Objective To analyze the status of persistent human papillomavirus (HPV) infection and the distribution of viral subtypes in the Zhengzhou region. Methods Clinical data of 55239 patients who underwent HPV-DNA genotyping tests from 2018 to 2024 were collected. On the basis of HPV follow-up results, patients were divided into three groups: 849 cases of infection with the same HPV type, 255 cases of persistent infection with different HPV types, and 857 cases of transient HPV infection. Results Among the 9232 initially-screened patients who were positive with HPV, the high-risk HPV (HR-HPV) positive rate was 84.6% (7813/9232), and predominant subtypes were HPV-16 (20.8%), HPV-52 (17.2%), and HPV-53 (9.6%). The low-risk HPV (LR-HPV) positive rate was 15.4% (1419/9232), mainly HPV-81 (28.1%) and HPV-42 (27.0%). Among the 1961 follow-up cases, the rates of persistent and non-persistent infections with the same HPV type were 35.7% (701/1961) and 7.5% (148/1961), respectively. The rates of persistent and non-persistent infections with different HPV types were 10.9% (214/1961) and 2.1% (41/1961), respectively. Meanwhile, 43.7% (857/1961) tested negative upon follow-up. Among the 701 cases of persistent infection with the same HPV type, HR-HPV accounted for 85.7% (601/701), and LR-HPV accounted for 14.3% (100/701). Among the 214 cases of persistent infection with different HPV types, 89.7% (192/214) were high-risk transitions, and 10.3% (22/214) were low-risk transitions. Regardless of HPV types, HR-HPV was more likely to cause persistent infection than LR-HPV. In addition, over 60% of HR-HPV persistent infections resolved within 18 months, 30% developed into persistent infections, and only 15% of patients had persistent infections that last more than 24 months. Conclusion Persistent HPV infections are predominantly high-risk types. Most patients clear the infection within 18 months, approximately 30% develop persistent infections, and about 15% of patients have persistent infections that last more than 24 months. However, the HR-HPV persistent infection rates across different age groups slightly differ.

Objective To explore the clinical significance of serum cytokine expression in the hepatitis B surface antigen(HBsAg)sero-clearance in patients with severe hepatitis B.Methods A nested case-control trial was conducted on 14 inpatients with severe hepatitis B admitted in our hospital from 2006 to 2020.Of them,7 patients(aged 36.57±3.15 years)achieved HBsAg sero-clearance within 1 year after the onset of hepatitis B flares(with abrupt rise of ALT level to＞5 times the upper limit of normal during HBV infection)and were assigned into HBsAg clearance group,while the other 7 patients(aged 34.14±2.97 years)only obtained HBsAg decreased less than 1 g within 1 year after the onset(HBsAg non-clearance group).Then,multiplex liquid-chip assay based on Luminex xMAP was used to detect the expression levels of 48 cytokines such as IFN-γ and IL-2 in serum samples of these 14 patients.Results The serum levels IFN-γ,IL-2Ra and SDF-1α were significantly lower in the HBsAg clearance group than the HBsAg non-clearance group(P＜0.05),but no statistical differences were observed in other 39 cytokines between the 2 groups.And there were 5 cytokines having no mutual expression in both groups.The copy number of HBV DNA was positively correlated with serum HGF(r=0.675,P=0.008)and SDF-1α levels(r=0.587,P=0.027),while negatively with IP-10(r=-0.600,P=0.023)and MIG level(r=-0.640,P=0.014).Meanwhile,a positive correlation was found between HBsAg titer and IL12-p70 level(r=0.593,P=0.025),and a negative correlation between HBsAg titer and TNF-α level(r=-0.609,P=0.021).In addition,the serum total bilirubin level was positively correlated with the expression of SCGF-β(r=0.543,P=0.045).Conclusion Three differentially expressed cytokines and some cytokines related to HBV DNA level and HBsAg titer are found,which may provide new insights into the underlying immunological mechanism of HBV virus clearance caused by hepatitis flares.Meanwhile,it also provides potential biomarkers for HBsAg serological clearance in patients with severe hepatitis B.

