Tricellulin, a key tricellular tight junction (TJ) protein, is essential for maintaining the barrier integrity of acinar epithelia against macromolecular passage in salivary glands. This study aims to explore the role and regulatory mechanism of tricellulin in the development of salivary gland hypofunction in Sjögren's syndrome (SS). Employing a multifaceted approach involving patient biopsies, non-obese diabetic (NOD) mice as a SS model, salivary gland acinar cell-specific tricellulin conditional knockout (Tric^CKO) mice, and IFN-γ-stimulated salivary gland epithelial cells, we investigated the role of tricellulin in SS-related hyposalivation. Our data revealed diminished levels of tricellulin in salivary glands of SS patients. Similarly, NOD mice displayed a reduction in tricellulin expression from the onset of the disease, concomitant with hyposecretion and an increase in salivary albumin content. Consistent with these findings, Tric^CKO mice exhibited both hyposecretion and leakage of macromolecular tracers when compared to control animals. Mechanistically, the JAK/STAT1/miR-145 axis was identified as mediating the IFN-γ-induced downregulation of tricellulin. Treatment with AT1001, a TJ sealer, ameliorated epithelial barrier dysfunction, restored tricellulin expression, and consequently alleviated hyposalivation in NOD mice. Importantly, treatment with miR-145 antagomir to specifically recover the expression of tricellulin in NOD mice significantly alleviated hyposalivation and macromolecular leakage. Collectively, we identified that tricellulin deficiency in salivary glands contributed to hyposalivation in SS. Our findings highlight tricellulin as a potential therapeutic target for hyposecretion, particularly in the context of reinforcing epithelial barrier function through preventing leakage of macromolecules in salivary glands.
Sjogren's Syndrome/complications* ; Animals ; Xerostomia/etiology* ; Mice ; Mice, Inbred NOD ; MARVEL Domain Containing 2 Protein/metabolism* ; Humans ; Mice, Knockout ; Disease Models, Animal ; Interferon-gamma ; Salivary Glands/metabolism* ; Tight Junctions/metabolism* ; MicroRNAs/metabolism* ; Female

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

Immunoglobulin G4-related sialadenitis (IgG4-RS) is an immune-mediated fibro-inflammatory disease and the pathogenesis is still not fully understood. The aim of this study was to explore the role and mechanism of interleukin-13 (IL-13) in the cellular senescence during the progress of IgG4-RS. We found that the expression of IL-13 and IL-13 receptor α1 (IL-13Rα1) as well as the number of senescent cells were significantly higher in the submandibular glands (SMGs) of IgG4-RS patients. IL-13 directly induced senescence as shown by the elevated activity of senescence-associated β-galactosidase (SA-β-gal), the decreased cell proliferation, and the upregulation of senescence markers (p53 and p16) and senescence-associated secretory phenotype (SASP) factors (IL-1β and IL-6) in SMG-C6 cells. Mechanistically, IL-13 increased the level of phosphorylated signal transducer and activator of transcription 6 (p-STAT6) and mitochondrial-reactive oxygen species (mtROS), while decreased the mitochondrial membrane potential, ATP level, and the expression and activity of superoxide dismutase 2 (SOD2). Notably, the IL-13-induced cellular senescence and mitochondrial dysfunction could be inhibited by pretreatment with either STAT6 inhibitor AS1517499 or mitochondria-targeted ROS scavenger MitoTEMPO. Moreover, IL-13 increased the interaction between p-STAT6 and cAMP-response element binding protein (CREB)-binding protein (CBP) and decreased the transcriptional activity of CREB on SOD2. Taken together, our findings revealed a critical role of IL-13 in the induction of salivary gland epithelial cell senescence through the elevated mitochondrial oxidative stress in a STAT6-CREB-SOD2-dependent pathway in IgG4-RS.
Cellular Senescence/genetics* ; Humans ; Immunoglobulin G/metabolism* ; Interleukin-13/pharmacology* ; Mitochondria/metabolism* ; Sialadenitis/metabolism*

