Objective:To investigate the protective effect of endogenous ω-3 polyunsaturated fatty acid(PUFA)against cisplatin-induced myelosuppression and the mechanism of reducing apoptosis in bone marrow nucleated cells using mfat-1 transgenic mice.Methods:The experimental animals were divided into 4 groups:wild-type mice normal control group,mfat-1 transgenic mice normal control group,wild-type mice model group and mfat-1 transgenic mice model group.The mice in the model group were injected intraperitoneally with 7.5 mg/kg cisplatin on day 0 and day 7 to construct a myelosuppression model,while the mice in the normal control group were injected intraperitoneally with an equal amount of saline,and their status was observed and their body weight was measured daily.Peripheral blood was taken after 14 day for routine blood analysis,and the content and proportion of PUFA in peripheral blood were detected using gas chromatography.Bone marrow nucleated cells in the femur of mice were counted.The histopathological changes in bone marrow were observed by histopathological staining.The apoptosis of nucleated cells and the expression level changes of apoptosis-related genes in the bone marrow of mice were detected by flow cytometry and fluorescence quantitative PCR.Results:Compared with wild-type mice,mfat-1 transgenic mice showed significantly increased levels of ω-3 PUFA in peripheral blood and greater tolerance to cisplatin.Peripheral blood analysis showed that endogenous ω-3 PUFA promoted the recovery of leukocytes,erythrocytes,platelets and haemoglobin in peripheral blood of myelosuppressed mice.The results of HE staining showed that endogenous ω-3 PUFA significantly improved the structural damage of bone marrow tissue induced by cisplatin.Flow cytometry and PCR showed that,compared with wild-type mice model group,the apoptosis rate of bone marrow nucleated cells in mfat-1 transgenic mice was significantly reduced(P＜0.001),and the expression of anti-apoptotic genes Bcl-2 mRNA was significantly increased(P＜0.01),while the expressions of pro-apoptotic genes Bax and Bak mRNA were significantly reduced(P＜0.001,P＜0.05).Conclusion:Endogenous ω-3 PUFA can reduce cisplatin-induced apoptosis in bone marrow nucleated cells,increase the number of peripheral blood cells and exert a protective effect against cisplatin-induced myelosuppression by regulating the expression of apoptosis-related genes.

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

OBJECTIVE: Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery. METHODS: We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated. RESULTS: A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery. CONCLUSION These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.
Female ; Humans ; Male ; Middle Aged ; Brucellosis ; COVID-19 ; Retrospective Studies ; SARS-CoV-2 ; Treatment Outcome ; Case Reports as Topic

Heat stroke(HS)is a serious life-threatening disease caused by heat injury and characterized by a core body temperature>40℃with central nervous system dysfunction and multi-organ failure.The main pathophysiological manifestations of HS are the thermal acute phase response and thermoregulatory imbalance.Proteins are particularly sensitive to heat,and the thermal environment can cause massive protein denaturation,resulting in the deposition of unfolded and misfolded proteins in the cytoplasm,causing cellular dysfunction and even death.The unfolded protein response(UPR),mainly divided into the endoplasmic reticulum UPR and the mitochondrial UPR,is an important physiological process that helps proteins to fold correctly or degrade irretrievably denatured proteins.This paper summarizes the regulatory mechanisms of UPR,the relationship between UPR and severe diseases,as well as the relationship between HS and UPR to provide new ideas for the treatment of HS.

