BACKGROUND:Traumatic brain injury is a condition in which the normal function of the brain is disrupted by a bump or impact to the head.It is necessary to find effective treatments and objective targets that can help doctors diagnose the injury status and restore the brain function of patients. OBJECTIVE:To explore the effect of electroacupuncture combined with low-frequency transcranial ultrasound stimulation on the electroencephalographic signals of rats with traumatic brain injury. METHODS:Forty 6-week-old SPF male Sprague-Dawley rats were randomly divided into five groups:sham group,model group,electroacupuncture group,low-frequency transcranial ultrasound stimulation group and combined group(electroacupuncture+low-frequency transcranial ultrasound stimulation),with eight rats in each group.Feeney weight-drop method was used to establish the animal model of traumatic brain injury.In the sham group,the bone window was only opened without impact.Interventions were started at 1 day after modeling.Electroacupuncture in the electroacupuncture group,low-frequency transcranial ultrasound stimulation in the low-frequency transcranial ultrasound stimulation group,and electroacupuncture+low-frequency transcranial ultrasound stimulation in the combined group were performed for days in total.The modified neurological severity scale score for assessing rats'neurological deficits was performed at 8 hours after modeling.The percentage of spontaneous alternation behavior in the Y-maze was measured at 7 days after modeling.Then,the electroencephalographic signals were collected and electroencephalographic data of α,β,θ,and δ waves were extracted by fast Fourier transform,and the value of oscillation amplitude and energy ratio were calculated in α,β,θ,and δ waves,as well as the Lempel-Ziv complexity and sample entropy. RESULTS AND CONCLUSION:Compared with the sham group,the modified neurological severity scale scores in the model group,electroacupuncture group,low-frequency transcranial ultrasound stimulation group and combined group were significantly increased at 8 hours after modeling(P<0.05).Compared with the sham group,the value of oscillation amplitude in δ wave and the value of δ energy ratio were significantly increased in the model group at 7 days after modeling,meanwhile the percentage of spontaneous alternation behavior in Y-maze,and the value of α/β energy ratio,Lempel-Ziv complexity,and sample entropy were significantly decreased(P<0.05).Compared with the model group,the value of oscillation amplitude in α and δ waves was significantly decreased in the combined group(P<0.05),while the value of α/β energy ratio was significantly increased(P<0.05)and the value of δ energy ratio was significantly decreased(P<0.05)in the electroacupuncture group,low-frequency transcranial ultrasound stimulation group and combined group.Compared with the electroacupuncture group and low-frequency transcranial ultrasound stimulation group,the value of δ energy ratio was significantly decreased in the combined group(P<0.05),while the percentage of spontaneous alternation behavior,the value of α/β energy ratio,the Lempel-Ziv complexity,and the sample entropy were significantly increased(P<0.05).To conclude,abnormal electroencephalographic signals can appear in rats with traumatic brain injury,while the electroacupuncture combined with low-frequency transcranial ultrasound stimulation can alleviate the abnormal electroencephalographic signals in rats,which suggests the electroencephalographic frequency domain value and nonlinear features can be used to assess the severity of traumatic brain injury.

ObjectiveBased on analytic hierarchy process（AHP）-criteria importance through intercriteria correlation（CRITIC） hybrid weighting method， grey relational analysis and backpropagation artificial neural network（BP-ANN）， to optimize the water extraction process of Qizhi prescription， so as to provide an experimental basis for optimization of the preparation process of this prescription and the establishment of quality standards. MethodsL₉（3⁴） orthogonal test was employed， and the AHP-CRITIC hybrid weighting method was utilized to determine the weight coefficients of the quality fractions of various components， including astragaloside Ⅳ， polygalaxanthone Ⅲ， calycosin-7-O-β-D-glucoside， tenuifolin， and 3，6′-disinapoylsucrose， as well as the dry extract yield. The comprehensive score of each factor level combination in the orthogonal test were calculated as evaluation indicator to select the optimal extraction process parameters. The effects of extraction times， extraction time， and solvent dosage on the aqueous extraction process of the formula were investigated through intuitive analysis， variance analysis， and grey relational analysis. Meanwhile， a BP-ANN model was established to reverse-predict the optimal extraction process parameters of Qizhi prescription， and the optimized process parameters were validated. ResultsThe weight coefficients of the five index components（astragaloside Ⅳ， tenuifolin， calycosin-7-O-β-D-glucoside， polygalaxanthone Ⅲ， and 3，6′-disinapoylsucrose） and dry extract yield were 25.7%， 20.82%， 16.41%， 12.45%， 15.96% and 8.67%， respectively. The optimized extraction process parameters were extracted 3 times with 8， 6， 6 times the amount of water， each time for 1 h. The network prediction results of BP-ANN test samples were consistent with the orthogonal test results， and the mean square error（MSE） of the predicted and measured values of the network was <1%. The water extraction process of Qizhi prescription analyzed and predicted by relevant mathematical models was stable and feasible， which could effectively improve the extraction efficiency of the active ingredients of Astragali Radix and Polygalae Radix， and the average comprehensive score of the validation test was 90.85 with the relative standard deviation（RSD） of 1.55%. ConclusionThis study establishes a water extraction process for compound Qizhi granules， and the optimized extraction process can effectively improve the extraction efficiency of active ingredients， which provides useful references for the optimization of preparation process and the establishment of quality standards for other clinical experience formulas.

