As one of the most common malignant tumors， digestive system tumors exhibit an increase in the incidence and mortality year by year. Its pathogenesis is complex， making it difficult to carry out early prevention. Autophagy is a process in which cells use lysosomes to degrade their organelles and macromolecules to maintain cellular homeostasis under the regulation of autophagy-related genes. Cellular autophagy has a dual regulatory effect on the tumor microenvironment， which always affects the occurrence and development of digestive system tumors. Therefore， the effect and mechanism of action of cellular autophagy on digestive system tumors have become a hot topic in tumor therapy in recent years. Meanwhile， the remarkable research results of targeted autophagy drugs indicate that cellular autophagy may become an important target for anti-digestive system tumors. Traditional Chinese medicine （TCM） has been widely used in the comprehensive treatment of digestive system tumors with good efficacy. A variety of active ingredients in TCM， such as flavonoids， glycosides， terpenoids， quinones， and alkaloids， can increase the expression of autophagy-associated proteins microtubule-associated protein 1 light chain 3 （LC3）Ⅱ/Ⅰ， autophagy-related gene （ATG）5， ATG7， inhibit the expression of autophagy-related protein p62 ， and induce autophagy in digestive system tumor cells， thereby exerting the anti-digestive system tumor effect. By summarizing the research results in recent years on the modulation of cell autophagy by active ingredients in TCM to fight against digestive system tumors， this paper analyzed the relevant signaling pathways， regulatory factors， and functional characteristics of cell autophagy modulation， so as to elucidate the mechanism by which active ingredients of TCM induce autophagy and to provide ideas and references for clinical application.

As one of the most common malignant tumors， digestive system tumors exhibit an increase in the incidence and mortality year by year. Its pathogenesis is complex， making it difficult to carry out early prevention. Autophagy is a process in which cells use lysosomes to degrade their organelles and macromolecules to maintain cellular homeostasis under the regulation of autophagy-related genes. Cellular autophagy has a dual regulatory effect on the tumor microenvironment， which always affects the occurrence and development of digestive system tumors. Therefore， the effect and mechanism of action of cellular autophagy on digestive system tumors have become a hot topic in tumor therapy in recent years. Meanwhile， the remarkable research results of targeted autophagy drugs indicate that cellular autophagy may become an important target for anti-digestive system tumors. Traditional Chinese medicine （TCM） has been widely used in the comprehensive treatment of digestive system tumors with good efficacy. A variety of active ingredients in TCM， such as flavonoids， glycosides， terpenoids， quinones， and alkaloids， can increase the expression of autophagy-associated proteins microtubule-associated protein 1 light chain 3 （LC3）Ⅱ/Ⅰ， autophagy-related gene （ATG）5， ATG7， inhibit the expression of autophagy-related protein p62 ， and induce autophagy in digestive system tumor cells， thereby exerting the anti-digestive system tumor effect. By summarizing the research results in recent years on the modulation of cell autophagy by active ingredients in TCM to fight against digestive system tumors， this paper analyzed the relevant signaling pathways， regulatory factors， and functional characteristics of cell autophagy modulation， so as to elucidate the mechanism by which active ingredients of TCM induce autophagy and to provide ideas and references for clinical application.

Natural flavonoids have attracted considerable attention owing to their favorable biosafety profiles and multiple pharmacological properties in recent years. Luteolin, a representative flavonoid compound, exhibits anti-inflammatory, antioxidant, anti-angiogenic, and neuroprotective effects in multiple ocular disease models by modulating key signaling pathways, including NF-κB, PI3K/Akt, Nrf2/HO-1, and AGE-RAGE. Accumulating experimental evidence supports the potential application of luteolin in various ocular diseases, including corneal and ocular surface diseases, inflammatory eye diseases, glaucoma, cataract, diabetic retinopathy, and age-related macular degeneration. However, clinical evidence remains limited. This review systematically summarizes research progress on luteolin in ocular diseases over the past five years, analyzes its molecular mechanisms and therapeutic potential, and discusses future directions,so as toprovide a theoretical basis for clinical translation.