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

Banxia Xiexin Tang is one of the classic prescriptions for treating digestive system diseases.In this paper，using the method of bibliometrics，information of Banxia Xiexintang in ancient Chinese medical literatures were collected and screened out 399 effective data from 238 kinds of ancient books．Based on the statistics and analysis of the history，drug composition，main disease and syndrome，principle of prescription，dosage，processing，preparation，decocting and taking methods of Banxia Xiexin Tang，it is found that Banxia Xiexin Tang originated from Treatise on Febrile and Miscellaneous Disease written by ZHANG Zhong-jing，a famous physician in the Eastern Han dynasty，it is composed of seven herbs，namely，Pinelliae Rhizoma，Scutellariae Radix，Zingiberis Rhizoma，Ginseng Radix et Rhizoma，Glycyrrhizae Radix et Rhizoma Praeparata cum Melle，Coptidis Rhizoma，and Jujubae Fructus. It was mainly used to treat pizheng of mixed cold and heat. Most of the Banxia Xiexin Tang recorded in later generations follow the prescription composition and indications in Treatise on Febrile and Miscellaneous Disease and its clinical application has been extended and expanded，among the 352 literatures with the main diseases and syndromes recorded，the most common （341） were pizheng，accounting for about 96.88%，in addition，it is also used sporadically for shuzheng，malaria，nausea，damp-wen，jaundice，etc. Among the 122 documents with drug dosage records，nearly half of them are identical with the original records in Treatise on Febrile and Miscellaneous Disease. Among the 112 literatures with pharmaceutical processing，licorice （86） was the most，most of them were roasted （80），followed by pinellia ternata （79），and most of them were "decoction washing and sliding" （67）. Among the 111 documents recorded in the decoction method，most of them inherited Treatise on Febrile and Miscellaneous Disease by "removing the dross and again cooking" （68），there are also "Water Decoction" （32） and "Ginseng Radix et Rhizoma and Jujubae Fructus Decoction" （11）. Among the 108 documents with the method of taking medicine，nearly half of them inherited Treatise on Febrile and Miscellaneous Disease，which is "a liter of warm taking ，three times daily". Based on the ancient Chinese medical literatures，Banxia Xiexintang was systematically analyzed in order to provide more accurate ancient literature reference for the clinical application and development of classic prescriptions.

BACKGROUND: Previous studies have found that polygonatum sibiricum polysaccharide (PSP) exhibits anti-osteoporosis effect, but its therapeutic effect in ovariectomized osteoporotic rats and the molecular mechanisms are poorly understood. OBJECTIVE: To investigate the effect of administration of PSP on the bone microstructure, bone mineral density as well as osteoblast- and osteoclast-related gene expression in rats. METHODS: Twenty-five infertile female Sprague-Dawley rats aged 3 months were randomly allotted into five groups (n=5 per group): sham operation (same volume normal saline), model, zoledronate (0.2 mg/kg?d), high-dose PSP (800 mg/kg?d) and medium-dose PSP (400 mg/kg?d) groups. All rats were subjected to ovariectomy except sham operation group. The administration was intragastrically given every 2 days beginning at 7 days after modeling and lasted 12 weeks. Then, the rats were sacrificed, and the uterus was weighed. The bilateral tibias were removed, one side for histomorphometric analysis by micro-CT, and the other one for RNA detection by qualified PCR. RESULTS AND CONCLUSION: Compared with the sham operation group, the rat body mass in the model group was significantly increased and the weight of uterus was significantly decreased (P < 0.05). Compared with the model group, zoledronate and high-dose PSP could significantly alleviate the excessive increase in body mass (P < 0.05). The bone mineral density in the model group was decreased by 63% compared with the sham operation group (P < 0.01), Compared with the model group, after 12-week high-dose PSP and zoledronate administration, the bone mineral density was increased by 44% and 38%, respectively (P < 0.01); the trabecular bone volume fraction and trabecular number rose significantly(P<0.05),while the trabecular separation decreased significantly(P<0.05).In vivo,PSP could significantly promote the expression levels of osteoblast-related genes (alkaline phosphatase, RUNX2, Col1a1 and osteocalcin), and significantly inhibit the expression levels of osteoblast-related genes (ACP5 and CTSK) (P < 0.05). These results imply that high-dose PSP can reduce bone loss and decrease of bone mineral density, improve the destruction of bone microstructure, as well as promote osteoblast-related genes but inhibit osteoclast-related gene mRNA expression in the ovariectomized rats.

OBJECTIVETo investigate the protective effect of ginsenoside Rg1 on oxygen-glucose deprivation (OGD) in PC-12 cells, and preliminarily discuss the potential molecular mechanism of mTOR/Akt/FoxO3 signaling pathway.

METHODThe OGD PC-12 cell model was established. The cell viability was measured by MTT assay. After the pretreatment with Rg1 with the concentration of 10, 20, 40 micromol x L(-1) for 24 h, the cell viability was observed. Lactate dehydrogenase (LDH) release, superoxide dismutase (SOD) ac- tivity and malondialdehyde (MDA) level were detected by colorimetry assay. mTOR, p-Akt(ser473), p-Akt(tjr308), Akt, p-FoxO3, FoxO3 in cytoplasm and nucleus, and total FoxO3 protein expression were detected by Western blot assay.

