Although clinical evidence suggests that nonalcoholic fatty liver disease is an established major risk factor for heart failure, it remains unexplored whether sleep disorder-caused hepatic damage contributes to the development of cardiovascular disease (CVD). Here, our findings revealed that sleep fragmentation (SF) displayed notable hepatic detrimental phenotypes, including steatosis and oxidative damage, along with significant abnormalities in cardiac structure and function. All these pathological changes persisted even after sleep recovery for 2 consecutive weeks or more, displaying memory properties. Mechanistically, persistent higher expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in the liver was the key initiator of SF-accelerated damage phenotypes. SF epigenetically controlled the acetylation of histone H3 lysine 27 (H3K27ac) enrichment at the Nox4 promoter and markedly increased Nox4 expression in liver even after sleep recovery. Moreover, fine coordination of the circadian clock and hepatic damage was strictly controlled by BMAL1-dependent Sirtuin 1 (Sirt1) transcription after circadian misalignment. Accordingly, genetic manipulation of liver-specific Nox4 or Sirt1, along with pharmacological intervention targeting NOX4 (GLX351322) or SIRT1 (Resveratrol), could effectively erase the epigenetic modification of Nox4 by reducing the H3K27ac level and ameliorate the progression of liver pathology, thereby counteracting SF-evoked sustained CVD. Collectively, our findings may pave the way for strategies to mitigate myocardial injury from persistent hepatic detrimental memory in diabetic patients.

A method based on ultra-high performance liquid chromatography coupled with triple quadrupole linear ion trap-tandem mass spectrometry(UHPLC-QTRAP-MS/MS) was developed for the simultaneous determination of 41 bioactive constituents of flavonoids, organic acids, nucleosides, and amino acids in Lysimachiae Herba. The content of multiple bioactive constituents was compared among the samples from different habitats. The chromatographic separation was performed in a Waters XBridge®C_(18) column(4.6 mm×100 mm, 3.5 μm) at 30 ℃. The gradient elution was performed with 0.4% methanol(A)-formic acid water(B) as the mobile phase at a flow rate of 0.8 mL·min~(-1), and the multiple-reaction monitoring(MRM) mode was adopted. According to the content of 41 constituents, hierarchical cluster analysis(HCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and gray relational analysis(GRA) were perfomed to comprehensively evaluate the samples from different habitats. The results showed that the 41 constituents exhibited good linear relationship within the tested concentration ranges, with the correlation coefficients(r) greater than 0.999 4. The method featured good precision, repeatability, and stability with the relative standard deviations(RSDs) less than 5.0%. The average recoveries of the 41 constituents ranged from 98.06% to 101.9%, with the RSDs of 0.62%-4.6%. HCA and OPLS-DA separated 48 batches of Lysimachiae Herba samples from different habitats into three categories: the producing areas in Sichuan and Chongqing, the producing areas in Jiangsu, Zhejiang, and Jiangxi, and the producing areas in Guizhou. The content of 41 constituents varied among the Lysimachiae Herba samples from different habitats. The GRA results revealed that the Lysimachiae Herba sample from Nanchong City, Sichuan Province had the best comprehensive quality. The method developed in this study was accurate and reliable and thus can be used for comprehensive evaluation of Lysimachiae Herba quality and provide basic information for the selection of habitats.
Tandem Mass Spectrometry/methods* ; Multivariate Analysis ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Amino Acids/analysis*

A comprehensive analytical method based on ultra-fast liquid chromatography coupled with triple quadrupole/linear ion trap tandem mass spectrometry(UFLC-QTRAP-MS/MS) was established for simultaneous determination of the content of 45 bioactive constituents including flavonoids, alkaloids, amino acids, phenolic acids, and nucleosides in Epimedium brevicornum. The multiple bioactive constituents in leaves, petioles, stems and rhizomes of E. brevicornum were analyzed. The gradient elution was performed at 30 ℃ in an XBridge~® C_(18) column(4.6 mm×100 mm, 3.5 μm) with 0.4% formic acid aqueous solution-acetonitrile as the mobile phase at a flow rate of 0.8 mL·min~(-1). Single factor experiment and response surface methodology were employed to optimize the extraction conditions. Multivariate statistical analyses including systematic cluster analysis(SCA), principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and one-way analysis of variance(One-way ANOVA) were carried out to classify the samples from different parts and identify different constituents. Grey relation analysis(GRA) and entropy weight-TOPSIS analysis were performed to build a multi-index comprehensive evaluation model for different parts of E. brevicornum. The results showed that there was a good relationship between the mass concentrations of 45 constituents and the corresponding peak areas, with the correlation coefficients(r) not less than 0.999 0. The precision, repeatability, and stability of the established method were good for all the target constituents in this study, with the relative standard deviations(RSDs) less than 5.0%(0.62%-4.9%) and the average recovery of 94.51%-105.7%. The above results indicated that the bioactive constituents varied in different parts of E. brevicornum, and the overall quality followed the trend of leaves > petioles > rhizomes > stems. This study verified the rationality of the Chinese Pharmacopoeia(2020 edition) stipulating that the medicinal part of E. brevicornum is the leaf. Moreover, our study indicated that the rhizome had the potential for medicinal development. The established method was accurate and reliable, which can be used to comprehensive evaluate and control the quality of E. brevicornum. This study provides data reference for clarifying the medicinal parts and rationally utilizing the resources of E. brevicornum.
Chromatography, High Pressure Liquid ; Epimedium ; Tandem Mass Spectrometry ; Chromatography, Liquid ; Multivariate Analysis

