Zhizichi Tang （栀子豉汤）， first recorded in Treatise on Febrile and Miscellaneous Diseases （《伤寒杂病论》） by ZHANG Zhongjing， a medical sage during the Han dynasty， is one of the classical prescriptions in traditional Chinese medicine （TCM）. It plays an important role in the clinical practice of TCM because of its dispersing and transparent characteristics. It is one of the representative parts of “dispersing fire stagnation” and is used mainly for the treatment of various symptoms caused by heat depression in the chest and diaphragm. Pharmacological research has found that it has multiple effects， such as sedative hypnosis and anti-depression， inhibiting oxidative stress and inflammatory responses， regulating the intestinal flora， improving insulin resistance and endocrine metabolism disorders， reducing liver toxicity， and protecting the nerve and heart. Clinical studies have confirmed that its treatment of anxiety， depression， insomnia， and other diseases has few side effects and high safety. Combined with the analysis of TCM syndrome and pharmacological effects， Zhizichi Tang also shows potential in treating other diseases such as heart， lung system， spleen and stomach， liver system， endocrine， and metabolic system diseases. Therefore， the authors， by searching Chinese and foreign literature， especially in recent five years， systematically reviewed and summarized the research progress on Zhizichi Tang in six aspects of TCM syndrome， dosage and administration， chemical composition， pharmacological effects， clinical application， and adverse reactions， aiming to provide a reference for further research and clinical application of Zhizichi Tang.

Sepsis is the organ dysfunction caused by infection.It is one of the most common critical diseases in clinic.Its morbidity and mortality are increasing year by year，which has seriously threatened human health.Innate immunity is the first line of defense against pathogens.Nature killer（NK）cells are important cells involved in the regulation of innate immunity in sepsis，and can play an important role on the progression of sepsis by secreting cytokines，inducing apoptosis and mediating cytotoxic effects.It has been found that the changes of NK cells in the early stage of sepsis are related to the prognosis of the disease.Therefore，further study on the role of NK cells in sepsis can provide a new idea for the clinical diagnosis and treatment of sepsis，and contribute to the early identification of sepsis and the improvement of prognosis.This review summarized the role and changes of NK cell in sepsis.

