Nodular goiter has become increasingly prevalent in recent years. Clinically, there has been a burgeoning interest in nodular goiter due to the risk of progression to thyroid cancer. This review aims to provide a comprehensive summary of the mechanisms underlying the therapeutic effect of Chinese medicine (CM) in nodular goiter. Articles were systematically retrieved from databases, including PubMed, Web of Science and China National Knowledge Infrastructure. New evidence showed that CM exhibited multi-pathway and multi-target characteristics in the treatment of nodular goiter, involving hypothalamus-pituitary-thyroid axis, oxidative stress, blood rheology, cell proliferation, apoptosis, and autophagy, especially inhibition of cell proliferation and promotion of cell apoptosis, involving multiple signal pathways and a variety of cytokines. This review provides a scientific basis for the therapeutic use of CM against nodular goiter. Nonetheless, future studies are warranted to identify more regulatory genes and pathways to provide new approaches for the treatment of nodular goiter.
Humans ; Goiter, Nodular/metabolism* ; Medicine, Chinese Traditional ; Thyroid Neoplasms ; Apoptosis ; China

Although there is guidance from different regulatory agencies, there are opportunities to bring greater consistency and stronger applicability to address the practical issues of establishing and operating a data monitoring committee (DMC) for clinical studies of Chinese medicine. We names it as a Chinese Medicine Data Monitoring Committee (CMDMC). A panel composed of clinical and statistical experts shared their experience and thoughts on the important aspects of CMDMCs. Subsequently, a community standard on CMDMCs (T/CACM 1323-2019) was issued by the China Association of Chinese Medicine on September 12, 2019. This paper summarizes the key content of this standard to help the sponsors of clinical studies establish and operate CMDMCs, which will further develop the scientific integrity and quality of clinical studies.

Objective:To study the quality evaluation method of Cyperi Rhizoma processed with four excipients. Method:Ultra-performance liquid chromatography （UPLC） fingerprints of raw products and processed products with four excipients of Cyperi Rhizoma were established， and the changes of chemical components in the fingerprints before and after processing were compared by chemometric analysis. The mobile phase was consisted of methanol （A）-water （B） for gradient elution （0-10 min， 5%-40%A； 10-30 min， 40%-70%A； 30-40 min， 70%A） at a flow rate of 0.3 mL·min^-1. The injection volume was 3 μL， the column temperature was 35 ℃， and the detection wavelength was 280 nm. The content changes of main index components in Cyperi Rhizoma before and after processing were compared by UPLC. The mobile phase was methanol-water （75∶25） and the detection wavelength was 242 nm. Result:Processing with four excipients had a significant impact on the overall characteristics of chemical components in the fingerprint of Cyperi Rhizoma. A total of 28 characteristic peaks were identified in fingerprints of the raw and processed products. Among them， peaks 1， 2 and 4 were specific peaks of the processed products， peak 5 was characteristic peak of the raw products. Peak 2 was identified as 5-hydroxymethylfurfural， peak 24 as cyperenone and peak 27 as α-cyperone. The 5-hydroxymethylfurfural produced by the processing with four excipients came from rice vinegar， rice wine and Maillard reaction of polysaccharides in Cyperi Rhizoma. The results of determination showed that there was no significant difference in the content of cyperenone after processing， but the content of α-cyperone decreased significantly. Conclusion:In the process of Cyperi Rhizoma processed with four excipients， there are new components produced by structural transformation， which are accompanied by changes in the content of index components. In this study， the quality of raw and processed products of Cyperi Rhizoma can be rapidly and effectively evaluated from qualitative and quantitative aspects.

Sterol-regulatory element binding proteins (SREBPs) are the key transcriptional regulators of lipid metabolism. The activation of SREBP requires translocation of the SREBP precursor from the endoplasmic reticulum to the Golgi, where it is sequentially cleaved by site-1 protease (S1P) and site-2 protease and releases a nuclear form to modulate gene expression. To search for new genes regulating cholesterol metabolism, we perform a genome-wide CRISPR/Cas9 knockout screen and find that partner of site-1 protease (POST1), encoded by C12ORF49, is critically involved in the SREBP signaling. Ablation of POST1 decreases the generation of nuclear SREBP and reduces the expression of SREBP target genes. POST1 binds S1P, which is synthesized as an inactive protease (form A) and becomes fully mature via a two-step autocatalytic process involving forms B'/B and C'/C. POST1 promotes the generation of the functional S1P-C'/C from S1P-B'/B (canonical cleavage) and, notably, from S1P-A directly (non-canonical cleavage) as well. This POST1-mediated S1P activation is also essential for the cleavages of other S1P substrates including ATF6, CREB3 family members and the α/β-subunit precursor of N-acetylglucosamine-1-phosphotransferase. Together, we demonstrate that POST1 is a cofactor controlling S1P maturation and plays important roles in lipid homeostasis, unfolded protein response, lipoprotein metabolism and lysosome biogenesis.

