OBJECTIVES: To study the therapeutic mechanism of Tuihuang Mixture against cholestasis. METHODS: Forty-eight Wistar rats were randomized equally into blank group, model group, ursodeoxycholic acid group and Tuihuang Mixture group. Except for those in the blank group, all the rats were given α‑naphthylisothiocyanate (ANIT) to establish rat models of cholestasis, followed by treatments with indicated drugs or distilled water. Serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL of the rats were determined, and hepatic expressions IL-1β, IL-18, FXR, NLRP3, ASC, Caspase-1 and GSDMD were detected using q-PCR, ELISA or Western blotting. Histopathological changes of the liver tissues were observed using HE staining. RESULTS: The rat models of cholestasis had significantly increased serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL with increased mRNA and protein expressions of IL-1β and IL-18, decreased protein and mRNA expressions of FXR, and increased protein expressions of NLRP3 and Caspase-1 and mRNA expressions of NLRP3, ASC, Caspase-1 and GSDMD in the liver tissue, showing also irregular arrangement of liver cells, proliferation of bile duct epithelial cells and inflammatory cells infiltration. Treatment of the rat models with Tuihuang Mixture significantly decreased serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL, lowered IL-1β and IL-18 and increased FXR protein and mRNA expressions, and reduced NLRP3, ASC, Caspase-1 and GSDMD proteins and NLRP3, ASC and Caspase-1 mRNA expressions in the liver tissue. Tuihuang Mixture also significantly alleviated hepatocyte injury, bile duct epithelial cell proliferation and inflammatory cell infiltration in the liver of the rat models. CONCLUSIONS Tuihuang Mixture can effectively improve cholestasis in rats possibly by inhibiting NLRP3 inflammatosome-mediated pyroptosis via regulating FXR.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein ; Rats ; Receptors, Cytoplasmic and Nuclear/metabolism* ; Cholestasis/drug therapy* ; Rats, Wistar ; Inflammasomes/metabolism* ; 1-Naphthylisothiocyanate ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Interleukin-18/metabolism* ; Caspase 1/metabolism* ; Interleukin-1beta/metabolism* ; Liver/metabolism*

As a type of endogenous small non-coding RNA， microRNA （miRNA） can regulate gene expression and thereby intervene against the development and progression of cardiovascular diseases， neurodegenerative diseases， metabolic diseases， and autoimmune diseases. The pathogenesis of cholestasis is complex and is mainly associated with the metabolism and transport of bile acids， oxidative stress， inflammatory response， and intestinal flora. Currently， ursodeoxycholic acid is the preferred drug for the clinical treatment of cholestasis， but it may cause adverse reactions and exhibit poor efficacy in some patients. Studies have shown that miRNA can intervene in the disease process of cholestasis through multiple mechanisms such as regulating bile acid metabolism and transport， alleviating oxidative stress， inhibiting inflammatory response， improving cholangiocyte proliferation， and regulating intestinal flora. It can be used as a new biomarker and action target for cholestasis， with high research potential and value. Therefore， this article summarizes the role and mechanisms of miRNA in regulating cholestasis in recent years， in order to provide a reference for further research on the prevention and treatment of cholestasis by targeting miRNA.

Objective:To improve the understanding of recurrent adult Langerhans cell histiocytosis complicated with diabetes insipidus.Methods:The clinical data of 1 patient with recurrent adult Langerhans cell histiocytosis complicated with diabetes insipidus admitted to the First Affiliated Hospital of Shihezi University in January 2024 was collected. Its disease characteristics, effectiveness and safety of treatment scheme were analyzed, and literatures were reviewed.Results:The 42-year-old female patient was diagnosed as Langerhans cell histiocytosis in June 2021. After treated with cytarabine, the symptoms improved and the patient achieved sustained remission. In January 2024, the patient was admitted to the hospital due to pain in the middle part of the front chest. The PET-CT results indicated disease progression, which was manifested by new bone destruction, enlarged lymph nodes, and increased nocturnal urination, with urine volume of 3-5 L within 24 h. Based on the clinical manifestations such as cranial bone lesions, periorbital soft tissue lesions, and enlarged lymph nodes at onset, multiple systems and multiple foci involvement was considered. The diagnosis of combined diabetes insipidus was confirmed through the water deprivation and pressure test. After MACOP-B regimen (doxorubicin liposome, cyclophosphamide, vincristine, bleomycin, prednisone), the patient's bone pain was completely relieved, and no serious complications occurred.Conclusions:Recurrent adult Langerhans cell histiocytosis complicated with diabetes insipidus is rare; MACOP-B regimen is safe and effective in treatment of the disease.

