Objective:To explore the relationship between serum microRNA (miR) -24-3p, H2A histone family member X (H2AFX) and clinical pathological features and postoperative recurrence in liver cancer patients.Methods:A total of 108 newly diagnosed liver cancer patients admitted to Tumor Hospital Affiliated to Nantong University from March 2018 to March 2022 were regarded as the liver cancer group. Eighty-six patients with benign liver lesions who visited our hospital during the same period were selected as the benign lesion group, and 64 healthy individuals who underwent physical examinations were selected as the control group. Quantitative real-time PCR method was applied to detect and analyze the levels of serum miR-24-3p and H2AFX mRNA in each group. The serum miR-24-3p and H2AFX levels in patients with recurrent and non-recurrent liver cancer were compared, and the comparison of clinicopathological characteristics of patients with liver cancer with different serum miR-24-3p and H2AFX levels was conducted. Logistic regression was applied to analyze the risk factors affecting postoperative recurrence in liver cancer patients.Results:To the end of follow-up, of the 108 patients with liver cancer, 46 relapsed. The serum miR-24-3p levels in control group, benign lesion group, and liver cancer group were 1.01±0.23, 0.79±0.21 and 0.55±0.13, respectively, with a statistically significant difference ( F=125.86, P<0.001), serum miR-24-3p level in benign lesion group and liver cancer group was lower than that in control group (both P<0.05), and serum miR-24-3p level in liver cancer group was lower than that in benign lesion group ( P<0.05). The serum H2AFX mRNA levels in control group, benign lesion group, and liver cancer group were 1.02±0.25, 1.27±0.31 and 1.59±0.37, respectively, with a statistically significant difference ( F=65.40, P<0.001), serum miR-24-3p level in benign lesion group and liver cancer group were higher than that in control group (both P<0.05), and serum miR-24-3p level in liver cancer group was higher than that in benign lesion group ( P<0.05). There were statistically significant differences in TNM stage ( χ2=7.85, P=0.005; χ2=6.32, P=0.012) and differentiation degree ( χ2=11.59, P=0.001; χ2=9.92, P=0.002) between patients with high and low level of miR-24-3p and H2AFX. Compared with the non-relapsed patients, the serum miR-24-3p level was significantly lower (0.44±0.12 vs. 0.64±0.14) and the H2AFX level was significantly higher (1.87±0.42 vs. 1.38±0.33) among the relapsed patients, with statistically significant differences ( t=7.79, P<0.001; t=6.79, P<0.001). Univariate analysis showed that TNM stage ( OR=1.57, 95% CI: 1.05-2.35, P=0.029), differentiation degree ( OR=2.20, 95% CI: 1.20-4.02, P=0.011), miR-24-3p level ( OR=0.66, 95% CI: 0.45-0.95, P=0.026), H2AFX level ( OR=1.73, 95% CI: 1.14-2.60, P=0.009) were all influential factors for postoperative recurrence in liver cancer patients. Multifactorial analysis showed that TNM stage ( OR=2.10, 95% CI: 1.14-3.86, P=0.017), differentiation degree ( OR=1.58, 95% CI: 1.12-2.23, P=0.009), miR-24-3p level ( OR=0.76, 95% CI: 0.63-0.92, P=0.005), H2AFX level ( OR=1.90, 95% CI: 1.20-2.99, P=0.006) were the independent influencing factors of postoperative recurrence in liver cancer patients. Conclusion:There are statistically significant differences in tumor TNM stage and differentiation degree among liver cancer patients with different serum miR-24-3p and H2AFX levels, and serum miR-24-3p and H2AFX levels are the influencing factors for postoperative recurrence in liver cancer patients.