Objective:To evaluate the utility of the 9-gene panel as a differential diagnostic method for thyroid nodules within determinate cytological diagnosis and as a parallel diagnostic method for thyroid fine-needle aspiration (FNA) cytology.Methods:579 liquid-based cytology samples from 544 patients were collected after thyroid FNA diagnosis in our hospital from December 2014 to April 2021. Mutations at any site of 9 genes, namely, BRAF, NRAS, HRAS, KRAS, GNAS, RET, TERT, TP53, and PIK3CA as recorded by the Catalogue of Somatic Mutations in Cancer (COSMIC), were analyzed by next-generation sequencing. Taking postoperative histopathology and cytology results with definite benign or malignant diagnosis as the gold standard, the diagnostic efficacy of the 9-gene panel as a reclassified method for thyroid nodules with indeterminate cytological diagnosis and as a parallel diagnostic method for thyroid FNA cytology were evaluated and compared with that of the BRAF V600E single-gene detection method.Results:Of the 579 thyroid nodules, 196 (33.85%) were Bethesda Ⅱ, 11 (1.90%) were Bethesda Ⅲ, 31 (5.35%) were Bethesda Ⅳ, 27 (4.66%) were Bethesda Ⅴ, and 314 (54.23%) were Bethesda Ⅵ, as diagnosed by thyroid FNA cytology. Among these 579 thyroid nodules, 275 were tested positive for 9-gene mutations, with a mutation rate of 47.5%. Of the 329 thyroid nodules surgically removed, 30 (9.12%) were benign, 5 (1.52%) were borderline, and 294 (89.36%) were malignant. Regarding borderline nodules as malignant nodules, the mutation rates of the 9 genes in the 299 malignant thyroid nodules from high to low were BRAF 62.21% (186/299), NRAS 5.02% (15/299), HRAS 1.00% (3/299), PIK3CA 0.67% (2/299), GNAS 0.67% (2/299), KRAS 0.33% (1/299), TP53 0.33% (1/299), TERT 0.33% (1/299) and RET 0.00% (0/299). The malignant risks of the 9 genes from high to low were BRAF 100% (186/186), PIK3CA 100.00% (2/2), GNAS 100.00% (2/2), TERT 100.00% (1/1), TP53 100.00% (1/1), NRAS 78.95% (15/19), HRAS 75.00% (3/4), and KRAS 50.00% (1/2). For thyroid nodules of Bethesda Ⅲ-Ⅳ (indeterminate diagnosis), the sensitivity (SN) of the 9-gene panel in diagnosing thyroid cancer is 34.48% (10/29), the specificity (SP) is 61.54% (8/13), and the accuracy is 42.86% (18/42); whereas the SN of the BRAF V600E detection method is 0%. Therefore, the diagnostic efficiency of the 9-gene panel is significantly better than that of BRAF V600E single gene detection. For thyroid nodules of Bethesda Ⅱ-Ⅵ, the SN of the 9-gene panel in diagnosing thyroid cancer was 68.83% (254/369), the SP was 90.00% (189/210), the accuracy was 76.51% (443/579), and the area under the curve (AUC) was 0.79; whereas the SN of BRAF V600E single-gene detection in diagnosing thyroid cancer was 63.69% (235/369), the SP was 99.52% (209/210), the accuracy was 76.68% (444/579), and the AUC was 0.82. The SP of BRAF V600E detection is higher than that of the 9-gene panel ( P＜0.01), but there is no significant difference in SN, accuracy (both P＞0.05), and AUC ( Z=0.85, P=0.396) between them. Gene mutations indicating poor prognosis were detected in 4 nodules of papillary thyroid carcinoma and 1 nodules of follicular thyroid carcinoma, including 2 nodules with TERT and BRAF V600E co-mutations, 1 nodule with TP53 mutation, and 2 nodules with PIK3CA mutation. Conclusions:As a reclassified method for thyroid lesions with indeterminate cytological diagnosis, the 9-gene panel is better than BRAF V600E single gene detection. As a parallel diagnostic method of thyroid FNA cytology, the 9-gene panel has similar diagnostic efficacy as BRAF V600E single-gene detection. The 9-gene panel can detect individual cases with gene mutations indicating poor prognosis. The identification of patients with these special gene mutations has certain implications for the clinical management of them.