An 18-day-old male infant was admitted to the hospital due to recurrent hyperkalemia for more than 10 days. The neonate had milk refusal and dyspnea. The blood gas analysis revealed recurrent hyperkalemia, hyponatremia and metabolic acidosis. Adrenocortical hormone replacement therapy was ineffective. Additional tests showed a significant increase in aldosterone levels. Family whole exome sequencing revealed that the infant had compound heterozygous in the SCNNIA gene, inherited from both parents. The infant was diagnosed with neonatal systemic pseudohypoaldosteronism type I. The infant's electrolyte levels were stabilized through treatment with sodium polystyrene sulfonate and sodium supplement. The infant was discharged upon clinical recovery. This study provides a focused description of differential diagnosis of salt-losing syndrome in infants and introduces the multidisciplinary management of neonatal systemic pseudohypoaldosteronism type I.
Infant ; Infant, Newborn ; Humans ; Male ; Pseudohypoaldosteronism/genetics* ; Hyperkalemia/etiology* ; Hyponatremia/diagnosis* ; Diagnosis, Differential

OBJECTIVE: To explore early efficacy of minimally invasive Chevron Akin(MICA) osteotomy for the treatment of mild to moderate hallux valgus. METHODS: From June 2019 to April 2021, a total of 26 patients (29 feet) with mild to moderate hallux valgus, including 1 male and 25 females aged from 19 to 78 years old with an average of(38.3±19.5) years old, were treated with MICA. Preoperative and postoperative hallux valgus angle(HVA), intermetatarsal angle(IMA) and shortening of the first metatarsal were observed and compared. American Orthopedic Foot and Ankle Society (AOFAS) forefoot scoring system and visual analogue scale (VAS) were applied to evaluate clinical outcome at the final follow-up, and complications were also recorded. RESULTS: All patients obtained followed up from 12 to 33 months with an average of(19.6±5.1) months. HVA and IMA was improved from (32.3±6.6)° and (11.7±3.2)° pre-operatively to (13.0±5.3)° and (6.1±3.2)° post-operatively, respectively, which had a significant difference (P<0.01). The average shortening of the first metatarsal was (2.7±1.1) mm. AOFAS and VAS was improved from (55.7±7.4) and (6.5±1.5) preoperatively and to (88.5±7.9) and (0.7±0.4) respectively at the final follow-up, which also had a significant difference(P<0.01). According to AOFAS score, 15 feet achieved an excellent result, 11 good and 3 moderate. CONCLUSION MICA osteotomy is a safe and reliable surgical technique for mild to moderate hallux valgus with advantages of minimally invasive, rapid recovery, low complication rate and an effect improvement of hallux valgus deformity.
Adolescent ; Adult ; Aged ; Bunion ; Female ; Hallux Valgus/surgery* ; Humans ; Male ; Metatarsal Bones/surgery* ; Middle Aged ; Osteotomy/methods* ; Treatment Outcome ; Young Adult

Objective To evaluate the effectiveness of a whole-process health education model among inpatients with ascites type of advanced schistosomiasis. Methods A “admission-hospitalization-discharge” whole-process health education model was created, 101 inpatients with ascites type of advanced schistosomiasis were given the whole-process health education. The scores of schistosomiasis control knowledge, attitudes towards schistosomiasis control and healthy behaviors, and awareness of schistosomiasis control knowledge, correct rate of attitudes towards schistosomiasis control and correct rate of healthy behaviors were compared among inpatients with ascites type of advanced schistosomiasis before and after implementation of the whole-process health education. Results The scores of schistosomiasis control knowledge, schistosomiasis control attitudes and healthy behaviors were all significantly higher among inpatients with ascites type of advanced schistosomiasis after implementation of the whole-process health education than before implementation (Z = −7.688, −3.576 and −4.328, all P values < 0.01). In addition, the awareness of schistosomiasis control knowledge increased from 54.3% to 82.7% (χ² = 188.886, P < 0.01), and the correct rate of attitudes towards schistosomiasis control increased from 88.4% to 98.0% (χ² = 22.001, P < 0.01), while the correct rate of healthy behaviors increased from 48.2% to 59.7% (χ² = 11.767, P < 0.01). Conclusions The whole-process health education model may remarkably improve the awareness of schistosomiasis control knowledge and promote the formation of positive attitudes towards schistosomiasis control and correct behaviors among inpatients with ascites type of advanced schistosomiasis, which is of great significance to facilitate patients’ cure.

