Pathological changes in the lacrimal glands， corneas， and uteri were observed using hematoxylin-eosin （HE） staining. Protein expression levels of SIRT3， HIF-1α， phosphorylated NF-κB p65 （p-NF-κB p65）， and total NF-κB p65 in the lacrimal glands were detected by Western blot. The expression of inflammatory cytokines interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the lacrimal glands was assessed by immunohistochemistry （IHC）. ResultsAfter model establishment， no significant differences were observed among the groups except the sham operation group. Compared with the sham operation group， the other groups exhibited slowed movement， dull responses， increased irritability， reduced body weight， elevated rectal temperature， decreased screen-grip test scores， reduced tear secretion， and significantly shortened TFBUT （P<0.05）. After treatment， compared with the model group， the sodium hyaluronate eye drop group and all RMDHD groups showed improved general conditions， significantly increased tear secretion （P<0.05）， prolonged TFBUT （P<0.05）， and elevated screen-grip test scores （P<0.05）. Serum ROS and FSH levels were significantly decreased， while E₂ and PROG levels were significantly increased （P<0.05）. Pathological damage to the cornea， lacrimal glands， and uterus was ameliorated. In addition， protein expression levels of SIRT3 and HIF-1α in the lacrimal glands were significantly upregulated （P<0.05）， whereas the expression of p-NF-κB p65， IL-1β， and TNF-α was significantly downregulated （P<0.05）. ConclusionRMDHD increases tear secretion and TFBUT， improves lacrimal gland and corneal injury， and alleviates dry eye symptoms in a perimenopausal dry eye rat model with liver-kidney Yin deficiency syndrome. The underlying mechanism may be related to regulation of the SIRT3/HIF-1α/NF-κB signaling pathway， inhibition of oxidative stress and inflammatory responses， and reduction of ocular surface tissue damage.

Tricellulin, a key tricellular tight junction (TJ) protein, is essential for maintaining the barrier integrity of acinar epithelia against macromolecular passage in salivary glands. This study aims to explore the role and regulatory mechanism of tricellulin in the development of salivary gland hypofunction in Sjögren's syndrome (SS). Employing a multifaceted approach involving patient biopsies, non-obese diabetic (NOD) mice as a SS model, salivary gland acinar cell-specific tricellulin conditional knockout (Tric^CKO) mice, and IFN-γ-stimulated salivary gland epithelial cells, we investigated the role of tricellulin in SS-related hyposalivation. Our data revealed diminished levels of tricellulin in salivary glands of SS patients. Similarly, NOD mice displayed a reduction in tricellulin expression from the onset of the disease, concomitant with hyposecretion and an increase in salivary albumin content. Consistent with these findings, Tric^CKO mice exhibited both hyposecretion and leakage of macromolecular tracers when compared to control animals. Mechanistically, the JAK/STAT1/miR-145 axis was identified as mediating the IFN-γ-induced downregulation of tricellulin. Treatment with AT1001, a TJ sealer, ameliorated epithelial barrier dysfunction, restored tricellulin expression, and consequently alleviated hyposalivation in NOD mice. Importantly, treatment with miR-145 antagomir to specifically recover the expression of tricellulin in NOD mice significantly alleviated hyposalivation and macromolecular leakage. Collectively, we identified that tricellulin deficiency in salivary glands contributed to hyposalivation in SS. Our findings highlight tricellulin as a potential therapeutic target for hyposecretion, particularly in the context of reinforcing epithelial barrier function through preventing leakage of macromolecules in salivary glands.
Sjogren's Syndrome/complications* ; Animals ; Xerostomia/etiology* ; Mice ; Mice, Inbred NOD ; MARVEL Domain Containing 2 Protein/metabolism* ; Humans ; Mice, Knockout ; Disease Models, Animal ; Interferon-gamma ; Salivary Glands/metabolism* ; Tight Junctions/metabolism* ; MicroRNAs/metabolism* ; Female