OBJECTIVE: To carry out genetic testing and clinical phenotypic characterization on a four-generation Chinese pedigree affected with Stickler syndrome type I and explore its genotype-phenotype correlation. METHODS: A child presented at the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine in February 2023 for micrognathia, glossoptosis and cleft palate and his family members were selected as the study subjects. Clinical data were collected from the affected members, and peripheral blood samples were obtained from 17 participants (including 4 patients and 13 asymptomatic individuals). Whole exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing. Genotype-phenotype correlation was analyzed by integrating the sequencing data with evidence from existing literature. This study has bee granted by the Ethics Committee of Guangdong Provincial Hospital of Traditional Chinese Medicine and Guangzhou Women and Children's Medical Center (Ethics No.: 2022-406B00). RESULTS: The four-generation pedigree has comprised 19 members. In addition to the proband, 5 affected individuals had manifested with high myopia, congenital cataracts, and progressive vision loss. Two deceased members reportedly exhibited similar ocular manifestations. Among the four living patients, two had developed retinal detachment, while two others presented with chronic joint pain onset between 35 ~ 40 years of age. One patient required hip replacement surgery at age 42 secondary to femoral head necrosis. The proband, the youngest affected member, exhibited characteristic phenotypes including congenital micrognathia and cleft palate, consistent with Pierre-Robin syndrome. Genetic analysis revealed a heterozygous nonsense mutation in COL2A1 (NM_001844.5: c.2668C>T; p.Gln890Ter) segregating with the disease in all four symptomatic patients. This variant was absent in asymptomatic family members and unaffected controls. While the mutation is listed in ClinVar, no clinical case report has associated it with this phenotypic spectrum. It was not recorded in population databases (gnomAD v4.1.0, 1000 Genomes Project, or ExAC), supporting its potential pathogenicity. CONCLUSION This study has diagnosed a four-generation Chinese pedigree with Stickler syndrome type I attributed to the pathogenic COL2A1 variant c.2668C>T (p.Gln890Ter), which is a rare nonsense mutation associated with ocular predominance and variable skeletal involvement. Notably, this family exhibited marked clinical heterogeneity despite sharing the identical genotype, which highlighted the challenges in phenotype-genotype correlation. The autosomal dominant transmission pattern observed in this pedigree has provided critical insights into COL2A1-related collagenopathies and underscored the necessity of ultrasonographic monitoring for ocular anomalies during prenatal diagnosis. Above findings have advanced our understanding of the pleiotropic effects in type Ⅱ collagen disorders and laid the foundation for precision-based genetic counseling, enabling targeted cascade screening and implementation of tertiary prevention strategies against congenital disabilities for high-risk families.
Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Arthritis/genetics* ; Collagen Type II/genetics* ; Connective Tissue Diseases/genetics* ; Exome Sequencing ; Genetic Association Studies ; Genotype ; Hearing Loss, Sensorineural/genetics* ; Mutation ; Pedigree ; Phenotype ; Retinal Detachment/genetics* ; East Asian People/genetics*