PURPOSE: This research examined road traffic injury mortality and morbidity disparities across of country development status, and discussed the possibility of reducing country disparities by various actions to accelerate the pace of achieving Sustainable Development Goals target 3.6 - to halve the number of global deaths and injuries from road traffic accidents by 2020. METHODS: Data for road traffic mortality, morbidity, and socio-demographic index (SDI) were extracted by country from the estimates of the Global Burden of Disease study, and the implementation of the three types of national actions (legislation, prioritized vehicle safety standards, and trauma-related post-crash care service) were extracted from the Global Status Report on Road Safety by World Health Organization. We fitted joinpoint regression analysis to identify and quantify the significant rate changes from 2011 to 2017. RESULTS: Age-adjusted road traffic mortality decreased substantially for all the five SDI categories from 2011 to 2017 (by 7.52%-16.08%). Age-adjusted road traffic mortality decreased significantly as SDI increased in the study time period, while age-adjusted morbidity generally increased as SDI increased. Subgroup analysis by road user yielded similar results, but with two major differences during the study period of 2011 to 2017: (1) pedestrians in the high SDI countries experienced the lowest mortality (1.68-1.90 per 100,000 population) and morbidity (110.45-112.72 per 100,000 population for incidence and 487.48-491.24 per 100,000 population for prevalence), and (2) motor vehicle occupants in the high SDI countries had the lowest mortality (4.07-4.50 per 100,000 population) but the highest morbidity (428.74-467.78 per 100,000 population for incidence and 1025.70-1116.60 per 100,000 population for prevalence). Implementation of the three types of national actions remained nearly unchanged in all five SDI categories from 2011 to 2017 and was consistently stronger in the higher SDI countries than in the lower SDI countries. Lower income nations comprise the heaviest burden of global road traffic injuries and deaths. CONCLUSION Global road traffic deaths would decrease substantially if the large mortality disparities across country development status were reduced through full implementation of proven national actions including legislation and law enforcement, prioritized vehicle safety standards and trauma-related post-crash care services.

Objective To predict the changes in the prevalence of Schistosoma japonicum infections in humans and livestock in Hunan Province using the exponential smoothing model and the ARIMA model. Methods The data pertaining to S. japonicum infections in humans and livestock in Hunan Province from 1957 to 2015 were collected, and the exponential smoothing model and the ARIMA model were created using the software Eviews and PASW Statistics 18.0. In addition, the effectiveness of these two models for the prediction of S. japonicum infections in humans and livestock in Hunan Province from 2016 to 2018 was evaluated. Results The exponential smoothing model and the ARIMA model had a high goodness of fit for prediction of S. japonicum infections in humans and livestock in Hunan Province from 1957 to 2015. There was a linear trend in the prevalence of S. japonicum infections in humans and livestock in Hunan Province from 1957 to 2015. The prevalence of S. japonicum infections in humans predicted with the Brown’s linear trend and the prevalence of S. japonicum infections in livestock predicted with the Holt’s linear trend in Hunan Province from 2016 to 2018 fitted better the actual data than the ARIMA model; however, prediction of the ARIMA model indicated that the endemic situation of schistosomiasis remained at a low level in Hunan Province. Conclusion At a low epidemic level, development of highly sensitive tools for monitoring schistosomiasis is urgently needed in Hunan Province to fit the current endemic situation, and the schistosomiasis control measures should be intensified to consolidate the control achievements.