Objective:To explore the effect of Simo decoction improving the low duodenal inflammation and protecting the du-odenal mucosal barrier in rats with functional dyspepsia(FD).Methods:Sixty SD rats were randomly divided into control group(10 rats)and model group(50 rats),and the modeling rats were prepared by multivariate intervention method.After successful modeling,the modeling rats were randomly divided into model group,Simo decoction high-dose,medium-dose,low-dose group and mosapride group,with 10 rats in each group.The high-dose,medium-dose,and low-dose groups of Simo decoction were ga-vage given 5.62 g/kg,2.81 g/kg,and 1.40 g/kg,respectively,and the mosapride group was gavage given 0.305 mg/kg of mosapride,and the control group and model group were gavage given the same amount of distilled water for 14 days.The body weight of rats was observed;gastric emptying rate and small bowel propulsion rate were measured;transmission electron microscopy was used to observe the morphology of duodenal epithelial cells;ELISA detected serum levels of IL-17A and IL-22;Western blot and immunohistochemis-try were used to detect the expressions of protease-activated receptor 2(PAR-2)and tight junction protein(ZO-1,claudin-1)in the duodenum.Results:Compared with the control group,the body weight,gastric emptying rate and small intestinal propulsion rate of the model group were significantly reduced(P<0.01),transmission electron microscopy showed widening of the duodenal epithelial cell space,serum IL-17A and IL-22 levels were significantly increased(P<0.01),the expression of PAR-2 in duodenal tissue was in-creased,and the expressions of ZO-1 and claudin-1 were downregulated(P<0.01).Compared with model group,the gastric emptying rate and small intestinal propulsion rate in Simo decoction high-dose,medium-dose and mosapride group were increased(P<0.05,P<0.01),the contents of IL-17A and IL-22 in serum decreased(P<0.05,P<0.01),and the expression of PAR-2 in duodenal tissues was down-regulated,the expressions of ZO-1 and claudin-1 was significantly increased(P<0.01).The low-dose group of Simo soup could improve weight loss(P<0.01),reduce IL-17A content and PAR-2 expression,and increase ZO-1 and claudin-1 expression(P<0.05,P<0.01),while the effect on other indexes was not obvious.Conclusion:Simo decoction may reduce low-grade duodenal in-flammation to repair the mucosal barrier by down-regulating the levels of IL-17A and IL-22 and the expression of PAR-2,and up-regu-lating the expression of ZO-1 and claudin-1,so as to exert the effect of FD treatment.

Thyroid-associated ophthalmopathy (TAO) is the ocular manifestation of thyroid autoimmune dysfunction.Its clinical feathers mainly include eyelid retraction, proptosis, and ocular movement disorders.TAO is the most common orbital diseases.The pathogenesis of TAO has not been fully elucidated, but researchers generally believe that T cells play an important role in the pathogenesis of TAO.In the early stage of TAO development, a large number of T cells are activated and infiltrated into the retroorbital soft tissue.T cells can be divided into CD4 + T cells and CD8 + T cells.CD4 + T cells play a more central role in TAO.CD4 + T cells include Th1, Th2, Treg and recently discovered Th17, Th22 and Tfh cells.In target tissues, the complete activation and later function of T cells largely rely on the costimulatory pathways, there needs to unravel the mechanism of these costimulatory pathways in TAO.This paper reviews the recent research progress of T cells and costimulatory signals required for their activation in the pathogenesis of TAO.

Objective:To explore the effect of Simo decoction improving the low duodenal inflammation and protecting the du-odenal mucosal barrier in rats with functional dyspepsia(FD).Methods:Sixty SD rats were randomly divided into control group(10 rats)and model group(50 rats),and the modeling rats were prepared by multivariate intervention method.After successful modeling,the modeling rats were randomly divided into model group,Simo decoction high-dose,medium-dose,low-dose group and mosapride group,with 10 rats in each group.The high-dose,medium-dose,and low-dose groups of Simo decoction were ga-vage given 5.62 g/kg,2.81 g/kg,and 1.40 g/kg,respectively,and the mosapride group was gavage given 0.305 mg/kg of mosapride,and the control group and model group were gavage given the same amount of distilled water for 14 days.The body weight of rats was observed;gastric emptying rate and small bowel propulsion rate were measured;transmission electron microscopy was used to observe the morphology of duodenal epithelial cells;ELISA detected serum levels of IL-17A and IL-22;Western blot and immunohistochemis-try were used to detect the expressions of protease-activated receptor 2(PAR-2)and tight junction protein(ZO-1,claudin-1)in the duodenum.Results:Compared with the control group,the body weight,gastric emptying rate and small intestinal propulsion rate of the model group were significantly reduced(P<0.01),transmission electron microscopy showed widening of the duodenal epithelial cell space,serum IL-17A and IL-22 levels were significantly increased(P<0.01),the expression of PAR-2 in duodenal tissue was in-creased,and the expressions of ZO-1 and claudin-1 were downregulated(P<0.01).Compared with model group,the gastric emptying rate and small intestinal propulsion rate in Simo decoction high-dose,medium-dose and mosapride group were increased(P<0.05,P<0.01),the contents of IL-17A and IL-22 in serum decreased(P<0.05,P<0.01),and the expression of PAR-2 in duodenal tissues was down-regulated,the expressions of ZO-1 and claudin-1 was significantly increased(P<0.01).The low-dose group of Simo soup could improve weight loss(P<0.01),reduce IL-17A content and PAR-2 expression,and increase ZO-1 and claudin-1 expression(P<0.05,P<0.01),while the effect on other indexes was not obvious.Conclusion:Simo decoction may reduce low-grade duodenal in-flammation to repair the mucosal barrier by down-regulating the levels of IL-17A and IL-22 and the expression of PAR-2,and up-regu-lating the expression of ZO-1 and claudin-1,so as to exert the effect of FD treatment.