Developing analytical methods for the chemical components of natural medicines remains a challenge due to its diversity and complexity. Miao-Fu-Zhi-Tong (MFZT) granules, an ethnic Yi herbal prescription, comprises 10 herbs and has been clinically applied for gouty arthritis (GA) therapy. Herein, a series of chemical profiling strategies including in-house library matching, molecular networking and MS/MS fragmentation behavior validation based on ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) were developed for qualitative analysis of MFZT granules. A total of 207 compounds were identified or characterized in which several rare guanidines were discovered and profiled into alkyl substituted or cyclic subtypes. Moreover, network pharmacology analysis indicated that MFZT's anti-gout mechanism was mostly associated with the nuclear factor kappa-B (NF-κB) signaling, nucleotide oligomerization domain (NOD)-like signaling and rheumatoid arthritis pathways, along with the synergistic effect of 84 potential active compounds. In addition, a quantitative analytical method was developed to simultaneously determine the 29 potential effective components. Among them, berberine, pellodendrine, 3-feruloylquinic acid, neoastilbin, isoacteoside and chlorogenic acid derivatives at higher concentrations were considered as the chemical markers for quality control. These findings provide a holistic chemical basis for MFZT granules and will support the development of effective analytical methods for the herbal formulas of natural medicines.
Humans ; Chromatography, High Pressure Liquid/methods* ; Tandem Mass Spectrometry/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Arthritis, Gouty

OBJECTIVE: To analyze the clinical phenotype and genetic basis for a male neonate featuring hypoparathyroidism, sensorineural hearing loss, and renal dysplasia (HDR) syndrome. METHODS: The child was subjected to genome-wide copy number variation (CNVs) analysis and whole exome sequencing (WES). Clinical data of the patient was analyzed. A literature review was also carried out. RESULTS: The patient, a male neonate, had presented with peculiar facial appearance, simian crease and sacrococcygeal mass. Blood test revealed hypocalcemia, hypoparathyroidism. Hearing test suggested bilateral sensorineural deafness. Doppler ultrasound showed absence of right kidney. Copy number variation sequencing revealed a 12.71 Mb deletion at 10p15.3-p13 (chr10: 105 001_12 815 001) region. WES confirmed haploinsufficiency of the GATA3 gene. With supplement of calcium and vitamin D, the condition of the child has improved. CONCLUSION The deletion of 10p15.3p13 probably underlay the HDR syndrome in this patient.
DNA Copy Number Variations ; Hearing Loss, Sensorineural/genetics* ; Humans ; Hypoparathyroidism/genetics* ; Infant, Newborn ; Kidney/abnormalities* ; Male ; Syndrome ; Urogenital Abnormalities/genetics*

Objective To compare curative effect between lenvatinib combined with locoregional therapy and locoregional therapy on PD-L1-positive hepatocellular carcinoma patients with type Ⅰ-Ⅲ portal vein tumor thrombus according to Cheng's classification. Methods The patients in lenvatinib combined with locoregional therapy group received orally-administered lenvatinib at a dose of 12 mg qd for patients≥60 kg or 8 mg qd for patients < 60 kg. The locoregional therapy group only received locoregional therapy. We retrospectively analyzed the clinical data and prognosis of two groups. Results The CR+PR were 78.1% and 53.6% in the combination group and locoregional therapy group, respectively (P < 0.05). The response rate, disease control rate and overall survival of the combination group were higher than those in the locoregional therapy group (P < 0.05). Conclusion The curative effect and overall survival of lenvatinib combined with locoregional therapy is better than locoregional therapy on PD-L1-positive hepatocellular carcinoma patients with type Ⅰ-Ⅲ portal vein tumor thrombus according to Cheng's classification.

Objective To evaluate the prognosis-related factors of colorectal cancer patients with positive PD-L1 expression in liver metastases after hepatectomy. Methods We reviewed retrospectively the clinical data of 68 colorectal cancer patients with positive PD-L1 expression in liver metastases receiving personalized comprehensive treatment which was mainly consisted of surgical resection. We observed the results and prognosis after surgical resection and analyzed related factors. Results Univariate analysis showed that no radiotherapy, N stage, RAS mutation status, T stage, dMMR, Duck stage, disease free interval from primary to metastases≤12 months and largest hepatic tumor diameter > 5 cm had obvious significance (all P < 0.05). Multivariate logistic analysis regression revealed that without dMMR (P=0.012), Duck A stage (P=0.000), disease free interval from primary to metastases > 12 months (P=0.020) and largest hepatic tumor diameter < 5 cm (P=0.006) were independent protective factors for the prognosis of colorectal cancer patients with positive PD-L1 expression in liver metastases after surgical resection. Conclusion Personalized comprehensive treatment which is mainly consisted of surgical resection still has a good effect on colorectal cancer patients with positive PD-L1 expression in liver metastases after hepatectomy. Without dMMR, Duck A stage, disease free interval from primary to metastases > 12 months and largest hepatic tumor diameter ≤5cm are independent protective factors for patients' prognosis.

