OBJECTIVE To evaluate the efficacy and safety of Weiyan Tongluo Granules in treating chronic atrophic gastritis(CAG)and explore its potential mechanisms.METHODS From June 2020 to December 2022,100 CAG patients with spleen defi-ciency and blood stasis syndrome were enrolled and randomly divided into a trial group(n=50)and a control group(n=50)using a random number table.The trial group received Weiyan Tongluo Granules plus a folic acid placebo,while the control group received fo-lic acid tablets plus a traditional Chinese medicine granule placebo.The treatment course for both groups was 24 weeks,with 8 and 10 dropouts in the trial and control groups,respectively.Post-treatment comparisons included OLGA/OLGIM staging reversal rates,low-grade intraepithelial neoplasia regression rate,SSDPRO-CG(Patient-Reported Outcome Scale for Chronic Gastritis in Spleen-Stomach Diseases)scores,TCM syndrome scores,and safety indicators.Serum levels of PG I,PGⅡ,PGR,and G-17 were measured via ELISA before and after treatment.Gastric mucosal p-NF-κB and CDX2 protein expression levels were analyzed by Western blot,while mRNA levels of IL-1β,IL-6,VIL1,and MUC2 were quantified via qPCR.RESULTS After treatment,the trial group showed sig-nificantly higher OLGA and OLGIM stage reversal rates than the control group(P<0.05,P<0.01),though no significant difference was observed in low-grade intraepithelial neoplasia regression.Both groups exhibited significant improvements in physiological domain scores and total SSDPRO-CG scores(P<0.01),with the trial group outperforming the control group in physiological,independence,psychological domains,and total scores(P<0.05,P<0.01).TCM syndrome scores(total and sub-items:gastric distension,pain,poor appetite,bloating)decreased significantly in both groups(P<0.01),while the trial group showed greater reductions in loose stools and dull complexion(P<0.01).After-treatment,the trial group had significantly lower TCM syndrome scores than the control group(P<0.05,P<0.01).Serum PG I,PGⅡ,PGR,G-17,gastric mucosal p-NF-κB,CDX2,and IL-1β,IL-6,VIL1,MUC2 mRNA levels improved significantly in the trial group(P<0.05,P<0.01),while the control group improved only in PGⅡ(P<0.05,P<0.01).The trial group's improvements in these biomarkers surpassed the control group's(P<0.05,P<0.01).No treatment-related adverse events occurred in either group.CONCLUSION Weiyan Tongluo Granules ameliorate gastric mucosal pathology,clinical symptoms,psychological state,and quality of life in CAG patients without significant adverse effects.Its mechanism may involve sup-pressing the NF-κB pathway to reduce IL-1β and IL-6 expression,downregulating CDX2 to inhibit VIL1 and MUC2 transcription,thereby reversing the vicious cycle of inflammation-intestinal metaplasia.