Objective Depression,a most common psychiatric disease,is defined in Traditional Chinese Medicine(TCM)as Yu Syndrome,i.e.,depression disorder,or Baihe Disease,i.e.,lily bulb disease,a category of emotional disorders treated with lily-based TCM preparations.In TCM,depression is managed through syndrome differentiation and treatment,which is characterized by high efficacy and safety.However,there is no unified standard for the classification of depression syndromes,which leads to a disconnection between the analysis of patients'medication patterns and their actual syndromes and hinders the study of medication patterns specific to particular syndromes.Therefore,this study is focused on investigating the medication patterns of different sub-types of depression patients based on an objective classification system of depression.Methods We searched for and retrieved clinical literature on TCM formulas for depression from relevant databases,including China National Knowledge Infrastructure(CNKI),Wanfang Data,VIP Database,Sinomed,Web of Science,and PubMed.Information on patient symptoms and medication was standardized.Then,the symptoms and the medication frequency of depression patients were statistically analyzed.We used the K-means clustering method combined with implicit structural analysis to objectively categorize depression patients into sub-types.In addition,the main symptoms and core TCM formulas of each sub-type of depression patients were identified.On the basis of objective classification system,we also statistically analyzed the characteristics of herbs used on depression patients,including the 4 basic properties,the 5 flavors,the attributes,the therapeutic efficacy,and the co-occurrence patterns,which may help reveal the medication patterns.Results A total of 3 537 publications and 4 434 prescriptions were included in the analysis.By using the K-means algorithm and latent structure analysis methods,patients with depression were categorized into 9 sub-types,with Cluster 6 accounting for the largest proportion.The most common symptoms among depression patients were insomnia and a depressed mood.Medication frequency analysis showed that Radix Bupleuri(Chai Hu),Radix Paeoniae Alba(Bai Shao),Poria(Fu Ling),Rhizoma Chuanxiong(Chuan Xiong),and Radix Curcumae(Yu Jin)were the most commonly used TCM herbs.For the depression sub-types of Clusters 1,2,and 6,blood-activating and stasis-dissolving herbs were used most often.The depression sub-types of Clusters 3,4,5,8,and 9 were mainly treated with qi-regulating herbs,while the depression sub-type of Cluster 7 was treated with qi-supplementing herbs.Depression patients were mostly treated with herbs that were cold or warm in nature and had sweet,bitter,and pungent flavors.Moreover,treatments for Cluster 1 and Cluster 6 mainly targeted the spleen meridian,while those for Cluster 2,Cluster 3,Cluster 4 and Cluster 5 mainly targeted the heart meridian.The treatments for the other sub-types mainly targeted the liver meridian.The core TCM formulas for the 9 depression sub-types included Zishui Qinggan Decoction,Danzhi Xiaoyao Powder,Huanglian Wendan Tang,Chaihu Guizhi Tang,Modified Xiaoyao Powder,Qinggan Jieyu Tang,Xiaoyao Powder,Xuefu Zhuyu Decoction,and Bazhen Decoction.The most commonly used Chinese herbal medicinal formulas were Gan Cao-Chai Hu,Bai Shao-Chai Hu,and Chen Pi-Chai Hu.Conclusion Based on machine learning,this study reveals the scientific aspects of TCM typing and syndrome-based treatment.It clarifies the rationale for targeting different symptoms in depression treatment and provides theoretical support for clinicians to make medication prescriptions.It also presents a new perspective for investigating TCM medication patterns.

