Objective To investigate the clinical features of rhino-orbital-cerebral mucormycosis(ROCM)with bilateral cranial nerve palsies as the clinical manifestation.Methods The related clinical data about ROCM with bilateral cranial nerve palsy as a clinical manifestation was collected,analyzed as well as discussed in the manuscript.And the relevant literatures were reviewed.Results This patient was a healthy young man with new-onset diabetes and diabetic ketoacidosis.The patient developed rapidly with acute onset,bilateral blindness,blepharoptosis and extraocular muscle paralysis.The presence of mucormycosis was confirmed by CSF second-generation sequencing,fungal fluorescent staining and culture.Although effective antifungal therapy was performed early,but the patient quickly presented with cerebral hemorrhage and herniation.Eventually,the patient died after discharge.Conclusions ROCM is a rare and high-mortality infectious disease.This case indicated that the clinicians should consider the presence of ROCM in patients with diabetes/diabetic ketoacidosis when the bilateral cranial nerves paralysis are the clinical symptom,whicn can not be explained by other lesions.CSF next-generation sequencing is helpful for rapid diagnosis.

A purified polysaccharide with a galactose backbone(SPR-1,Mw 3,622 Da)was isolated from processed Polygonati Rhizoma with black beans(PRWB)and characterized its chemical properties.The backbone of SPR-1 consisted of[(4)-β-D-Galp-(1]9→ 4,6)-β-D-Galp-(1 → 4)-α-D-GalpA-(1 → 4)-α-D-GalpA-(1 →4)-α-D-Glcp-(1 → 4,6)-α-D-Glcp-(1 → 4)-α/β-D-Glcp,with a branch chain of R1:β-D-Galp-(1 → 3)-β-D-Galp-(1 → connected to the →4,6)-β-D-Galp-(1 → via O-6,and a branch chain of R2:α-D-Glcp-(1 →6)-α-D-Glcp-(1 → connected to the →4,6)-α-D-Glcp-(1 → via O-6.Immunomodulatory assays showed that the SPR-1 significantly activated macrophages,and increased secretion of NO and cytokines(i.e.,IL-1β and TNF-α),as well as promoted the phagocytic activities of cells.Furthermore,isothermal titration calorimetry(ITC)analysis and molecular docking results indicated high-affinity binding between SPR-1 and MD2 with the equilibrium dissociation constant(KD)of 18.8 μM.It was suggested that SPR-1 activated the immune response through Toll-like receptor 4(TLR4)signaling and downstream responses.Our research demon-strated that the SPR-1 has a promising candidate from PRWB for the TLR4 agonist to induce immune response,and also provided an easily accessible way that can be used for PR deep processing.

Sepsis-associated encephalopathy (SAE) is the most common neurological complication of sepsis, with an incidence of up to 70% in sepsis, and contributes to the increased mortality and disability in sepsis. To date, the exact pathogenesis of SAE is not clear. Most of current researches indicated that blood-brain barrier (BBB) dysfunction, active neuroinflammation, glial cell over activation as well as cerebral microcirculation dysfunction contributed to the pathophysiology of SAE. BBB, as a complex cellular structure between the central nervous system and the peripheral system, strictly controls the entrance and discharge of substances and plays an important role in maintaining the balance between biochemical system and immune system of central system. During the progress of sepsis, inflammatory cytokines and reactive oxygen species resulting from peripheral system directly or indirectly resulted in the damage to the integrity and structure of BBB, which helped above species easily enter into the central system. Above these damages caused glial cell activation (microglia and astrocyte), the imbalance of neurotransmitters, mitochondrial dysfunction and neural apoptosis, which also reversely contributed to the damage to the integrity and permeability of BBB via decreasing the expression of tight junctional protein between cells. Therefore, this review focuses on the structural and functional changes of BBB in SAE, and how these changes lead to the development of SAE, in order to seek a BBB-targeted therapy for SAE.