OBJECTIVE To evaluate the efficacy and safety of Weiyan Tongluo Granules in treating chronic atrophic gastritis(CAG)and explore its potential mechanisms.METHODS From June 2020 to December 2022,100 CAG patients with spleen defi-ciency and blood stasis syndrome were enrolled and randomly divided into a trial group(n=50)and a control group(n=50)using a random number table.The trial group received Weiyan Tongluo Granules plus a folic acid placebo,while the control group received fo-lic acid tablets plus a traditional Chinese medicine granule placebo.The treatment course for both groups was 24 weeks,with 8 and 10 dropouts in the trial and control groups,respectively.Post-treatment comparisons included OLGA/OLGIM staging reversal rates,low-grade intraepithelial neoplasia regression rate,SSDPRO-CG(Patient-Reported Outcome Scale for Chronic Gastritis in Spleen-Stomach Diseases)scores,TCM syndrome scores,and safety indicators.Serum levels of PG I,PGⅡ,PGR,and G-17 were measured via ELISA before and after treatment.Gastric mucosal p-NF-κB and CDX2 protein expression levels were analyzed by Western blot,while mRNA levels of IL-1β,IL-6,VIL1,and MUC2 were quantified via qPCR.RESULTS After treatment,the trial group showed sig-nificantly higher OLGA and OLGIM stage reversal rates than the control group(P<0.05,P<0.01),though no significant difference was observed in low-grade intraepithelial neoplasia regression.Both groups exhibited significant improvements in physiological domain scores and total SSDPRO-CG scores(P<0.01),with the trial group outperforming the control group in physiological,independence,psychological domains,and total scores(P<0.05,P<0.01).TCM syndrome scores(total and sub-items:gastric distension,pain,poor appetite,bloating)decreased significantly in both groups(P<0.01),while the trial group showed greater reductions in loose stools and dull complexion(P<0.01).After-treatment,the trial group had significantly lower TCM syndrome scores than the control group(P<0.05,P<0.01).Serum PG I,PGⅡ,PGR,G-17,gastric mucosal p-NF-κB,CDX2,and IL-1β,IL-6,VIL1,MUC2 mRNA levels improved significantly in the trial group(P<0.05,P<0.01),while the control group improved only in PGⅡ(P<0.05,P<0.01).The trial group's improvements in these biomarkers surpassed the control group's(P<0.05,P<0.01).No treatment-related adverse events occurred in either group.CONCLUSION Weiyan Tongluo Granules ameliorate gastric mucosal pathology,clinical symptoms,psychological state,and quality of life in CAG patients without significant adverse effects.Its mechanism may involve sup-pressing the NF-κB pathway to reduce IL-1β and IL-6 expression,downregulating CDX2 to inhibit VIL1 and MUC2 transcription,thereby reversing the vicious cycle of inflammation-intestinal metaplasia.

Primary central nervous system lymphoma (PCNSL) is a highly aggressive malignant lymphoma. As most chemotherapy drugs have difficulty in crossing the blood-brain barrier, PCNSL shows a difficulty in clinical treatment, a high recurrence rate and a poor prognosis. Early identification of relapsed patients and prompt initiation of salvage therapy play a critical role in the improvement of patients' prognosis. Brain biopsy is the gold standard to identify recurrence, while the risk of operation failure and complications is still high. Non-invasive imaging techniques are beneficial for early identification of recurrence in PCNSL and can provide an important basis for guiding relapsed patients to adjust treatment plans in time. However, there is no unified evaluation standard for imaging methods of monitoring the relapsed lesions of PCNSL. With the further research of the pathophysiological mechanism of PCNSL, biomarker detection has become a new method to identify recurrence and more clinical evidence is still needed in the future.

Insomnia is an important problem facing the global public health field,presenting high morbidity and low treatment efficiency,while Tibetan medicine has rich clinical experience in treating insomnia,showing certain regional characteristics.The article adopts the method of documentary evidence to trace and analyse the diagnosis and treatment theories of Tibetan doctors on insomnia through the ages,It was found that due to three functional disorders,Bacon's inability to concentrate on the heart was the main pathogenesis of the disease,and divides into Tsh yer,Grng yer,and Gdon yer,three mainstream types of evidence.The treatment method adopted the traditional"quadruple"therapy of Tibetan medicine and carried out step treatment or comprehensive conditioning.To achieve three factors of balance,awakening and sleep in tune with the state.The article provides theoretical references to promote the standardization of the clinical diagnosis and treatment application of insomnia in Tibetan medicine and to promote the diversification of the insomnia treatment field.

Insomnia is an important problem facing the global public health field,presenting high morbidity and low treatment efficiency,while Tibetan medicine has rich clinical experience in treating insomnia,showing certain regional characteristics.The article adopts the method of documentary evidence to trace and analyse the diagnosis and treatment theories of Tibetan doctors on insomnia through the ages,It was found that due to three functional disorders,Bacon's inability to concentrate on the heart was the main pathogenesis of the disease,and divides into Tsh yer,Grng yer,and Gdon yer,three mainstream types of evidence.The treatment method adopted the traditional"quadruple"therapy of Tibetan medicine and carried out step treatment or comprehensive conditioning.To achieve three factors of balance,awakening and sleep in tune with the state.The article provides theoretical references to promote the standardization of the clinical diagnosis and treatment application of insomnia in Tibetan medicine and to promote the diversification of the insomnia treatment field.