Objective:To observe and analyze the ocular clinical features and pathogenic genes of Alstr?m syndrome (ALMS).Methods:A retrospective clinical study. From October 2020 to July 2022, 3 patients and 5 normal family members from 2 families affected with ALMS who visited in the Ophthalmology Department of Henan Children's Hospital were enrolled in the study. These 2 families were without blood relationship. The medical history and family history were inquired. Best corrected visual acuity (BCVA), fundus color photography, full-field electroretinogram (ERG), frequency domain optical coherence tomography (OCT) and systemic examination were performed. 3 ml peripheral venous blood of patients and their family members were collected, and the whole genomic DNA was extracted. The second generation sequencing analysis was performed on these members. The suspected pathogenic mutation sites were verified by Sanger, and the pathogenicity of the gene mutation sites were determined by bioinformatics analysis.Results:Three patients from two families all developed nystagmus and photophobia in infancy. In the family 1, the BCVA of both eyes of the proband was no light perception. The fundus examination revealed vascular attenuation and retinal pigment abnormality. OCT showed retinal thinning, loss of photoreceptor layer and atrophy of the retinal pigment epithelium layer. ERG examination showed extinguished. The BCVA of the proband’s younger brother was 0.04 in the right eye and 0.02 in the left eye. The fundus examination revealed vascular attenuation but the pigment distribution was roughly normal. OCT showed blurred photoreceptor layers in both eyes. ERG examination showed extinguished. Two patients developed sensorineural deafness, obesity, acanthosis nigricans, insulin resistance/diabetes, and abnormal liver function. In addition, the proband also had left heart enlargement, hyperlipidemia and abnormal kidney function. The results of genetic testing showed that the proband and his younger brother had compound heterozygous mutations in exon 8 (c.1894C>T/p.Gln632*, M1) and exon 10 (c.9148_9149delCT/p.Leu 3050 Leufs*9, M2) of ALMS1, which were both known mutations. The father of the proband was a carrier of M1 and the mother of the proband was a carrier of M2. The proband of the family 2 had a normal fundus at 23 months old. The amplitude of ERG b wave under the stimulation of the dark adaptation 0.01 and a, b wave under the stimulation of dark adaptation 0.3 were all mild reduced. The amplitude of ERG a, b wave under the stimulation of the light adaptation 0.3 was severity decreased. At 4 years old, the BCVA was 0.01 in the right eye and 0.05 in the left eye. The fundus examination revealed vascular attenuation and bilateral blunted foveal reflex. In addition to severely diminished of a, b wave under the stimulation of dark adaptation 0.3, the rest showed extinguished. There were no systemic abnormalities. The results of genetic testing showed that the proband had compound heterozygous mutations in exon 11 (c.9627delT/p.Pro3210Glnfs*22, M3) and exon 5 (c.1089delT/p.Asp364Ilefs*13, M4) of ALMS1, which were both novel mutations. The father of the proband was a carrier of M3 and the mother of the proband was a carrier of M4. Conclusions:Nystagmus and photophobia are often the first clinical manifestations of ALMS. In the early stage, the fundus can be basically normal. As the disease progresses, the fundus examination reveals vascular attenuation and retinal pigment abnormality, and the reflection of the fovea is unclear. OCT shows the photoreceptor cell layers are blurred or even lost. The final ERG is extinguished. M1, M2, and M3, M4 compound heterozygous mutations may be the pathogeny for family 1 and family 2, respectively.

Objective:To analyze 18F-FDG PET/CT imaging features of non-functional pancreatic neuroendocrine neoplasms (NF-pNENs) and investigate its correlation with pathology and prognosis. Methods:A total of 35 cases (17 males, 18 females; age (51±12) years) of pathologically confirmed NF-pNENs who underwent pretherapeutic 18F-FDG PET/CT from January 2011 to July 2017 in Peking Union Medical College Hospital were retrospectively enrolled. Clinical data were collected and patients were followed up. PET/CT parameters including number and maximum diameter of lesions, SUV max and pancreatic tumor-to-liver ratio (T/L) were measured. Mann-Whitney U test and Kruskal-Wallis rank sum test, Spearman correlation analysis were used to analyze the data. Results:Among the included 35 NF-pNENs patients (G1, n=6; G2, n=21; G3, n=8) with maximum diameter of 3.0(2.1, 6.1) cm and SUV max of 5.5(4.0, 8.9), 32 were positive in PET/CT. There were 1 patient with cystic, 2 with calcification and 3 with dilatation of pancreaticobiliary duct. Among 10 patients with metastases, 8 revealed multiple liver metastases. There was statistical difference of T/L among G1-G3 tumor (1.23(0.60, 2.00), 3.05(1.80, 4.00), 3.90(1.90, 7.60); H=8.29, P=0.016), but there were no statistical differences of SUV max or maximum diameter among G1-G3 tumor ( H values: 4.34, 3.37, P values: 0.114, 0.186). There was a significant correlation between T/L (2.78(1.48, 3.94)) and Ki-67 index (8.0(3.0, 20.0); rs=0.631, P<0.001). Among 27 patients with available follow-up results, T/L in patients with complete remission or stable disease ( n=20) was statistically lower than that in patients with progressive disease or death ( n=7) (2.1(1.2, 3.2) vs 7.5(3.4, 13.4); z=-3.37, P=0.001). Conclusions:18F-FDG PET/CT can detect primary and metastatic lesions of NF-pNENs. T/L can better reflect the proliferative activity based on Ki-67 index than SUV max and it may be favorable on prognostic value.

Objective: To investigate vitamin D levels among primary and middle school students in Xicheng District, Beijing Municipality, and to examine the association of vitamin D levels with hemoglobin (Hb) and serum ferritin (SF) levels, so as to provide insights into the prevention of anemia among primary and middle school students. Methods: The first, third and fifth grade primary school students and the first grade junior high school students were sampled from Xicheng District in 2019, using the multistage stratified cluster sampling method, and students' gender, age, height, weight and Hb levels were collected. The 25-hydroxyvitamin D [25-( OH )D] was measured using electrochemiluminescence assay, and SF was detected using immunoturbidimetry. The vitamin D deficiency was determined according to the American College of Endocrinology guidelines. The associations of 25-( OH) D levels with Hb and SF levels were examined using Pearson correlation analysis and Spearman rank correlation analysis. Results: Totally 403 primary and junior high school students were investigated, including 196 boys ( 48.64% ) and 207 girls ( 51.36% ). There were 179, 114 and 110 students at ages of 6 to 8 years ( 44.41% ), 9 to 11 years ( 28.29% ) and 12 to 13 years ( 27.30% ), respectively. The mean 25-( OH )D level was ( 14.80±5.96 ) ng/mL among the study students, and there were 90 students ( 22.33% ) with severe vitamin D deficiency, 243 students ( 60.30% ) with vitamin D deficiency, 63 students ( 15.63% ) with vitamin D inadequacy and 7 students ( 1.74% ) with vitamin D sufficiency. The mean Hb level was ( 136.28±8.33 ) g/L and the median SF level (interquartile range) was 56.80 (14.36) ng/mL among the study students, respectively. The 25-( OH )D level positively correlated with Hb ( r=0.364, P<0.001 ) and SF levels ( rs=0.374, P<0.001 ), and after adjustment for age and body mass index, the 25-( OH )D still correlated positively with Hb ( r=0.157, P=0.048 ) and SF levels ( rs=0.174, P=0.022 ) . Conclusions Vitamin D deficiency is prevalent among primary and middle school students in Xicheng District, and the 25-(OH)-D levels correlate positively with Hb and SF levels. 25-( OH )-D deficiency may contribute to the development of anemia.
vitamin D ; hemoglobin ; serum ferritin ; primary and middle school student

Objective:To analyze the incidence, biochemical and molecular characteristics, and gene mutation spectrum of neonatal methylmalonic acidemia (MMA) in Shaanxi province.Methods:This study involved 146 152 newborns undergoing neonatal screening for methylmalonic acidemia by tandem mass spectrometry in Northwest Women's and Children's Hospital from January 2014 and December 2019. Clinical manifestations and follow-up data of newborns diagnosed with MMA and their acylcarnitine profiles and gene mutations were analyzed. According to whether they had elevated homocysteine or not, these patients were divided into two groups, the complicated group and the isolated MMA group. The control neonates were those excluded from having methylmalonic acid by re-examination. Kruskal-Wallis and Mann-Whitney U test was conducted for statistical analysis. Results:(1) Twenty-one cases of MMA were confirmed with an incidence of 1/6 960, including 11 cases (52.4%) of isolated MMA (isolated MMA group) and 10 (47.6%) complicated by elevated homocysteine (complicated group). Eight patients in the isolated group had symptoms within one month after birth, mainly feeding difficulties, vomiting, drowsiness, poor response and infection, and five died. Patients in the complicated group were all diagnosed before developing typical clinical symptoms, and no developmental abnormalities were reported during follow-up. (2) Blood propionyl carnitine and its ratios to acetylcarnitine and free carnitine in the isolated MMA and complicated groups were higher than those in the control group [ M (min-max), 9.26 (3.70-37.78) μmol/L and 7.27 μmol/L (3.58-13.62 μmol/L) vs 4.51 μmol/L (1.48-8.69 μmol/L), H=23.239; 1.12 (0.32-2.43) and 0.74 (0.36-1.90) vs 0.25 (0.09-0.45), H=47.061; 0.94 (0.12-1.92) and 0.56 (0.18-1.03) vs 0.17 (0.06-0.38), H=36.868; all P<0.001]. The blood methionine level in the complicated group was significantly lower than that in the isolated MMA group [7.64 μmol/L (3.40-19.25 μmol/L) vs 24.22 μmol/L (10.73-56.55 μmol/L), U=3.000, P<0.001]. (3) All 21 patients carried complex heterozygous mutations or homozygous mutations in pathogenic genes, including 15 distinct MMUT mutations and 13 distinct MMACHC mutations. In the isolated MMA group, the most common mutation was c.323G>A (p.Arg108His) in the MMUT gene with a positive rate of 13.6%, and an unreported mutation, c.1676+11A>G, with unidentified clinical significance, was also found. The most common mutations in the complicated group were c.609G>A (p.Trp203Ter) and c.567dupT (p.Ile190fs) in the MMACHC gene, and the positive rates were both 20.0%. Moreover, two unreported variants, c.430-2A>C and c.648_650delAGA (p.216_217delSEinsS), were detected and suspected to be pathogenic. Conclusions:MMA is not uncommon in Shaanxi province. Children with isolated MMA tend to be more severe clinically. The identification of hotspot mutations, including c.609G>A (p.Trp203Ter) and c.567dupT (p.Ile190fs) in MMACHC gene and c.323G>A (p.Arg108His) in MMUT gene, provides a foundation for further genetic screening, counseling, and prenatal diagnosis, and is conducive to reduce the mortality and disability rate of neonatal MMA.

