Oral submucous fibrosis (OSF), characterized by excessive deposition of extracellular matrix (ECM) that causes oral mucosal tissue sclerosis, and even cancer transformation, is a chronic, progressive fibrosis disease. However, despite some advancements in recent years, no targeted antifibrotic strategies for OSF have been approved; likely because the complicated mechanisms that initiate and drive fibrosis remain to be determined. In this review, we briefly introduce the epidemiology and etiology of OSF. Then, we highlight how cell-intrinsic changes in significant structural cells can drive fibrotic response by regulating biological behaviors, secretion function, and activation of ECM-producing myofibroblasts. In addition, we also discuss the role of innate and adaptive immune cells and how they contribute to the pathogenesis of OSF. Finally, we summarize strategies to interrupt key mechanisms that cause OSF, including modulation of the ECM, inhibition of inflammation, improvement of vascular disturbance. This review will provide potential routes for developing novel anti-OSF therapeutics.
Humans ; Oral Submucous Fibrosis/immunology* ; Extracellular Matrix/metabolism* ; Myofibroblasts

Objective:To evaluate the epidemiological characteristics and influencing factors of out-of-hospital sudden cardiac death (SCD) in Hangzhou from 2016 to 2019.Methods:SCD events recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019 were reviewed. Demographic and mortality data were recorded, and the distribution patterns of SCD events in terms of date, time, and population with different characteristics were observed. Time series analysis method and a distributed lag nonlinear model based on quasi-Poisson distribution were used to explore the possible nonlinear association between ambient temperature and SCD incidence.Results:A total of 4 744 out-of-hospital sudden death events were recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019. After excluding non-SCD events and observed events with missing items, 3 743 SCD events were finally included in the study. The survey results showed that the incidence of out-of-hospital SCD in Hangzhou was 96.5 cases per 100 000 person-years. Most of the people who experienced SCD were aged ≥60 years. The incidence in males (2 462 cases, 66%) was significantly higher than that in females (1 281 cases, 34%), and the proportion of events occurring during the day (2 737 cases, 73%) was significantly higher than that at night (1 006 cases, 27%), mainly occurring between 7: 00 and 9: 00. High temperature was associated with an increased risk of SCD. When the average daily temperature was higher than 25.5 ℃, the risk of SCD increased with the further increase of average daily temperature.Conclusions:SCD events mainly occur in the elderly population aged ≥60 years, with a significantly higher incidence in males than in females, and more frequently during the day than at night, mainly between 7: 00 and 9: 00 in the morning. High temperature is closely related to the risk of SCD. It is particularly important to carry out targeted SCD screening and prevention for different populations and implement appropriate prevention strategies for high-risk groups of SCD in high-temperature weather.

Objective:To evaluate the epidemiological characteristics and influencing factors of out-of-hospital sudden cardiac death (SCD) in Hangzhou from 2016 to 2019.Methods:SCD events recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019 were reviewed. Demographic and mortality data were recorded, and the distribution patterns of SCD events in terms of date, time, and population with different characteristics were observed. Time series analysis method and a distributed lag nonlinear model based on quasi-Poisson distribution were used to explore the possible nonlinear association between ambient temperature and SCD incidence.Results:A total of 4 744 out-of-hospital sudden death events were recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019. After excluding non-SCD events and observed events with missing items, 3 743 SCD events were finally included in the study. The survey results showed that the incidence of out-of-hospital SCD in Hangzhou was 96.5 cases per 100 000 person-years. Most of the people who experienced SCD were aged ≥60 years. The incidence in males (2 462 cases, 66%) was significantly higher than that in females (1 281 cases, 34%), and the proportion of events occurring during the day (2 737 cases, 73%) was significantly higher than that at night (1 006 cases, 27%), mainly occurring between 7: 00 and 9: 00. High temperature was associated with an increased risk of SCD. When the average daily temperature was higher than 25.5 ℃, the risk of SCD increased with the further increase of average daily temperature.Conclusions:SCD events mainly occur in the elderly population aged ≥60 years, with a significantly higher incidence in males than in females, and more frequently during the day than at night, mainly between 7: 00 and 9: 00 in the morning. High temperature is closely related to the risk of SCD. It is particularly important to carry out targeted SCD screening and prevention for different populations and implement appropriate prevention strategies for high-risk groups of SCD in high-temperature weather.

