Objective To explore the regulation of the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)-mediated inflammatory response in chronic obstructive pulmonary disease(COPD)by modified Shengxian Decoction through the lung-gut axis.Methods Thirty rats were divided into three groups:Control group,COPD group,and COPD+modified Shengxian Decoction(SXT)group,with 10 rats in each.The COPD model was established using passive smoking combined with intratracheal instillation of lipopolysaccharide(LPS).General symptoms and signs of the rats were monitored during the modeling and intervention periods.Hematoxylin and eosin(HE)staining and immunohistochemistry(IHC)were used to observe lung tissue structure.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of inflammatory cytokines interleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α)in lung tissues.Flow cytometry was used to detect the number of type Ⅱ innate lymphoid cells(nILC2)and type 2 innate lymphoid cells(iILC2)in lung and intestinal tissues.Illumina MiSeq sequencing technology was used to perform 16S rRNA gene sequencing on rat feces to analyze the gut microbiota structure.Gas chromatography-mass spectrometry(GC-MS)was used to determine the content of short-chain fatty acids(SCFAs)in rat feces.Western blotting was used to detect the expressions of related proteins in the PI3K/AKT pathway.Results Compared with the Control group,the COPD group showed significantly reduced lung function indicators,increased heart rate and decreased body mass,while the SXT group showed significant improvement in lung function and general signs(P＜0.05).HE staining showed that the COPD group had lung tissue damage filled with inflammatory cells,while the SXT group had significantly fewer inflammatory cells.IHC results showed that the SXT group had significantly reduced expression of caspase-3 protein(P＜0.05).ELISA results showed that the levels of IL-6 and TNF-α were significantly increased in the COPD group,while the SXT group showed significant improvement in inflammatory damage.The ratio of nILC2 to iILC2 in lung and intestinal tissues was significantly reduced in the COPD group,indicating a significant inflammatory response,while the SXT group showed significant improvement(P＜0.05).The levels of ILC2 cytokines IL-13 and IL-4 were significantly increased in the COPD group,while the SXT group had significantly reduced IL-13 and IL-4 levels.The relative abundance of lung and gut microbiota in the SXT group was significantly higher than that in the Control and COPD groups(P＜0.05).Beta diversity index analysis showed significant differences in species diversity among the three groups(P＜0.05).GC-MS detected six types of SCFAs in rat feces:acetic acid,propionic acid,isobutyric acid,butyric acid,isovaleric acid,and valeric acid.Their levels were lower in the COPD group than in the Control group,but the levels in the SXT group were higher than those in the COPD group.Western blotting results showed that the expressions of p-PI3K,PI3K,p-AKT,AKT,p-NF-κB,and NF-κB proteins were significantly reduced in the SXT group compared to the COPD group(P＜0.05).ELISA results showed that the SXT group had significantly downregulated expression levels of IL-1β and IL-10 compared to the COPD group(P＜0.05).Conclusion Modified Shengxian Decoction can alleviate COPD inflammation.It may mediate the inflammatory response in COPD by inhibiting iILC2 cell activity and expressions of related proteins in the PI3K/AKT signaling pathway through gut microbiota metabolism.

