AIM: To investigate the relationship between the levels of interleukin-6(IL-6)and IL-2 in aqueous humor and the severity of optic nerve injury in patients with primary open-angle glaucoma(POAG), and to construct a decision tree model for the severity of optic nerve injury in POAG patients.METHODS: A prospective study was conducted on 107 patients(107 eyes)with POAG who were admitted to the hospital from May 2021 to October 2023. According to the mean defect(MD)value, the degree of optic nerve injury was judged and divided into three groups: mild, moderate and severe. The general data, IL-6 and IL-2 levels in aqueous humor of patients with different severity of optic nerve injury were compared, and the correlation between the levels of IL-6 and IL-2 in aqueous humor and the severity of optic nerve injury in POAG patients was analyzed. Multivariate Logistic regression analysis was used to test the influencing factors of the severity of optic nerve injury in POAG patients, and the decision tree model was constructed based on influencing factors.RESULTS: The proportion of patients with hypertension, intraocular pressure and binocular intraocular pressure difference in the severe group was higher than that in the mild and moderate groups, and the levels of IL-6 and IL-2 in the aqueous humor were significantly lower than those in the mild and moderate groups(all P<0.05). The levels of IL-6 and IL-2 in aqueous humor of POAG patients were negatively correlated with the severity of optic nerve injury(r=-0.361, -0.358, all P<0.001). Hypertension, intraocular pressure, binocular intraocular pressure difference, IL-6 and IL-2 levels in aqueous humor were independent factors affecting the degree of optic nerve injury in POAG patients(all P<0.05). Based on the above factors, a decision tree model was constructed, and three explanatory variables of IL-6, IL-2 levels in aqueous humor and hypertension were screened out. Among them, IL-2 level in aqueous humor was the most important root node variable and the most important predictor. The AUC of the decision tree model was 0.710(95% CI: 0.599-0.820, P=0.001), the sensitivity was 0.581, the specificity was 0.737, and the Youden index was 0.318, with a high predictive value.CONCLUSION: The levels of IL-6 and IL-2 in aqueous humor were significantly correlated with the severity of optic nerve injury in POAG patients. The decision tree model based on hypertension, intraocular pressure, binocular intraocular pressure difference, IL-6 and IL-2 levels in aqueous humor has a high evaluation value for the severity of optic nerve injury in POAG patients.

AIM: To investigate the relationship between the levels of interleukin-6(IL-6)and IL-2 in aqueous humor and the severity of optic nerve injury in patients with primary open-angle glaucoma(POAG), and to construct a decision tree model for the severity of optic nerve injury in POAG patients.METHODS: A prospective study was conducted on 107 patients(107 eyes)with POAG who were admitted to the hospital from May 2021 to October 2023. According to the mean defect(MD)value, the degree of optic nerve injury was judged and divided into three groups: mild, moderate and severe. The general data, IL-6 and IL-2 levels in aqueous humor of patients with different severity of optic nerve injury were compared, and the correlation between the levels of IL-6 and IL-2 in aqueous humor and the severity of optic nerve injury in POAG patients was analyzed. Multivariate Logistic regression analysis was used to test the influencing factors of the severity of optic nerve injury in POAG patients, and the decision tree model was constructed based on influencing factors.RESULTS: The proportion of patients with hypertension, intraocular pressure and binocular intraocular pressure difference in the severe group was higher than that in the mild and moderate groups, and the levels of IL-6 and IL-2 in the aqueous humor were significantly lower than those in the mild and moderate groups(all P<0.05). The levels of IL-6 and IL-2 in aqueous humor of POAG patients were negatively correlated with the severity of optic nerve injury(r=-0.361, -0.358, all P<0.001). Hypertension, intraocular pressure, binocular intraocular pressure difference, IL-6 and IL-2 levels in aqueous humor were independent factors affecting the degree of optic nerve injury in POAG patients(all P<0.05). Based on the above factors, a decision tree model was constructed, and three explanatory variables of IL-6, IL-2 levels in aqueous humor and hypertension were screened out. Among them, IL-2 level in aqueous humor was the most important root node variable and the most important predictor. The AUC of the decision tree model was 0.710(95% CI: 0.599-0.820, P=0.001), the sensitivity was 0.581, the specificity was 0.737, and the Youden index was 0.318, with a high predictive value.CONCLUSION: The levels of IL-6 and IL-2 in aqueous humor were significantly correlated with the severity of optic nerve injury in POAG patients. The decision tree model based on hypertension, intraocular pressure, binocular intraocular pressure difference, IL-6 and IL-2 levels in aqueous humor has a high evaluation value for the severity of optic nerve injury in POAG patients.