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a rapidly spreading disease that has caused an extensive burden to the world. Consequently, a large number of clinical trials have examined the efficacy of traditional Chinese medicine (TCM) for treating and preventing COVID-19, with coinciding proliferation of reviews summarizing these studies. OBJECTIVE: This study aimed to evaluate the methodological quality and evidence quality of systematic reviews and meta-analyses on the efficacy of TCM. SEARCH STRATEGY: Seven electronic databases, including PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chongqing VIP, Wanfang Data and SinoMed, were searched for systematic reviews and meta-analyses in October 2021. Search terms such as "Chinese medicine," "Lianhua Qingwen" and "COVID-19" were used. INCLUSION CRITERIA: Systematic reviews and meta-analyses of randomized controlled trials that evaluated the efficacy of TCM treatment of COVID-19 were included. DATA EXTRACTION AND ANALYSIS: A Measurement Tool to Assess Systematic Reviews Version 2.0 (AMSTAR 2) was used to evaluate the methodological quality. The quality of evidence was graded using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Data extraction and analysis were performed by two reviewers independently. RESULTS: There were 17 meta-analyses included in our overview. The intervention group was defined as TCM combined with Western medicine, while the control group was Western medicine alone. The methodological quality of all the included studies was moderate to poor. A total of 89 outcome indicators were evaluated, of which, 8 were rated as moderate quality, 39 as low quality, and 41 as very low quality. Only one outcome measure was graded as being of high quality. The moderate quality of evidence indicated that, for the treatment of COVID-19, the clinical efficacy of TCM in combination with Western medicine was better, in terms of lung recovery, rate of conversion to severe/critical cases, symptom scores, duration of symptoms, mortality, and length of hospital stay. CONCLUSION Evidence from the included studies shows that, compared with conventional Western medical therapy alone, the addition of TCM to COVID-19 treatment may improve clinical outcomes. Overall, the quality of evidence of TCM for COVID-19 was moderate to poor. Meta-analyses of the use of TCM in the treatment of COVID-19 can be used for clinical decision making by accounting for the experiences of clinical experts, medical policies, and other factors.
COVID-19/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Meta-Analysis as Topic ; Systematic Reviews as Topic ; Treatment Outcome

Along with increasing degree of population aging globally， senility， good health and long life have become the focus of the world. Guided by Qiluo doctrine， an essence， Qi and spirit theory is proposed as below， essence is the origin of life， Qi is the impetus of life and spirit is the embodiment of life. Based on holistic view of kidney deficiency involving the five internal organs and injuries of the five internal organs definitely affecting the kidney， a mechanism of aging is proposed as below， deficiency of kidney essence is the foundation of aging， deficiency of promordial Qi is the key of aging and physical and spiritual loss is the manifestation of aging. It provides a theoretical guidance for anti-aging study of rejuvenating the elderly and making the strong person stronger. By virtue of the experiences in kidney-tonifying medication accumulated for more than two thousand years， Bazi Bushen capsules has been developed， which has anti-aging efficacy， including tonifying kidney， replenishing essence， coordinating Yin and Yang， supplementing primordial Qi and nourishing body and spirit. Experimental researches have demonstrated that Bazi Bushen capsules can improve overall aging and systemic aging， as well as prevent and treat aging related diseases. Preliminary clinical studies demonstrate that this capsules can enhance athletic ability and improve sexual function， and is expected to become a representative Chinese patent medicine of anti-aging. This paper addresses aging and anti-aging on the basis of Qiluo doctrine， in the hope of helping prevention and treatment of aging related diseases.

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

Objective:To examine the surgical treatment of Stanford type A aortic dissection (type A dissection) after thoracic endovascular aortic repair (TEVAR).Methods:The data of 58 patients with reoccurrence of type A dissection after TEVAR admitted into the Department of Cardiovascular Surgery, Henan Chest Hospital from February 2012 to January 2020 were analyzed retrospectively. There were 40 males and 18 females, aged (57.0±6.7) years (range: 31 to 71 years). The time between recurrence of type A dissection and TEVAR ( M( Q R)) was 37 days (72.8 months) (range: 1 h to 14 years). Forty-eight cases underwent emergency operation, 9 cases underwent sub-emergency operation, and 1 case died of dissection rupture on the way to the operating room. All 57 patients underwent radical treatment. Fifty-four cases underwent the frozen elephant trunk technique under deep hypothermia circulatory arrest and selective cerebral perfusion, and 3 cases (>65 years old) underwent arch debranch anastomosis+ascending aorta replacement+descending arch covered stent implantation under mild hypothermia. Results:The operation time was (445±32) minutes (range: 382 to 485 minutes), the aortic crossclamp time was (103±19) minutes (range: 89 to 133 minutes), the cardiopulmonary bypass time was (189±27) minutes (range: 162 to 221 minutes), and the intraoperative blood loss was (665±343) ml (range: 450 to 1 750 ml). Postoperative ICU stay time was 5 (6) days (range: 2 to 27 days), and postoperative hospital stay was 14.0 (4.5) days (range: 2 to 36 days). Three cases died, including 2 cases with severe brain complications and 1 case with systemic multiple organ failure caused by severe liver insufficiency and gastrointestinal hemorrhage. Postoperative follow-up was 0.5 to 7.0 years, which showed that 1 case had left coronary artery anastomotic stoma fistula 3 months after operation and underwent reoperation, 2 cases underwent thoracoabdominal aortic replacement again, and the rest of patients had no anastomotic stoma fistula and incomplete stent distortion and expansion on CT angiography. Four cases died during follow-up, and 1 case died of sudden cerebral infarction 2 years after operation.Conclusion:The recurrent type A dissection after TEVAR is mostly related to stent graft, and the patients can undergo operation actively with good prognosis.