Objective To analyze the risk factors for meconium-stained amniotic fluid(MSAF)in preterm infants and the clinical outcome and prognosis of preterm infants.Methods Preterm infants with gestational age＜37 weeks delivered in Zhangjiajie People's Hospital from January 2022 to December 2023 were used as the study subjects,31 cases with MSAF were in MSAF group,and 31 cases of preterm infants hospitalized during the same period without MSAF were randomly paired in the ratio of 1∶1 to select with gestational age-body mass matching as non-MSAF group.Retrospective collection and analysis of pregnancy and perinatal conditions of mothers of preterm infants in two groups,comparing the differences of related factors between two groups of children;Logistic regression analysis of risk factors related to MSAF in preterm infants;comparing the complications and clinical outcomes of preterm infants in two groups.Results A total of 387 preterm infants with gestational age＜37 weeks were collected during the study period,including 31 preterm infants with comorbid MSAF,and the prevalence of MSAF in preterm infants was 8.0％.MSAF group had a higher incidence of advanced maternal age,premature rupture of membranes＞18 hours,antepartum fever,and cholestasis during pregnancy than non-MSAF group.Logistic regression analysis suggested that combined cholestasis during pregnancy and white blood cell count ≥ 30× 109/L within 6 hours after birth increased the incidence of MSAF in preterm infants.There was no statistically significant difference in the results of postnatal umbilical artery blood gas analysis between two groups of preterm infants.The proportion of leukocyte count ≥30×109/L,ultrasensitive C-reactive protein＞0.8 mg/L,and interleukin 6＞6 pg/L in MSAF group was higher than that of non-MSAF group in the 6 hours after birth.MSAF group had a higher incidence of intrauterine infectious pneumonia,feeding intolerance,and necrotizing small bowel colitis in neonates than non-MSAF group.Conclusion Advanced maternal age,intrauterine infections,and combined intrahepatic cholestasis during pregnancy may be the major risk factors for MSAF in preterm infants.MSAF preterm infants have a higher prevalence of intrauterine infectious pneumonitis,feeding intolerance,and necrotizing small bowel colitis in newborns,as well as longer hospital stays.

Objective To observe the complication incidences after percutaneous lung biopsy and sealed the tract with different sealants.Methods A total of 129 patients with solitary pulmonary nodule who underwent CT-guided percutaneous lung biopsy were retrospectively included and divided into group A(n=37),B(n=47)and C(n=45).The biopsy tract was sealed with sealant A(1 g gelatin sponge particles mixed with 10 ml 50％glucose solution)in group A,with sealant B(1 g gelatin sponge particles mixed with 10 ml normal saline)in group B,while with sealant C(1 g gelatin sponge particles mixed with the coagulant enzyme from Bothrops atrox venom and 10 ml normal saline)in group C.The incidence rate of complications such as pneumothorax and hemoptysis were comparatively observed among groups.Binary logistic regression was performed to screen the independent influencing factors associated with complications of percutaneous lung biopsy.Results No significant difference of gender,age,proportion of smoking history nor emphysema,diameter of pulmonary nodules,depth of puncture into lung parenchyma nor times of puncture was found among groups(all P＞0.05).Complications occurred in 43 cases(43/129,33.33％),i.e.27 cases in group B(27/47,57.45％),11 cases in group A(11/37,29.73％)and 5 cases in group C(5/45,11.11％),and the complication rates decreased order of group B,A and C(all P＜0.05).Compared with sealant A,sealant B was associated with increased risk(OR[95％CI]=3.190[1.183,8.598],P=0.022),whereas sealant C was associated with reduced risk(OR[95％CI]=0.266[0.079,0.889],P=0.031)of complications.Conclusion After percutaneous lung biopsy,the complication incidences decreased sequentially when the needle tract was sealed with saline B,A and C.