Objective: To investigate the effect of DAMP (damaged associated molecular pattern) on the inhibition of RAS-mutant A549 lung adenocarcinoma cells by CIK cells and its mechanism. Methods: Human peripheral blood mononuclear cells were isolated in vitro and CIK cells were cultured. A549 cells were treated with cisplatin (DDP) and doxorubicin (ADM) alone or in combination, and the morphology of A549 cells was observed under a microscope. The supernatant of A549 cells was co-cultured with CIK cells. Flow cytometry was used to detect the CIK cell immunophenotype after co-culture. MTT assay was used to detect the inhibition of A549 lung cancer cell proliferation induced by A549 cell supernatant. The concentration of chemotherapeutic drugs kills A549 cell supernatant CRT, ATP, HMGB1 content. Results: Low-level chemotherapeutic drugs showed more immunogenic death characteristics after killingA549 cells. The ratio of CD8+ and CD56+ in CIK cells was significantly higher than that in control CIK cells (P<0.05). The inhibition rate of CIK cells induced byA549 cells after injury onA549 lung adenocarcinoma cells was significantly higher than that of the same dose chemotherapy group [DDP group (31.34±1.51)% vs (5.97±1.74)%, ADM group (45.46±1.78)% vs (6.22±1.34)%, DDP+ ADM group (45.78±1.14)% vs (11.94±3.11)%, all P<0.05], and low-mass chemotherapeutic agents killed C549 induced by A549 cell supernatant on A549 The inhibition rate of the cells was higherthan that of the supernatant induced by the higher concentration of chemotherapeutic drugs (all P<0.05). The level of CRT,ATP, and HMGB1 in immunogenicity-related molecules in the supernatant ofA549 cells was significantly increased by low-concentration chemotherapy drugs (all P<0.05). In the low-concentration group, the supernatant-induced inhibition of the proliferation of A549 lung adenocarcinoma cells increased with the increase of CRT, ATP, and HMGB1 levels. Conclusion: The combination of lower concentration of DDP and ADM alone or in combination could more easily induce the immunogenic death of A549 cells and release higher levels of DAMP molecules, which could promote the inhibitory effect of CIK on lung cancerA549 cells.

OBJECTIVE: To noninvasively assess the neurodegenerative changes in the brain of patients with Niemann-Pick type C (NPC) disease by measuring the lesion tissue with the iterative decomposition of water and fat with echo asymmetry and least square estimation-iron quantification (IDEAL-IQ). MATERIALS AND METHODS: Routine brain MRI, IDEAL-IQ and 1H-proton magnetic resonance spectroscopy (1H-MRS, served as control) were performed on 12 patients with type C Niemann-Pick disease (4 males and 8 females; age range, 15–61 years; mean age, 36 years) and 20 healthy subjects (10 males and 10 females; age range, 20–65 years; mean age, 38 years). The regions with lesion and the normal appearing regions (NARs) of patients were measured and analyzed based on the fat/water signal intensity on IDEAL-IQ and the lipid peak on 1H-MRS. RESULTS: Niemann-Pick type C patients showed a higher fat/water signal intensity ratio with IDEAL-IQ on T2 hyperintensity lesions and NARs (3.7–4.9%, p < 0.05 and 1.8–3.0%, p < 0.05, respectively), as compared to healthy controls (HCs) (1.2–2.3%). After treatment, the fat/water signal intensity ratio decreased (2.2–3.4%), but remained higher than in the HCs (p < 0.05). The results of the 1H-MRS measurements showed increased lipid peaks in the same lesion regions, and the micro-lipid storage disorder of NARs in NPC patients was detectable by IDEAL-IQ instead of 1H-MRS. CONCLUSION: The findings of this study suggested that IDEAL-IQ may be useful as a noninvasive and objective method in the evaluation of patients with NPC; additionally, IDEAL-IQ can be used to quantitatively measure the brain parenchymal adipose content and monitor patient follow-up after treatment of NPC.
Brain ; Female ; Follow-Up Studies ; Healthy Volunteers ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Male ; Methods ; Niemann-Pick Diseases ; Proton Magnetic Resonance Spectroscopy ; Water