Background Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the development of metabolic syndrome (MS). However, the role of amino acids in PAH-induced MS remains unclear. Objective To explore the impact of PAHs exposure on the incidence of MS among coking workers, and to determine potential modifying effect of amino acid on this relationship. Methods Unmatched nested case-control design was adopted and the baseline surveys of coking workers were conducted in two plants in Taiyuan in 2017 and 2019, followed by a 4-year follow-up. The cohort comprised 667 coking workers. A total of 362 participants were included in the study, with 84 newly diagnosed cases of MS identified as the case group and 278 as the control group. Urinary levels of 11 PAH metabolites and plasma levels of 17 amino acids were measured by ultrasensitive performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Logistic regression was used to estimate the association between individual PAH metabolites and MS. Stratified by the median concentration of amino acids, Bayesian kernel machine regression (BKMR) model was employed to assess the mixed effects of PAHs on MS. Due to the skewed data distribution, all PAH metabolites and amino acids in the analysis were converted by natural logarithm ln (expressed as lnv). Results The median age of the 362 participants was 37 years, and 83.2% were male. Compared to the control group, the case group exhibited higher concentrations of urinary 2-hydroxyphenanthrene (2-OHPhe), 9-hydroxyphenanthrene (9-OHPhe), and hydroxyphenanthrene (OHPhe) (P=0.005, P=0.049, and P=0.004, respectively), as well as elevated levels of plasma branched chain amino acid (BCAA) and aromatic amino acid (AAA) (P<0.05). After being adjusted for confounding factors, for every unit increase in lnv_2-OHPhe in urine, the OR (95%CI) of MS was 1.57 (1.11, 2.26), and for every unit increase in lnv_OHPhe, the OR (95%CI) of MS was 1.82 (1.16, 2.90). Tyrosine, leucine, and AAA all presented a significant nonlinear correlation with MS. At low levels, tyrosine, leucine, and AAA did not significantly increase the risk of MS, but at high levels, they increased the risk of MS. In the low amino acid concentration group, as well as in the low BCAA and low AAA concentration groups, it was found that compared to the PAH metabolite levels at the 50th percentile (P₅₀), the log-odds of MS when the PAH metabolite levels was at the 75th percentile (P₇₅) were 0.158 (95%CI: 0.150, 0.166), 0.218 (95%CI: 0.209, 0.227), and 0.262 (95% CI: 0.241, 0.282), respectively, However, no correlation between PAHs and MS was found in the high amino acid concentration group. Conclusion Amino acids modify the effect of PAHs exposure on the incidence of MS. In individuals with low plasma amino acid levels, the risk of developing MS increases with higher concentrations of mixed PAH exposure. This effect is partly due to the low concentrations of BCAA and AAA.

Polygonatum sibiricum， as a traditional Chinese medicine with both medicinal and edible properties， has attracted considerable attention due to its functions of nourishing Yin and moistening the lungs， tonifying the spleen and benefiting Qi， and nourishing the kidneys and filling essence. Recent studies have demonstrated that Polygonatum sibiricum plays a significant role in regulating the immune system， effectively enhancing and improving the morphology and function of immune organs， stimulating the proliferation and activation of immune cells， and regulating the secretion and release of immune factors， thereby enhancing the immune function of the body and improving various immune-related diseases. Although a large number of studies have explored the pharmacological effects and mechanisms of P. sibiricum， there has been no systematic review and summary of its immune regulatory activity and mechanisms. Therefore， this article comprehensively reviews the research achievements of P. sibiricum polysaccharides and saponins in the field of immune regulation in recent years， and further sorts out the immune regulatory mechanisms of P. sibiricum in multiple aspects： including increasing the organ index of the spleen and thymus， increasing the number and activity of tumor-suppressive bone marrow hematopoietic stem cells， improving intestinal flora imbalance， regulating the quantity and proportion of T lymphocyte subsets， increasing the level of immunoglobulin， promoting the proliferation of macrophages， enhancing the activity of natural killer cells， increasing the number of white blood cells， and promoting the maturation of dendritic cells， providing a solid theoretical basis and scientific evidence for the research and application of P. sibiricum， and promoting its development and application in traditional Chinese medicine immune enhancers and various functional products.