Objective:To investigate the causes of immune failure in the population with high vaccination rate of measles and rubella vaccine in Beijing by detecting the IgG antibody affinity in suspected cases of measles and rubella.Methods:Serum samples of 276 suspected cases of measles and rubella were tested for IgM and IgG antibodies by enzyme-linked immunosorbent assay (ELISA). The affinity of IgG antibody was detected, and the relative affinity index was calculated.Results:Among the 276 suspected cases, 104 were measles and 108 were rubella. Six measles cases had vaccination history and were caused by primary immunization failure ( n=3) and secondary immunization failure ( n=3). Twelve rubella cases had vaccination history and were due to primary immunization failure ( n=4) and secondary immunization failure ( n=8). Specific high-affinity antibodies were detected in nine measles cases and seven rubella cases without vaccination history, which indicated that these cases were reinfected. In the cases without measles or rubella, other pathogenic infections including mixed infections were detected, which were mainly caused by EB virus. Conclusions:Both primary and secondary immunization failure occurred in the population with immunization history. Reinfection was found in the patients who had not received vaccination against measles or rubella. Other pathogenic infections were existed among the cases without measles or rubella. Thus, misdiagnosis was responsible for the increased proportion of measles and rubella patients with immunization history in suspected cases in recent years. Full-course vaccination was conducive to produce high-affinity antibodies against measles and rubella. A supplementary vaccination campaign should be launched to consolidate the immune barrier against measles and rubella in key population or high-risk population, aiming to block the circulation of measles virus and achieve the goal of eliminating measles.

Objective:To investigate the role of neurite outgrowth inhibitor (Nogo)-oligodendrocyte myelin glycoprotein (Omgp)/Ras homologous (Rho)-Rho-associated coiled-coil forming protein kinase (Rock) signaling pathway in acute brain injury of carbon monoxide (CO) poisoning rats and treatment feasibility with Rho kinase inhibitor hydrochloride fasudil.Methods:According to random number table method, 135 healthy male SD rats were divided into three groups: a normal control group, a CO poisoning group and a fasudil treatment group ( n=45). Rat models of acute severe CO poisoning were established in the CO poisoning group and fasudil treatment group by inhalation method in a hyperbaric oxygen chamber. All rats received hyperbaric oxygen therapy for two weeks. Rats in the farsudil treatment group were intraperitoneally injected with hydrochloride farsudil for intervention (15 mg/[kg·d], once a d for 2 weeks), while those in the CO poisoning and normal control groups received the same volume of normal saline. The ultrastructures of rat brain tissues were observed by transmission electron microscopy one week after modeling. Staining intensities of Nogo- and OMgp-positive cells were detected by immunohistochemistry, and those of Rock-positive cells were analyzed by immunofluorescence one d, one week, one month and two months after modeling. The protein expressions of Nogo, OMgp and Rock in brain tissues were detected by Western blotting one d, one week, one month and two months after modeling. Results:In the CO poisoning group, the ultrastructures of brain tissues and blood-brain barrier were damaged obviously, and the changes in nucleus, mitochondria and synaptic structure were obvious; while fasudil treatment could effectively maintain the integrity of ultrastructures and functions of brain tissues, and reduce brain edema. One d, one week, one month and two months after modeling, the staining intensities of Nogo, OMgp and Rock positive cells and protein expression levels of Nogo, OMgp and Rock in the CO poisoning group were significantly higher than those in the normal control group at the same time point ( P<0.05); the staining intensities of Nogo, OMgp and Rock positive cells and protein expression levels of Nogo, OMgp and Rock in the fasudil treatment group were significantly lower than those in the CO poisoning group at the same time point ( P<0.05). Conclusion:The activation of Nogo-OMgp/Rho-Rock signaling pathway related molecules (Nogo, OMgp and Rock) is closely related to acute brain injury caused by CO poisoning; hydrochloride fasudil can effectively down-regulate the protein expressions of Nogo, OMgp and Rock, therefore obviously alleviate brain injury after CO poisoning.