AIM:To investigate the effect of small interfering RNA(siRNA)-mediated progranulin(PGRN) gene silencing on the proliferation and migration abilities of human non-small-cell lung cancer A549 cells and its mecha-nism.METHODS:The mRNA and protein expression levels of PGRN in the A 549 cells and human bronchial epithelial (HBE)cells were detected by qPCR and Western blot.A549 cells were transfected with PGRN-siRNA by liposome meth-od.The expression of PGRN at mRNA and protein levels in the A 549 cells transfected with PGRN-siRNA was detected by qPCR and Western blot, respectively.The cell viability was measured by MTT assay.The cell proliferation ability was measured by living cells counting and crystal violet staining assays.The cell migration ability was measured by wound-heal-ing and Transwell assays.The protein levels of proliferating cell nuclear antigen(PCNA),cyclin D1,Bcl-2 and Bax were determined by Western blot.The protein levels of phosphorylated extracellular signal-regulated kinase 1/2(p-ERK1/2) and phosphorylated protein kinase B(p-Akt)were also determined by Western blot.RESULTS:The expression of PGRN at mRNA and protein levels was higher in the A 549 cells than that in the HBE cells(P<0.05).The expression of PGRN at mRNA and protein levels in the A549 cells transfected with PGRN-siRNA was significantly decreased,and the cell pro-liferation and migration abilities were significantly decreased.The protein expression levels of PCNA,cyclin D1 and Bcl-2 were significantly reduced and the protein expression level of Bax was significantly increased(P<0.05).Meanwhile,the protein levels of p-ERK1/2 and p-Akt were down-regulated(P<0.05).CONCLUSION:PGRN gene silencing obviously inhibits the proliferation and migration abilities of human non-small-cell lung cancer A549 cells.The PI3K/Akt and MAPK/ERK signaling pathways may play an important role in these processes.

AIM: To investigate the effects of marrow stromal cell line HS-5 on human lung adenocarcinoma A549 cells in the tumor microenvironment.METHODS:The effects of HS-5 cell-conditioned medium(HS-5-CM)on the viability and migration ability of A549 cells were detected by MTT assay and wound-healing assay.After treatment with HS-5-CM,the expression of CX3C chemokine receptor 1(CX3CR1)at mRNA level in the A549 cells was examined by qPCR. The protein levels of p-ERK and ERK in the A549 cells treated with MAPK/ERK pathway inhibitor U0126 were observed by Western blot,the migration ability of the A549 cells was measured by wound-healing assay,and the protein expression of CX3CR1 was determined by Western blot.RESULTS: HS-5-CM promoted the viability and migration ability of the A549 cells(P<0.01).The expression of CX3CR1 at mRNA level in the A549 cells was increased after treatment with HS-5-CM.MAPK/ERK inhibitor U0126 inhibited the activation of MAPK/ERK signaling pathway(P<0.01), and re-duced the migration ability(P<0.01)and the expression of CX3CR1(P<0.05)in the A549 cells.CONCLUSION:HS-5-CM significantly promotes the A549 cell viability and migration ability.Activation of MAPK/ERK signaling pathway and the expression of CX3CR1 may play a important role in this process.

BACKGROUNDHypoparathyroidism-deafness-renal dysplasia (HDR) syndrome is an autosomal dominant disorder primarily caused by haploinsufficiency of GATA binding protein 3 (GATA3) gene mutations, and hearing loss is the most frequent phenotypic feature. This study aimed at identifying the causative gene mutation for a three-generation Chinese family with HDR syndrome and analyzing auditory phenotypes in all familial HDR syndrome cases.

METHODSThree affected family members underwent otologic examinations, biochemistry tests, and other clinical evaluations. Targeted genes capture combining next-generation sequencing was performed within the family. Sanger sequencing was used to confirm the causative mutation. The auditory phenotypes of all reported familial HDR syndrome cases analyzed were provided.

RESULTSIn Chinese family 7121, a heterozygous nonsense mutation c.826C>T (p.R276*) was identified in GATA3. All the three affected members suffered from sensorineural deafness and hypocalcemia; however, renal dysplasia only appeared in the youngest patient. Furthermore, an overview of thirty HDR syndrome families with corresponding GATA3 mutations revealed that hearing impairment occurred earlier in the younger generation in at least nine familial cases (30%) and two thirds of them were found to carry premature stop mutations.

CONCLUSIONSThis study highlights the phenotypic heterogeneity of HDR and points to a possible genetic anticipation in patients with HDR, which needs to be further investigated.

Child ; Female ; GATA3 Transcription Factor ; genetics ; Genotype ; Hearing Loss ; genetics ; Hearing Loss, Sensorineural ; genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Hypoparathyroidism ; genetics ; Male ; Mutation ; genetics ; Nephrosis ; genetics ; Pedigree