Objective To investigate the effect of dexmedetomidine on the median effect concentration(EC50)of ropivacaine during sciatic nerve block combined with femoral nerve block in patients undergoing lower extremity surgery.Methods Patients with sciatic nerve block combined with femoral nerve block anesthesia who underwent lower extremity surgery from November 2021 to November 2023 were selected as the study objects.They were randomly divided into control group(0.9％saline),group D1(0.50 μg·kg-1 dexmedetomidine),group D2(0.75 μg·kg-1 dexmedetomidine)and group D3(1.00 μg·kg-1 dexmedetomidine).The stress response,serum pain mediators,vital signs and visual analogue scale(VAS)of patients at different time points during operation were analyzed by repeated measures ANOVA.ropivacaine EC50 was measured by sequential method,and the relationship between dexmedetomidine dose and ropivacaine EC50 was analyzed by Logistic regression.Results A total of 208 patients were include and each group was 52 patients.Compared with the same group before surgery,the stress response level of the 4 groups after surgery and 1 h after surgery was significantly decreased,and the serum pain mediators level was significantly increased(P＜0.05).Compared with the control group,the stress response and serum pain mediators levels in groups D1,D2 and D3 were more normal after surgery and 1 h after surgery,among them,group D3 was most close to the normal value(P＜0.05).There were no significant differences in blood oxygen saturation and bifrequency index of EEG among the four groups at each time point(P＞0.05).At T1 and T2,the heart rate(HR)of the control group was significantly higher than that of the group D2 and D3(P＜0.05).At T1,the control group had a significantly higher mean arterial pressure(MAP)than the other three groups,at T2,the control group had a significantly higher MAP than the group D2 and D3,and at T3,the control group had a significantly higher MAP than the group D3(P＜0.05).VAS scores in 4 groups were significantly lower after surgery and 1 h after surgery than before surgery(P＜0.05).The VAS score in group D3 was significantly lower than that in group D1 and D2(P＜0.05).Repeated measurement ANOVA showed that the effects of time on stress response and serum pain mediators were different with different anesthesia methods.The influence of time on HR,MAP and VAS scores varied with different anesthesia methods.Sequential assay results showed that the EC50 of ropivacaine in control group,group D1,group D2 and group D3 was 5.985,5.631,5.329 and 5.125 μg·mL-1,respectively.Logistic results showed that the dose of dexmedetomide was a protective factor for ropivacaine EC50 in sciatic nerve block combined with femoral nerve block in limb surgery patients(P＜0.05).Conclusion The ropivacaine EC50 can be significantly reduced by 1.00 μg·kg-1 dexmedetomidine.This is a protective factor for sciatic nerve block combined with femoral nerve block in patients undergoing lower limb surgery,and it can be applied clinically.

Objective To investigate the effects of simulated-microgravity on the osteogenic differentiation,primary cilia status,cytoskeleton structure,and the YAP(Yes-associated protein)expression in primary osteoblasts.Methods Primary osteoblasts were isolated from the skull bones of neonatal Wistar rats and cultured in random positioning machine system to simulate the cellular effects of microgravity.The calcified nodules were stained with Arlizarin to assess the cellular mineralization ability,the primary cilia and cytoskeleton were detected by immunofluorescence staining of Arl13b/γ-Tubulin and α-Tubulin,respectively,and the expression of YAP was measured by western blot.Results The cellular osteogenic differentiation were markedly suppressed after treated with simulated microgravity for 24 h,and the ciliated cells decreased from(58.44±3.65)%to(15.76±1.84)%in parallel with a decline of average cilium length from(3.19±0.51)μm to(1.59±0.46)μm.In addition,simulated microgravity induced disassembly of microtubules.Notably,simulated microgravity interfered YAP expression and the inhibition of YAP into nucleus.Furthermore,knockdown of YAP expression in osteoblasts notably reduced primary cilia expression and inhibited osteogenic differentiation.Conclusion Primary cilia is a key organelle of osteoblasts in sensing microgravity and regulating osteogenic differentiation.Interference with YAP expression and inhibition of nuclear YAP entry may play an important role in the deaggregation of primary cilia induced by microgravity.

