Objective:To investigate the efficacy of programmed death receptor-1(PD-1)/ programmed death-ligand 1 (PD-L1) inhibitors in the treatment of recurrent or metastatic cervical cancer and its effect on serum levels of squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen (CEA), and carbohydrate antigen 125 (CA125) in patients.Methods:This study was a retrospective study. Ninety patients with cervical cancer treated at Lishui Municipal Central Hospital between January 2019 and December 2022 were randomly divided into two groups. Forty-five patients in the control group received routine radiotherapy and chemotherapy, while forty-five patients in the observation group received PD-1/PD-L1 inhibitors in addition to the treatment provided to the control group. The effectiveness and safety were compared between the two groups.Results:The effectiveness in the observation group was superior to that in the control group ( P < 0.05). After treatment, the levels of serum tumor markers, including SCC-Ag, CA125, CEA, and human epididymal protein 4, were significantly lower in the observation group compared with the control group ( t = 5.44, 6.20, 14.74, 4.06, all P < 0.001). After treatment, the levels of interferon-γ, interleukin-2, and interleukin-6 in the observation group were significantly lower compared with the control group ( t = 6.24, 8.95, 8.38, all P < 0.001). After treatment, the levels of CD 3+, CD 4+, and CD 4+/CD 8+ in the observation group were significantly higher compared with those in the control group ( t = 8.82, 6.53, 5.27, all P < 0.001). After treatment, the Functional Assessment of Cancer Therapy-Cervix score in the observation group was significantly higher than that in the control group ( t = 4.35, 4.35, 5.17, 5.24, all P < 0.001). The incidence of various adverse reactions in the observation group was significantly lower than that in the control group ( χ2 = 3.85, 3.87, 5.08, 4.44, all P < 0.05). The cumulative survival rate in the observation group was significantly higher than that in the control group [60.00% (27/45) vs. 40.00% (18/45), P < 0.05]. The median survival time in the observation group was significantly longer than that in the control group (365 days vs. 222 days, P < 0.05). Conclusion:PD-1/PD-L1 inhibitors are effective in the treatment of recurrent or metastatic cervical cancer. They can reduce the serum levels of SCC-Ag, CEA, and CA125, prolong the survival time of patients, and improve their quality of life.

Objective:To investigate the characteristics of HBV-specific T cell reactivity among pregnant, postpartum and non-pregnant women at childbearing age with chronic HBV infection.Methods:A total of 100 patients with chronic HBV infection were enrolled in this study, including 43 pregnant women (pregnant group), 26 patients giving birth within six months (postpartum group), and 31 non-pregnant patients at childbearing age (non-pregnant group). The functional HBV-specific T cells in peripheral blood were detected by ELISPOT. Clinical data as well as the results of virological and serological tests of HBV were collected for stratified analysis.Results:There was no significant difference in the number of functional HBV-specific T cells between the pregnant group and the postpartum group, but the number was significantly lesser in the pregnant group than in the non-pregnant group ( P<0.05). Furthermore, the number of functional HBV-specific T cells was significantly higher in the nucleoside analogues (NUCs)-treated pregnant women than in the NUCs-untreated pregnant women ( P<0.05). Among the patients without NUCs treatment, there were no significant differences in the numbers of hepatitis B envelope antigen/hepatitis B core antigen (HBeAg/HBcAg)-specific T cells between the pregnant group and the postpartum group, but the numbers were lower in the pregnant group than in the non-pregnant group ( P<0.05). Among the NUCs-treated patients, there was no significant difference in the number of functional HBV-specific T cells between the pregnant group and the non-pregnant group, and the numbers in the two groups were significantly higher than that in the postpartum group (both P<0.05). Additionally, receiver operating characteristic (ROC) curve indicated that the number of functional HBV-specific T cells in combination with HBV DNA load [area under the curve (AUC)=0.807] or hepatitis B surface antigen (HBsAg) levels (AUC=0.916) had a good predictive performance for hepatitis progression during pregnancy. Conclusions:Pregnancy can reduce HBV-specific T cell reactivity in women with chronic HBV infection, but NUCs treatment may improve the function of specific T cells. Routine monitoring of HBV-specific T cells during pregnancy and postpartum period can provide valuable guidance for the evaluation of immune function and treatments.