Thyroid-associated ophthalmopathy (TAO) is the ocular manifestation of thyroid autoimmune dysfunction.Its clinical feathers mainly include eyelid retraction, proptosis, and ocular movement disorders.TAO is the most common orbital diseases.The pathogenesis of TAO has not been fully elucidated, but researchers generally believe that T cells play an important role in the pathogenesis of TAO.In the early stage of TAO development, a large number of T cells are activated and infiltrated into the retroorbital soft tissue.T cells can be divided into CD4 + T cells and CD8 + T cells.CD4 + T cells play a more central role in TAO.CD4 + T cells include Th1, Th2, Treg and recently discovered Th17, Th22 and Tfh cells.In target tissues, the complete activation and later function of T cells largely rely on the costimulatory pathways, there needs to unravel the mechanism of these costimulatory pathways in TAO.This paper reviews the recent research progress of T cells and costimulatory signals required for their activation in the pathogenesis of TAO.

China has classified the Corona Virus Disease 2019(COVID-19) as a statutory category B infectious disease and managed it according to Category B since January 8, 2023.In view that Omicron variant is currently the main epidemic strain in China, in order to guide the treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection in children with the times, refer to the Diagnosis and Treatment Protocol for Novel Coronavirus Infection (Trial 10 th Edition), Expert Consensus on Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fourth Edition) and the Diagnosis and Treatment Strategy for Pediatric Related Viral Infections.The Expert Consensus on the Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fifth Edition) has been formulated and updated accordingly on related etiology, epidemiology, pathogenic mechanism, clinical manifestations, auxiliary examination, diagnosis and treatment, and added key points for the treatment of COVID-19 related encephalopathy, fulminating myocarditis and other serious complications for clinical reference.

Objective:Use linear programming model to predict the allocation of surgical nursing human resources, and optimize the allocation of nursing staff.Methods:This study was a controlled clinical trial. A total of 91 nurses from 5 surgical departments in Affiliated Hospital of Qingdao University were selected by convenience sampling method. The nurses who participated in the scheduling in August and September 2020 were the routine scheduling groups, and in March and April 2021 were the linear scheduling groups. The linear programming model of surgical nursing human resources was established. The LINGO 11.0 software was used to calculate the minimum number of nurses required for the next day operation. According to the predicted results and the requirements of the operation specialty and rank level, the surgical staff was arranged for the next day. The overtime hours of nurses in the routine scheduling groups and the linear scheduling groups were compared and analyzed.Results:The number of on-duty nurses was the same in 4 groups, the overtime hours of the conventional scheduling groups in August and September 2020 and the linear scheduling groups in March and April 2021 were 865 (505, 1 435), 780 (475, 1 355), 650 (460, 910) and 720 (350, 915) min, the difference of overtime hours was statistically significant ( H=13.66, P<0.05). The overtime hours of the routine scheduling group in August 2020 were significantly different from those of the linear scheduling group in March 2021 and April 2021 respectively ( Z=-2.69, -2.55, both P<0.05). The overtime hours of the routine scheduling group in September 2020 were significantly different from those of the linear scheduling group in March 2021 and April 2021 respectively ( Z=-2.62, -2.58, both P<0.05). Conclusions:The linear programming model was used to predict the human resource allocation of surgical nursing staff, optimized the allocation of operating room human resources. It reduced the overtime hours of surgical nursing staff effectively. Indirectly, it accelerated operations, improved operation efficiency and ensured the safety of patients.

Novel coronavirus Omicron variant infection can cause severe illness and even death in certain populations. Omicron variant infection may lead to systemic inflammatory response, coagulation disorder, multi-organ dysfunction and other pathophysiological changes, which are different from other Novel coronavirus variants to a certain extent, so therapeutic strategies should not be the same. The National Medical Center for Major Public Health Events invited experts in fields of infectious diseases, respiratory medicine, intensive care, pediatrics and fever clinic to develop this quick guideline based on the current best evidence and extensive clinical practices. This quick guideline aims to standardize the diagnosis and treatment of novel coronavirus Omicron infection, and to improve the disease management abilities of clinicians.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases