Objective To investigate the causal relationship between gut microbiota and idiopathic pulmonary fibrosis (IPF). Methods Genome-wide association studies (GWAS) data of gut microbiota and IPF were obtained from MiBioGen and IEU OpenGWAS, respectively. Instrumental variables were screened by means of significance, linkage disequilibrium, weak instrumental variable screening, and removal of confounding factors (genetics, smoking, host characteristics). Inverse variance weighted (IVW) was used as the main Mendelian randomization (MR) analysis method, and the weighted median, simple mode, MR-Egger, and weighted mode were used to perform MR to reveal the causal effect of gut microbiota and IPF. The Cochrane's Q, leave-one-out, MR-Egger-intercept, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and Steiger tests were used to analyze the heterogeneity, horizontal pleiotropy, outliers, and directionality, respectively. Results IVW analysis results showed that Actinobacteria [OR=1.773, 95%CI (1.323, 2.377), P<0.001], Erysipelatoclostridium [OR=2.077, 95%CI (1.107, 3.896), P=0.023], and Streptococcus [OR=1.35, 95%CI (1.100, 1.657), P=0.004] could increase the risk of IPF. Bifidobacterium [OR=0.668, 95%CI (0.620, 0.720), P<0.001], Ruminococcus [OR=0.434, 95%CI (0.222, 0.848), P=0.015], and Tyzzerella [OR=0.479, 95%CI (0.304, 0.755), P=0.001] could reduce the risk of IPF. No significant heterogeneity, horizontal pleiotropy, outliers, and reverse causality were found. Conclusion Actinobacteria, Erysipelatoclostridium and Streptococcus may increase the risk of IPF, while Bifidobacterium, Ruminococcus and Tyzzerella may reduce the risk of IPF. Regulation of the above gut microbiota may become a new direction in the study of the pathogenesis of IPF.

The aim of this experiment was to investigate the effects of daidzein(DZ)on mammary gland development in mice during pregnancy.A total of 36 pregnant mice were randomly divided into a control group(treated with sterile PBS),a DZ group(DZ working fluid by intraperitoneal injection)and a E2 group(E2 working fluid by intraperitoneal injection),once daily,for 7 days.Af-ter normal delivery of pregnant mice,6 mice were selected from each group on the 1st and 10th day of the lactation period,then executed after blood sampling,and all mammary gland tissue were taken for the following experiments:1)mammary gland tissue was weighted and the mammary gland index was calculated;preparation of mammary gland tissue sections,HE staining;2)ELISA of estradiol,prolactin and insulin-like growth factor concentrations in serum;3)Western blot and RT-qPCR were used to analyze the expression of cell cyclin proteins and ER-a,ER-β proteins and genes in mammary gland tissues.The results showed that:compared with control group,DZ signif-icantly increased the area ratio of acinar in the mammary gland of mice(P＜0.05),decreased the area ratio of adipose tissue and increased proliferative expansion of adenohypophysis;DZ highly significantly increased serum PRL levels(P＜0.01)and serum IGF-1 content,reduced serum E2 levels;DZ significantly up-regulated the expression of CyclinD1,CyclinD3,PCNA and ER-β pro-teins(P＜0.05),and the mRNA level of ER-β gene was significantly up-regulate(P＜0.01).In conclusion,DZ can promote cell proliferation and division by increasing the expression of cell cycle proteins and proliferation proteins,promotes the proliferation of mammary gland follicles and in-creases mammary gland weight during pregnancy in mice,and at the same time increase the serum levels of IGF-1 and PRL in the female rats,which jointly promote the development of the mamma-ry glands during lactation.

Purpose To summarize the clinical pathological and immunohistochemical characteristics of esophage-al carcinoma with ductal differentiation of esophageal gland,and analyze the somatic mutation characteristics,key driv-ing mutation genes,and significantly mutated genes based on whole exome sequencing.Methods The clinicopatho-logical features of 9 cases of esophageal carcinoma with esophageal duct differentiation were retrospectively analyzed,and the immunohistochemistry EnVision two-step method was used to stain them,and 3 of the samples were subjected to whole exome sequencing and data analysis.Results Among the 9 patients,6 were males and 3 were females.The average age was 68.3 years old(61-80 years old).All 9 cases were located in the middle-lower segment of the e-sophagus.The diameter of the lesion was from 1.5 cm to 3.5 cm.Most areas of the tumor had a double-layer epithelial structure,including the inner layer of luminal epithelium and the outer layer of basal epithelium.Focal areas could be seen with keratinization and mucinous cells.Immunohistochemistry showed that CK7 was positive in the inner epitheli-um,while p63 was positive in the outer basal epithelium.S-100,SOX10 and c-myb were all negative,and p53 was mutated(diffuse strongly positive).The results of whole exome sequencing analysis showed somatic mutation character-istics(796 SNV,37 InDel,482 CNV),key driving mutation genes(12),and significantly mutated genes(TP53).No intraepithelial neoplasia was observed on the surface squamous epithelium of all cases,and no Barrett's esophagus or ectopic gastric mucosa was observed.The average follow-up time was 21.9 months(8 days-51 months),with 8 ca-ses surviving and 1 case dying of severe pulmonary infection 8 days after surgery.Conclusion Esophageal carcinoma with ductal differentiation of esophageal gland is a rare epithelial derived malignant tumor of the esophagus,character-ized by unique morphological,immunohistochemical,and molecular changes.

Purpose To summarize the clinical pathological and immunohistochemical characteristics of esophage-al carcinoma with ductal differentiation of esophageal gland,and analyze the somatic mutation characteristics,key driv-ing mutation genes,and significantly mutated genes based on whole exome sequencing.Methods The clinicopatho-logical features of 9 cases of esophageal carcinoma with esophageal duct differentiation were retrospectively analyzed,and the immunohistochemistry EnVision two-step method was used to stain them,and 3 of the samples were subjected to whole exome sequencing and data analysis.Results Among the 9 patients,6 were males and 3 were females.The average age was 68.3 years old(61-80 years old).All 9 cases were located in the middle-lower segment of the e-sophagus.The diameter of the lesion was from 1.5 cm to 3.5 cm.Most areas of the tumor had a double-layer epithelial structure,including the inner layer of luminal epithelium and the outer layer of basal epithelium.Focal areas could be seen with keratinization and mucinous cells.Immunohistochemistry showed that CK7 was positive in the inner epitheli-um,while p63 was positive in the outer basal epithelium.S-100,SOX10 and c-myb were all negative,and p53 was mutated(diffuse strongly positive).The results of whole exome sequencing analysis showed somatic mutation character-istics(796 SNV,37 InDel,482 CNV),key driving mutation genes(12),and significantly mutated genes(TP53).No intraepithelial neoplasia was observed on the surface squamous epithelium of all cases,and no Barrett's esophagus or ectopic gastric mucosa was observed.The average follow-up time was 21.9 months(8 days-51 months),with 8 ca-ses surviving and 1 case dying of severe pulmonary infection 8 days after surgery.Conclusion Esophageal carcinoma with ductal differentiation of esophageal gland is a rare epithelial derived malignant tumor of the esophagus,character-ized by unique morphological,immunohistochemical,and molecular changes.

The aim of this experiment was to investigate the effects of daidzein(DZ)on mammary gland development in mice during pregnancy.A total of 36 pregnant mice were randomly divided into a control group(treated with sterile PBS),a DZ group(DZ working fluid by intraperitoneal injection)and a E2 group(E2 working fluid by intraperitoneal injection),once daily,for 7 days.Af-ter normal delivery of pregnant mice,6 mice were selected from each group on the 1st and 10th day of the lactation period,then executed after blood sampling,and all mammary gland tissue were taken for the following experiments:1)mammary gland tissue was weighted and the mammary gland index was calculated;preparation of mammary gland tissue sections,HE staining;2)ELISA of estradiol,prolactin and insulin-like growth factor concentrations in serum;3)Western blot and RT-qPCR were used to analyze the expression of cell cyclin proteins and ER-a,ER-β proteins and genes in mammary gland tissues.The results showed that:compared with control group,DZ signif-icantly increased the area ratio of acinar in the mammary gland of mice(P＜0.05),decreased the area ratio of adipose tissue and increased proliferative expansion of adenohypophysis;DZ highly significantly increased serum PRL levels(P＜0.01)and serum IGF-1 content,reduced serum E2 levels;DZ significantly up-regulated the expression of CyclinD1,CyclinD3,PCNA and ER-β pro-teins(P＜0.05),and the mRNA level of ER-β gene was significantly up-regulate(P＜0.01).In conclusion,DZ can promote cell proliferation and division by increasing the expression of cell cycle proteins and proliferation proteins,promotes the proliferation of mammary gland follicles and in-creases mammary gland weight during pregnancy in mice,and at the same time increase the serum levels of IGF-1 and PRL in the female rats,which jointly promote the development of the mamma-ry glands during lactation.

Objective:To summarize and analyze the real experience of conscious patients in Intensive Care Unit (ICU) during hospitalization.Methods:Qualitative researches on the real experience of conscious patients in ICU during hospitalization were searched through computer on China National Knowledge Infrastructure, WanFang Data, VIP, China Biology Medicine disc, PubMed, Embase, Web of Science, CINAHL, Cochrane Library and so on. The search period was from the establishment of the database to April 30, 2022. The quality evaluation was conducted using the quality evaluation criteria for qualitative research of the Joanna Briggs Institute Evidence-Based Health Care Center in Australia. The aggregation integration method was used to summarize and integrate the results.Results:A total of 12 articles were included, and 54 results were extracted and categorized into 11 categories. Four integrated outcomes were formed, including physiological discomfort, psychological discomfort, desire for support, active response and self-reflection.Conclusions:ICU conscious patients experience severe physiological and psychological discomfort during hospitalization. While patients themselves actively respond, medical and nursing staff should further provide high-quality nursing care and psychological counseling to patients, optimize their support system, improve the hospitalization experience of ICU patients, and promote disease recovery.

Objective:To systematically synthesize qualitative research on the emotional experience of fathers of premature infants hospitalized in neonatal intensive care unit (NICU), so as to provide a basis for the care guidance and psychological care of fathers of premature infants.Methods:The articles on the qualitative study of emotional experience of fathers of premature infants in NICU were systematically searched through computers in PubMed, Embase, Web of Science, CINAHL, Cochrane Library, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biomedical Medline Disc. The search period was from the establishment of the database to May 15, 2022. The article quality evaluation was conducted using the quality evaluation criteria for qualitative research of the Joanna Briggs Institute Evidence-Based Health Care Center in Australia. The aggregation integration method was used to summarize and synthesize the results.Results:A total of 9 articles were included, 33 research results were extracted, summarized into 9 categories, and ultimately integrated into 3 synthesized results, namely facing multiple pressures and challenges, craving support, actively responding and reflecting on growth.Conclusions:The fathers of NICU premature infants have heavy physical and mental burdens, and hope to receive support from multiple parties. It is recommended that medical and nursing staff pay attention to the inner experiences and needs of fathers of NICU premature infants, optimize the support system, and improve their coping ability and promote their mental health.

Objective:To observe the effects of acupuncture and moxibustion on phosphatase and PTEN-induced putative kinase 1(PINK1)/Parkin signaling pathway in the midbrain substantia nigra of Thy1-α synuclein(αSyn)transgenic model mice with Parkinson disease(PD). Methods:Twenty-four Thy1-αSyn transgenic mice were randomly divided into a model group,an acupuncture group,an acupuncture + moxibustion group,and a Western medicine group.Six wild-type mice in the same litter were used as the wild-type group.In the acupuncture group,Baihui(GV20)and Yanglingquan(GB34)were selected for acupuncture.In the acupuncture + moxibustion group,Guanyuan(CV4)was added on the basis of the acupuncture group.The Western medicine group was given rapamycin intraperitoneal injection at a dose of 10 mg/(kg·bw).The wild-type group and the model group were fixed without intervention.The overall rod performance(ORP)score of mice was observed in each group.The immunohistochemical method was used to detect the tyrosine hydroxylase(TH)positive neurons in the substantia nigra of mice in each group.The αSyn was detected by the immunofluorescence chemical method.The expression levels of αSyn,microtubule-associated protein 1 light chain 3(LC3)-Ⅱ/LC3-Ⅰ,autophagy protein sequestosome-1/protein 62(SQSTM-1/p62),PINK1,Parkin,and ubiquitin-specific protease 30(USP30)proteins were detected by Western blotting assay.The expression levels of LC3B,p62,PINK1,Parkin,and USP30 mRNAs were detected by fluorescence quantitative polymerase chain reaction. Results:Compared with the wild-type group,the ORP score,the p62,PINK1,and Parkin protein expression levels decreased significantly(P<0.01),the PINK1 mRNA expression level decreased(P<0.05),while the protein and mRNA expression levels of USP30 increased(P<0.05)in the model group.Compared with the model group,the ORP score in the acupuncture group and the acupuncture + moxibustion group increased(P<0.05);the expression level of LC3-Ⅱ/LC3-Ⅰ protein in the acupuncture + moxibustion group and the Western medicine group increased(P<0.05);the protein expression levels of p62,PINK1,and Parkin increased(P<0.05),while the USP30 protein expression level decreased significantly(P<0.01)in the acupuncture group,the acupuncture + moxibustion group,and the Western medicine group;the Parkin mRNA expression level in the acupuncture group and the acupuncture + moxibustion group increased(P<0.05);the USP30 mRNA expression level in the acupuncture + moxibustion group decreased(P<0.05). Conclusion:Acupuncture and moxibustion regulate the related molecule expression levels of PINK1/Parkin signaling pathway in the Thy1-αSyn transgenic PD model mice and promote the autophagy degradation of αSyn to exert the protective effect of dopaminergic neurons.

Objective To analyze the characteristics of nerve damage in diabetic peripheral neuropathy by ultrasound and neuroelectrophysiological techniques and provide a basis for early diagnosis and treatment of diabetic peripheral neuropathy. Methods From January 2016 to May 2018, 225 patients with type 2 diabetes admitted to the hospital were divided into DPN group (110 cases) and non-diabetic peripheral neuropathy (NDPN) group (115 cases),and 120 healthy volunteers were as controls. Ultrasound and nerve conduction velocity(NCV) were used to analyze the characteristics of nerve damage in diabetic peripheral neuropathy(DPN). Results Among the three study groups, the sensory nerves conduction velocity and motor nerves conduction velocity of the ulnar nerve, median nerve, and common peroneal nerve were significantly reduced in the DPN group. But in the same group,the ulnar nerve, median nerve, and common peroneal nerve cross-sectional area (CSA) was significantly increased [(8.68 ± 1.89) mm2 vs. (6.79 ± 1.69) and (5.82 ± 1.57) mm2, (10.59 ± 1.82) mm2 vs. (7.98 ± 1.97) and (7.25 ± 1.71) mm2, (21.24 ± 2.53 )mm2 vs. (16.54 ± 2.49) and (15.40 ± 2.20) mm2]. In the measurement of sensory nerve conduction velocity, the abnormalities of ulnar nerve, median nerve and common peroneal nerve were significantly higher than thoseof motor nerve [34.54%(38/110) vs. 18.18%(20/110), 36.36% (40/110)vs. 20.90% (23/110), 52.72% (58/110) vs. 20.00% (22/110)]. In ultrasound and SCV, the proportion of ulnar nerve and median nerve injury was higher in patients aged 45 years or older or patients over 10 years of course (P<0.05). The proportion of median nerve injury was higher in patients with larger MAGE (P < 0.05). In the abnormal performance of ultrasound: the proportion of abnormal ulnar nerve, median nerve and common peroneal nerve in patients with large MAGE was significantly higher than that in patients with small MAGE (P<0.05); the results of ultrasound measurement of CSA showed that the ulnar nerve, median nerve and common peroneal nerve thickening were more obvious in patients with MAGE>4 mmol/L. Conclusions DPN affects sensory nerves first, and the proportion of injury is significantly higher than that of motor nerves; lower limb nerves are more susceptible to damage, compared with upper limb nerves; patients aged 45 years or older or patients with course over 10 years have a higher proportion of ulnar nerve and median nerve damage; patients with larger MAGE (>4 mmol/L) have a higher proportion of median nerve damage. The characteristics above can provide an effective basis for the prevention, diagnosis and treatment of DPN.

Objective To study on whitening and anti -aging effect of ginseng saponin and its safety.Methods Whitening effect:using vitamin C as the control drug, the inhibition rate of tyrosinase was determined.Anti senescence effect: the aging model of D-was established, and the DPPH was applied to the skin of the rat's neck, and the drug was prepared by 2 times a day.Skin safety evaluation: the skin changes of the skin of the ginseng saponins were observed after the skin was given ginseng saponin and control drugs.Results When the concentration of ginsenoside was 7 mg/mL, the inhibition rate order was, the water solution of vitamin C >ginsenoside nano >ginsenoside aqueous solution ; In the aging model, the surface of the elastic fibers and the skin surface was parallel to the skin, but the elastic fibers were arranged in a more tortuous and non parallel to the skin;DPPH free radical scavenging effect order was, Vitamin C aqueous solution>ginsenoside nano>ginsenoside aqueous solution, and with the dosage of ginsenoside increasing, the efficiency of ginsenoside DPPH scavenging free radical increased significantly;Skin safety evaluation results showed that ginseng saponin nanometer milk smeared skin, no redness, irritation and other phenomena occured.Conclusion Ginseng saponin nanometer milk has obvious whitening effect, and can not cause damage to the skin, is safe and reliable.