BACKGROUND: The American Heart Association (AHA) introduced the concept of cardiovascular-kidney-metabolic (CKM) health and stage, reflecting the interaction among metabolism, chronic kidney disease (CKD), and the cardiovascular system. However, the association between CKM stage and the long-term risk of cardiovascular disease (CVD) has not been validated. This study aimed to evaluate the long-term CVD risk associated with CKM health metrics and CKM stage using data from a population-based cohort study. METHODS: In total, 5293 CVD-free participants were followed up to around 13 years in the Chinese Multi-provincial Cohort Study (CMCS). Considering the pathophysiologic progression of CKM health metrics abnormalities (comprising obesity, central adiposity, prediabetes, diabetes, hypertriglyceridemia, CKD, and metabolic syndrome), participants were divided into CKM stages 0, 1, and 2. The time-dependent Cox regression models were used to estimate the cardiovascular risk associated with CKM health metrics and stage. Additionally, broader CVD outcomes were examined, with a specific assessment of the impact of stage 3 in 2581 participants from the CMCS-Beijing subcohort. RESULTS: Among participants, 91.2% (4825/5293) had at least one abnormal CKM health metric, 8.8% (468/5293), 13.3% (704/5293), and 77.9% (4121/5293) were in CKM stages 0, 1, and 2, respectively; and 710 incident CVD cases occurred during a median follow-up time of 13.3 years (interquartile range: 12.1 to 13.6 years). Participants with each poor CKM health metric exhibited significantly higher CVD risk. Compared with stage 0, the hazard ratio (HR) (95% confidence interval [CI]) for CVD incidence was 1.31 (0.84-2.04) in stage 1 and 2.27 (1.57-3.28) in stage 2. Significant interactive impacts existed between CKM stage and age or sex, with higher CVD risk related to increased CKM stages in participants aged <60 years or females. CONCLUSION These findings highlight the contribution of CKM health metrics and CKM stage to the long-term risk of CVD, suggesting the importance of multi-component recognition and management of poor CKM health in CVD prevention.
Humans ; Female ; Male ; Cardiovascular Diseases/etiology* ; Middle Aged ; Adult ; Cohort Studies ; Renal Insufficiency, Chronic/metabolism* ; Aged ; Risk Factors ; Metabolic Syndrome/metabolism* ; China ; East Asian People

Objective To explore the mechanism by which electroacupuncture improves ocular surface inflammation in dry eye mice.Methods 30 SPF-grade healthy male ICR mice were randomly divided into a blank group,a model group,a sham electroacupuncture group,a western medicine group and an electroacupuncture group,with 6 mice in each group.Mice in the blank group and other four groups were subcutaneously injected 200 μL of sterile physiological saline and 200 μL of scopolamine hydrobromide(0.5 mg dissolved in 0.2 mL of sterile physiological saline)at 8:00,11:00,14:00,and 17:00 every day for 35 consecutive days,respectively.From the 22nd day,mice in the sham electroacupunc-ture group were given blunt scalp acupuncture intervention at bilateral Jingming and Taiyang points,without subcutaneous penetration.In the western medicine group,fluorometholone eye drops were applied to both eyes of the mice at 8:00,13:00,and 18:00 daily,with 1 drop each time.Mice in the electroacupuncture group were given electroacupuncture in-tervention,with the same acupoint location and acupuncture time as the sham electroacupuncture group.The electroacu-puncture frequency was 2 Hz/20 Hz,the waves were sparse-dense and the intensity was 1 mA,once a day for 15 min.All groups were intervened for 14 days.The corneal fluorescein(FL)staining scores of mice in each group were detected be-fore modeling,after modeling,and after intervention.The corneal tissue morphology was observed under a light micro-scope.Immunohistochemistry staining and quantitative reverse transcription polymerase chain reaction(qRT-PCR)were used to detect the protein and mRNA expression of high mobility group box 1(HMGB1)and receptor for advanced glyca-tion end products(RAGE)in the cornea,respectively.Results The FL scores of mice in model,sham electroacupunc-ture,western medicine,and electroacupuncture groups all significantly increased after modeling and intervention,com-pared with those before modeling(all P＜0.01).The FL scores of mice in electroacupuncture and western medicine groups significantly decreased after intervention,compared with those after modeling(both P＜0.01).Compared with the model group,electroacupuncture and western medicine groups showed a significant drop in FL score after intervention(both P＜0.01).HE staining showed that after intervention,mice in electroacupuncture and western medicine groups had a basically normal number of corneal epithelial layers,no obvious shedding of epithelial cells,and neatly arranged and slightly swollen collagen fibers in the stromal layer.The relative protein expression levels of HMGB1 and RAGE in the corneal tissue of both model and sham electroacupuncture groups were significantly higher than those of the blank group(allP＜0.01).The rela-tive protein expression levels of HMGB1 and RAGE in the corneal tissue of both electroacupuncture and western medicine groups were significantly lower than those of the model group(all P＜0.01).The relative mRNA expression levels of HMGB1 and RAGE in the corneal tissue of both model and sham electroacupuncture groups were significantly higher than those of the blank group(all P＜0.01).The relative mRNA expression levels of HMGB1 and RAGE in the corneal tissue of both electroacupuncture and western medicine groups were significantly lower than those of the model group(all P＜0.01).Conclusion Electroacupuncture mitigates corneal epithelial injury,reduces the expression of HMGB1 in the cor-neal tissue,inhibits the binding of HMGB1 and RAGE,and ultimately alleviates ocular surface inflammation responses of dry eye mice.