The robotic bronchoscopy system is a new technology for lung lesion location, biopsy and interventional therapy. Its safety and effectiveness have been clinically proven. Based on many advanced technologies carried by the robotic bronchoscopy system, it is more intelligent, convenient and stable when clinicians perform bronchoscopy operations. It has higher accuracy and diagnostic rates, and less complications than bronchoscopy with the assistance of magnetic navigation and ordinary bronchoscopy. This article gave a review of the progress of robotic bronchoscopy systems, and a prospect of the combination with artificial intelligence.

Objective:To estimate the effect of comorbid gestational diabetes mellitus (GDM) and depression on glucose metabolism and neonatal morphology.Methods:From March 2015 to October 2018, recruited 18 to 28 weeks pregnant women who met the criteria in the Hefei First People′s Hospital or First Affiliated Hospital of Anhui Medical University or Anhui Maternal and Child Health Hospital, including a total of 4 380 study subjects, of which the birth outcome information of 3 827 newborns were collected. The self-made questionnaire "Maternal Health Questionnaire for Hefei City" and Edinburgh Postpartum Depression Scale were used to obtain basic demographic characteristics and emotional state of depression. Data from the 75-g oral-glucose-tolerance test were obtained at 24-28 weeks of gestation. After delivery, delivery outcome information were collected from the hospital medical records. Covariance analysis was used to analyze the differences in glucose metabolism indicators and neonatal outcome indicators in pregnant women with different GDM and depression status. Multiple logistic regression model was used to analyze the correlation between GDM and depression, with different groups of GDM and depression status (no GDM and depression, simple depression, simple GDM, comorbid GDM and depression)as independent variables and whether they were large for gestational age as dependent variables. The interaction between GDM and depression was also analyzed.Results:The 4 380 pregnant women were (28.8±4.2) years old. The incidence of GDM was 19.5% (852/4 380), and the detection rates of depression in the second and third trimesters were 12.1% (526/4 380) and 12.3% (536/4 367). PG-1h and AUC in the comorbid GDM and depression group were significantly higher than those in the group with no GDM and depression ( P<0.05) and the single GDM group ( P<0.05). After adjusting for factors such as the childbirth age, education level, family′s main economic income, BMI before pregnancy, parity, number of physical activities, and weight gain during pregnancy, compared with the group with no GDM and depression, the RR(95% CI) of LGA occurred in the single depression group, the single GDM group and the comorbid group were 1.31(0.89-1.91), 1.51(1.14-2.00) and 2.43(1.29-4.57), respectively. Further analysis showed that the association between GDM pregnant women with depression and newborn LGA ［ RR (95% CI): 2.12 (1.01-4.49)］ was stronger than that between GDM pregnant women without depression and newborn LGA ［ RR (95% CI): 1.50 (1.12-1.99)］, the P interaction value was<0.05. Conclusion:The status of comorbid GDM and depression can impair glucose metabolism and increase the risk of LGA.