Objective To study the clinical efficacy of Xiaoqinglong decoction combined with the conventional protocol of western medicine in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD)presenting with exterior cold and interior fluid retention syndrome,and to evaluate its effect on the short-term prognosis of patients.Methods A total of 124 AECOPD patients presenting exterior cold and interior fluid retention syndrome were divided into an observation group(62 cases)and a control group(62 cases)using a random number table.Patients in the control and observation groups were managed with conventional western medicine treatment protocols consisting of bronchodilators,glucocorticoids,and antibacterial drugs.In addition,patients in the observation group were also given Xiaoqinglong decoction at one dose per day for 10 days in succession.The primary outcome indicators included the total effective treatment rate and the main traditional Chinese medicine(TCM)syndrome scores before treatment and after 10 days of Xiaoqinglong decoction treatment.The secondary outcome indicators included infection and inflammatory indicators,including white blood cell count(WBC),procalcitonin(PCT),interleukin(IL)-6,C-reactive protein(CRP),and arterial blood gas indicators,including arterial partial pressure of oxygen(PaO2),arterial partial pressure of carbon dioxide(PaCO2),and arterial oxygen saturation(SaO2),measured before treatment and after 10 days of treatment,adverse drug reactions during treatment,and the severity of dyspnea assessed by the modified Medical Research Council(mMRC)dyspnea scale at the 1-month follow-up after discharge.Results Compared with baseline findings for the same group before treatment,the main TCM syndrome scores and the total score were reduced in both groups after treatment(P<0.05).After treatment,compared with those of the control group,the syndrome scores for cough,aversion to cold,nasal congestion,and runny nose,and the total score in the observation group were lower(P<0.05).The total effective treatment rate in the observation group(94.91%)was significantly higher than that in the control group(82.76%)(P<0.05).After 10 days of treatment,the levels of PaCO2,WBC,PCT,IL-6,and CRP in both groups were significantly reduced compared with those before treatment(P<0.05).After treatment,the levels of PaCO2,WBC,PCT,IL-6,and CRP in the observation group were lower than those in the control group(P<0.05).Compared with those before treatment,PaO2 and SaO2 levels in both groups increased significantly after 10 days of treatment(P<0.05).During the course of treatment,no severe adverse reactions,such as liver or kidney dysfunction,occurred in either group.No adverse reactions associated with Xiaoqinglong decoction were observed.No patients in either group reached mMRC grade 4 at the 1-month follow-up after discharge.The mMRC grades in both groups declined at the 1-month follow-up after discharge compared to those before treatment(P<0.05).At the 1-month follow-up after discharge,the mMRC grades of patients in the observation group were lower than those of the control group(P<0.05).Conclusion Xiaoqinglong decoction combined with the conventional protocol of western medicine deminstrates good clinical efficacy in treating patients with AECOPD of exterior cold and interior fluid retention syndrome,and can effectively improve the TCM syndromes,relieve the symptoms of dyspnea,reduce the inflammatory response,promote the resolution of infection,delay disease progression,improve short-term prognosis,and shows better safety.

Objective To explore the influencing factors of depression risk in elderly patients with hypertension and construct and validate a nomogram prediction model.Methods A total of 869 elderly patients with hypertension were selected from national survey database of the China Health and Retirement Longitudinal Study(CHARLS)in 2018.Multivariate Logistic regression analysis was used to identify the risk factors for depression in elderly patients with hypertension,and a nomogram prediction model was constructed.The accuracy and effectiveness of the model were validated by the Hosmer-Lemeshow(H-L)goodness-of-fit test,the area under the curve(AUC)of the receiver oper-ating characteristic(ROC)curve,and the calibration curve.Results The incidence of depression in elderly patients with hypertension was 47.18％.Factors influencing the risk of depression included rural residence(OR=2.191,P＜0.05),impaired basic activities of daily living(BADL)(OR=2.338,P＜0.05),impaired instrumental activitiesofdaily living(IADL)(OR=1.674,P＜0.05),poor life satisfaction(OR=7.348,P＜0.05),fair self-rated health(OR=0.441,P＜0.05),good self-rated health(OR=0.259,P＜0.05),and sleep duration of 6 to 9 hours(OR=0.510,P＜0.05).The AUC of the ROC curve was 0.795,the slope of the calibration curve was close to 1,and the H-L goodness-of-fit test yielded x2=5.074.The validation set showed an AUC of 0.703.Conclusion The prediction model established in this study has high accuracy and discriminative ability.Healthcare professionals can take effective preventive measures based on individual patient factors.