Objective To explore the mechanism by which electroacupuncture improves ocular surface inflammation in dry eye mice.Methods 30 SPF-grade healthy male ICR mice were randomly divided into a blank group,a model group,a sham electroacupuncture group,a western medicine group and an electroacupuncture group,with 6 mice in each group.Mice in the blank group and other four groups were subcutaneously injected 200 μL of sterile physiological saline and 200 μL of scopolamine hydrobromide(0.5 mg dissolved in 0.2 mL of sterile physiological saline)at 8:00,11:00,14:00,and 17:00 every day for 35 consecutive days,respectively.From the 22nd day,mice in the sham electroacupunc-ture group were given blunt scalp acupuncture intervention at bilateral Jingming and Taiyang points,without subcutaneous penetration.In the western medicine group,fluorometholone eye drops were applied to both eyes of the mice at 8:00,13:00,and 18:00 daily,with 1 drop each time.Mice in the electroacupuncture group were given electroacupuncture in-tervention,with the same acupoint location and acupuncture time as the sham electroacupuncture group.The electroacu-puncture frequency was 2 Hz/20 Hz,the waves were sparse-dense and the intensity was 1 mA,once a day for 15 min.All groups were intervened for 14 days.The corneal fluorescein(FL)staining scores of mice in each group were detected be-fore modeling,after modeling,and after intervention.The corneal tissue morphology was observed under a light micro-scope.Immunohistochemistry staining and quantitative reverse transcription polymerase chain reaction(qRT-PCR)were used to detect the protein and mRNA expression of high mobility group box 1(HMGB1)and receptor for advanced glyca-tion end products(RAGE)in the cornea,respectively.Results The FL scores of mice in model,sham electroacupunc-ture,western medicine,and electroacupuncture groups all significantly increased after modeling and intervention,com-pared with those before modeling(all P＜0.01).The FL scores of mice in electroacupuncture and western medicine groups significantly decreased after intervention,compared with those after modeling(both P＜0.01).Compared with the model group,electroacupuncture and western medicine groups showed a significant drop in FL score after intervention(both P＜0.01).HE staining showed that after intervention,mice in electroacupuncture and western medicine groups had a basically normal number of corneal epithelial layers,no obvious shedding of epithelial cells,and neatly arranged and slightly swollen collagen fibers in the stromal layer.The relative protein expression levels of HMGB1 and RAGE in the corneal tissue of both model and sham electroacupuncture groups were significantly higher than those of the blank group(allP＜0.01).The rela-tive protein expression levels of HMGB1 and RAGE in the corneal tissue of both electroacupuncture and western medicine groups were significantly lower than those of the model group(all P＜0.01).The relative mRNA expression levels of HMGB1 and RAGE in the corneal tissue of both model and sham electroacupuncture groups were significantly higher than those of the blank group(all P＜0.01).The relative mRNA expression levels of HMGB1 and RAGE in the corneal tissue of both electroacupuncture and western medicine groups were significantly lower than those of the model group(all P＜0.01).Conclusion Electroacupuncture mitigates corneal epithelial injury,reduces the expression of HMGB1 in the cor-neal tissue,inhibits the binding of HMGB1 and RAGE,and ultimately alleviates ocular surface inflammation responses of dry eye mice.