BACKGROUND:Apoptosis and autophagy imbalance in the hippocampal region of perimenopausal depressed rats are closely related to cognitive decline.Whether aerobic exercise can reduce apoptosis by promoting hippocampal autophagy and thus improve the learning and memory abilities of perimenopausal depressed rats is not clear.OBJECTIVE:To investigate the possible mechanism by which 4-week moderate-intensity treadmill exercise improves learning memory ability in ovariectomized stressed rats.METHODS:Forty Sprague-Dawely rats were randomly divided into four groups,namely,sham operation group(n=10),ovariectomized group(n=10),ovariectomized stress group(n=10)and ovariectomized stress exercise group(n=10).Except for the sham operation group,the ovaries were removed in the other three groups to establish a perimenopausal rat model,and then a depressed rat model was established by chronic unpredictable stress in the latter two groups.The rats in the ovariectomized stress exercise group underwent a 4-week moderate-intensity treadmill exercise.Tail suspension test and sucrose preference test were performed to text depression-like behaviors in rats after exercise and stress.The eight-arm maze experiment was used to test the learning and memory behaviors of rats after exercise and stress.Western blot was used to detect the protein levels of AMP-activated protein kinase/UNC-51 like autophagy activating kinase 1/mammalian target of rapamycin(AMPK/mTOR/ULK1),hippocampus apoptotic factor Caspase-3 and the protein expression of autophagy markers LC-3II/Beclin-1 in the hippocampus.RESULTS AND CONCLUSION:(1)Compared with the sham operation group,rats in the ovariectomized and ovariectomized stress groups had prolonged resting time in the tail suspension test and decreased sugar-water intake and sugar-water preference in the sucrose preference test.(2)Ovary removal reduced the learning memory capacity of rats,as evidenced behaviorally by a significant increase in the number of working memory errors,the number of reference memory errors,and the completion time,and an even more pronounced increase in the above measures in the ovariectomized stress group.(3)Compared with the ovariectomized group,there was a significant reduction in the number of working memory errors,the number of reference memory errors,and the completion time in the ovariectomized stress group.(4)Compared with the sham operation group,in the ovariectomized and ovariectomized stress groups,the expression of hippocampal apoptotic factor Caspase 3 protein was significantly elevated,the expression of autophagy-related factors proteins Beclin-1 and LC3II,as well as the protein expression of AMPK and ULK1,was decreased,whereas the expression of mTOR protein was elevated.Changes in the above indicators were more significant in the ovariectomized stress group.(5)Compared with the ovariectomized stress group,in the ovariectomized stress exercise group,the protein expression of Caspase 3 was significantly decreased,the protein expression of Beclin-1 and LC3II was significantly increased,the protein expression of AMPK and ULK1 was significantly increased,and the protein expression of mTOR was significantly reduced.To conclude,4-week moderate-intensity treadmill exercise may promote cellular autophagy and reduce apoptosis through the AMPK/mTOR/ULK1 autophagy signaling pathway,thereby enhancing the learning and memory capacity of rats with ovariectomized depression

Objective:To explore the clinical characteristics and genetic etiology of a child with Neurofibromatosis-Noonan syndrome (NFNS).Methods:A child with NFNS who was treated at the Department of Endocrinology of Hangzhou Children′s Hospital in January 2024 was selected as the study subject. Clinical data of the child was collected by retrospective analysis method. Peripheral venous blood samples (2 mL each) were collected from the child and his parents. Genomic DNA was extracted, and trio whole exome sequencing (Trio-WES) of the family was carried out. Sanger sequencing was used to perform family verification on the candidate variants. The identified variants were classified for pathogenicity according to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG) (hereafter referred to as the " ACMG guidelines" ). This study has been approved by the Medical Ethics Committee of Hangzhou Children′s Hospital (Ethics No. 2021-06).Results:The child was a 7-year and 4-month-old male. He has short stature, numerous café-au-lait spots on the neck and trunk, and special facial features such as a full forehead, wide interpupillary distance, a low nasal bridge, and low-set ears.The results of Trio-WES showed that he has harbored a NF1 gene c. 3773G>T (p.W1258L) mutation, which was verified by Sanger sequencing to be de novo in origin. The NF1 gene child was associated with NFNS, which was an autosomal dominant inheritance. According to the ACMG guidelines, this variant was judged to be a likely pathogenic variant (PS2+ PM2+ PP3+ PP2). No pathogenic variant in genes associated with Noonan syndrome, such as those in PTPN11, SOS1, RAF1, RIT1, and KRAS, was found. Conclusion:The child with NFNS has clinical features such as short stature, special facial features, and café-au-lait spots. The c. 3773G>T (p.W1258L) variation in the NF1 gene may be the genetic etiology of the NFNS child in this study. The results of this study has enriched the variation spectrum of the NF1 gene.

