This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals ; Male ; Rats ; Nucleus Accumbens/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Depression/complications* ; Membrane Glycoproteins/genetics* ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders/complications* ; Neurons/metabolism* ; Receptors, Immunologic/genetics* ; Signal Transduction/drug effects* ; Synapses/metabolism*

OBJECTIVE: To explore the application of targeted mRNA sequencing in fusion gene diagnosis of hematologic diseases. METHODS: Bone marrow or peripheral blood samples of 105 patients with abnormally elevated eosinophil proportions and 291 acute leukemia patients from January 2015 to June 2023 in the First Affiliated Hospital of Soochow University were analyzed and gene structural variants were detected by targeted mRNA sequencing. RESULTS: Among 105 patients with abnormally elevated eosinophil proportions, 6 cases were detected with gene structural variants, among which fusion gene testing results in 5 cases could serve as diagnostic indicators for myeloid neoplasms with eosinophilia. In addition, a IL3∷ETV6 fusion gene was detected in one patient with chronic eosinophilic leukemia, not otherwise specified. Among 119 patients with acute myeloid leukemia (AML), 38 cases were detected structural variants by targeted mRNA sequencing, accounting for 31.9%, which was significantly higher than 20.2% (24/119) detected by multiple quantitative PCR (P < 0.05). We also found one patient with AML had both NUP98∷PRRX2 and KCTD5∷JAK2 fusion genes. A total of 104 patients were detected structural variants by targeted mRNA sequencing in 172 cases with acute B-lymphoblastic leukemia who were tested negative by multiple quantitative PCR, with a detection rate of 60.5% (102/172). CONCLUSION Targeted mRNA sequencing can effectively detect fusion gene and has potential clinical application value in diagnosis and classificatation in hematologic diseases.
Humans ; Hematologic Diseases/diagnosis* ; RNA, Messenger/genetics* ; Oncogene Proteins, Fusion/genetics* ; Sequence Analysis, RNA ; Leukemia, Myeloid, Acute/diagnosis*

ObjectiveTo analyze the clinical characteristics and the use of traditional Chinese medicine （TCM） therapy in cancer patients with COVID-19， and to provide reference for making TCM prevention and treatment strategies and determining diagnosis and treatment priorities for patients with malignant tumors in the COVID-19 epidemic. MethodsThe medical records of 225 malignant tumor cases with COVID-19 who were admitted to 7 national research centers from January 1st to 20th， 2023 were retrospectively collected， and the main symptoms and duration after infection， nucleic acid negative conversion time， use of TCM therapy， and changes in adverse reactions after resuming anti-tumor treatment were analyzed. ResultsA total of 222 malignant tumor patients with COVID-19 were included in the analysis， involving 205 mild cases and 17 moderate cases. The top four most frequently reported clinical symptoms were fever （165 cases）， expectoration or dry cough （99 cases）， decreased appetite （95 cases） and fatigue （85 cases）， of which 40 expectoration or dry cough cases ， 37 fatigue cases and 29 decreased appetite cases lasted for more than 14 days. One hundred and five patients with nucleic acid detection report had a median negative conversion time of 14 days. The nucleic acid negative conversion time was significantly longer in patients with lung cancer compared to those with digestive system malignant tumors， and in those with myelosuppression than those without （P＜0.01）. During the infection period， 47.30% （105/222） of the patients used Chinese patent medicine， and 21.17% （47/222） were treated with herbal decoctions. The use of TCM in patients during the prevention and rehabilitation period， was 1.80%（4/222） and 7.21%（16/222）， respectively. Fifty-five patients resumed anti-tumor treatment after nucleic acid negative conversion， and received TCM simultaneously. Observed adverse reactions， including gastrointestinal reactions， bone marrow suppression， and neurotoxicity， were all grade 1 to 2， and no new adverse events occurred during follow-up. ConclusionCertain malignant tumor patients with COVID-19 had prolonged symptoms and nucleic acid negative conversion time Rational use of TCM can help to promote the rehabilitation of the patients and ensure the smooth process of anti-tumor treatment after infection.