In order to promote the innovative application of Sanjiao theory and Yingwei theory， this paper tries to apply the ''Sanjiao-Yingwei'' Qi transformation theory to the treatment of tumor diseases， integrating it with T cell exhaustion mechanism to elaborate on its scientific connotation and using network pharmacology and bioinformatics to elucidate the correlation between the anti-tumor mechanism of ''Sanjiao-Yingwei'' Qi transformation and T cell exhaustion. The ''Sanjiao-Yingwei'' Qi transformation function is closely related to the immunometabolic ability of the human body， and the ''Sanjiao-Yingwei'' Qi transformation system constitutes the immunometabolic exchange system within and outside the cellular environment. Cancer toxicity is generated by the fuzzy Sanjiao Qi， and the long-term fuzzy Sanjiao Qi is the primary factor leading to T cell exhaustion， which is related to the long-term activation of T cell receptors by the high tumor antigen load in the tumor microenvironment. Qi transformation malfunction of the Sanjiao produces phlegm and collects stasis， which contributes to T cell exhaustion and is correlated with nutrient deprivation， lipid accumulation， and high lactate levels in the immunosuppressed tumor microenvironment， as well as with the release of transforming growth factor-β and upregulated expression of programmed death receptor-1 by tumor-associated fibroblasts and platelets in the tumor microenvironment. Ying and Wei damage due to Sanjiao Qi transformation malfunction is similar to the abnormal manifestations such as progressive loss of exhausted T cell effector function and disturbance of cellular energy metabolism. Guizhi decoction， Shengming decoction， and Wendan decoction can correct T cell exhaustion and exert anti-tumor effects through multi-target and multi-pathways by regulating ''Sanjiao-Yingwei'' Qi transformation， and hypoxia inducible factor-1α （HIF-1α） may be one of the main pathways to correct T cell exhaustion. It was found that HIF-1α may be one of the important prognostic indicators in common tumors by bioinformatics. The use of the ''Sanjiao-Yingwei'' Qi transformation method may play an important part in improving the prognosis of tumor patients in clinical practice.

Objective:To investigate the value of ultrasonography in diagnosis of transposition of great arteries of the fetus at 11-13 + 6 weeks gestation. Methods:A prospective study was conducted on fetuses screened by ultrasound in the first trimester in Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region between January 2015 and March 2022. Fetal heart structure was screened by three-section screening method. Fetuses with suspected transposition of the great arteries at 11-13 + 6 weeks gestation underwent followed-up ultrasound examination, chromosome and gene test results. The ultrasound characteristics and prognosis pregnancy outcomes were summarized. Results:Twenty-one cases of transposition of the great arteries were detected by ultrasonography, including complete transposition of great arteries (20 cases) and congenitaly corrected transposition of the great arteries (1 case). Two cases were miss diagnosed. Twenty-one cases showed parallel signs of two major arteries on grayscale outflow section at 11-13 + 6 weeks gestation. There were 6 cases with aneuploid ultrasonographic soft markers abnormality, 2 cases with extracardiac malformation. Chromosome and microarray analysis were performed in 13 cases. 4 cases with chromosomal abnormality. Four cases of chromosomal abnormalities were associated with ultrasonographic soft markers abnormality, and 1 case with extracardiac malformation.In the 23 cases, 20 cases were induced, 1 miscarried, and 2 delivered to term. Among the fetuses delivered at term, 1 case died before neonatal operation and 1 case survived. Conclusions:Standardized ultrasound scan at 11-13 + 6 weeks has high accuracy in diagnosis of transposition of the great arteries. And the incidence of chromosomal abnormality is high with ultrasonographic soft markers abnormality or extracardiac malformation.