Objective:To evaluate the short-term efficacy and safety of HA280 immunoadsorption (IA) column in idiopathic inflammatory myopathies (IIM).Methods:The clinical data of 72 patients with IIM admitted to the Department of Rheumatology of Xiangya No.2 Hospital of Central South University from January 2015 to March 2018 were analyzed. Of these patients, 22 patients were treated with HA280 immunoadsorption column for three times (the immunoadsorption group) and 50 patients were treated with drugs only (the control group). The changes of clinical symptoms and signs, autoimmune antibodies, myocardial enzyme spectrum, the inflammatory markers [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and ferritin], immunoglobulin, complement, other biochemical indexes and pulmonary images of the patients were detected and analyzed before and after the treatment. And then the data were analyzed by Chi-square test, samples t testand Wilcoxon rank sum test. Results:Compared with the control group, the symptoms and signs were obviously improved after treatment with HA280 immunoadsorption column. In particular, the clinical improvement rate of non-specific myositis (89%, 16/18) was higher than that of the control group [(58%, 22/38), χ2=5.379, P<0.05]. And the clearance of autoantibody (control group) was grade 39.41 in average, 28.38 in average in the immunoadsorption group( Z=-2.51, P=0.01), myocardial enzyme spectrum [control 717(1 564) U/L, immunoadsorption group 126(432) U/L , Z=3.09, P<0.01], the inflammatory markers such as ESR [the control group was 24(22) mm/1 h, the immunoadsorption group was 10(7) mm/1 h, Z=-3.0, P=0.003] and immunoglobulin G [the control group was 11(5) g/L, the immunoadsorption group was 9(2) g/L, Z=-4.8, P=0.001] and immunoglobulin M [the control group was 0.9(0.4) g/L, the immunoadsorption group was 1.2(0.8) g/L, Z=-2.0, P=0.05]. Moreover, the lung CT scan showed that pulmonary lesions of the patients in the immunoadsorption group (89%, 17/19) was much more improved than the control group [(61%, 27/44), χ2=4.98, P<0.05]. No serious adverse reactions occurred. Conclusion:HA280 immunoadsorption therapy can significantly clear the autoantibodies, decrease muscle enzymes, inflammatory markers and immunoglobulin, improve lung images of some patients in a short time. It has been shown that it is safein patients with IIM. HA280 immunoadsorption therapy could be an effective treatment for IIM.

Objective To evaluate the clinical characteristics and pregnant outcomes of gravidae with COVID-19. Methods This study involved nine gravidae with COVID-19 admitted to the Renmin Hospital of Wuhan University from January 22 to February 1, 2020. Their clinical data, including epidemiological history, clinical symptoms, laboratory examinations, chest CT, treatment, delivery mode, and pregnancy outcomes, were analyzed retrospectively. Specimens of maternal vaginal swab were collected in six pregnant women, and the specimens of amniotic fluid, cord blood, neonatal throat swab and breast milk samples were collected in four pregnant women who had a delivery during our study. All samples were tested for the existence of COVID-19. Descriptive analysis was applied in this study. Results (1) Among the nine cases, five were admitted in the third trimester and four in the second trimester. The median incubation period of COVID-19 was 8 (1-14) d. Fever was presented in all cases on admission, and the other commonly seen symptoms were cough (seven cases) and diarrhea (five cases). Other signs and symptoms were also reported, including shortness of breath, myalgia and fatigue (four cases in each), nasal obstruction, pharyngalgia, chest pain, and headache/dizziness (three cases in each), rash (two cases), and chills and expectoration (one case in each). The most common laboratory abnormalities were a decreased number of lymphocytes (seven cases) and elevated C-reactive protein (six cases). Chest CT scans were performed in seven women, and all showed patchy areas or ground-glass opacity in both lungs. Oligohydramnios was detected in only one case at 37 +5 weeks, which was 7 d after the diagnosis of COVID-19. (2) All nine cases received empiric antibiotic and antiviral therapy with Chinese medicine as adjuvant treatment. Eight patients required oxygen inhalation, and eight were treated with glucocorticoid. Six cases received immunotherapy. (3) Four of the nine cases had delivered, including three cesarean sections and one spontaneous vaginal preterm birth after premature rupture of membranes, and the mother was transferred to the intensive care unit 2 d after delivery due to acute respiratory distress syndrome. One case was terminated at 26 gestational weeks. Of the four neonates, there were two term and two premature babies, and one preterm baby was small-for-gestational-age. No neonatal asphyxia was observed. Serial real-time quantitative reverse transcription-polymerase chain reaction showed negative results in the detection of 2019-novel coronavirus in all samples obtained from amniotic fluid, umbilical cord blood, neonatal nasopharynx, breast milk, and vagina. Maternal conditions were all stable in all cases, including the four continuing pregnancy, and the terminated ones, except the case mentioned above. Conclusions There is no distinguishable clinical feature between pregnant and non-pregnant COVID-19 patients. So far, there is no evidence for vertical transmission or worsening perinatal outcome in mothers and babies.

