OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Objectives: To summarize the clinical phenotypes and the variation spectrum of ATP7B gene in Chinese children with Wilson's disease (WD) and to investigate their significance for early diagnosis. Methods: Retrospective analysis was performed on the clinical data of 316 children diagnosed as WD in Guangzhou Women and Children's Medical Center during the period from January 2010 to June 2021. The general situations, clinical manifestations, lab test results, imaging examinations, and ATP7B gene variant characteristics were collected. The patients were divided into asymptomatic WD group and symptomatic WD group based on the presence or absence of clinical symptoms at the time that WD diagnosis was made. The χ² test, t test or Mann-Whitney U test were used to compare the differences between groups. Results: Among the 316 children with WD, 199 were males and 117 were females, with the age of 5.4 (4.0, 7.6) years at diagnosis; 261 cases (82.6%) were asymptomatic with the age of 4.9 (3.9, 6.4) years; whereas 55 cases (17.4%) were symptomatic with the age of 9.6 (7.3, 12.0) years. The main symptoms invloved liver, kidney, nervous system, or skin damage. Of all the patients, 95.9% (303/316) had abnormal liver function at diagnosis; 98.1% (310/316) had the serum ceruloplasmin lever lower than 200 mg/L; 97.7% (302/309) had 24-hour urine copper content exceeding 40 μg; only 7.4% (23/310) had positive corneal K-F rings, 8.2% (23/281) had abnormal MRI signals in the lenticular nucleus, and all of them had symptoms of damage in liver, kidney or nervous system. Compared with the group of symptomatic WD, asymptomatic group had higher levels of serum alanine aminotransferase and lower levels ceruloplasmin and 24-hour urine copper [(208±137) vs. (72±78) U/L, (55±47) vs. (69±48) mg/L, 103 (72, 153) vs. 492 (230, 1 432) μg; t=9.98, -1.98, Z=-4.89, all P<0.001]. Among the 314 patients completing genetic sequencing, a total of 107 mutations in ATP7B gene were detected, of which 10 are novel variants, and 3 cases (1.0%) had large heterozygous deletion (exons 10 to exon 11) in ATP7B gene. The percentage of missense mutation in asymptomatic WD children was significantly higher than that in symptomatic WD (81.5% (422/518) vs. 69.1% (76/110), χ²=8.47, P<0.05). WD patients carrying homozygous variant of c.2 333G>T had significantly low levels of ceruloplasmin than those not carrying this variant ((23±5) vs. (61±48) mg/L, t=-2.34, P<0.001). Conclusions: The elevation of serum ALT is an important clue for early diagnosis of WD in children, while serum ceruloplasmin and 24-hour urine copper content are specific markers for early diagnosis of WD. In order to confirm the diagnosis of WD, it is necessary to combine the Sanger sequencing with multiplex ligation-dependent probe amplification or other testing technologies.
Ceruloplasmin/metabolism* ; Child ; Child, Preschool ; Copper/metabolism* ; Copper-Transporting ATPases/genetics* ; Female ; Hepatolenticular Degeneration/genetics* ; Humans ; Male ; Mutation ; Phenotype ; Retrospective Studies

: AbstractObjective: To investigate the effect of γδ T cells on the proliferation, apoptosis and autophagy of multiple myeloma cells. METHODS: Peripheral blood mononuclear cells (PBMNC) were isolated from healthy volunteers, and stimulated with zoledronic acid (Zol) in combination with rhIL-2. Flow cytometry analysis was used to detected the purity of γδ T cells. γδ T cells were collected and co-cultured with RPMI-8226 or U-266 cells at different effector target ratios. The proliferation of RPMI-8226 or U-266 cell lines were detected by CCK-8. Cell cycle and cell apoptosis were detected by flow cytometry and Western blot．The expressions of autophagy-related proteins were detected by Western blot. RESULTS: γδ T cells can be expanded in vitro. γδ T cells could inhibit the proliferation of RPMI-8226 or U-266 cells, induced cell cycle arrest and promoted apoptosis in an effector target-dependent manner. In addition, γδ T cells could induce autophagy of myeloma cells, inhibited the expression of autophagy-related PI3K, P-AKT and P-mTOR, while increased the expression of AMPK and Beclin-1. CONCLUSION γδ T cells can inhibit the proliferation of RPMI-8226 and U-266 myeloma cells, induce cell cycle arrest, promote apoptosis, and enhance autophagy in vitro. The mechanism may be related to inhibition of PI3K/AKT/mTOR signaling pathway and/or activation of AMPK/Beclin-1 signaling pathway.
AMP-Activated Protein Kinases/pharmacology* ; Apoptosis ; Autophagy ; Beclin-1/pharmacology* ; Cell Proliferation ; Humans ; Leukocytes, Mononuclear/metabolism* ; Multiple Myeloma/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; T-Lymphocytes ; TOR Serine-Threonine Kinases/metabolism*

ObjectiveTo analyze the clinical characteristics of brucellosis patients from two tertiary hospitals in epidemic and non-epidemic areas. MethodsThe clinical data of 67 brucellosis patients hospitalized in The Affiliated Kashi Hospital of Sun Yat-sen University （Kashi， 53） and The Third Affiliated Hospital of Sun Yat-sen University （Guangzhou， 14） from January 2019 to December 2019 were retrospectively reviewed， including demographic data， medical history， symptoms， signs， laboratory tests and treatment， and the differences between the two groups were compared. ResultsThere were 23 patients in Kashi and 11 patients in Guangzhou with definite epidemiological history， respectively （P = 0.019）. Fever， fatigue and arthralgia were the most common symptoms of brucellosis. In addition to anorexia， the onset symptoms of patients in the two hospitals were roughly the same. The incidence of fever， muscle pain and fever peak was similar， but the symptoms of hyperhidrosis， fatigue， arthralgia and rash in Kashi were more common in Guangzhou. There were cases of hepatosplenomegaly in both hospitals， but there was no obvious superficial lymphedema. Complications occurred in 39（73.6%） and 11（78.6%） patients in Kashi and Guangzhou， respectively， with no statistical difference （P =0.971）， and hepatitis and bone damage were the most common. The incidence of spondylitis （P =0.042） and neurodegenerative brucellosis （P =0.041） in Guangzhou was higher than that in Kashi， and there was no significant difference in other complications. Of the patients in Kashi， 7.5 % were treated with single antibiotics， and 59.7 % were with dual therapy， which were higher than those in Guangzhou （0， 50.0 %）. The proportion of the triple scheme in Guangzhou was higher than that of Kashi （50.0 % vs. 11.3 %）. ConclusionsThe clinical characteristics of brucellosis in different regions are generally similar， but there are some differences in epidemiological history， symptoms， complications and treatment options. The characteristics of local cases should be concerned in clinical practice to reduce misdiagnosis of brucellosis.

The chemical constituents from methanol extract of Dichroa hirsuta were separated by silica gel and Sephadex LH-20 column chromatography,high pressure preparative liquid chromatography( HPLC) and recrystallization. Their structures were elucidated by NMR and MS. Nine compounds were obtained and their structures were identified as 3β,21α-O-diacetyl-lup-9( 11)-en-7β-ol( 1),( Z)-methyl p-hydroxycinnamate( 2),cis-p-coumaric acid ethyl ester( 3),( E)-methyl p-hydroxycinnamate( 4),trans-p-coumaric acid ethyl ester( 5),4( 3 H)-quinazolinone( 6),7-hydroxycoumarin( 7),hydrangenol( 8) and thunberginol C( 9). Compound 1 is a new lupane-type triterpenoid,and compounds 1-5,8-9 were firstly isolated from this plant. Dual reporter assay results showed that compounds 2-5 could activate the Nrf2-ARE signaling pathway.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Hydrangea ; chemistry ; Phytochemicals ; isolation & purification ; pharmacology ; Triterpenes ; isolation & purification ; pharmacology

The quality of compound traditional Chinese medicine is the prerequisite and foundation for its stable efficacy. Based on the quality by design( QbD) concept,the controllable extraction times,extraction time and the ratio of water were the critical process parameters( CPPs) in the Tuomin Dingchuan Prescription extraction process. The CQAs corresponding to CPPs were screened from the four potential critical quality attributes( p CQAs),namely the extraction amount of solid matter,the content of amygdalin,the content of cimicifugoside and the content of 5-O-methylvisammioside by orthogonal experiment. The extraction amount of solid matter and the content of amygdalin were determined as CQAs in the extraction process by the variance analysis of Box-Behnken experimental. The optimal extraction process based on the linear model between CQAs and CPPs of the extraction process was immersion in water for 30 minutes,extraction for three times,extraction for 100 minutes each time and 10 times of water volume. The control space was established for the extraction amount of solid matter and the content of amygdalin,and both of them could be controlled simultaneously to achieve the optimization objective. The molding ratio of Tuomin Dingchuan granules was regarded as CQA in forming process. On the basis of the single factor investigation,the ratio of dry extract powder to excipient and the ratio of ethanol were determined as CPPs. The central composite design( CCD) was used to optimize the forming process of Tuomin Dingchuan granules. The results showed that the dextrin was used as the filler; the ratio of dry paste to dextrin was 1 ∶1; and 0. 3 m L·g-1 of 70% ethanol was added as binder. The soft material and granules conformed to the actual production requirements.
Acupuncture Points ; Drugs, Chinese Herbal ; Ethanol ; Medicine, Chinese Traditional ; Water