ObjectiveTo observe and compare the electrocardiogram index， myocardial morphology， and connexin 43 （Cx43） expression of two rat models of acute cerebral infarction （ACI） due to stasis combined with toxin complicated with cerebral-cardiac syndrome （CCS）， and to provide experimental evidence for the research on the occurrence mechanism of cardiac diseases induced by ACI and the clinical diagnosis and treatment of CCS. MethodSixty SPF-grade male SD rats were randomized into six groups （n=10）： normal ， syndrome of stasis combined with toxin induced by carrageenin combined with dry yeast （CA/Y）， multi-infarct induced by micro-embolism （ME）， middle cerebral artery occlusion （MCAO）， CA/Y+ME， and CA/Y+MCAO groups. The model of syndrome of stasis combined with toxin was established by intraperitoneal injection with carrageenan （CA） at 10 mg·kg^-1 on the first day and subcutaneous injection with dry yeast （Y） suspension （2 mg·kg^-1） on the second day of modeling. Twenty-four hours after the modeling of ACI， the electrocardiograms （ECGs） of rats in each group were collected and the number/percentage （%） of abnormal ECG was calculated. The infarct area of the brain was evaluated by 2，3，5-triphenyltetrazolium chloride （TTC） staining， and myocardial injury was assessed by hematoxylin-eosin （HE） staining. Immumohistochemical staining and Western blot were employed to determine the expression of Cx43 in the myocardium. ResultA certain number of rats in each model group presented abnormal ECG. Compared with the normal group and CA/Y group， CA/Y+MCAO group had the highest rate of abnormal ECG （P<0.01）. Compared with the normal， CA/Y， ME， and CA/Y+ME groups， the CA/Y+ME and CA/Y+MCAO groups showed decreased amplitudes of P-wave and T-wave， shortened P-R interval， and extended Q-T interval， which were particularly obvious in the CA/Y+MCAO group （P<0.05， P<0.01） and in accordance with the cerebral infarction area and pathological changes. The expression of Cx43 was up-regulated in both CA/Y+ME and CA/Y+MCAO groups， especially in the CA/Y+MCAO group （P<0.01）. ConclusionThe two rat models of ACI due to stasis combined with toxin complicated with CCS can be used to study the mechanism of heart diseases caused by cerebrovascular diseases and the therapeutic effects of Chinese medicines with the functions of resolving stasis and detoxifying. Moreover， the CA/Y+MCAO method has higher abnormal electrocardiogram rate， severer myocardial pathological injury， and higher expression of Cx43 protein. The models can be chosen according to specific experimental purpose.