Objective:To evaluate the utility of the 9-gene panel as a differential diagnostic method for thyroid nodules within determinate cytological diagnosis and as a parallel diagnostic method for thyroid fine-needle aspiration (FNA) cytology.Methods:579 liquid-based cytology samples from 544 patients were collected after thyroid FNA diagnosis in our hospital from December 2014 to April 2021. Mutations at any site of 9 genes, namely, BRAF, NRAS, HRAS, KRAS, GNAS, RET, TERT, TP53, and PIK3CA as recorded by the Catalogue of Somatic Mutations in Cancer (COSMIC), were analyzed by next-generation sequencing. Taking postoperative histopathology and cytology results with definite benign or malignant diagnosis as the gold standard, the diagnostic efficacy of the 9-gene panel as a reclassified method for thyroid nodules with indeterminate cytological diagnosis and as a parallel diagnostic method for thyroid FNA cytology were evaluated and compared with that of the BRAF V600E single-gene detection method.Results:Of the 579 thyroid nodules, 196 (33.85%) were Bethesda Ⅱ, 11 (1.90%) were Bethesda Ⅲ, 31 (5.35%) were Bethesda Ⅳ, 27 (4.66%) were Bethesda Ⅴ, and 314 (54.23%) were Bethesda Ⅵ, as diagnosed by thyroid FNA cytology. Among these 579 thyroid nodules, 275 were tested positive for 9-gene mutations, with a mutation rate of 47.5%. Of the 329 thyroid nodules surgically removed, 30 (9.12%) were benign, 5 (1.52%) were borderline, and 294 (89.36%) were malignant. Regarding borderline nodules as malignant nodules, the mutation rates of the 9 genes in the 299 malignant thyroid nodules from high to low were BRAF 62.21% (186/299), NRAS 5.02% (15/299), HRAS 1.00% (3/299), PIK3CA 0.67% (2/299), GNAS 0.67% (2/299), KRAS 0.33% (1/299), TP53 0.33% (1/299), TERT 0.33% (1/299) and RET 0.00% (0/299). The malignant risks of the 9 genes from high to low were BRAF 100% (186/186), PIK3CA 100.00% (2/2), GNAS 100.00% (2/2), TERT 100.00% (1/1), TP53 100.00% (1/1), NRAS 78.95% (15/19), HRAS 75.00% (3/4), and KRAS 50.00% (1/2). For thyroid nodules of Bethesda Ⅲ-Ⅳ (indeterminate diagnosis), the sensitivity (SN) of the 9-gene panel in diagnosing thyroid cancer is 34.48% (10/29), the specificity (SP) is 61.54% (8/13), and the accuracy is 42.86% (18/42); whereas the SN of the BRAF V600E detection method is 0%. Therefore, the diagnostic efficiency of the 9-gene panel is significantly better than that of BRAF V600E single gene detection. For thyroid nodules of Bethesda Ⅱ-Ⅵ, the SN of the 9-gene panel in diagnosing thyroid cancer was 68.83% (254/369), the SP was 90.00% (189/210), the accuracy was 76.51% (443/579), and the area under the curve (AUC) was 0.79; whereas the SN of BRAF V600E single-gene detection in diagnosing thyroid cancer was 63.69% (235/369), the SP was 99.52% (209/210), the accuracy was 76.68% (444/579), and the AUC was 0.82. The SP of BRAF V600E detection is higher than that of the 9-gene panel ( P＜0.01), but there is no significant difference in SN, accuracy (both P＞0.05), and AUC ( Z=0.85, P=0.396) between them. Gene mutations indicating poor prognosis were detected in 4 nodules of papillary thyroid carcinoma and 1 nodules of follicular thyroid carcinoma, including 2 nodules with TERT and BRAF V600E co-mutations, 1 nodule with TP53 mutation, and 2 nodules with PIK3CA mutation. Conclusions:As a reclassified method for thyroid lesions with indeterminate cytological diagnosis, the 9-gene panel is better than BRAF V600E single gene detection. As a parallel diagnostic method of thyroid FNA cytology, the 9-gene panel has similar diagnostic efficacy as BRAF V600E single-gene detection. The 9-gene panel can detect individual cases with gene mutations indicating poor prognosis. The identification of patients with these special gene mutations has certain implications for the clinical management of them.

Alzheimer's disease(AD)is a severe threat to human health and one of the three major causes of human death.Double-stranded RNA-dependent protein kinase(PKR)is an interferon-induced protein kinase involved in innate immunity.In the occurrence and development of AD,PKR is upregulated and continu-ously activated.On the one hand,the activation of PKR triggers an integrated stress response in brain cells.On the other hand,it indirectly upregulates the expression of 3-site amyloid precursor protein cleaving enzyme 1 and facilitates the accumulation of amyloid-β protein(Aβ),which could activate PKR activator to further activate PKR,thus forming a sustained accumulation cycle of Aβ.In addition,PKR can promote Tau phosphorylation,thereby reducing microtubule stability in nerve cells.Inflammation in brain tissue,neurotoxicity resulted from Aβaccumulation,and disruption of microtubule stability led to the progression of AD and the declines of memory and cognitive function.Therefore,PKR is a key molecule in the development and progression of AD.Effective PKR detection can aid in the diagnosis and prediction of AD progression and provide opportunities for clinical treat-ment.The inhibitors targeting PKR are expected to control the activity of PKR,thereby controlling the progression of AD.Therefore,PKR could be a target for the development of therapeutic drugs for AD.

Objective:To systematically integrate qualitative studies on psychological experience of breast cancer patients in rehabilitation period, so as to provide basis for improving psychological care and rehabilitation efficacy.Methods:Qualitative research on psychological experience of breast cancer patients during rehabilitation was electronically retrieved in databases, including PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang data, and China Biology Medical disc. The search period was from database establishment to September 2023. The quality evaluation of the literature was conducted using the 2020 version of the quality evaluation criteria for qualitative research of the Joanna Briggs Institute Evidence-Based Health Care Center. The results were integrated using the aggregative Meta integration method.Results:A total of 18 articles were included. Sixty-six research topics were extracted and categorized into 10 new categories, forming three integrated results, namely, psychological adjustment of patients with negative emotions and rehabilitation needs in the process of coping, family and social factors affecting patient rehabilitation experience, and patients perceiving that the healthcare system was not yet perfect.Conclusions:Medical and nursing staff should pay attention to the psychological problems of breast cancer patients in the rehabilitation period, understand their rehabilitation needs, provide targeted counseling and services, pay attention to the family and social support factors of breast cancer patients, help them improve their quality of life, and actively promote rehabilitation.