Background/Aims: Oral EDP-514 is a potent core protein inhibitor of hepatitis B virus (HBV) replication, which produced a >4-log viral load reduction in HBV-infected chimeric mice with human liver cells. This study evaluated the safety, pharmacokinetics, and antiviral activity of three doses of EDP-514 in treatment-naive viremic patients with HBeAgpositive or -negative chronic HBV infection. Methods: Patients with HBsAg detectable at screening and at least 6 months previously were eligible. HBeAg-positive and -negative patients had a serum/plasma HBV DNA level ≥20,000 and ≥2,000 IU/mL, respectively. Twenty-five patients were randomized to EDP-514 200 (n=6), 400 (n=6) or 800 mg (n=7) or placebo (n=6) once daily for 28 days. Results: A dose-related increase in EDP-514 exposure (AUClast and Cmax) was observed across doses. At Day 28, mean reductions in HBV DNA were –2.9, –3.3, –3.5 and –0.2 log10 IU/mL with EDP-514 200 mg, 400 mg, 800 mg, and placebo groups, respectively. The corresponding mean change from baseline for HBV RNA levels was –2.9, –2.4, –2.0, and –0.02 log10 U/mL. No virologic failures were observed. No clinically meaningful changes from baseline were observed for HBsAg, HBeAg or HBcrAg. Nine patients reported treatment emergent adverse events of mild or moderate severity with no discontinuations, serious AEs or deaths. Conclusions In treatment-naïve viremic patients, oral EDP-514 was generally safe and well-tolerated, displayed PK profile supportive of once-daily dosing, and markedly reduced HBV DNA and HBV RNA.

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.
China ; Gastrointestinal Agents/therapeutic use* ; Gastrointestinal Neoplasms ; Humans ; Pharmaceutical Preparations ; United States ; United States Food and Drug Administration

Background/Aims: Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disease characterized by recurrent abdominal pain and bowel dysfunction. However, the majority of previous neuroimaging studies focus on brain structure and connections but seldom on the inter-hemispheric connectivity or structural asymmetry. This study uses multi-modal imaging to investigate the abnormal changes across the 2 cerebral hemispheres in patients with IBS. Methods: Structural MRI, resting-state functional MRI, and diffusion tensor imaging were acquired from 34 patients with IBS and 33 healthy controls. The voxel-mirrored homotopic connectivity, fractional anisotropy, fiber length, fiber number, and asymmetry index were calculated and assessed for group differences. In addition, we assessed their relevance for the severity of IBS. Results: Compared with healthy controls, the inter-hemispheric functional connectivity of patients with IBS showed higher levels in bilateral superior occipital gyrus, middle occipital gyrus, precuneus, posterior cingulate gyrus, and angular gyrus, but lower in supplementary motor area. The statistical results showed no significant difference in inter-hemispheric anatomical connections and structural asymmetry, however negative correlations between inter-hemispheric connectivity and the severity of IBS were found in some regions with significant difference. Conclusions The functional connections between cerebral hemispheres were more susceptible to IBS than anatomical connections, and brain structure is relatively stable. Besides, the brain areas affected by IBS were concentrated in default mode network and sensorimotor network.

Background/Aims: Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disease characterized by recurrent abdominal pain and bowel dysfunction. However, the majority of previous neuroimaging studies focus on brain structure and connections but seldom on the inter-hemispheric connectivity or structural asymmetry. This study uses multi-modal imaging to investigate the abnormal changes across the 2 cerebral hemispheres in patients with IBS. Methods: Structural MRI, resting-state functional MRI, and diffusion tensor imaging were acquired from 34 patients with IBS and 33 healthy controls. The voxel-mirrored homotopic connectivity, fractional anisotropy, fiber length, fiber number, and asymmetry index were calculated and assessed for group differences. In addition, we assessed their relevance for the severity of IBS. Results: Compared with healthy controls, the inter-hemispheric functional connectivity of patients with IBS showed higher levels in bilateral superior occipital gyrus, middle occipital gyrus, precuneus, posterior cingulate gyrus, and angular gyrus, but lower in supplementary motor area. The statistical results showed no significant difference in inter-hemispheric anatomical connections and structural asymmetry, however negative correlations between inter-hemispheric connectivity and the severity of IBS were found in some regions with significant difference. Conclusions The functional connections between cerebral hemispheres were more susceptible to IBS than anatomical connections, and brain structure is relatively stable. Besides, the brain areas affected by IBS were concentrated in default mode network and sensorimotor network.

【Objective】 To compare sound touch elastography(STE), a new technique for the measurement of liver stiffness, and two-dimensional shear wave elastography(2D-SWE), and to provide an evidence base for STE’s clinical practice. 【Methods】 The study included forty-three healthy volunteers and sixty-three patients with liver cirrhosis, in which liver stiffness was measured by means of STE and 2D-SWE. We compared the technical success rate, intra-operator reproducibility and liver stiffness values. 【Results】 The success rates of STE and 2D-SWE were 100%(106/106) and 96.2%(102/106), respectively(χ²=2.320, P=0.128), with four 2D-SWE examination failures in four patients with liver cirrhosis. Compared with those assessed by 2D-SWE, liver stiffness values assessed by STE were higher [5.83(5.30~ 6.37) kPa vs. 5.00(4.80~5.20) kPa, Z=4.419, P<0.001] in the healthy group, but lower [15.82(11.71~25.02) kPa vs. 18.50(11.95~29.93) kPa, Z=-2.981, P=0.003] in the liver cirrhosis group. The Spearman's rank correlation coefficient of STE and 2D-SWE was 0.896(95%CI: 0.849~0.928, P<0.001) . 【Conclusion】 With equally good reproducibility, STE is superior to 2D-SWE due to its higher success rate and better penetration especially in patients with cirrhosis. The liver stiffness values assessed by STE and 2D-SWE are not equivalent, which deserves our special attention in clinical application.