BACKGROUND: There are few multi-city studies on the association between temperature and mortality in basin climates. This study was based on the Sichuan Basin in southwest China to assess the association of basin temperature with non-accidental mortality in the population and with the temperature-related mortality burden. METHODS: Daily mortality data, meteorological and air pollution data were collected for four cities in the Sichuan Basin of southwest China. We used a two-stage time-series analysis to quantify the association between temperature and non-accidental mortality in each city, and a multivariate meta-analysis was performed to obtain the overall cumulative risk. The attributable fractions (AFs) were calculated to access the mortality burden attributable to non-optimal temperature. Additionally, we performed a stratified analyses by gender, age group, education level, and marital status. RESULTS: A total of 751,930 non-accidental deaths were collected in our study. Overall, 10.16% of non-accidental deaths could be attributed to non-optimal temperatures. A majority of temperature-related non-accidental deaths were caused by low temperature, accounting for 9.10% (95% eCI: 5.50%, 12.19%), and heat effects accounted for only 1.06% (95% eCI: 0.76%, 1.33%). The mortality burden attributable to non-optimal temperatures was higher among those under 65 years old, females, those with a low education level, and those with an alternative marriage status. CONCLUSIONS Our study suggested that a significant association between non-optimal temperature and non-accidental mortality. Those under 65 years old, females, and those with a low educational level or alternative marriage status had the highest attributable burden.
Female ; Humans ; China/epidemiology* ; Cities ; Cold Temperature ; Hot Temperature ; Mortality ; Temperature ; Time Factors ; Middle Aged ; Male

Objective To investigate the correlation between brain injury and spleen damage in a rat model of acute ischemic stroke and stasis interaction,and its effect on the MCP-1/CCR2 axis,and to provide an experimental basis for the mechanism of brain-spleen inflammatory coupling in spleen lesions caused by acute ischemic stroke.Methods Forty male SD rats were randomly divided into a sham group,carrageenan/yeast stasis syndrome group(carrageenan/yeast,CA/Y),middle cerebral artery occlusion group(MCAO),and middle cerebral artery stasis syndrome group(MCAO CA/Y)with 10 rats in each group.CA/Y and MCAO CA/Y groups were injected with 10 mg/kg carrageenan and 10 mg/kg intraperitoneally on the first day of modeling.2 mg/kg of dry yeast suspension were injected subcutaneously on the second day.MCAO and MCAO CA/Y groups were established by wire embolism on the second day.At 24 h after cerebral infarction modeling,the neurological deficit score was calculated in each group,the percentage of the cerebral infarction area was determined by TTC staining,the spleen weight was measured,and the correlation between the percentage of the cerebral infarction area and spleen weight was analyzed by the Spearman correlation coefficient.Furthermore,the pathological morphology of brain and spleen tissues was observed by hematoxylin-eosin(HE)staining,and chemotactic protein 1(MCP-1)and interferon-γ(IFN-γ)contents were measured in rat plasma by enzyme-linked immunosorbent assays.Western blot was used to detect chemokine C-C-motif receptor 2(CCR2)protein expression in the ischemic side of brain tissue.Results Compared with the sham group,the neurological deficit score,cerebral infarction area,and MCP-1 and IFN-γ contents in plasma were significantly increased(P＜0.01),spleen weight was decreased significantly(P＜0.01),and CCR2 protein expression in brain tissue was significantly upregulated(P＜0.05)in MCAO and MCAO CA/Y groups.Moreover,the area of cerebral infarction was increased significantly(P＜0.01),the spleen weight was decreased significantly(P＜0.01),and CCR2 protein expression in brain and spleen tissues was significantly upregulated(P＜0.05)Compared with the MCAO group,the area of cerebral infarction in the MCAO CA/Y group was significantly increased(P＜0.01)and the spleen weight was decreased significantly(P＜0.05).Spearman correlation analysis showed that the spleen weight was negatively correlated to the percentage of the cerebral infarction area(P＜0.01,r=-0.9711).Pathological morphology observation revealed that the pathological changes in the MCAO CA/Y group were the most serious,cerebral liquefaction necrosis foci were seen in the brain tissue cortex,arrangement of neuronal cells in the lesions was sparse and disordered with volume atrophy and a small number of vacuoles and nuclear solidification,most neuronal cells were degenerated and necrotic,microglia hyperplasia was obvious,small blood vessels were significantly increased,and interstitial lipid degeneration was severe.The density of periarterial lymph sheath cells in some of the spleen tissue was reduced and the marginal area is widened.Conclusions A correlation between brain and spleen injury was found after acute ischemic stroke with stasis and toxin syndrome,and the chemokine signaling axis of MCP-1/CCR2 might be involved in the mechanism of brain-spleen inflammation coupling.