Objective:To investigate the value of atrioventricular valve regurgitation in predicting atrioventricular septal defect (AVSD) in the first trimester.Methods:Fetuses were examined prospectively by ultrasound at 11-13 + 6 weeks in Maternity & Child Healthcare Hospital of Guangxi Zhuang Autonomous Region between February 2016 and February 2021. Congenital heart disease was screened and atrioventricular valve regurgitation was observed in fetuses of gestational age 11 to 13 + 6 weeks using color Doppler in four-chamber view and three vessels and trachea view. Results:Totally 43 549 fetuses of gestational age 11 to 13 + 6 weeks were screened by echocardiography, of whom 37 cases were screened out with AVSD, including complete atrioventricular septal defect (31 cases), partial atrioventricular septal defect(3 cases) and intermediate atrioventricular septal defect(1 cases), 2 cases were misdiagnosed, and ultrasonic scanning in the second trimester found 2 missed cases of intermediate atrioventricular septal defect. Atrioventricular valve regurgitation was observed in 91.89% of atrioventricular septal defects (34/37) in the first trimester, 59.46% (22/37) nuchal translucency greater than 95th percentile, 29.73% (11/37) absence of nasal bone, 32.43% (12/37) ductus venosus A wave inversion, and 40.54% (15/37) had tricuspid regurgitation. The sensitivity of common atrioventricular valve regurgitation in predicting atrioventricular septal defect is better than other ultrasonic indexes. Conclusions:Atrioventricular regurgitation can be used as a clue to predict atrioventricular septal defect in the first trimester, which is beneficial to detect atrioventricular septal defect in the first trimester.

Objective:To assess the value of ultrasonography in the diagnosis of fetal isomerism syndrome in the first trimester.Methods:Sonographic features of 15 fetuses with isomerism syndrome diagnosed in the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from January 2015 to March 2020 were reviewed. Ultrasonic characteristics in the first trimester were analyzed, and the ultrasonic characteristics of early mid-trimester and pathological anatomical results were combined for comparison.Results:There were 6 cases of left isomerism syndrome (LIS) and 9 cases of right isomerism syndrome (RIS) in the 15 fetues.Increased nuchal translucency(NT) (≥3.0 mm, 6 cases), reversed A wave in ductus venosus (10 cases), and atrio-ventricular valve regurgitation (14 cases) were found during the first trimester. There were 14 cases with abnormal visceral laterality. Of the 15 fetues, 14 cases with cardiac malformations, including 6 cases of functional single ventricle, 8 cases of complete atrioventricular septal defect (CAVSD), and 12 cases with great artery abnormalities. All of the 6 LIS cases had bradycardia, 3 cases had interruption of inferior vena cava (IVC). Six cases of RIS had juxtaposition of descending aorta and IVC, and 1 case of RIS had total anomalous pulmonary vein drainage. The major structural malformations were consistent with the early mid-trimester ultrasound examination or autopsy. Karyotype and chromosomal microarray were available in 12 cases and all were normal.Conclusions:Isomerism syndrome has high positive rate of fetal aneuploidies ultrasonographic marker, especially with the atrio-ventricular valve regurgitation, but the risk of chromosome abnormality is low. Ultrasound screening for fetal cardiac structural abnormalities is beneficial to the early diagnosis of isomerism syndrom in the first trimester.

Objective:To explore the feasibility and prognosis of prenatal ultrasonic diagnosis of fetal isolated vascular ring at 11-13 + 6 weeks. Methods:A total of 36 996 fetuses were selected to compare the results of ultrasound screening at 11-13 + 6 weeks and 20-24 weeks of pregnancy in Guangxi Maternity & Child Healthcare Hospital from January 2016 to January 2020, the reasons for missed diagnosis and misdiagnosis of fetal isolated vascular ring by ultrasonography in the first trimester were summarized. Results:Thirty-five cases were diagnosed as isolated vascular ring in the first trimester, including 19 cases right aortic arch combined with aberrant left subclavian artery with "U-shaped" vascular ring, 7 cases double aortic arch with "O-shaped" vascular ring, and 9 cases aberrant right subclavian artery with "C-shaped" vascular ring. While 155 cases were diagnosed as isolated vascular ring at 20-24 weeks of pregnancy, consisting of 18 cases of combined with aberrant left subclavian artery, 9 cases of double aortic arch, 126 cases of aberrant right subclavian artery and 2 cases of pulmonary artery sling, the diagnosis coincidence rates were 94.74%, 77.78%, 7.14%, 0(Kappa value were 0.97, 0.88, 0.13, 0). For the diagnosis of right aortic arch combined with aberrant left subclavian artery, double aortic arch and aberrant right subclavian artery in the first trimester, the specificities were 99.99%, 100%, 100%, the sensitivities were 100%, 77.78%, 7.14%, the false-positive rates were 0.01%, 0, 0, the false-negative rates were 0, 22.22%, 92.86%, and the Youden′s indices were 0.99, 0.78, 0.07.Conclusions:Right aortic arch combined with aberrant left subclavian artery and double aortic arch have high coincidence rate by ultrasonography in the first trimester, while the diagnostic coincidence rate of isolated aberrant right subclavian artery was low. Ultrasound screening for isolated vascular ring in the first trimester still needs ultrasound examination in the second trimester to exclude the minor cardiac malformations that are difficult to diagnose in the first trimester.