This study was performed to investigate the features of HBV-specific CD8+T cell reactivity in patients with chronic hepatitis B(CHB),HBV-induced liver cirrhosis(LC)or hepatocellular carcinoma(HCC).A total of 124 CHB patients,36 LC patients,and 114 HCC patients were enrolled in this study.The reactive HBV-specific CD8+T cells in peripheral blood were enumerated using an innovative ELISPOT system.In addition,19 CHB patients and 20 HCC patients were longitudinally monitored with an interval of 3-5 months.Data showed that the numbers of reactive HBV-specific CD8+T cells in CHB group were not significantly different from that in LC group,but obviously lower than that in HCC group(P=0.009 9),especially HBsAg-,HBpol-and HBe/cAg-specific CD8+T cells.In CHB group,the patients with normal ALT level,AST level,or low HBV-DNA load showed significantly more reactive HBV-specific CD8+T cells than the patients with abnormal ALT level,abnormal AST level,or high HBV-DNA load.Furthermore,the duration of NUCs treatment had an impact on the HBV-specific CD8+T cell reactivity in CHB patients,while different NUCs at the same treatment duration did not bring different reactivity of HBV-specific T cells.In LC group,the HBeAg-positive patients presented much more reactive HBV-specific CD8+T cells than the HBeAg-negative patients did.In HCC group,the numbers of reactive HBV-specific CD8+T cells in the patients with normal AFP level or normal DCP level were significantly higher than that in the patients with abnormal AFP level or abnormal DCP level.Longitudinal monitoring results showed that HBV-specific CD8+T cell reactivity displayed a slow upward trend in the CHB patients undergoing NUCs treatment,and an obvious increasing in the HCC patients undergoing combined treatment of targeted drugs and immunotherapy.Taken together,the features of HBV-specific CD8+T cell reactivity are distinct among the CHB,LC and HCC patients,and are influenced by virological indicators,tumor markers and treatment regimens.Therefore,more attention should be paid to the changes of HBV-specific CD8+T cell reactivity during clinical treatment.

Objective:To establish UPLC fingerprint method of Buddlejae Flos standard decoction and determination method of acteoside and linarin.Methods:UPLC method was used to establish the fingerprints of 17 batches of Buddlejae Flos standard decoction. Similarity evaluation and clustering analysis were carried out on the fingerprints of Buddlejae Flos standard decoction; the chromatographic peaks of standard decoction were identified by mass spectrometry and compared with the reference materials; the contents of acteoside and linarin in Buddlejae Flos standard decoction were determined by HPLC.Results:There were 11 common peaks in the fingerprint of Buddlejae Flos standard decoction and 6 of them were identified. The similarity of the 17 batch samples was between 0.972 and 0.999. Clustering analysis classified 17 batches of Buddlejae Flos standard decoction into two categories; edgeworthia chrysantha standard decoction was identified by the method of fingerprint as counterfeit; the content determination results showed that the contents of acteoside and linarin in the standard decoction prepared from Buddlejae Flos of in Hubei and Sichuan Provinces were higher than others and were more stable.Conclusion:The method can be used to comprehensively evaluate the quality of Buddlejae Flos standard decoction and provide reference for establishing the quality standard of Buddlejae Flos dispensing granules.