Objective:To evaluate the role of P2X4 receptor (P2X4R) in the maintenance of trigeminal neuralgia and the relationship with p38 mitogen-activated protein kinase (p38 MAPK)/brain-derived neurotrophic factor (BDNF) signaling pathway in rats.Methods:Forty-eight clean-grade healthy adult male Sprague-Dawley rats, weighing 190-230 g, aged 2-3 months, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (S group), trigeminal neuralgia group (TN group), trigeminal neuralgia+ dimethylsulfoxide (DMSO) group (TN+ DMSO group), and trigeminal neuralgia+ P2X4R specific antagonist 5-BDBD group (TN+ 5-BDBD group). The model was developed by chronic constriction of the infraorbital nerve. The infraorbital nerve was only exposed without ligation in group S. At 3, 7, 10 and 14 days after developing the model, 5 μg/μl 5-BDBD 10 μl was intrathecally injected in TN+ 5-BDBD group, and 2% DMSO 10 μl was intrathecally injected in TN+ DMSO group. The facial mechanical pain withdrawal threshold (MWT) was measured at 1 day before developing the model and 1, 3, 7, 10, 14 and 28 days after developing the model (T 0-6). The rats were sacrificed and the trigeminal ganglia were taken for determination of the expression of P2X4R, p38 MAPK, phosphorylated p38 MAPK (p-p38 MAPK) and BDNF (by Western blot) and contents of tumor necrosis factor (TNF)-α and interleukin (IL)-1β and IL-6 (by enzyme-linked immunosorbent assay). Results:Compared with group S, the MWT was significantly decreased at T 1-6, the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased in TN group ( P<0.05). Compared with TN group, the MWT was significantly increased at T 3-6, and the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was down-regulated, and the contents of TNF-α, IL-1β and IL-6 were decreased in TN+ 5-BDBD group ( P<0.05), and no significant change was found in the indexes mentioned above in TN+ DMSO group ( P>0.05). Conclusions:P2X4R is involved in the maintenance of trigeminal neuralgia in rats, which may be related to the activation of p38 MAPK/BDNF signaling pathway and the increase in inflammatory mediator release.

Objective To explore the clinical features of critical cases of coronavirus disease 2019 (COVID-19). Methods The clinical data of nine patients who were diagnosed with critical COVID-19 in Hainan General Hospital from January 21, 2020 to February 6, 2020 were retrospectively analyzed. RT-PCR testing for 2019 novel coronavirus (2019-nCoV) was performed with multi-sites synchronize specimens including pharyngeal swab, blood, excrement, and urine. The serum levels of leucocyte, C-reactive protein, procalcitonin and lactic acid between the improved group (five cases) and the deteriorated group (four cases) were compared. The t test was used for comparison of normally distributed continuous data between groups. Results There were eight males (88.9%) and 1 female enrolled. The patients aged 28-77 years old, with an age of (52.9±18.0) years. By March 4, 2020, all five cases in improved group were cured and discharged, three cases in deteriorated group died and 1case remained in critical condition. All multi-sites specimens of patients in improved group turned negative in 2-4 weeks of illness onset, while those of cases in deteriorated group showed sustained viral nucleic acid positive (up to 48th day of illness onset). The white blood cell counts ((13.52±8.24)×10 9 /L vs (10.49±4.46) ×10 9 /L), C-reactive protein ((139.71±87.46) mg/L vs (78.60±55.40) mg/L) and procalcitonin ((2.32±4.03) ng/mL vs (0.28±0.58) ng/mL) , lactic acid ((3.70±4.14) mmol/L vs (2.33±0.53) mmol/L) in deteriorated group were all significantly higher than those in improved group ( t =2.908, 5.009, 4.391 and 2.942, respectively, all P <0.01). A rapid rise of serum IL-6 level up to 8 500 pg/mL was observed in one patient three days prior to death. Conclusion Among the patients with critical COVID-19, serum levels of inflammatory cytokines of the death cases are higher than those of improved and discharged cases.