Objective: To investigate the echocardiographic characteristics, pathological anatomy and genetic abnormality of congenital absent semilunar valves in first trimester. Methods: Eleven cases of congenital absent semilunar valve fetus diagnosed at 11-13^{+ 6} weeks of gestation in Guangxi Magernity & Child Healthcare Hospital from December 2014 to December 2018 were analyzed. The characteristics of echocardiography and the abnormal microanatomy of cardiac tissue after labor induction was compared. Results: The crown-lump length of the 11 fetus was 46-74(62.0±9.2)mm, and nuchal translucency thickness(NT) was 2.4-10.4 (6.4±2.6)mm. The NT of 10 cases were greater than 3.0 mm. Color Doppler flow imaging revealed that biphasic bidirectional flow in the aortic arch and/or pulmonary artery at the 3VT view( "to-and-fro" ) in those 11 cases, and pansystolic turbulence and pandiastolic reflux spectrum were showed on spectral Doppler. Among them, there were 10 cases of " stealing type" , including 2 cases of isolate absent aortic valves, 3 cases of absent pulmonary valves and 5 cases of absent both aortic and pulmonary valves; and all the 10 cases had secondary ultrasonic manifestations of fetal heart failure. Chromosome analysis and detection of genes showed that 4 cases with Trisomy 13 syndrome, 3 cases with Trisomy 18 syndrome, 1 case with 22q11.2 deletion, 1 case with 12q24.32q24.33 deletion and 1 case was normal. Pathological anatomy revealed enlarged heart in 8 cases, isolate absent aortic valves in 2 cases (1 case complicated with pulmonary atresia, absence of ductus arteriosus and thymus), absent pulmonary valves in 3 cases, absent both aortic and pulmonary valves in 3 cases, relics of semilunar valves in 3 cases. And 2 cases of absent pulmonary valves and 3 cases of absent both aortic and pulmonary valves with short and thick ductus arteriosus. Only 1 case was congenital absent semilunar valve in " non-stealing type" without secondary ultrasonic manifestations of fetal heart failure. Chromosome analysis and detection of genes showed 22q11.2 deletion, and there were relics of semilunar valves in the pathological anatomy. It also combined with tetralogy of Fallot and absence of ductus arteriosus. Conclusions In first trimester, congenital absent semilunar valves are more common as " stealing type" . The echocardiographic features of congenital absent semilunar valves are the " in-out sign" of aorta arch and/or pulmonary artery and biphasic spectrum in spectral Doppler. Trisomy 13 syndrome and trisomy 18 syndrome significantly increased the risk of congenital absent semilunar valves in " stealing type" in first trimester.

Objective To investigate the effects of low-frequency sound waves (16~160 Hz) of somatosensory music on healthy people’s microcirculation in kidney and bladder meridians;To discuss the collateral channels biophysical mechanisms in somatosensory music treatment. Methods Low-frequency sound waves of somatosensory music were played near the 30 healthy people’s kidney and bladder meridians orderly. At the same time, Laser Doppler Flowmetry was used to analyze microcirculation in meridian acupoints.Results The low-frequency acoustic waves with different frequencies had significantly different effects on kidney and bladder meridians. The effects of the same frequency on different acupoints of the same meridian were similar. The G1 (49.00 Hz) showed the most significant effects on the kidney meridian (P<0.01);G2 (98.00 Hz) showed the most significant impact on bladder meridian (P<0.01).Conclusion The kidney and bladder meridians have selective absorption characteristics to the low-frequency sound waves of different frequencies. Specific frequency sound waves can cause resonance in kidney and bladder meridians.