Objective:To explore the neuroprotective effects and mechanisms of memantine on sepsis-associated encephalopathy (SAE) model mice.Methods:Totally 90 male C57BL/6J mice aged 8-12 weeks were randomly divided into 3 groups (with 30 mice in each group) : sham group, model group and memantine group. The SAE mouse model was established by cecum ligation and puncture while mouse in sham group received open and closed abdomen only. The mice in the memantine group were irrigation with memantine (15 mg · kg -1· d -1) 3 hours before surgery and 7 consecutive days after modeling. The mice in the model group and sham group were irrigation with an equal volume of 0.9% sodium chloride solution. The 7-day survival rate was observed, neurobehavioral and cognitive function scores of each group of mice after modeling were assessed.Blood-brain barrier permeability was measured by detecting the content of Evans blue. Immunofluorescence staining was used to detect the expression of astrocytes. Enzyme linked immunosorbent assay was conducted to detect cellular inflammatory factors and the glutamic acid content detection kit was used to detect the expression of glutamic acid. All data were analyzed by Graphpad Prism 8.3.0 software, survival rate was analyzed using Kaplan-Meier survival curve.Multigroup comparisons were conducted by one-way ANOVA or Kruskal-Wallis test. Results:(1) There was a statistically significant difference in the 7-day survival rate among the three groups of mice after modeling ( F=24.11, P<0.01), and the 7-day survival rate of the memantine group was higher than that of the model group (57% (17/30), 27% (8/30), P<0.01). (2)The behavioral results showed that after 7 days of modeling, there were statistically significant differences in the total distance of the open field test, central area stay time, four corner area stay time, neurobehavioral scores, pole climbing test, and preference index for new object recognition test among the three groups of mice ( F/ χ2=17.67, 17.30, 9.39, 14.06, 10.36, 14.81, all P<0.05).The neurobehavioral score, pole climbing test score, preference index for new object recognition test, total distance of open field test, and central area stay time of the model group were all lower than those of the sham group (all P<0.05), while four corner area stay time of the model group was higher than that of the sham group ( P<0.05).The total distance of open field test (1 564.07(1 363.24, 1 988.19) cm, 913.91 (574.32, 1 096.23) cm), central area stay time (5.21 (4.91, 8.76) s, 1.09 (0.25, 1.64) s), neurobehavioral scores (9.75±0.50, 8.25±0.50), pole climbing test scores (5.67±0.52, 4.56±0.53), and preference index for new object recognition test (56.50±10.59, 26.84±2.91) of the memantine group were all higher than those of the model group (all P<0.05). The four corner area stay time was lower than that of the model group ((480.30±50.64) s, (529.80±36.20) s, P<0.05).(3)The comparison of molecular indicators showed that there were statistically significant differences in the content of Evans blue in the brain, the number of astrocytes in the hippocampus and cerebral cortex, pro-inflammatory cytokines (TNF-α、IL-1β、IL-6), anti-inflammatory cytokines (IL-10), and glutamic acid among the three groups of mice ( F/ χ2=8.84, 6.43, 28.46, 23.63, 12.23, 16.04, 69.22, 6.65, all P<0.05).The content of Evans blue, the number of astrocytes in the hippocampus and cerebral cortex, the expression of TNF-α、IL-1β、IL-6, and glutamate in the model group were all lower than those in the sham group(all P<0.05). The levels of IL-10 in the model group was lower than that in the sham group ( P<0.05).The content of Evans blue ((5.67±1.38)μg/g, (11.08±2.79)μg/g), the number of astrocytes in the hippocampus (16.50 (13.75, 22.25)/μm 2), 80.00 (73.50, 83.50)/μm 2) and the cerebral cortex (40.00 (29.00, 48.00)/μm 2, 81.50 (72.25, 89.00)/μm 2) in the memantine group were lower than those in the model group (all P<0.05).The pro-inflammatory factor TNF-α, IL-1β, IL-6 and glutamic acid expression in the memantine group were lower than those in the model group (all P<0.05), and the anti-inflammatory cytokine IL-10 was higher than that in the model group ( P<0.05). Conclusions:Memantine can improve the neurobehaviors and cognitive functions of SAE mice through improving the integrity of the damaged blood-brain barrier, alleviating inflammation in the brain, as well as reducing glutamate levels in the brain.

The "brain electric field" therapy is a novel electroacupuncture method created by Professor GAO Weibin to treat cerebral infarction in the recovery period. This therapy is suitable for the treatment of motor disorders, sensory disorders, cognitive disorders, hemianopsia and bulbar paralysis during the recovery period of cerebral infarction. Based on the different symptoms, the corresponding brain functional areas are selected, supplemented with Taiyang 2, Tunyan 2, Tiyan, Gongxue and Xiatianzhu. These points are attached to electric acupuncture apparatus, and stimulated with dense wave, at frequency of 50 Hz and tolerable intensity. This therapy presents a remarkable effect on cerebral infarction in the recovery period, providing the new approach to the treatment of this disease.
Humans ; Cerebral Infarction/therapy* ; Electroacupuncture ; Acupuncture Points ; Brain/physiopathology* ; Male ; Middle Aged ; Female