OBJECTIVE: To investigate the clinical features and genetic etiology of a case of Turner syndrome (TS) with rapidly progressive puberty. METHODS: A child who had presented at the Pediatric Endocrinology Clinic of the Shenzhen People's Hospital on January 19, 2022 was selected as the study subject. Clinical data of the child were collected. Peripheral blood sample of the child was subjected to chromosomal microarray analysis (CMA) and multiple ligation-dependent probe amplification (MLPA). Previous studies related to TS with rapidly progressive puberty were retrieved from the CNKI, Wanfang Data Knowledge Service Platform, Boku, CBMdisc and PubMed databases with Turner syndrome and rapidly progressive puberty as the keywords. The duration for literature retrieval was set from November 9, 2021 to May 31, 2022. The clinical characteristics and karyotypes of the children were summarized. RESULTS: The child was a 13-year-and-2-month-old female. She was found to have breast development at 9, short stature at 10, and menarche at 11. At 13, she was found to have a 46,X,i(X)(q10) karyotype. At the time of admission, she had a height of 143.5 cm (< P3), with 6 ~ 8 nevi over her face and right clavicle. She also had bilateral simian creases but no saddle nasal bridge, neck webbing, cubitus valgus, shield chest or widened breast distance. She had menstruated for over 2 years, and her bone age has reached 15.6 years. CMA revealed that she had a 58.06 Mb deletion in the Xp22.33p11.1 region and a 94.49 Mb duplication in the Xp11.1q28 region. MLPA has confirmed monosomy Xp and trisomy Xq. A total of 13 reports were retrieved from the CNKI, Wanfang Data Knowledge Service Platform, Boku, CBMdisc and PubMed databases, which had included 14 similar cases. Analysis of the 15 children suggested that their main clinical manifestations have included short stature and growth retardation, and their chromosomal karyotypes were mainly mosaicisms. CONCLUSION The main clinical manifestations of TS with rapidly progressive puberty are short stature and growth retardation. Deletion in the Xp22.33p11.1 and duplication in the Xp11.1q28 probably underlay the TS with rapid progression in this child, which has provided a reference for clinical diagnosis and genetic counselling for her.
Humans ; Female ; Adolescent ; Puberty ; Turner Syndrome/genetics* ; Chromosomes, Human, X ; Karyotyping