RESULTOGD could significantly in- hibit cell proliferation in 4-24 h in a time-dependent manner. After pretreatment for 24 h, Rg1 (20, 40 micromol x L(-1)) could notably elevate the cell viability and SOD viability and reduce the LDH release and MDA content. Besides, Rg1 also inhibited OGD-induced mTOR and p-Akt(ser473) decreases. After treatment for 6 h, OGD could reduce FoxO3 phosphorylation and promote FoxO3 in cytoplasm. This data suggested that Rg1 could protect PC-12 cell injury through mTOR/p-Akt/FoxO3 signaling pathway.

CONCLUSIONGinsenoside Rg1 could attenuate OGD-induced PC-12 cell injury. Its action mechanism may be closely related to activation of mTOR/p-Akt/FoxO3 signaling pathway.

Animals ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Forkhead Box Protein O3 ; Forkhead Transcription Factors ; genetics ; metabolism ; Ginsenosides ; pharmacology ; Glucose ; metabolism ; Oxygen ; metabolism ; PC12 Cells ; Protective Agents ; pharmacology ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Rats ; Signal Transduction ; drug effects ; TOR Serine-Threonine Kinases ; genetics ; metabolism

OBJECTIVETo investigate the therapeutic efficacy of double-mutated oncolytic adenovirus AxdAdB-3 in combination with gemcitabine for treating bladder cancer in an orthotopic nude mouse model.

METHODSThe susceptibility to the adenovirus was evaluated in bladder cancer cell lines YTS-1, T24, 5637 and KK47, and normal cell lines HCV29 and WI38. The cells were infected with AxCAlacZ and stained with 5-bromo-4-chloro-3-indolyl-β-galactoside (X-Gal). Immunostaining against adenoviral hexon protein was performed to determine the selective replication of AxdAdB-3 in the cancer cells. Flow cytometry was used to determine the YTS-1 cells in S phase of cell cycle after adenovirus infection. Cell viability after AxdAdB-3 and/or gemcitabine was measured by CCK-8 assay. Orthotopic bladder cancer model was established in nude mice, and the inhibitory efficacy of intravesical instillation therapy with AxdAdB-3 or/and gemcitabine was assessed.

RESULTSGene transduction efficiency was different among the cell lines, and correlated with expression of CAR. 5637 and KK47 cells with high expression of CAR were more susceptible to the adenovirus, whereas YTS-1 and T24 cells with little CAR expression were resistant to adenoviral infection. Immunostaining showed that the expression levels of hexon protein varied among the cell lines. Normal cells infected with AxdAdB-3 expressed little hexon protein. The proportion of S-phase cells was (39 ± 3) % and (49 ± 5) % in the AxCAlacZ- and AxdAdB-3-infected bladder cancer cells, respectively. AxdAdB-3 effectively induced S-phase entry of cell cycle (P < 0.05). AxdAdB-3 combined with gemcitabine significantly inhibited the growth of bladder cancer cell lines. In vivo, the mean weight of the bladder tumors in mice treated with intravesical instillation of AxCAlacZ, gemcitabine, AxdAdB-3, and AxdAdB-3 + gemcitabine were 400.6, 126.4, 82. 0, 40.4 mg, respectively. Either AxdAdB-3 (P < 0.0001) and gemcitabine (P < 0.0001) suppressed the tumor growth in nude mice, and the combination therapy reduced tumors more effectively than either AxdAdB-3 (P < 0.0001) or gemcitabine (P < 0.0001) alone.

CONCLUSIONSIntravesical instillation therapy with AxdAdB-3 in combination with gemcitabine can effectively inhibit the orthotopic bladder cancer in nude mouse, and further relevant clinical studies are guaranteed.

Adenoviridae ; genetics ; Administration, Intravesical ; Animals ; Antimetabolites, Antineoplastic ; administration & dosage ; pharmacology ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; pharmacology ; therapeutic use ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; pharmacology ; therapeutic use ; Galactosides ; Indoles ; Mice ; Mice, Nude ; Models, Animal ; Urinary Bladder Neoplasms ; drug therapy