Objective To investigate the refractive development parameters of primary school students aged 7 to 12 years in Chuxiong City,Yunnan Province,analyze their relationship with equivalent spherical power(SE),and evaluate the monitoring role of refractive parameters in myopia.Methods A total of 1463 primary school students aged 7-12 from Beipu Primary School in Chuxiong City,Yunnan Province were selected.Spherical degree(DS),cylindrical degree(DC),and equivalent spherical degree(SE)were obtained using a computer autorefractor.Axial length(AL),corneal curvature(K1,K2),anterior chamber depth(ACD),central corneal thickness(CCT),lens thickness(LT),and vitreous depth(VD)were measured using a biometer.The corneal curvature radius(CR),the ratio of axial length to corneal curvature radius(AL/CR),and lens power(LP)were calculated.Participants were divided into 7～8 years old group(n=518),9～10 years old group(n=547),and 11～12 years old group(n=398)according to age;and categorized into myopic group(n=647),emmetropic group(n=532),and hyperopic group(n=284)based on refractive status to analyze the characteristics of refractive parameters and their impact across different age groups and refractive categories.Results(1)SE,DS,LT,and LP decreased with age(P<0.05);(2)AL,AL/CR,ACD,and VD increased with age(P<0.05);(3)K,CR and CCT showed no significant change with age(P>0.05);(4)In both myopic and hyperopic groups,AL was negatively correlated with SE(rs=-0.617,rs=-0.318,both P<0.05),AL/CR was negatively correlated with SE(rs=-0.737,rs=-0.406,both P<0.05),LP was positively correlated with SE(rs=0.412,rs=0.182,both P<0.05),while CR showed no correlation with SE(P>0.05).Conclusion The refractive development parameters AL,AL/CR,ACD,and VD increased with age in primary school students aged 7 to 12,while SE,DS,LT,and LP decreased with age,and K,CR,and CCT showed no significant changes.AL/CR and AL can serve as monitoring indicators for myopia,with AL/CR demonstrating a higher correlation with SE than AL.

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with Neurofibromatosis-Noonan syndrome (NFNS). METHODS: A child with NFNS who was treated at the Department of Endocrinology of Hangzhou Children's Hospital in January 2024 was selected as the study subject. Clinical data of the child was collected by retrospective analysis. Peripheral venous blood samples (2 mL each) were collected from the child and his parents. Genomic DNA was extracted, and trio-whole exome sequencing (Trio-WES) of the family was carried out. Sanger sequencing was used to perform family verification on the candidate variants. The identified variants were classified for pathogenicity according to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG) (hereafter referred to as the "ACMG guidelines"). This study has been approved by the Medical Ethics Committee of Hangzhou Children's Hospital (Ethics No. 2021-06). RESULTS: The child was a 7-year and 4-month-old male. He has short stature, numerous café-au-lait spots on the neck and trunk, and special facial features such as a full forehead, wide interpupillary distance, a low nasal bridge, and low-set ears. The results of Trio-WES showed that the he had harbored the NF1 gene c.3773G>T (p.W1258L) mutation, which was verified by Sanger sequencing to be de novo in origin. The NF1 gene was associated with NFNS, which has an autosomal dominant inheritance. According to the ACMG guidelines, this variant was judged to be a likely pathogenic variant (PS2+PM2+PP3+PP2). No pathogenic variant in genes associated with Noonan syndrome, such as PTPN11, SOS1, RAF1, RIT1, and KRAS, was found. CONCLUSION The child with NFNS has clinical features such as short stature, special facial features, and café-au-lait spots. The c.3773G>T (p.W1258L) variation in the NF1 gene may be the genetic etiology of the NFNS child in this study. The results of this study has enriched the variation spectrum of the NF1 gene.