ObjectiveTo investigate the brain absorption components of Tianyuan Zhitong prescription and their distribution based on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， desorption electrospray ionization mass spectrometry imaging（DESI-MSI） and hyperspectral imaging techniques. MethodTen BALB/c mice were randomly divided into blank group（n=3） and administration group（n=7）， the administration group was gavaged with 0.3 mL of Tianyuan Zhitong prescription liquid at a concentration of about 5 g·mL^-1 of the raw material， and the blank group was gavaged with an equal volume of normal saline， and the whole brain of the mice were taken for the preparation of tissue homogenates and frozen sections， respectively. The tissue homogenates were qualitatively analyzed by UPLC-Q-TOF-MS for the brain absorption components in positive and negative ion modes， frozen sections were used for imaging to observe the distribution of these components in the brain. Cytoviva dark-field enhancement microscope was used to perform hyperspectral imaging scanning on the brain sections of mice from each group， and the scattered light data of at least 1 000 pixels in the visible-near-infrared（400-1 000 nm） band in the microscopic field of view were collected and average spectrum were created， which were used to compare the components in the brain tissues of mice from the blank and administration groups. ResultA total of 27 brain absorption components of Tianyuan Zhitong prescription were identified by UPLC-Q-TOF-MS， including 10 organic acids， 5 glycosides， 4 alkaloids， 1 phenol， 4 flavonoids， 2 phthalides and 1 other compound， which were mainly derived from Gastrodiae Rhizoma， Chuanxiong Rhizoma， vinegar-processed Corydalis Rhizoma， Ziziphi Spinosae Semen and processed Morindae Officinalis Radix. A total of 14 components were identified by mass spectrometry imaging， of which ferulic acid， tetrahydropalmatine and N-methyl dehydroberberine were mainly distributed in the cerebral cortex， vitamin B₅， vemonoic acid and ricinoleic acid were mainly distributed in the hypothalamus， elemicin， octadecenic acid and octadecanoic acid were mainly distributed in the cortex and hypothalamus， while senkyunolide B， ligustilide， linoleic acid， 9，12-octadecadienoyl ethyl ester and spinosin were distributed in most regions of the brain tissues. Hyperspectral imaging showed that in the visible-near-infrared band range， the average spectrum of the brain tissues of mice in the administration group was significantly red-shifted， indicating that there were differences in the physical properties or contents of the chemical components in the brain between mice in the blank group and those in the administration group， and further verified the results of mass spectrometry imaging. ConclusionThrough the combination of UPLC-Q-TOF-MS and imaging techniques， the pharmacodynamic components of Tianyuan Zhitong prescription in the treatment of headache and the regional characteristics in brain tissue are clarified， which can provide reference for the selection of the index components of the research on the quality standard of this prescription and the research on the mechanism of the pharmacological effect.

Objective Taking Sortilin as the entry point,this study aims to explore the mechanism of vascular calcification in chronic renal failure(CRF)and explore the influence of Sanqi on Sortilin,TLRs and vascular calcification,and to provide an effective method for clinical reduction of cardiovascular events in CRF.Methods Thirty-six male SD rats were randomly divided into normal group,model group,low-,medium-and high-dose Sanqi group and calcitriol group,with 6 rats in each.The replicative CRF vascular calcification rat model was fed with adenine combined with high phosphorus diet.Aortic calcium salt deposition,serum creatinine(Scr),urea nitrogen(BUN),blood calcium(Ca),blood phosphorus(P),total cholesterol(TC),triglyceride(TG),TLRs and Sortilin protein in aorta and inflammatory factors were detected.Results In the model group,renal fibrosis was obvious and many adenine crystals were found in renal interstitium.Large deposits of calcium salts were found.Renal fibrosis and calcium salt deposition were alleviated in different degrees in all treatment groups.Compared with those in the normal group,the level of BUN,Cr,P,TG,TC,IFN-γ,IL-6,IL-10 and IL-17A in the serum of the model group was ascended(P<0.01),while the level of Ca was descended(P<0.01).Compared with those in the model group,the level of BUN,Cr,P,TG,TC,IFN-γ,IL-6,IL-10 and IL-17A in the serum of rats in the Sanqi medium and high dose group and calcitriol group was significantly decreased(P<0.01),and the contents of Ca were significantly increased(P<0.05 or P<0.01).Compared with those in the normal group,the protein expression of BMP2,RUNX2,Sortilin,TLR7 and TLR9 in aortic tissue of rats in the model group was elevated(P<0.01),while the protein expression of SM22α was declined(P<0.01).Compared with those in the model group,the protein expression of BMP2,RUNX2,Sortilin,TLR7,and TLR9 in the low-,medium-,and high-dose Sanqi group and calcitriol group was decreased significantly(P<0.01);the protein expression of SM22α was increased significantly(P<0.05 or P<0.01),and the high-dose Sanqi group and calcitriol group had more significant effects.Conclusion Sanqi can improve renal fibrosis and vascular calcification in CRF model rats,and its mechanism may be related to the regulation of biological functions of Sortilin and TLRs.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Fanconi anemia (FA) is an inheritable disorder that presents with bone marrow failure, developmental anomalies, and an increased susceptibility to cancer. The etiology of this condition stems from a genetic mutation that disrupts the proper repair of interstrand DNA cross-links (ICLs). The resultant dysregulation of the DNA damage response mechanism can induce genomic instability, thereby elevating the mutation rates and the likelihood of developing cancer. The FA pathway assumes a pivotal role in safeguarding genome stability through its involvement in the repair of DNA cross-links and the maintenance of overall genomic integrity. A mutation in the germ line of any of the genes responsible for encoding the FA protein results in the development of FA. The prevalence of aberrant FA gene expression in somatic cancer, coupled with the identification of a connection between FA pathway activation and resistance to chemotherapy, has solidified the correlation between the FA pathway and cancer. Consequently, targeted therapies that exploit FA pathway gene abnormalities are being progressively developed and implemented. This review critically examines the involvement of the FA protein in the repair of ICLs, the regulation of the FA signaling network, and its implications in cancer pathogenesis and prognosis. Additionally, it explores the potential utility of small-molecule inhibitors that target the FA pathway.