Objective:To analyze the clinical characteristics and all-cause mortality influencing factors of patients with Keshan disease.Methods:Clinical data of patients with Keshan disease from Keshan disease areas in Sichuan Province and Yunnan Province were collected and retrospectively analyzed for clinical characteristics and survival status during regular follow-up. According to the survival status of patients, the survey subjects were divided into a survival group and a death group. All-cause mortality (referring to the death caused by various reasons throughout the follow-up period) was used as the study endpoint. Kaplan-Meier (K-M) survival curve analysis and log-rank χ 2 test were performed, univariate and multivariate Cox regression analysis were used for all-cause mortality factor analysis. Results:A total of 176 patients with Keshan disease were collected, including 92 cases in Sichuan Province and 84 cases in Yunnan Province. Among all the patients, there were 105 males, accounting for 59.66%, and 71 females, accounting for 40.34%. The age was (53.89 ± 13.19) years old. Thirty-five cases died from all causes, with a mortality rate of 19.89%. There were significant differences in age ( t = 2.09, P = 0.038), New York Heart Association (NYHA) cardiac function grading (χ 2 = 14.62, P < 0.001) and ventricular premature contraction (χ 2 = 6.82, P = 0.009) between the survival group and the death group. K-M survival curve analysis showed that patients with Keshan disease complicated by premature ventricular contraction and high NYHA cardiac function grading (Ⅲ and Ⅳ) had higher all-cause mortality (log-rank χ 2 = 8.72, 22.49, P < 0.05). Univariate Cox regression analysis showed that NYHA cardiac function grading and ventricular premature contraction ( HR = 3.09, 2.71, P < 0.05) were predictive influencing factors for all-cause mortality in patients with Keshan disease. Multivariate Cox regression analysis showed that NYHA cardiac function grading ( HR = 6.57, P = 0.002) and ventricular premature contraction ( HR = 2.98, P = 0.050) were independent factors for all-cause mortality in patients with Keshan disease. Conclusions:Among 176 patients with Keshan disease, the number of patients with poor cardiac function (NYHA cardiac function grading Ⅲ and Ⅳ) and arrhythmia is high. NYHA cardiac function grading and ventricular premature contractions are independent influencing factors for all-cause mortality in patients with Keshan disease.