OBJECTIVE To assess the effi-cacy and safety of acupuncture-related treat-ments for postherpetic neuralgia(PHN),identify the most effective acupuncture and related treat-ments.METHODS PubMed,Cochrane Central Register of Controlled Trials,Embase,Web of Science,and four Chinese databases,a clinical research registration platform,and grey literature were searched.We evaluated the risk of bias and quality in the included studies and per-formed a Bayesian multiple network meta-analy-sis.RESULTS We included 29 randomized con-trolled trials comprising 1973 patients,of which approximately 17.24%showed a high risk of bi-as.According to the Jadad scale,2,16,and 11 studies were high,medium,and low quality,respectively.The pairwise meta-analysis results revealed that the efficacy of all acupuncture-related treatments for pain relief related to PHN showed the difference was statistically significant com-pared with that of antiepileptics.The network meta-analysis results showed that pricking and cupping plus antiepileptics were the most effec-tive,followed by electroacupuncture(EA)plus antiepileptics for pain relief in patients with PHN.EA plus antiepileptics ranked the best regarding reduced Pittsburgh Sleep Quality Index and Self-Rating Depression Scale scores in patients with PHN.No results were found regarding total response rate or quality of life among this study.Acupuncture-related treatments showed a lower incidence of adverse events than that of antiepi-leptics-related treatments.CONCLUSION Acu-puncture-related therapies may be potential treat-ment options for PHN and are relatively safe.Pricking and cupping plus antiepileptics are the most effective techniques for pain relief.EA plus antiepileptics is the best approach for improving insomnia and depression symptoms of PHN.

OBJECTIVE To systematically assess the efficacy and safety of acupuncture in treating acute tonsillitis,providing a reference for clinical decision-making.METHODS We searched PubMed,CENTRAL,Embase,Web of Science,China National Knowledge Infrastruc-ture,China Biomedical,clinical research registra-tion platforms,grey literature,and the reference lists of the selected studies from inception to Oct.30,2022.The risk of bias assessment used Rev-Man.Meta-analysis was performed using STATA with Hedges' g value.In addition,we performed subgroup analysis,meta-regression,and publica-tion bias detection with Harbord's and Egger's tests.RESULTS We included 19 randomized controlled trials comprising 1701 patients,of which 1 study was assessed high risk of bias.The primary outcome,the response rate,revealed that acupuncture was more effective than antibi-otics.The secondary outcomes showed that the difference in the reduction of the VAS scores,sore throat time,and white blood cell counts was statistically significant with acupuncture compared to antibiotics.However,the difference in modulat-ing neutrophil percentage and C-reactive protein was not statistically significant.Besides,acupunc-ture treatments showed a lower incidence of adverse events than antibiotics.CONCLUSION Acupuncture therapy on acute tonsillitis is safe,and the response rate is superior to antibiotics.For alleviating sore throat symptoms,shortening sore throat time,and improving immune inflam-mation index,acupuncture has positive signi fi cance.Nevertheless,because of the limitations of this study,our conclusions should be inter-preted with caution.Future efforts still need more high-quality trials to improve the methodology and reporting quality.

Objective To understand the current situation of practice and cognition of ICU nurses on intra-abdominal pressure monitoring in tertiary general hospitals in Shandong Province,and to analyze the factors affecting their cognition,so as to provide references for formulating intra-abdominal pressure monitoring standards and procedures,and carrying out targeted training in the future.Methods A convenience sampling method was used,and a self-designed questionnaire on practice and cognition of intra-abdominal pressure monitoring was used to survey ICU nurses from tertiary general hospitals in 16 prefecture-level cities in Shandong Province from September to November 2022.Results A total of 627 valid questionnaires were collected,involving 31 tertiary general hospitals(24 tertiary A hospitals,77.42%;7 tertiary B hospitals,22.58%).The operation rate of intra-abdominal pressure monitoring was low(73.37%),and the main reasons were that they had not received intra-abdominal pressure monitoring related training(61.08%),with only 111(24.94%)nurses choosing the intersection of the mid-axillary line and the iliac crest as the reference zero point measurement,274(61.57%)nurses not taking an reading at the end of expiration.The intra-abdominal pressure monitoring cognition score was 0～16(7.88±2.79)points,and only 5 questions had a correct answer rate of≥50%.Conclusion The standardization of intra-abdominal pressure monitoring practice by ICU nurses in tertiary general hospitals in Shandong Province needs to be strengthened,and their cognition needs further training.It is suggested to unify and implement the standards and procedures of intra-abdominal pressure monitoring,further accelerate the training of intra-abdominal pressure monitoring technology,and improve the standard execution rate and cognitive level of ICU nurses on intra-abdominal pressure monitoring.