Asthma ; therapy ; Humans ; Patient Education as Topic ; Physician-Patient Relations ; Self Care

Objective To observe the effects of acupuncture treatment on the levels of HPA axis related hormones and acupoint compatibility in insomnia rats; To discuss the mechanism of action for acupuncture treatment. Methods Chlorophenylalanine suspension was under intraperitoneal injection to establish insomnia model rats. Sixty SD rats were randomly divided into blank group, model group, Baihui+Shenmen group, Baihui+Sanyinjiao group, Baihui+non-acupoint group, with 12 rats in each group. Each treatment group received acupuncture in relevant acupoints, 30 min each time, for 7 d. ELISA was used to measure the levels of CRH, ACTH and CORT. Results Compared with the model group, the levels of CRH, ACTH and CORT of the acupuncture groups decreased to some extent. In the three acupuncture groups, the efficacy of Baihui+Shenmen group was better than that of Baihui+Sanyinjiao group and Baihui+non-non-acupoint group. Conclusion Acupuncture treatment may calm and soothe the nerves to release the insomnia through regulating HPA axis related hormones. Acupuncture acupoints at different meridians may be one of the factors that cause the difference of acupoints compatibility effect.

Objective To investigate potential human leucocyte antigen (HLA)-A2-restricted epitope peptides of glypican-3 (GPC3) and determine the cytotoxicity of peptide-specific cytotoxic T lymphocytes (CTLs) against hepatocellular carcinoma (HCC) cells. Methods The potential HLA-A*0201-restricted GPC3 peptides were screened using computer algorithms, T2 cell-binding affinity and stability of peptide/HLA-A*0201 complex assay. The peptide-specific CTLs were generated and their cytotoxicity against GPC3

OBJECTIVETo investigate the effect of Chinese medicine (CM) and Western medicine (WM) on quality of life (QOL) after conservative surgery for endometriosis.

METHODSA total of 320 patients with endometriosis were randomized into two groups by using random block design, CM group (160 cases, activating blood circulation and removing blood stasis treatment based on syndrome differentiation) and WM group (160 cases, gonadotropin-releasing hormone agonist or gestrinone treatment) after conservative surgery. Treatment was given for 3-6 months (according to the revised American Fertility Society scoring system stage), and the World Health Organization QOL-BREF (WHOQOL-BREF) was applied to patients before and after treatment to assess QOL.

RESULTSThere were 136 cases in the CM group and 141 cases in the WM group completing therapy. In the CM group, the use of the WHOQOL-BREF showed that the physical, psychological and environmental scores posttreatment were significantly higher than those at pre-treatment (P < 0.05), and for 12 items (pain and discomfort, energy and fatigue, sleep and rest, mobility, activities of daily living, work capacity, negative feelings, health and social care: accessibility and quality, participation in and opportunities for recreation/leisure activities, appetite, QOL score, overall health status and QOL), the difference in scores was significant (P < 0.05). In the WM group, 4 items (pain and discomfort, opportunities for acquiring new information and skills, QOL score, overall health status and QOL) had significantly different scores post-treatment compared with those at pre-treatment (P < 0.05). Before treatment, the QOL in the two groups of patients showed no significant difference (P > 0.05). After treatment, the scores for physical health in the CM group were significantly higher than those of the WM group (P < 0.05) and the scores of 4 items (mobility, activities of daily living, sexual activity, QOL score) in the CM group were significantly higher than those in the WM group (P < 0.05).

CONCLUSIONSCM and WM treatment could improve the QOL of patients with endometriosis after conservative surgery. CM treatment is more effective than WM.

Adolescent ; Adult ; China ; Drugs, Chinese Herbal ; therapeutic use ; Endometriosis ; diagnosis ; surgery ; Female ; Follow-Up Studies ; Gonadotropin-Releasing Hormone ; antagonists & inhibitors ; therapeutic use ; Humans ; Middle Aged ; Pain Measurement ; Pain, Postoperative ; drug therapy ; physiopathology ; Patient Satisfaction ; statistics & numerical data ; Postoperative Care ; methods ; Prospective Studies ; Quality of Life ; Reference Values ; Risk Assessment ; Treatment Outcome ; Young Adult