Objective:To analyze the clinical characteristics, prognosis and gene mutation in patients with dilated cardiomyopathy (DCM) in Keshan disease area of Sichuan Province, and to explore the risk factors for all-cause death in DCM patients.Methods:In June 2016, 55 DCM patients diagnosed at the local disease prevention and control center through clinical manifestations, electrocardiogram examination, and echocardiography were selected as the survey subjects in Mianning County, Liangshan Yi Autonomous Prefecture, and Renhe District, Panzhihua City, Keshan disease areas of Sichuan Province. Baseline clinical data were analyzed and long-term follow-up was conducted. The follow-up period ended June 15, 2021, with the endpoint of all-cause death. Univariate Cox regression was used to analyze the influencing factors of all-cause death in patients, and Kaplan-Meier (K-M) survival curve was used to analyze the survival time of patients. At the same time, peripheral venous blood was collected from 27 DCM patients. After separating white blood cells, DNA was extracted, and whole exome sequencing was performed to screen potential pathogenic genes.Results:Among the 55 DCM patients, 40 were males and 15 were females. The age was (54.09 ± 12.38) years old. The heart function classification of New York Heart Association (NYHA) was mainly grade Ⅱ and Ⅲ, accounting for 94.55% (52/55). The follow-up time for 55 DCM patients was (7.02 ± 2.96) years, and 17 patients experienced all-cause death, accounting for 30.91% (17/55), including 15 males and 2 females. Compared with the survival group, the death group had a lower incidence of syncope (χ 2 = 6.57, P = 0.010), but higher rates of bilateral lower limb edema (χ 2 = 6.43, P = 0.017), pulmonary congestion (χ 2 = 7.61, P = 0.006), intraventricular conduction block (χ 2 = 6.41, P = 0.011), and angiotensin-converting enzyme inhibitor (ACEI) use (χ 2 = 6.57, P = 0.010), as well as increased left ventricular diameter ( t = 2.36, P = 0.022). Univariate Cox regression analysis showed that bilateral lower limb edema [hazard ratio ( HR) = 4.61, P = 0.042] and intraventricular conduction block ( HR = 3.20, P = 0.019) were risk factors for all-cause death of DCM patients. The results of K-M survival curve analysis showed that patients with bilateral lower limb edema and intraventricular conduction block had higher all-cause death rates (log-rank χ 2 = 5.02, 6.24, P = 0.025, 0.012). Whole exome sequencing results showed that 4 patients were detected to carry pathogenic or suspected pathogenic gene mutations, with a positive rate of 14.81% (4/27), involving three genes: β-myosin heavy chain 7 (MYH7), calreticulin 3 (CALR3), and gelsolin (GSN). Conclusions:The all-cause death rate of DCM patients in the Keshan disease area of Sichuan Province is relatively high. Dead patients are prone to bilateral lower limb edema, pulmonary congestion, and intraventricular conduction block, as well as increased left ventricular diameter. Bilateral lower limb edema and intraventricular conduction block are independent predictive risk factors for all-cause death in DCM patients. MYH7, CALR3 and GSN are involved in the pathogenesis of DCM.

To carry out phylogenetic analysis for drug-resistance genes from clinical isolates of Helicobacter pylori (Hp) among patients with gastric diseases from Tibet, China.

METHODSHp strains were isolated and cultured from saliva and gastric mucosal tissues derived from patients with gastric diseases. Nine strains (including 5 isolated from oral tissues, 1 isolated from gastric tissues, and 3 representative strains of SS international standard strains used for animal models) were tested for common antibiotic resistance. Together with an ACTT 11637 international standard strain, these were subjected to re-sequencing to obtain drug-resistance genes. Such genes from various sources were compared with the resistance genes of Hp strains recorded by the NCBI website. Combined with results of drug-resistance experiments, correlation between molecular evolution and drug-resistance was analyzed.

RESULTSTesting of gastric mucosal tissues and salivary samples from 217 patients has found 89 Hp strains, which yielded a total infection rate of 41.01%. The resistance rates of 9 representative Hp strains for clarithromycin, amoxicillin, metronidazole, levofloxacin and tetracycline were 77.8%, 77.8%, 44.4%, 77.8%, and 77.8%, respectively. Compared with the reference strain, the similarity between clarithromycin-resistance genes was 99%, and that between amoxicillin- and metronidazole-resistance genes was 96%-97%. A2143G mutation was also found in clarithromycin-resistant genes of three Hp strains.

CONCLUSIONThe sensitivity of Hp to metronidazole is much higher in patients from Tibet region, and the sensitivity of Hp to clarithromycin, amoxicillin, levofloxacin and tetracycline is poor. Resistance mutations are consistent with drug resistance.