Objective: Investigate the effects of inducible ppp2r1a knockout on main physiological function in adult mice and study the mechanism. Methods: Ppp2r1a^flox/flox mice and CAGG-CreER mice were hybridized to obtain 20 CAGG-CreER ppp2r1a^flox/flox and 20 mice in homozygous group. Two groups of mice were divided into 4 groups respectively, finally we got 8 groups with 5 mice in each group. Tamoxifen was injected intraperitoneally to acquire inducible ppp2r1a knockout mice. The knockout efficiency of PP2A Aα in vital organs was measured by Western blot. At 0, 2, 4 and 6 days after injection, we measured body weight, histopathological change, peripheral blood cell counts and blood biochemical. Real-time PCR was performed to measure expression of liver glucolipid metabolism genes. Results: After tamoxifen injection for 6 days, the knockout efficiency of PP2A Aα in vital organs was 35%, 12%, 15%, 60%, 69% and 72%, respectively in heart, liver, spleen, lung, kidney and brain. After tamoxifen injection for 6 days, the weight of homozygous mice was lower than that of wild type mice, with values of (17.42±1.76) g and (21.69±1.82) g, respectively (P<0.05). Moreover, the activity level, abdominal and renal fat were significantly decreased in homozygous mice. Homozygous mice survived no more than 7 days. Compared with wild type mice, the organ coefficient of spleen of homozygous mice was decreased at the 6th day, with values of (0.59±0.10)% and (0.36±0.05)% respectively (P<0.05). Obvious spleen atrophy and marked decrease of nucleated cells were showed by performing HE staining. Tunel staining revealed increased apoptosis ratio of splenic lymphocytes in homozygous mice. The levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) of homozygous mice were higher than wild type mice (P<0.05). The values of ALT and AST in homozygous mice were (153.68±62.80) U/L and (193.2±44.28) U/L. The corresponding values in wild type mice were (41.02±12.91) U/L and (69.40±9.55) U/L. The above results indicated that ppp2r1a knockout caused liver damage. Blood sugar level of homozygous mice was lower than in wild type mice (P<0.05), with values of (4.20±1.99) mmol/L and (8.88±0.65) mmol/L respectively. Plasma total cholesterol (TC), high density lipoprotein (HDL) and β-hydroxybutyric acid (β-HB) level of homozygous mice were higher than those of wild type mice (P<0.05). The values of TC, HDL and β-HB in homozygous mice were (3.12±0.39), (1.53±0.38) and (2.49±0.89) mmol/L. The corresponding values in wild type mice were (1.69±0.92), (0.78±0.50) and (0.45±0.30) mmol/L respectively. The above results indicated that ppp2r1a loss interfered glucose and cholesterol metabolism. In addition, we also found that the white blood cell count (WBC) and lymphocyte count (LYM) of homozygous mice were lower than in wild type mice (P<0.05). The values of WBC and LYM in homozygous mice were (1.88±0.89)×10⁹/L and (0.92±0.37)×10⁹/L respectively. The corresponding values in wild type mice were (3.91±0.80)×10⁹/L and (2.74±0.52)×10⁹/L respectively. The mRNA levels of glucose-6-phosphatase (G6P) and phosphoenolpyruvate carboxykinase (PEPCK) of homozygous were lower than wild type mice (P<0.05). The fold change of G6P and PEPCK in homozygous mice was 0.46±0.11 and 0.72±0.07 respectively. The corresponding fold change in wild type mice was 1.02±0.07 and 1.02±0.06 respectively. Conclusion Whole body ppp2r1a is essential for the survival of adult mice, due to the important role in maintaining the metabolism of glucose and cholesterol of liver.

Objective: To evaluate the efficacy and safety of maintenance therapy with reduced dose of rhTPO in the patients with primary immune thrombocytopenia (ITP) who attained stable platelet (PLT) counts after daily administration of rhTPO. Methods: Treatment was started with a daily administration of rhTPO (300 U/kg) for 2 consecutive weeks. Patients who attained stable PLT≥50×10⁹/L were enrolled to maintenance therapy starting with every other day administration of rhTPO, then adjusted dose interval to maintain platelet count (30-100) ×10⁹/L. Results: A total of 91 eligible patients were enrolled. Fourteen patients discontinued the study due to noncompliance (12/14) and investigator decision (2/14) . Among 77 patients who completed the study, 38 patients with the administration of rhTPO at every other day or less could maintain PLT≥30×10⁹/L for 12 weeks. The percentage of patients with a platelet response (PLT≥30×10⁹/L) at 4^th week, 8^th week and 12^th week of maintain therapy was 92.6% (63/68) , 82.7% (43/52) and 85.0% (34/40) , respectively. Median platelet counts remained in the range of (70-124) ×10⁹/L. The overall incidence of rhTPO-related adverse events was 7.7%. All the adverse events were generally mild. Conclusion Extending the dose interval of rhTPO is feasible to maintain stable platelet count in the patients with ITP, but the optimal dose interval is uncertain and might vary with individuals.