Objective:To examine the surgical treatment of Stanford type A aortic dissection (type A dissection) after thoracic endovascular aortic repair (TEVAR).Methods:The data of 58 patients with reoccurrence of type A dissection after TEVAR admitted into the Department of Cardiovascular Surgery, Henan Chest Hospital from February 2012 to January 2020 were analyzed retrospectively. There were 40 males and 18 females, aged (57.0±6.7) years (range: 31 to 71 years). The time between recurrence of type A dissection and TEVAR ( M( Q R)) was 37 days (72.8 months) (range: 1 h to 14 years). Forty-eight cases underwent emergency operation, 9 cases underwent sub-emergency operation, and 1 case died of dissection rupture on the way to the operating room. All 57 patients underwent radical treatment. Fifty-four cases underwent the frozen elephant trunk technique under deep hypothermia circulatory arrest and selective cerebral perfusion, and 3 cases (>65 years old) underwent arch debranch anastomosis+ascending aorta replacement+descending arch covered stent implantation under mild hypothermia. Results:The operation time was (445±32) minutes (range: 382 to 485 minutes), the aortic crossclamp time was (103±19) minutes (range: 89 to 133 minutes), the cardiopulmonary bypass time was (189±27) minutes (range: 162 to 221 minutes), and the intraoperative blood loss was (665±343) ml (range: 450 to 1 750 ml). Postoperative ICU stay time was 5 (6) days (range: 2 to 27 days), and postoperative hospital stay was 14.0 (4.5) days (range: 2 to 36 days). Three cases died, including 2 cases with severe brain complications and 1 case with systemic multiple organ failure caused by severe liver insufficiency and gastrointestinal hemorrhage. Postoperative follow-up was 0.5 to 7.0 years, which showed that 1 case had left coronary artery anastomotic stoma fistula 3 months after operation and underwent reoperation, 2 cases underwent thoracoabdominal aortic replacement again, and the rest of patients had no anastomotic stoma fistula and incomplete stent distortion and expansion on CT angiography. Four cases died during follow-up, and 1 case died of sudden cerebral infarction 2 years after operation.Conclusion:The recurrent type A dissection after TEVAR is mostly related to stent graft, and the patients can undergo operation actively with good prognosis.

Acute-on-chronic liver failure (ACLF) is a life-threatening disease with a high risk of multiple organ failure, sepsis, and death. ACLF activates innate and acquired immune responses in human body and thus leads to the progression of persistent systemic inflammatory response syndrome and multiple organ dysfunction, leading to the high mortality rate of this disease. Dysregulated immune response plays a key role in disease progression, and immunotherapy may help to target immune-mediated organ damage and inhibit the progression of liver failure. This article reviews the role and mechanism of drugs and means with a potential immune regulatory effect in ACLF, in order to provide a reference for immunotherapy for ACLF.

Objective: To know the pre-treatment drug resistance ( PDR ) status of newly reported human immunodeficiency virus type 1 ( HIV-1 ) infected individuals in Wenzhou, so as to provide guidance for antiretroviral therapy ( ART ). Methods: Totally 232 plasma samples of newly reported HIV-1 infected individuals who had not received ART were collected in Wenzhou in 2019. Virus ( HIV-1 ) RNA was extracted, followed by reverse transcription PCR and nested PCR to amplify the pol region and sequence. Resistance mutations and resistance to non-nucleoside reverse transcriptase inhibitors ( NNRTIs ), nucleoside reverse transcriptase inhibitors ( NRTIs ) and protease inhibitors ( PIs ) was analyzed. Results: The pol region sequences from 199 infected patients were obtained and the incidence of PDR was 8.04% ( 16/199 ). Eight genotypes were detected, including circulating recombinant forms ( CRFs ) CRF07_BC ( 47.24%, 94/199 ) and CRF01_AE ( 29.15%, 58/199 ) which were the dominant types. Two unique recombinant forms ( URFs ) were detected, namely URF( CRF01_AE/BC ) and URF( B/C ) . Thirty-one cases ( 15.58% 31/199 ) had drug-resistant mutations. For NNRTIs, NRTIs and PIs, 20 cases ( 64.52% ) , 2 cases ( 6.45% ) and 9 cases ( 29.03% ) with drug resistance mutations were detected, respectively. The resistance mutations to NNRTIs included K101E, K103N/R, V106I, E138K, V179D/E/T, Y181C, G190A and H221Y. Four cases each had two resistance mutations to NNRTIs. The resistance mutations to NRTIs were V75M and M184V. The resistance mutations to PIs were M46I, L33F and Q58E. For the newly released NNRTI drug Doravirine ( DOR ), two cases were found to have mutations of resistance. Conclusions The incidence of PDR among newly reported HIV-1 patients in Wenzhou is 8.04%, mainly caused by NNRTIs drug-resistant mutation. Resistance to the new drug DOR has emerged. The surveillance of drug resistance should continue to be strengthened.