Child ; Humans ; Male ; Exome Sequencing ; Mutation ; Neurofibromatosis 1/genetics* ; Neurofibromin 1/genetics* ; Noonan Syndrome/genetics*

Objective:To observe the clinical effect of comprehensive reconstruction of grades Ⅰ-Ⅱ thumb and finger defects with hallux osteo-onychocutaneous flaps of great toe.Methods:This is a retrospective study. From June 2020 to December 2023, comprehensive reconstruction surgery for Grade Ⅰ-Ⅱ digital defect were performed with hallux osteo-onychocutaneous flaps of great toe for 3 thumbs and 7 fingers in 9 patients in the Department of Hand and Microsurgery of Baoji Third Hospital. Causes of digital injury were: 4 of machine crush, 3 of electric saw cut, 1 of door crush, and 1 of electrical burn. There were 6 grade I digital defects (beyond the nail root) and 4 grade Ⅱ defects (last segment of digit). The defects of the digits were reconstructed by taking references of the shape and structure of the contralateral normal thumbs and fingers. Then the hallux osteo-onychocutaneous flaps of great toe were designed and harvested accordingly from the left and right great toes. Donor sites were covered by skin grafting or local dressing change. One patient was treated in emergency surgery, 6 in sub-emergency surgery and 2 in elective surgery. Integrated perioperative patient management was provided to all of the patients. Postoperative follow-ups were conducted through the visit of outpatient clinic, telephone calls or WeChat interviews. Flap survival, appearance and sensation recovery were evaluated according to the Evaluation Standard of Upper Limb Functional of Hand Surgery of Chinese Medical Association.Results:Vascular insufficiency of 1 digit occurred in surgery, and relieved by local treatment with lidocaine and warm saline. All 10 digits successfully survived, and all donor sites healed spontaneously. The postoperative follow-up period was 10 to 30 months, with an average of 18 months. One transferred nail was found in poor appearance (not flat), the rest of the reconstructed digits were good in appearance and function. The nail, finger print and fine sensation (TPD 5~8 mm), as well as digital flexion, extension, grasping and opposition of the reconstructed digits were all good. According to the Evaluation Standard of Upper Limb Functional of Hand Surgery of Chinese Medical Association, at the last follow-up visit, 5 digits were in excellent, 4 in good and 1 in fair.Conclusion:The comprehensive reconstruction of grades Ⅰ-Ⅱ digital defects with hallux osteo-onychocutaneous flap of great toe is an ideal surgical technique that can reconstruct the nail, finger print and sensation of a digit, with good postoperative function as well as an aesthetic and realistic appearance.

Objective In order to understand the current status and influencing factors of perioperative pulmonary rehabilitation knowledge,attitude,and practice among Chinese thoracic surgery nurses,and to provide references for managers to take targeted measures to improve their pulmonary rehabilitation knowledge,attitude,and practice level.Methods From August to October 2023,a convenience sampling method and cross-sectional descriptive survey were used to anonymously survey 1 167 thoracic surgery nurses from tertiary-level A cancer specialty hospitals and tertiary-level A general hospitals in 24 provinces through the Wenjuanxing platform.A general information questionnaire and a knowledge,attitude and practice questionnaire for lung cancer perioperative pulmonary rehabilitation nurses were used,including knowledge dimension(14 items),belief dimension(6 items),and behavior dimension(14 items),totaling 34 items.Univariate analysis and linear regression multivariate analysis were used to determine the influencing factors of the knowledge,attitude and practice level of thoracic surgery nurses in perioperative pulmonary rehabilitation.Results 1 089 nurses completed the investigation.The total standard score and the dimension scores on knowledge,attitude,and behavior of the perioperative pulmonary rehabilitation questionnaire for thoracic surgery nurses were(80.45±11.84)(73.72±14.68)(89.61±11.38)and(83.46±14.48),respectively.The nature of the hospital,whether there is an administrative position,whether the department carries out ERAS,and whether they have received pulmonary rehabilitation training are the influencing factors of the perioperative pulmonary rehabilitation knowledge,attitude,and practice level of thoracic surgery nurses(P＜0.05).Conclusion The knowledge,attitude,and practice of perioperative lung rehabilitation among thoracic surgery nurses are generally at a moderate level.However,their knowledge of perioperative lung rehabilitation is relatively insufficient,and there are many influencing factors.Managers should strengthen pulmonary rehabilitation training for thoracic surgery nurses,improve their knowledge reserves and evidence conversion capabilities,and coordinate cross-integration among multidisciplinary teams to improve their knowledge,attitude and practice in perioperative pulmonary rehabilitation.