OBJECTIVE: To assess the association of KIR/HLA alleles with hepatocellular carcinoma (HCC) and hepatitis B virus (HBV) infection among ethnic Han Chinese patients from southern China. METHODS: For 95 patients with HCC and 171 healthy controls, the genotype of HLA-C alleles was determined with a PCR sequence-specific oligonucleotides typing method on an Illumina GenDx NGSgo platform. Genotypes comprised of HLA-C and KIR gene alleles were also subjected to statistical analysis. RESULTS: In total 16 KIR genes (2DL2, 2DS2, 2DS3, 2DS5, 3DS1, 2DS1, 2DL5, 2DS4, 3DL1, 3DP1, 2DL3, 2DP1, 3DL3, 2DL1, 3DL2 and 2DL4) were discovered in the two groups. The frequencies of KIR2DL3 alleles and combinational genotypes of KIR2DL3/HLA-C1C2 were significantly lower in the patient group compared with the controls (0.9368 vs. 0.9883, χ²>3.84; P<0.05, OR = 0.1; 0.0112 vs. 0.2663, χ²>3.84; P<0.05, RR = 0.03). The frequency of HLA-C2C2 genotype of the patient group was significantly lower than that of the controls (0.0316 vs. 0.2690, P<0.05, RR = 0.09), while the frequency of HLA-C1C2 genotype was significantly higher than that of the controls (0.2316 vs. 0.0058, P<0.05, RR = 51.23). CONCLUSION Above results suggested that the KIR2DL3 allele is associated with lower risk for HCC. There may be individual difference in patients with HCC and HBV infection but various combinations of KIR/HLA alleles.
Alleles ; Carcinoma, Hepatocellular ; genetics ; China ; Gene Frequency ; Genotype ; Humans ; Liver Neoplasms ; genetics ; Polymorphism, Genetic ; Receptors, KIR

To investigate the correlation between peripheral concentration of infliximab (IFX) or anti-IFX antibody titers and short-term therapeutic effect of IFX in patients with active rheumatoid arthritis (RA).
 Methods: Twenty patients with active RA were treated with combination of methotrexate (MTX), leflunomide (LEF) with IFX, and the clinical and laboratory index and the side effects were recorded before and after IFX treatment. Twenty healthy subjects were chosen as a control group.
 Results: After 14-week treatment, patients were categorized into good, moderate or no responders according to EULAR remission criteria. There were no significant differences in peripheral IFX concentration, anti-IFX antibody titers and TNF-α levels among the 3 groups, and there were no significant correlations among ΔDAS28-CRP, peripheral IFX concentration, anti-IFX antibody titers and TNF-α levels.
 Conclusion: Peripheral IFX concentration, anti-IFX antibody titers and TNF-α levels can not be used as reliable predictive index for short-term effect of IFX in active RA.
Antibodies, Monoclonal ; blood ; Antirheumatic Agents ; therapeutic use ; Arthritis, Rheumatoid ; drug therapy ; Drug Therapy, Combination ; Humans ; Infliximab ; blood ; therapeutic use ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; blood

Objective:To evaluate therapeutic effects and adverse reactions of tocilizumab on patients with severe active rheumatoid arthritis (RA).Methods:Twelve patients with severe refractory RA were treated with tocilizumab.The clinical and laboratory indices and the side effects were recorded after treatment.Results:The clinical and laboratory indices and the disease activity score 28 (DAS28) were observed in all patients,which were significantly improved after TCZ therapy (P＜0.05),and no obvious adverse reactions were found.Conclusion:Tocilizumab can effectively relieve the symptoms and improve the conditions of severe active RA.