Objective:To investigate the effects of miRNA-30a-5p (miR-30a-5p) and metadherin (MTDH) on the proliferation, invasion and migration abilities of human breast cancer cells in vitro.Methods:The expression of MTDH in cancer and paracancerous tissues of 112 breast cancer patients in the database and miR-30a-5p in cancer and paracancerous tissues of 103 breast cancer patients in the database were analyzed using data from The Cancer Genome Atlas (TCGA) database. Pearson correlation analysis was used to analyze the correlation between miR-30a-5p and MTDH in 1 222 breast cancer patients in the database; the data were updated to August 2022. Breast cancer MDA-MB-231 cells were divided into negative control group (transfected with negative control sequence), miR-30a-5p overexpression group (transfected with miR-30a-5p mimics), siMTDH group [transfected with small interfering RNA against MTDH (siMTDH)], siMTDH+miR-30a-5p overexpression group (transfected with both siMTDH and miR-30a-5p mimics); cell proliferation ability was detected by methyl thiazol tetrazolium (MTT) assay, cell migration ability was detected by cell scratch assay, cell invasion ability was detected by Transwell assay. The relative expressions of miR-30a-5p, MTDH, matrix metalloproteinase (MMP)-2, MMP-9, vimentin and β-catenin mRNA in cells were detected by quantitative real-time fluorescence polymerase chain reaction (qRT-PCR), and the expressions of MTDH, N-cadherin (N-cad), β-catenin, Snail and MMP-9 proteins were detected by Western blotting.Results:In the TCGA database, MTDH expression level was higher and miR-30a-5p expression level was lower in breast cancer tissues compared with paracancerous tissues, and the differences were statistically significant (both P < 0.001). There was a negative correlation between MTDH and miR-30a-5p expressions in 1 222 patients with breast cancer ( r=-0.134, P < 0.001). Compared with the negative control group, the cell proliferation ability was reduced in both siMTDH group and miR-30a-5p overexpression group at 24, 48 and 72 h (all P < 0.001). The cell scratch healing rate in miR-30a-5p overexpression group and siMTDH group was lower than that in negative control group [(61.6±1.6)%, (54.7±5.9)% vs. (80.3±3.0)%] (both P < 0.05). Compared with the negative control group, The number of migrated cells in miR-30a-5p overexpression group and siMTDH group was less than that in negative control group (881±50, 725±63 vs. 1 172±66) (both P < 0.05). Compared with the negative control group, the relative expressions of MMP-2, MMP-9, vimentin and β-catenin mRNA were all down-regulated in MDA-MB-231 cells of miR-30a-5p overexpression group and siMTDH group (all P < 0.05). Compared with the negative control group, the relative expressions of N-cad, β-catenin, Snail and MMP-9 proteins were down-regulated in MDA-MB-231 cells of miR-30a-5p overexpression group and siMTDH group (all P < 0.05). There was no statistical difference in the number of migrated MDA-MB-231 cells between siMTDH+miR-30a-5p overexpression group and siMTDH group (476±5 vs. 389±46, t = 3.37, P = 0.078). There was no statistical difference in the number of migrated cells between siMTDH+miR-30a-5p overexpression group and miR-30a-5p overexpression group (476±5 vs. 477±22, t = 0.02, P = 0.983). Conclusions:The expression of miR-30a-5p is negatively correlated with the expression of MTDH in breast cancer tissues, and either overexpression of miR-30a-5p or silence of MTDH in breast cancer MDA-MB-231 cells in vitro can inhibit cell proliferation, invasion and migration, but MTDH may not be a target gene of miR-30a-5p.

Humans ; Diabetic Neuropathies/diagnostic imaging* ; Diabetes Mellitus, Type 2 ; Ultrasonography ; Diabetic Foot/diagnostic imaging*

Objective:To investigate the value of net water uptake (NWU) for predicting early neurological improvement (ENI) after endovascular treatment in patients with acute anterior circulation large vessel occlusion stroke.Methods:A case-control study. A total of 132 patients (80 men, 52 women, median age 68 years) with acute anterior circulation large vessel occlusive stroke receiving endovascular treatment were retrospectively analyzed at Jinling Hospital from October 2014 to September 2019. Patients were divided into two groups based on the occurrence of ENI, which was defined as either an improvement of NIHSS score of ≥4 points, or an NIHSS score of 0 or 1 at 24 hours after endovascular treatment. The rank sum test, Chi square test, and other methods were used to compare differences in baseline characteristics between the two groups. Logistic regression analysis was used to investigate independent predictors of postoperative ENI. Receiver operating characteristic curve analysis used to assess the capacity of NWU to predict ENI.Results:Of the 132 patients in the study, ENI occurred in 47 and did not occur in 85. In multivariate logistic regression analysis age [odds ratio ( OR)=0.940, 95% confidence interval ( CI) 0.903-0.979, P=0.003], time from stroke onset to puncture ( OR=0.995, 95% CI 0.991-0.999, P=0.025), time from puncture to recanalization/end of operation ( OR=0.985, 95% CI 0.974-0.996, P=0.007), NWU ( OR=0.762, 95% CI 0.620-0.937, P=0.010), and mTICI ( OR=1.644, 95% CI 1.043-2.590, P=0.032) were predictive factors for ENI. Receiver operating characteristic curve analysis indicated that NWU could effectively predict ENI (area under the curve=0.642, 95% CI 0.543-0.741, P=0.007), and prediction accuracy was improved when it was combined with other clinical parameters. Conclusion:NWU is an independent predictor of ENI in patients with acute anterior circulation large vessel occlusive stroke undergoing endovascular treatment.