Objective: To evaluate the influence of oral hygiene on risk of oral cancer in non-smoking and non-drinking women. Methods: From September 2010 to February 2016, 242 non-smoking and non-drinking female patients with pathologically confirmed oral cancer were recruited in a hospital of Fuzhou, and another 856 non-smoking and non-drinking healthy women from health examination center in the same hospital were selected as control group. Five oral hygiene related variables including the frequency of teeth brushing, number of teeth lost, poor prosthesis, regular dental visits and recurrent dental ulceration were used to develop oral hygiene index model. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95%CI). The area under the receiver operating characteristic curve (AUROC) was used to evaluate the predictability of the oral hygiene index model. Multivariate logistic regression model was used to analyze the association between oral hygiene index and the incidence of oral cancer. Results: Teeth brushing <2 twice daily, teeth lost ≥5, poor prosthesis, no regular dental visits, recurrent dental ulceration were risk factors for the incidence of oral cancer in non-smoking and non-drinking women, the corresponding OR (95%CI) were 1.50 (1.08-2.09), 1.81 (1.15-2.85), 1.51 (1.03-2.23), 1.73 (1.15-2.59), 7.30 (4.00-13.30), respectively. The AUROC of the oral hygiene index model was 0.705 9, indicating a high predictability. Multivariate logistic regression showed that the oral hygiene index was associated with risk of oral cancer. The higher the score, the higher risk was observed. The corresponding OR (95%CI) of oral hygiene index scores (score 1, score 2, score 3, score 4-5) were 2.51 (0.84-7.53), 4.68 (1.59-13.71), 6.47 (2.18-19.25), 15.29 (5.08-45.99), respectively. Conclusion Oral hygiene could influence the incidence of oral cancer in non-smoking and non-drinking women, and oral hygiene index has a certain significance in assessing the combined effects of oral hygiene.

Objective: To investigate the effects between fish, seafood and pickled food intakes on oral squamous cell carcinoma (OSCC). Methods: A case-control study was carried out in Fujian area during September 2010 to December 2016, in which 604 newly diagnosed primary OSCC cases confirmed by pathological diagnosis were collected from hospital and 1 343 control subjects were enrolled from community and healthy hospital population. Demographic data, history of smoking drinking and tea drinking, oral hygiene status and dietary behaviors (fish, seafood and pickled food intakes) were collected by in-person interviews using a standard questionnaire.Using unconditional logistic regression to estimate adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to assess the effects of fish, seafood and pickled food intakes on OSCC. Analysis stratified by smoking, alcohol drinking and bad prosthesis to explore the possible difference in association between subgroups. Multiplicative interactions and additive interactions between fish and bad prosthesis, seafood and alcohol drinking, pickled food and bad prosthesis were assessed by unconditional logistic regression, relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (S). Results: The average age of case group and control group were separately (58.69±13.92) years old and (59.27±11.37) years old (χ²=4.75, P=0.191). The people whose fish and seafood intakes ≥3 times/week had the lower risk of OSCC, the adjusted OR (95%CI) values were 0.63 (0.52-0.77) and 0.51 (0.41-0.64); The stratified analysis indicated that the people having bad prosthesis had the lower risk of OSCC if they eating fish ≥3 times/week, and the adjusted OR (95%CI) values was 0.53 (0.39-0.71); the people having bad prosthesis had the higher risk of OSCC if they eating pickled food ≥3 times/week, the adjusted OR (95%CI) values was 1.37 (1.02-1.88). Regularly eating seafood can decrease the risk of OSCC for non-smokers, smokers, non-drinkers, drinkers, people without bad prosthesis and had bad prosthesis, the adjusted OR (95%CI) values were 0.49 (0.36-0.68), 0.52 (0.37-0.73), 0.41 (0.31-0.55), 0.77 (0.51-0.96), 0.49 (0.36-0.67), 0.59 (0.42-0.83). Crossover analysis showed fish and bad prosthesis exist multiplication interaction relationship (adjusted OR=0.66, 95%CI: 0.44-0.97) and additional interaction relationship (RERI=-0.81, 95%CI:-1.43--0.19; AP=-0.76, 95%CI:-1.35--0.17; S=0.08, 95%CI: 0.01-0.98); pickled food and bad prosthesis exist multiplication interaction relationship (adjusted OR=1.63, 95%CI: 1.06-2.51) and addition interaction relationship (RERI=0.65, 95%CI:0.08-1.22; AP=0.36, 95%CI:0.10-0.62; S=5.19, 95%CI:1.32-54.49). Conclusion Reducing the consumption of pickled food, quitting smoking and limiting alcohol consumption, and regularly eating fish and seafood can prevent the occurrence of OSCC.