OBJECTIVE: To observe the correlation between referred pain distribution and acupoint sensitization in patients with intestinal diseases. METHODS: In clinical research, 443 patients from 8 hospitals were recruited, including the outpatients and inpatients of Crohn's disease (=143), ulcerative colitis (=108), chronic appendicitis (=87) and other intestinal diseases (=105). The site with tenderness on the body surface and the morphological changes of local skin were observed and recorded in the patients. Using a sensory tenderness instrument, the pain threshold at the sensitization point was measured in 60 patients with ulcerative colitis. In animal experiment, SD rats were used and divided into a enteritis group (=8), in which the enteritis model were established, and a control group (=3), in which no any intervention was given. After the injection of Evans blue (EB) at caudal vein, the blue exudation points on the body surface were observed and the distribution rule was analyzed statistically. RESULTS: The referred pain on the body surface in the patients with intestinal diseases was mainly located in the lower abdomen (93.9%, 416/443), the lumbar region (70.9%, 314/443) and the lower legs (33.0%, 146/443). The diameter of tenderness region was 1.5 to 2.5 cm. Compared with the region without sensitization, the pain threshold of the sensitization point in the patients with ulcerative colitis was reduced significantly (<0.001). The referred pain on the body surface in the patients with appendicitis was located in the right lower abdomen (97.7%, 85/87), the waist and back (54.0%, 47/87) and the right lower limbs on the medial side (71.3%, 62/87). The tenderness region was 1 to 2 cm in diameter and was irregular in form. After modeling of enteritis in the rats, the EB exudation points were visible from T to L. CONCLUSION Intestinal diseases induce referred pain on the body surface where is the same as or adjacent to the location of the spinal segment corresponding to the affected intestinal section. These sensitization regions are related to the locations of acupoints.
Acupuncture Points ; Animals ; Colitis, Ulcerative ; Humans ; Intestinal Diseases ; Pain Threshold ; Pain, Referred ; diagnosis ; therapy ; Rats ; Rats, Sprague-Dawley ; Sensation

Objective: To introduce a new method for assessing coronal balance in surgical treatment of scoliosis, and to explore its effectiveness in preventing postoperative coronal imbalance. Methods: The data of forty-six consecutive patients, who underwent posterior surgery for spine deformity correction from January 2016 to December 2016, were retrospectively analyzed. The series included 19 males and 27 females with an average age of 28.24±21.16 years (7-76 years), and with lower instrumented vertebra (LIV) located at the level of L3 or below. Point-line method was used to evaluate coronal balance by determining whether the center of upper instrumented vertebra was located at the measuring rod passing through the centers of symphysis pubis and LIV among all patients during surgery. Preoperative, postoperative 1 week and 3 months Cobb angle, coronal balance distance (CBD), Oswestry Disability Index (ODI), Visual Analogue Scale (VAS), and Scoliosis Research Society Questionnaires-22 (SRS-22) were measured and recorded, and statistical analysis was conducted. And then, subgroup analysis was performed according to preoperative coronal imbalance classification to further evaluate the effectiveness of the new method. Results: Among 46 patients in this study, the prevalence of preoperative coronal imbalance was 47.82% (22/46). Of them, ten patients were type B coronal imbalance and eleven patients were type C coronal imbalance. The prevalence of coronal imbalance at one week after operation was 17.39% (8/46), and the prevalence of coronal imbalance at final follow-up was 10.87% (5/46). The results showed that the mean main Cobb angle was 57.24°±26.51° and 14.71°±10.17° at pre-operation and immediate post-operation, respectively. The difference was statistically significant compared to preoperative value (t=13.211, P=0.000), and the average improvement rate was 73.53%±1.88%. Preoperative coronal balance distance CBD ranged from 2.76 mm to 66.73 mm, with an average of 22.54±13.97 mm; the mean CBD was 16.00±14.85 mm at immediate post-operation. The difference was statistically significant (t=3.665, P=0.001), with an average correction rate of 25.58%±52.39%. Our clinical outcome analysis showed that among 46 patients, the preoperative VAS was 8.11±0.89, and the final follow-up VAS was 4.15±0.79. There was a significant difference between pre-operation and the last follow-up (t=21.529, P=0.000). The preoperative ODI score was 49.76±5.84, and the final follow-up ODI score was 25.74±3.92. The difference was statistically significant (t=44.434, P=0.000). The preoperative SRS-22 was 10.57±2.13, and the final follow-up SRS-22 was 21.89±2.35. Compared to pre-operation, the difference was statistically significant (t=24.023, P=0.000). The subgroup analysis showed that in patients with type B coronal imbalance, the mean Cobb angle correction rate was 70.34%±6.02% at immediate post-operation, and there was a significant difference compared to pre-operation (t=5.437, P=0.000); the average CBD correction rate was 37.45%±29.03%, and significant difference was found (t=2.607, P=0.028). In type C patients, the average Cobb angle and CBD correction rate at immediate post-operation was 72.92%±3.67% and 44.79%±5.63%, respectively, and significant difference was found (t=7.319, P=0.000; t=7.545, P=0.000). Conclusion Point-line method was a simple and effective technique for intraoperative assessment of coronal balance, which could assist surgeons to objectively evaluate the result of restoration of the coronal alignment. The use of point-line method is contributed to improve clinical outcomes of spinal deformity correction surgery, and to prevent the occurrence of postoperative coronal imbalance.