OBJECTIVETo judge whether algesia sensitization of some acupoints is existed and whether the acupoint algesia sensitization area is expanded in the patients of intestinal cancer.

METHODSTotally, 30 patients of intestinal cancer and 30 healthy subjects were included. The electronic Von Fray was used to determine the pressure-pain thresholds at 13 acupoints relevant with gastrointestinal disorders and the reference points at the sites 1and 2lateral to those points as well as the sites at the corresponding nerve segments. Compared with the pressure-pain thresholds at the reference points of the different segments, the relative value was calculated. The changes were analyzed in the pressure-pain thresholds at the relevant acupoints on the body surface in the patients of intestinal cancer as compared with the relative pressure-pain thresholds in the healthy volunteers.

RESULTSThe pressure-pain thresholds at Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Quchi (LI 11) and Dachangshu (BL 25) in the patients of intestinal cancer were all significantly reduced as compared with those of the healthy subjects (<0.05,<0.01,<0.001). At the non-acupoint sites 1and 2lateral to those acupoints as well as at the sites of the same segments, the pressure-pain thresholds were reduced significantly as compared with the control group (<0.05,<0.01,<0.001). Particularly, the sensitization zone of Yinlingquan (SP 9) focused on the acupoint, the site 1lateral to it as well as the non-acupoint sites of the same segments (<0.01,<0.001).

CONCLUSIONThe acupoint sensitization is displayed at Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Quchi (LI 11), Dachangshu (BL 25) and Yinlingquan (SP 9) and the sensitization area is expended in the patients of intestinal cancer.

Objective To investigate the clinical significance of combined heart and lung ultrasound in patients with severe left heart failure and pulmonary hypertension. Methods From March 2016 to June 2017, 75 patients with grade Ⅲ and Ⅳ heart failure and dyspnea were enrolled in Qingdao Municipal Hospital Affiliated to Qingdao University. Thirty-three patients had normal pulmonary artery pressure (normal pulmonary arterial pressure group), 25 patients had mild pulmonary hypertension (mild pulmonary hypertension group), and 17 patients had moderate to severe pulmonary hypertension (moderate to severe pulmonary hypertension group). The patient′s plasma B-type natriuretic peptide (BNP) was measured. Left ventricular diameter (LVD), right ventricular diameter (RVD), and left ventricular ejection fraction (LVEF) were measured by echocardiography. The patient′s lungs were observed by lung ultrasonography, and its number was recorded. One-way analysis of variance was used to compare the differences of LVD, RVD, and LVEF in three groups of patients with severe left heart failure. Further comparison between groups was performed using LSD-t test. Kruskal-wallis H test was used to compare the plasma BNP concentration and B-line number in three groups of patients with severe left heart failure. The Mann-Whitney U test was used to further compare the groups. The receiver operating characteristic (ROC) curve of pulmonary hypertension diagnosed by plasma BNP concentration and B line number in patients with severe left heart failure were drwan. Results The concentrations of BNP in patients with normal pulmonary arterial pressure, mild pulmonary hypertension, and moderate to severe pulmonary hypertension were 890 (614, 1516), 1460 (1245, 1950), and 2660 (1670, 3279) ng/L, respectively. The number of B line was 12 (9, 16), 17 (14, 18), 26 (20, 28), and the RVD was (22.1±1.7), (24.9±2.0), (26.3±2.8) mm, respectively. The number of B-line and RVD in the moderate-severe pulmonary hypertension group were both lager than those in the mild pulmonary hypertension group, and the number of B-line and RVD in the mild pulmonary hypertension group were both lager than those in the normal pulmonary artery pressure group. There was significant difference between any two groups (BNP concentration: U=210.500, P < 0.05; U=47.000, 73.000, both P < 0.001;B line number:U=189.000,P < 0.05;U=38.5000,64.000,both P < 0.001;RVD:t=0.553, 0.623, both P<0.001; t=0.656, P<0.05). There was no significant difference in LVD and LVEF between the three groups of patients. The ROC curve showed that the optimal threshold for the diagnosis of pulmonary hypertension in patients with severe left heart failure with BNP concentration was 1225 ng/L. The sensitivity was 85.7%,the specificity was 69.7%,the area under the curve was 0.814,and the 95% CI was 0.717 to 0.911. The optimal threshold for diagnosis of pulmonary hypertension in patients with severe left heart failure was B line number 14, the sensitivity was 88.1%, specificity was 66.7%, the area under the curve was 0.836, and 95%CI was 0.747 to 0.925.Conclusion Patients with severe left heart failure at different pulmonary artery pressure levels have different B-line findings, and the number of B-line increases with the severity of pulmonary hypertension, which warrants further study and application.