OBJECTIVE: To investigate the relationship between OPRM1 118A/G gene polymorphism and oxycodone analgesic dose in patients with cancer pain. METHODS: DNA sequencing was used to detect the genotypies of OPRM1 118 A/G site in 203 patients with moderate and severe cancer pain, and to compare the relationship between the pain degree and the dose of oxycodone at 3 and 30 days after treatment in patients with different genotypes. RESULTS: The fequencies of AA, AG and GG genotypes at the OPRM1 118 A/G site were 34.78%, 52.70%, and 12.52%, respectively. The dosage of oxycodone in GG genotype was significantly higher than that in AA genotype and AG genotype (15.44±10.19 vs. 10.25±4.53, 10.49±5.26; 89.15±27.69 vs. 43.59±12.19, 48.27±18.79) on the 3 and 30 day after treatment, difference was statistically significant (P< 0.05). CONCLUSION For cancer pain patients with GG genotype of OPRM1 118A/G site, if they need to achieve the same analgesic effect as patients with AA and AG genotype, the dose of oxycodone should be increased.
Analgesics, Opioid ; administration & dosage ; Cancer Pain ; drug therapy ; Dose-Response Relationship, Drug ; Genotype ; Humans ; Oxycodone ; administration & dosage ; Polymorphism, Single Nucleotide ; Receptors, Opioid, mu ; genetics

Objective Changes of small intestine villus microcirculation perfusion in sidestream dark-field (SDF) imaging in the rabbits during endotoxic shock after fluid resuscitation with different target mean arterial pressure (MAP), and evaluation of feasibility of monitoring small intestine villus microcirculation by SDF were studied. Methods Sixty standard New Zealand white rabbits were randomly divided into two groups: low target MAP group (group A, n = 30) and high target MAP group (group B,n = 30). Fistula operation of ileum was madein vitro, and lipopolysaccharide (LPS, 2 mg/kg) was injected to establish endotoxic shock model. Group A was administered with the lower dose fluid resuscitation (lactated Ringer solution, 20 mL·kg-1·h-1) for target MAP of 65 mmHg (1 mmHg =0.133 kPa); group B was administered with the higher dose fluid resuscitation (lactated Ringer solution, 30 mL·kg-1·h-1) for MAP of 80 mmHg. Continuous norepinephrine intravenous injection (0.5-1.0μg·kg-1·min-1) was administered only after fluid therapy couldn't reach the target MAP. The changes of small intestine villus microcirculation perfusion indexes such as vessels per villus (VV), proportion of perfused villi (PPV), microvascular flow index (MFI), borders of villus score (BVS), vessels villus score (VVS) were continuously observed and recorded before the shock, during the shock and after fluid resuscitation using SDF imaging. The differences of microcirculation perfusion were compared between two groups using the specific parameter evaluation system to determine severity of villi microcirculation and injury scores at different stages.Results VV and borders of villus were clear and contact before shock in two groups. After shock, VV, PPV were significantly decreased in both two groups, the borders of villus were destroyed, MFI, BVS, VVS and the total score of villi injury microcirculation were obviously and severely decreased. Partial blood flow of villous capillaries after fluid resuscitation was recovered in two groups, but the perfusion of some region was un-balanced with the outworn borders of villus. VV were rose as compared before and after fluid resuscitation in groups A and B (vessels: 1.21±0.22 vs. 0.81±0.12, 1.54±0.28 vs. 0.79±0.13), and PPV [(31±4)% vs. (12±2)%, (38±5)% vs. (13±3)%], MFI (1.55±0.09 vs. 1.09±0.03, 1.97±0.11 vs. 1.05±0.03), VVS (points: 1.22±0.08 vs. 0.89±0.02, 2.06±0.15 vs. 0.90±0.02) and the sum of MFI, BVS, VVS (3.70±0.19 vs. 2.85±0.07, 5.01±0.29 vs. 2.88±0.08) were significant rose (allP< 0.05). The recovery of group B was better than that of group A, and the injury score was reduced. But BVS were not increased in both groups compared with before and after shock (points: 0.93±0.05 vs. 0.87±0.03, 0.98±0.09 vs. 0.93±0.05, bothP > 0.05).Conclusions For the small intestine villus microcirculation perfusion, the higher target MAP (80 mmHg) after fluid resuscitation or/and vasoconstrictor drugs usage were probably better than the relatively lower target MAP (65 mmHg) during endotoxic shock. SDF imaging is a very promising technique for intestinal villi microcirculatory visualization and assessment.