Objective To analyze the clinical characteristics of thyroid dysfunction induced by camrelizumab in the treatment of classical Hodgkin lymphoma(cHL)and explore the influencing factors.Methods The medical records of cHL patients treated with camrelizumab from January 1st,2017 to December 31st,2020,were collected.The clinical characteristics of thyroid dysfunction induced by camrelizumab were analyzed,and the influencing factors of adverse drug reactions(ADRs)were discussed.Results A total of 47 patients were included,12 patients(25.53%)experiencing thyroid dysfunction after receiv-ing camrelizumab.Among them,3 patients had hypothyroidism,7 had subclinical hypothyroidism,and 2 had subclinical hyperthy-roidism.The severity of ADRs was between grade 1 and 2(mild to moderate).None of the patients with thyroid dysfunction dis-continued camrelizumab.Thyroid dysfunction occurred between 1 and 22 months after camrelizumab treatment,with a median time of 6 months.2 patients with hypothyroidism treated with levothyroxine,the thyroid function returned to normal in 1 patient and was improved in the other.1 patient with subclinical hypothyroidism was treated with levothyroxine with the thyroid function continued to be abnormal.The rest of the 9 patients with thyroid dysfunction received no intervention,and 4 of them returned to normal,and others remained with no obvious change or loss in follow-up.Thyroid dysfunction was associated with baseline thyroid stimulating hormone level(P=0.03).The level of thyroglobulin antibodies and thyroid peroxidase antibodies was increased in 2 patients a-mong 3 patients with moderate thyroid dysfunction.Conclusion The incidence of thyroid dysfunction induced by camrelizum-ab in cHL was high.Camrelizumab-induced thyroid dysfunction was related to TSH baseline level(P=0.03).The severity was between grade 1 and 2,which was related to the level of TgAb and TPOAb.The subtype of thyroid dysfunction was mainly sub-clinical hypothyroidism with a long period.Patients could continue camrelizumab treatment,and the thyroid function of patients with grade 2 hypothyroidism was improved after the treatment with levothyroxine.

【Objective】 To establish a blood quality monitoring indicator system, in order to continuously improve blood quality and standardized management. 【Methods】 Based on the research of literature and standards, and guided by the key control points of blood collection and supply process, the blood quality monitoring indicator system was developed. Through two rounds of Delphi expert consultation, the indicator content was further revised and improved according to expert opinions after six months of trial implementation. The indicator weight was calculated by questionnaire and analytic hierarchy process. 【Results】 A blood quality monitoring indicator system covering the whole process of blood collection and supply was constructed, including five primary indicators, namely blood donation service, blood component preparation, blood testing, blood supply and quality control, as well as 72 secondary indicators, including definitions, calculation formulas, etc. Two rounds of expert consultation and two rounds of feasibility study meeting were held to revise 17 items and the weight of each indicator was obtained through the analytic hierarchy process. After partial adjustments, a blood quality monitoring indicator system was formed. 【Conclusion】 A blood quality monitoring indicator system covering the whole process of blood collection and supply has been established for the first time, which can effectively evaluate the quality management level of blood banks and coordinate blood quality control activities of blood banks in Shandong like pieces in a chess game, thus improving the standardized management level