Objective To explore the regulation of the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)-mediated inflammatory response in chronic obstructive pulmonary disease(COPD)by modified Shengxian Decoction through the lung-gut axis.Methods Thirty rats were divided into three groups:Control group,COPD group,and COPD+modified Shengxian Decoction(SXT)group,with 10 rats in each.The COPD model was established using passive smoking combined with intratracheal instillation of lipopolysaccharide(LPS).General symptoms and signs of the rats were monitored during the modeling and intervention periods.Hematoxylin and eosin(HE)staining and immunohistochemistry(IHC)were used to observe lung tissue structure.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of inflammatory cytokines interleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α)in lung tissues.Flow cytometry was used to detect the number of type Ⅱ innate lymphoid cells(nILC2)and type 2 innate lymphoid cells(iILC2)in lung and intestinal tissues.Illumina MiSeq sequencing technology was used to perform 16S rRNA gene sequencing on rat feces to analyze the gut microbiota structure.Gas chromatography-mass spectrometry(GC-MS)was used to determine the content of short-chain fatty acids(SCFAs)in rat feces.Western blotting was used to detect the expressions of related proteins in the PI3K/AKT pathway.Results Compared with the Control group,the COPD group showed significantly reduced lung function indicators,increased heart rate and decreased body mass,while the SXT group showed significant improvement in lung function and general signs(P＜0.05).HE staining showed that the COPD group had lung tissue damage filled with inflammatory cells,while the SXT group had significantly fewer inflammatory cells.IHC results showed that the SXT group had significantly reduced expression of caspase-3 protein(P＜0.05).ELISA results showed that the levels of IL-6 and TNF-α were significantly increased in the COPD group,while the SXT group showed significant improvement in inflammatory damage.The ratio of nILC2 to iILC2 in lung and intestinal tissues was significantly reduced in the COPD group,indicating a significant inflammatory response,while the SXT group showed significant improvement(P＜0.05).The levels of ILC2 cytokines IL-13 and IL-4 were significantly increased in the COPD group,while the SXT group had significantly reduced IL-13 and IL-4 levels.The relative abundance of lung and gut microbiota in the SXT group was significantly higher than that in the Control and COPD groups(P＜0.05).Beta diversity index analysis showed significant differences in species diversity among the three groups(P＜0.05).GC-MS detected six types of SCFAs in rat feces:acetic acid,propionic acid,isobutyric acid,butyric acid,isovaleric acid,and valeric acid.Their levels were lower in the COPD group than in the Control group,but the levels in the SXT group were higher than those in the COPD group.Western blotting results showed that the expressions of p-PI3K,PI3K,p-AKT,AKT,p-NF-κB,and NF-κB proteins were significantly reduced in the SXT group compared to the COPD group(P＜0.05).ELISA results showed that the SXT group had significantly downregulated expression levels of IL-1β and IL-10 compared to the COPD group(P＜0.05).Conclusion Modified Shengxian Decoction can alleviate COPD inflammation.It may mediate the inflammatory response in COPD by inhibiting iILC2 cell activity and expressions of related proteins in the PI3K/AKT signaling pathway through gut microbiota metabolism.