Objective: To explore the association between soil selenium levels and the risk of diabetes in Chinese adults aged 35-74 years. Methods: Data for this study were derived from the China Chronic Diseases and Behavioral Risk Factors Surveillance 2010 survey. Selenium concentrations in soil were obtained from the Atlas of Soil Environmental Background Values in China. A two-level binary logistic regression model was used to determine the association between soil selenium concentrations and the risk of diabetes, with participants nested within districts/counties. Results: A total of 69,332 participants aged 35-74 years, from 158 districts/counties were included in the analysis. Concentrations of selenium in soil varied greatly across the 158 districts/counties, with a median concentration of 0.219 mg/kg ( : 0.185-0.248). The results showed that both Quartile 1 (0.119-0.185 mg/kg) and Quartile 4 (0.249-0.344 mg/kg) groups were positively associated with diabetes compared to a soil selenium concentration of 0.186-0.219 mg/kg (Quartile 2), crude odds ratios ( s) (95% ) were 1.227 (1.003-1.502) and 1.280 (1.048-1.563). The values were 0.045 and 0.013, for Quartile 1 and Quartile 4 groups, respectively. After adjusting for all confounding factors of interest, the Quartile 1 group became non-significant, and the Quartile 4 group had an adjusted (95% ) of 1.203 (1.018-1.421) relative to the reference group (Quartile 2), the values was 0.030. No significant results were seen for the Quartile 3 group (0.220-0.248 mg/kg) compared to the reference group. Conclusion Excessive selenium concentrations in soil could increase the risk of diabetes among Chinese adults aged 35-74 years.
Adult ; Aged ; China ; epidemiology ; Diabetes Mellitus ; chemically induced ; epidemiology ; Diet ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Risk Factors ; Selenium ; deficiency ; metabolism ; Soil ; chemistry

Objective: To investigate the effect of cartilage tissue engineering scaffold PVA/ι-CA on the biological behavior of the ATDC-5 cells,and to evaluate its feasibility on constructing tissue engineering cartilage. Methods:The polyvinyl alcohol (PVA)and carrageenan were used to make the composite scaffold material PVA/ι-CA according to a certain proportion by physical blending technology and repeated freezing thawing method,and the porosity and pore size of PVA/ι-CA were detected.The ATDC-5 cells were seeded into the composite scaffold and its growth was observed; the expressions of collagen type Ⅱ in the ATDC-5 cells were tested by immunohistochemical staining and immunofluorescence staining; the morphology of the ATDC-5 cells was confirmed by Toluidine blue staining.The growth and secretion of extracellular matrix of the ATDC-5 cells were observed under scanning electron microscope (SEM);the proliferative rates of ATDC-5 cells in composite scaffold materials in negative control group (added with DMEM culture media)and experimental group (added with DMEM contain scaffold)were determined by MTT assay.The composite scaffolds were implanted subcutaneously in the SD rats.The histocompatibility and vascularization in vivo of the composite scaffolds were evaluated.Results:The average porosity of cartilage tissue engineering scaffold PVA/ι-CA was (86.88±3.88)%,and the average pore size was 20-40 μm.The HE staining results showed that the ATDC-5 cells grew well with the polygon and plumpness morphology. All the samples were stained positive for collagen type Ⅱ by immunohistochemistry and immunofluorescence staining,which verified the normal phenotype of chondrocytes on the scaffolds. All the sample were stained positive for toluidine blue staining,which verified ECM deposition of the ATDC-5 cells on the scaffolds.The number of the positive cells was significantly increased with the prolongation of time.After cultured for 7 d,few of the ATDC-5 cells presented polygonal;after cultured for 14 d,the ATDC-5 cells distributed more densely,and contacted with each other on the scaffold;after cultured for 21 - 28 d,the ATDC-5 cells filled the interconnected pores of the scaffolds,synthesizing a significant amount of neo-formed ECM.The proliferation of ATDC-5 cells in PVA/ι-CA grew fast during 7-14 d,and it became slow during 21-28 d;the difference was not statistically significant compared with control group (P >0.05).The subcutaneous implantation results showed the inflammatory reactions were slight at the early stage and eviated gradually,there was an increasing angiogenesis at the late stage,and the degradation and absorption of the meterial were slight.Conclusion:PVA/ι-CA composite material will be an ideal material for the cartilage tissue engineering.