Objective To explore the effects of N-butylphthalide on the expressions of ZO-1 and claudin-5 in blood-brain barrier (BBB) in rats with acute carbon monoxide (CO) poisoning. Methods A total of 144 adult healthy male Sprague-Dawley (SD) rats were randomly divided into normal control group, CO poisoning group, and NBP treatment group, with 48 rats in each group. The acute CO poisoning model was reproduced in hyperbaric oxygen chamber, and all model rats were given hyperbaric oxygen therapy once daily. The rats in the normal control group were free to breathe fresh air. The rats in NBP treatment group were administered orally NBP 60 mg/kg twice a day at 2 hours after poisoning until death. The rats in normal control group and CO poisoning group were treated with equal amount of pure olive oil. Four rats were sacrificed from each group at 1, 3, 7, 14 days after model reproducing, respectively. The changes in ultrastructure of BBB were observed under transmission electron microscope. The expressions of ZO-1 and claudin-5 proteins were determined by immunofluorescence staining and Western Blot. The localization of the two target proteins was observed by immunofluorescence double staining. The correlation between the two proteins was analyzed by linear regression. Results The ultrastructure of BBB was normal in normal control group, some ZO-1 and a large number of claudin-5 positive cells were observed. The ultrastructure of BBB was seriously injured, ZO-1 and claudin-5 positive cells in brain tissue were significantly decreased, and the expressions of ZO-1 and claudin-5 proteins in brain tissue at 1 day after poisoning in CO poisoning group were significantly lower than those of normal control group (ZO-1 protein:3.38±0.30 vs. 24.50±5.62, claudin-5 protein: 11.38±0.93 vs. 46.35±6.88, both P < 0.05), and although gradually restored, they were maintained at relatively lower levels until 14 days as compared with those in normal control group (ZO-1 protein: 10.35±0.80 vs. 24.63±3.57, claudin-5 protein: 32.35±3.11 vs. 46.43±7.20, both P < 0.05). NBP treatment could significantly alleviate the ultrastructure injury of BBB induced by acute CO poisoning, the amount of ZO-1 and claudin-5 positive cells in brain tissue were significantly increased, as well as the expressions of ZO-1 and claudin-5 proteins were significantly increased, which were significantly higher than those of CO poisoning group from 1 day and 3 days on, respectively (1-day ZO-1 protein: 7.57±0.69 vs. 3.38±0.30, 3-day claudin-5 protein:20.46±1.42 vs. 11.43±0.86, both P < 0.05), and which showed an increase tendency with time prolongation. The results of immunofluorescence double staining showed that ZO-1 and claudin-5 proteins could not only coexist in the same cell, but also could be expressed separately in different cells. Linear regression analysis showed the positive correlation between the expressions of ZO-1 and claudin-5 proteins in brain tissue of rats with acute CO poisoning (R2= 0.917, P = 0.022). Conclusion NBP could markedly improve the ultrastructure and functional integrity of BBB through up-regulating the expressions of ZO-1 and claudin-5 proteins, and then reduce brain damage caused by CO poisoning.

Objective To investigate the therapeutic effects of Xingzhi Yinao (XZYN) particles combined with hyperbaric oxygen therapy on cognitive impairment and motor dysfunction in patients with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). Methods Sixty-seven patients with DEACMP were admitted to the Affiliated Yantai Yuhuangding Hospital of Qingdao University from January 2011 to December 2015, and they were randomly divided into a control group (given conventional treatment such as inhalation of oxygen, cytidine diphosphate cholin and vitamin B, 19 cases), a hyperbaric oxygen (HBO) treatment group (given conventional treatment + hyperbaric oxygen therapy once a day, 24 cases) and a XZYN particles treatment (XZYN group, given conventional treatment, hyperbaric oxygen and XZYN particles, 24 cases), the therapeutic course being 2 months in the three groups. Before and after treatment for 1 and 2 months, the cognitive function and motor function of the patients were evaluated by the use of activity of daily living (ADL) scale, Montreal cognitive assessment (MoCA) scale, and mini-mental state examination (MMSE) scale; the severity of cerebral white matter injury was assessed by age related white matter changes (ARWMC) scale; and the electromyographic evoked potential was used to detect the amplitude and latency of P300 to assess the severity of cognition impairment and prognosis. Results With the prolongation of therapeutic time, after treatment, the neurological function scores of ADL, MoCA, MMSE and amplitude of P300 were increased, while ARWMC was decreased and the latency of P300 was shortened gradually in the three groups, and the changes of above indexes after treatment for 2 months in XZYN group were more significant than those in either HBO group or control group[ADL score: 70.2±8.3 vs. 60.5±8.1, 23.0±6.1, MoCA score: 26.1±3.1 vs. 22.2±2.7, 18.2±3.6, MMSE score:25.9±4.1 vs. 22.4±3.5, 18.1±4.5, ARWMC score: 7.0±2.1 vs. 8.7±2.2, 15.2±3.3, latency of P300 (ms):332.9±20.4 vs. 352.5±23.6, 381.7±30.3, amplitude of P300 (μV): 6.5±1.6 vs. 5.6±1.3, 4.1±1.5, all P < 0.05]. Conclusion The hyperbaric oxygen therapy combined with XZYN particles for treatment of patients with DEACMP can significantly improve their cognitive and motor functions and ameliorate the severity of cerebral white matter injury.