Objective:A high performance liquid chromatography (HPLC) method was developed to determine the enzymatic activity of CD38 in blood, which was the major enzyme responsible for consuming nicotinamide adenine dinucleotide (NAD). Additionally, the study aimed to detect the differences in CD38 enzymatic activity among individuals of varying ages and health statuses.Methods:A 50 μl whole blood matrix and enzyme reaction substrate of 150 μl β-NAD at a concentration of 500 μmol/L were selected for the analysis. To eliminate the impact of endogenous β-NAD, the whole blood sample was pre-incubated at 37 ℃ for 20 minutes before adding the substrate. The reaction was terminated by perchloric acid (PCA) after incubation at 37 ℃ for 40 min. The change in product nicotinamide (NAM) before and after the enzymatic reaction was measured by HPLC to calculate the CD38 activity. The linearity, limit of detection, limit of quantification, precision, and stability of the method were evaluated. The CD38 enzymatic activities in 60 healthy volunteers and 30 colorectal cancer patients in blood were determined by the developed method.Results:Pre-incubation at 37 ℃ for 20 minutes eliminated the effect of endogenous β-NAD. The correlation coefficient of NAM was 0.999 in the concentration range of 0.1-3.2 μmol/L, with limit of detection of 0.5 nmol/L and limit of quantification of 2.1 nmol/L. The average within-run imprecision ( CV) and total CV were 3.22%-4.03% and 2.91%-4.70%, respectively. The recovery rate ranged from 94.82% to 96.81%. The CD38 activity of whole blood was stable by storage at 4 ℃ for 48 hours, storage at room temperature for 8 hours, thawing of frozen whole blood at room temperature for 2 hours, or repeated freeze-thawing three times. NAM, NAD standards, and pre-treatment samples were stable after 48 hours at 4 ℃ and 8 hours at room temperature. CD38 activity gradually decreased with increasing concentration of the added CD38 inhibitor 4-aminoquinoline derivative (78c). Measurement of 60 healthy physical examination population samples showed significantly higher CD38 enzyme activity in the elderly group than that in the young group ( t=-2.776, P=0.007) and measurement of 30 colorectal cancer patients showed significantly higher CD38 enzyme activity than that in healthy people ( t=-2.572, P=0.012). Conclusion:The established HPLC method for determining CD38 enzymatic activity is characterized by its simplicity, efficiency, accuracy, and reproducibility. This technique serves as a valuable tool for investigating aging and aging-related diseases.

Objective:To explore whether barium chloride (BaCl 2) preconditioning has the protective effect on lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) model in mice and the possible mechanism. Methods:Sixty 8-12 week old healthy C57BL/6 male mice were randomly divided into control group, ARDS model group and BaCl 2 pretreatment group, with 20 mice in each group. The BaCl 2 pretreatment group was continuously injected with BaCl 2 (4 mg/kg through the tail vein) for 3 days before ARDS model establishment. ARDS model was established by intratracheally injecting (3 mg/kg) LPS. The control group was intratracheally given the same volume of 0.9% normal saline. On 24th hour after ARDS model establishment, some mice were sacrificed for obtaining fresh lung tissue. And the right lower lobe of the lung was separated for observing the pathological changes of lung tissue while the left lung tissue was used to measure the wet/dry weight ratio (W/D) of the lung. Some mice were sacrificed for observing pulmonary microvascular permeability at 2nd hours after injecting Evans blue (EB) through tail vein. The left mice were killed for alveolar lavage to measure the levels of tumor necrosis factor-α (TNF-α) via enzyme linked immunosorbent assay (ELISA). Results:Comparing with the control group, ARDS model group showed typical ARDS pathological changes, which included the increased W/D ratio (4.951±0.161 vs. 3.449±0.299, P < 0.01) and the content of EB in the lung tissue (μg/g: 0.130±0.027 vs. 0.085±0.011, P < 0.01), the damaged alveolar wall structure, lung congestion and exudates in the alveoli, as well as amounts of inflammatory cells. The pathological score of lung injury (10.33±1.15 vs. 1.67±0.58) and the level of TNF-α in BALF (ng/L: 900.85±247.80 vs. 68.21±5.79) were significantly increased in the ARDS model group (both P < 0.01). Comparing with the ARDS model group, the lung W/D ratio (4.620±0.125 vs. 4.951±0.161) and the EB content in the lung tissue (μg/g: 0.108±0.011 vs. 0.130±0.027) of BaCl 2 pretreatment group were significantly reduced (both P < 0.01). And the damaged pulmonary structural BaCl 2 pretreatment group were significantly alleviated. In addition, the pulmonary pathological score (5.00±1.00 vs. 10.33±1.15) and the level of TNF-α in BALF (ng/L: 169.16±73.33 vs. 900.85±247.80) were significantly decreased (both P < 0.01). Conclusion:Barium chloride pretreatment can improve the lung histopathological changes of ARDS model mice induced by LPS by reducing the permeability of pulmonary capillaries and local inflammatory reaction.Barium chloride has the protective effect against LPS attack in mice model of ARDS.