Objective:Adenoid cystic carcinoma (ACC) is an uncommon malignant neoplasm, which mostly originates from the major and minor salivary glands of the head and neck region. This study aims to provide new information on head and neck ACC with cervical lymph node metastasis. Methods:Out of the 616 patients who underwent primary tumor resection from 1995 to 2008 in the authors' hospital, 62 cases with cervical lymph node metastasis were analyzed. Results:The general incidence rate of cervical lymph node me-tastasis in ACC was approximately 10%. The base of the tongue, mobile tongue, and mouth floor were the most frequent sites of lymph node metastasis with incidence rates of 19.2%, 17.6%, and 15.3%, respectively. Most cases exhibited the classictunnel-stylemetastatic pattern of occurrence, and the levelⅠb andⅡregions were the most frequently involved areas. Primary site and lympho-vascular invasions were significantly associated with lymph node metastasis. High patient mortality rate was also significantly correlat-ed with a high number of lymph node positive cases. Conclusion:Cervical lymph node metastasis has a high tendency of occurrence in the tongue-mouth floor complex, following the classictunnel-stylemetastatic pattern. Peritumoral lymphovascular invasion could be taken as a strong predictor for the occurrence of lymph node metastasis, which ultimately leads to poor prognosis of ACC patients. A selective neck dissection should be considered as a management in such patients.

BACKGROUND:The carriers made from biodegradable and biocompatible polymeric materials represent an exciting approach to increase the bioavailability and stability of oral y administered insulin by the chemical reaction or physical encapsulation of insulin.
OBJECTIVE:To mainly review the research progress of the material types, preparation methods, physicochemical characteristics, in vitro release kinetics, and bioavailability of polymeric materials adopted as oral insulin carriers.
METHODS:The first author searched PubMed, Elsevier and CNKI databases for articles (2002-01/2013-02) concerning the polymeric materials and oral insulin carriers with the key words of“polymeric biomaterials, oral insulin, carrier”in English and in Chinese.
RESULTS AND CONCLUSION:Currently, there are mainly two kinds of polymeric biomaterials used for oral insulin delivery systems, that is, natural polymeric biomaterials (such as chitosan and alginates) and synthetic polymeric biomaterials. The most commonly used synthetic polymeric materials for the preparation of these vehicles are polyesters, polyacrylates and their copolymers, which are wel known for their good biodegradability, biocompatibility, and physiological properties. Although researchers have tried to develop promptly oral insulin formulation using various technologies, the reports about clinical application or commercial success have not been seen because of several questions such as polymer material as a carrier, the lower bioavailability of insulin, the quality standards and stability of the formulation. Hence, future studies wil focus on the development of a new type of polymer-based material as carriers by choosing the new materials or modifying physical and chemical characteristics of existing polymers, to avoid gastrointestinal destruction of the insulin and increase bioavailability of insulin in the body, so as to obtain the good control ed release rate and effect.