Objective To investigate the effects of N-butylphthalide (NBP) on cognitive function in acute severe carbon monoxide (CO) poisoning rats and its mechanism. Methods 120 health Sprague-Dawley (SD) rats were randomly divided into three groups (n = 40): normal control group (NC group), CO poisoning group (CO group) and NBP treatment group (NBP group). The acute severe CO poisoning model was established in a hyperbaric oxygen chamber by intoxicated with 1 000 ×10-6CO for 40 minutes, followed with 3 000 ×10-6CO for another 20 minutes, and then received hyperbaric oxygen therapy 1.5 hours once a day until sacrificed. Rats in NBP group were administered orally NBP 60 mg/kg for 2 times daily until death. NC group and CO group were treated with equal amount of pure olive oil. Four rats in each group were taken from 1, 3, 7, 14, 30 days after model setup, respectively. The cognitive function score was assessed by Morris water maze test. The changes in ultrastructure of hippocampus were observed under transmission electron microscope. The expressions of calpain 1 and Ca2+/calmodulin dependent protein kinase Ⅱ(CaMK Ⅱ) in hippocampus of brain tissue were detected by immunofluorescence staining, and the localization of the two target proteins in neurons was observed by immunofluorescence double staining. Results Compared with NC group, the escape latency at 1 day after poisoning in CO group was significantly prolonged (s: 55.6±3.2 vs. 44.5±3.5, P < 0.05), and the times of the platform crossing was significantly decreased (times: 1.3±0.8 vs. 6.6±1.2, P < 0.05);the ultrastructure of hippocampus was obviously injured; the protein expressions of calpain 1 and CaMK Ⅱ in brain tissue were significantly increased at 1 day after CO poisoning [calpain 1 (A value): 41.24±5.21 vs. 6.44±1.13, CaMK Ⅱ (A value): 56.19±5.04 vs. 9.84±1.53, both P < 0.05], and the protein expression of calpain 1 reached the peak at 3 days (A value: 59.34±6.11), the protein expression of CaMK Ⅱ reached the peak at 1 day (A value:56.19±5.04). Compared with CO group, the cognitive function was significantly improved in NBP group in the late stage of poisoning [7-30 days, escape latency (s): 40.3±1.9 vs. 49.1±3.1 at 7 days, 30.1±2.9 vs. 39.4±3.1 at 30 days;times of the platform crossing (times): 2.8±1.0 vs. 1.0±0.9 at 14 days, 3.2±0.8 vs. 1.0±0.9 at 30 days, all P < 0.05];the degree of injury of hippocampal neuron was relatively slight; the protein expression of calpain 1 in brain tissue was significantly decreased from 3 days after CO poisoning (A value: 39.63±3.03 vs. 59.34±6.11, P < 0.05), and the protein expression of CaMK Ⅱ was significantly decreased from 1 day after CO poisoning (A value: 42.22±3.84 vs. 56.19±5.04, P < 0.05). Immunofluorescence double staining suggested that calpain 1 and CaMK Ⅱ protein could not only coexist in the same cell, but also could be expressed separately in different cells. Linear regression analysis showed that the expression of calpain 1 and CaMK Ⅱ was positively correlated (R 2= 0.852, P = 0.002). Conclusions NBP treatment could maintain ultrastructure integrity of hippocampus, balance the expression levels of calpain 1 and CaMK Ⅱproteins, and significantly improve cognitive impairment induced by CO poisoning, thus play a protective role against hippocampus damage in rats with acute severe CO poisoning.