Objective In order to understand the current status and influencing factors of perioperative pulmonary rehabilitation knowledge,attitude,and practice among Chinese thoracic surgery nurses,and to provide references for managers to take targeted measures to improve their pulmonary rehabilitation knowledge,attitude,and practice level.Methods From August to October 2023,a convenience sampling method and cross-sectional descriptive survey were used to anonymously survey 1 167 thoracic surgery nurses from tertiary-level A cancer specialty hospitals and tertiary-level A general hospitals in 24 provinces through the Wenjuanxing platform.A general information questionnaire and a knowledge,attitude and practice questionnaire for lung cancer perioperative pulmonary rehabilitation nurses were used,including knowledge dimension(14 items),belief dimension(6 items),and behavior dimension(14 items),totaling 34 items.Univariate analysis and linear regression multivariate analysis were used to determine the influencing factors of the knowledge,attitude and practice level of thoracic surgery nurses in perioperative pulmonary rehabilitation.Results 1 089 nurses completed the investigation.The total standard score and the dimension scores on knowledge,attitude,and behavior of the perioperative pulmonary rehabilitation questionnaire for thoracic surgery nurses were(80.45±11.84)(73.72±14.68)(89.61±11.38)and(83.46±14.48),respectively.The nature of the hospital,whether there is an administrative position,whether the department carries out ERAS,and whether they have received pulmonary rehabilitation training are the influencing factors of the perioperative pulmonary rehabilitation knowledge,attitude,and practice level of thoracic surgery nurses(P＜0.05).Conclusion The knowledge,attitude,and practice of perioperative lung rehabilitation among thoracic surgery nurses are generally at a moderate level.However,their knowledge of perioperative lung rehabilitation is relatively insufficient,and there are many influencing factors.Managers should strengthen pulmonary rehabilitation training for thoracic surgery nurses,improve their knowledge reserves and evidence conversion capabilities,and coordinate cross-integration among multidisciplinary teams to improve their knowledge,attitude and practice in perioperative pulmonary rehabilitation.

BACKGROUND:Apoptosis and autophagy imbalance in the hippocampal region of perimenopausal depressed rats are closely related to cognitive decline.Whether aerobic exercise can reduce apoptosis by promoting hippocampal autophagy and thus improve the learning and memory abilities of perimenopausal depressed rats is not clear.OBJECTIVE:To investigate the possible mechanism by which 4-week moderate-intensity treadmill exercise improves learning memory ability in ovariectomized stressed rats.METHODS:Forty Sprague-Dawely rats were randomly divided into four groups,namely,sham operation group(n=10),ovariectomized group(n=10),ovariectomized stress group(n=10)and ovariectomized stress exercise group(n=10).Except for the sham operation group,the ovaries were removed in the other three groups to establish a perimenopausal rat model,and then a depressed rat model was established by chronic unpredictable stress in the latter two groups.The rats in the ovariectomized stress exercise group underwent a 4-week moderate-intensity treadmill exercise.Tail suspension test and sucrose preference test were performed to text depression-like behaviors in rats after exercise and stress.The eight-arm maze experiment was used to test the learning and memory behaviors of rats after exercise and stress.Western blot was used to detect the protein levels of AMP-activated protein kinase/UNC-51 like autophagy activating kinase 1/mammalian target of rapamycin(AMPK/mTOR/ULK1),hippocampus apoptotic factor Caspase-3 and the protein expression of autophagy markers LC-3II/Beclin-1 in the hippocampus.RESULTS AND CONCLUSION:(1)Compared with the sham operation group,rats in the ovariectomized and ovariectomized stress groups had prolonged resting time in the tail suspension test and decreased sugar-water intake and sugar-water preference in the sucrose preference test.(2)Ovary removal reduced the learning memory capacity of rats,as evidenced behaviorally by a significant increase in the number of working memory errors,the number of reference memory errors,and the completion time,and an even more pronounced increase in the above measures in the ovariectomized stress group.(3)Compared with the ovariectomized group,there was a significant reduction in the number of working memory errors,the number of reference memory errors,and the completion time in the ovariectomized stress group.(4)Compared with the sham operation group,in the ovariectomized and ovariectomized stress groups,the expression of hippocampal apoptotic factor Caspase 3 protein was significantly elevated,the expression of autophagy-related factors proteins Beclin-1 and LC3II,as well as the protein expression of AMPK and ULK1,was decreased,whereas the expression of mTOR protein was elevated.Changes in the above indicators were more significant in the ovariectomized stress group.(5)Compared with the ovariectomized stress group,in the ovariectomized stress exercise group,the protein expression of Caspase 3 was significantly decreased,the protein expression of Beclin-1 and LC3II was significantly increased,the protein expression of AMPK and ULK1 was significantly increased,and the protein expression of mTOR was significantly reduced.To conclude,4-week moderate-intensity treadmill exercise may promote cellular autophagy and reduce apoptosis through the AMPK/mTOR/ULK1 autophagy signaling pathway,thereby enhancing the learning and memory capacity of rats with ovariectomized depression