Objective: To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m², 10 mg/m² or 12 mg/m² as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) . Methods: A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m²) as induction chemotherapy in newly diagnosed patients of adult AML. Results: Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m² group, IDA 10 mg/m² group and IDA 12 mg/m² group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m² group and IDA 12 mg/m² group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m² group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m² was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m² when compared with the IDA 8 mg/m² was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×10⁹/L in IDA 8 mg/m² group, IDA 10 mg/m² group and IDA 12 mg/m² group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×10⁹/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) . Conclusions For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m² is clinically superior to IDA 8 mg/m² and IDA 12 mg/m² in favorable intermediate AML subgroup. However, idarubicin 12 mg/m² is more suitable to adverse AML subgroup.

Objective To explore the survival factors for oral squamous cell carcinoma (OSCC). Methods A total of 492 patients with OSCC were recruited from the First Affiliated Hospital of Fujian Medical University from June 2003 to December 2014. Then, 456 cases were included in the present study according to inclusion and exclusion criteria. Clinical and follow-up data were collected to evaluate survival factors of OSCC. Survival rates were calculated using the Kaplan-Meier method and compared using the Log-rank test. The Cox proportional hazards regression model was used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of survival factors. We also stratified by TNM Classification of Malignant Tumours stage and BMI to assess the association between treatments and OSCC outcomes. Results The age of the recruited patients was (57.89±11.61) years, and the proportions in TNM stagesⅠ,Ⅱ,Ⅲ, andⅣwere 14.0%(64), 23.7%(108), 16.1%(73) and 42.5%(194), respectively. The multivariate Cox regression indicated that the HR (95% CI) of the increase to mortality risk associated with stage T2-T3, T4(T1 as reference), stage N2-N3 (N0 as reference), poor-moderate differentiation, BMI<18.5 kg/m2 (compared with BMI 18.5-23.9 kg/m2), alcohol consumption≥20 g/d (compared with no alcohol) before treatment were 2.69 (1.21-5.95), 3.40 (1.54-7.53), 2.65 (1.17-6.00), 2.56 (1.39-4.71), 2.00 (1.15-3.50), 2.09 (1.11-3.93), and 1.68 (1.03-2.73), respectively. The stratification analysis demonstrated that, compared with surgery alone, surgery combined with radiotherapy reduced the mortality risk of stage Ⅲ-Ⅳ, HR (95% CI) 0.33 (0.12-0.93). Surgery combined with chemoradiotherapy reduced the mortality risk of OSCC with normal BMI, HR(95%CI) were 0.39 (0.17-0.87). Conclusions Clinical stage and histological grade are survival factors for patients with OSCC.