Objective:To investigate the clinical and gene variant characteristics of PCDH19 gene related epilepsy, and improve the ability of clinicians in early disease identification. Methods:The clinical data of 3 PCDH19 gene related epilepsy patients admitted to Children′s Hospital Affiliated to Zhengzhou University from October 2018 to August 2023 diagnosed by gene detection were reviewed and analyzed. Results:All the patients are female, and the onset age of seizure ranged in their infancy. Seizures in clusters and fever sensitivity were observed in all patients, and were very hard to control by single-drug treatment. Proband 1 was seizure-free after 2 kinds of anti-epileptic drug treatment, but with mild degree of intellectual disability. Proband 2 had refractory epilepsy with severe degree of intellectual disability. Proband 3 was seizure-free after 2 kinds of anti-epileptic drug treatment and without intellectual disability. In the first family, the proband carried heterozygous c.369C>G variant in the PCDH19 gene which was identified as de novo after parental validation. In the second family, the proband carried c.1652T>A variant inherited from her mother. In the third family, the proband carried c.278G>A variant inherited from her father. The 3 mutations had not been reported in the Human Gene Mutation Database. Conclusions:PCDH19 gene related epilepsy is one special kind of X-linked inherited epilepsy syndrome characterized by seizures in clusters and sensitivity to fever. And gene detection can help with early diagnosis and make rational clinical strategies in time. The variants c.369C>G, c.1652T>A and c.278G>A have enriched the gene variant spectrum of PCDH19.

This article is an excerpt from the Expert Management of Congenital Portosystemic Shunts and Their Complications, which was published by the European Association for the Study of the Liver (EASL). Some of the most challenging systemic complications that often associated with congenital portosystemic shunts (CPSS) are liver nodules, pulmonary hypertension, endocrine abnormalities, and neurocognitive dysfunction. This article mainly provides expert clinical guidance for the management of liver nodules, pulmonary hypertension, and endocrine abnormalities, along with recommendations for shunt closure and follow-up.

Objective:Analyze the impact of smoking on the mortality and life expectancy of residents in Tianjin in 2019.Methods:Use mortality case-control study method to collect all cause of death cases of residents in Tianjin in 2019 for analysis. After adjusting for the 5-years-old age group, education level, and marital status, the smoking attributed deaths from different diseases of different genders, smoking attributed deaths in different age groups, and their impact on life expectancy were analyzed.Results:The total number of deaths in 2019 was 75 254, with 42 201 males (56.1%). Among male deaths, 3 215 (9.9%) were attributed to smoking, of which 2 157 (50.2%) lung cancer deaths were attributed to smoking; The risk of lung cancer death among smokers was 3.075 times higher than that of non-smokers (95% CI: 2.812-3.364); Among the 33 053 female deaths (43.9%), 1 396 (5.8%) were caused by smoking, with 744 (29.1%) lung cancer deaths attributed to smoking. The age group with the highest number of deaths attributed to smoking for women was the 75-<80 years old age group, followed by the 70-<75 and 80-<85 years old age groups. The age group with the highest proportion of deaths attributed to smoking for men was the 55-<60 years old age group. In addition, smoking accounts for more than 60% of deaths in the 60-<65, 45-<50, 55-<60, and 65-<70 years old age groups. In 2019, the loss of life expectancy attributed to smoking deaths among all residents in Tianjin was 1.13 years, with a loss of 1.15 years for males and 0.57 years for females. The expected life expectancy excluding deaths caused by smoking was 82.92 years, 80.77 years for males and 84.61 years for females. Conclusions:Smoking remains one of the important risk factors for death among residents. Promoting effective measures to reduce smoking rates is an effective way to increase life expectancy.

Objective:This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients.Methods:Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy.Results:A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P＜0.001). Conclusions:Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.

Objective:To explore the trends and distribution of liver cancer between sexes, ages, and urban-rural areas in Tianjin, China from 1999 to 2021, and provide data for targeted prevention and control strategies of liver cancer in Tianjin.Methods:Liver cancer mortality data of Tianjin during 1999-2021 were from the Tianjin population based mortality surveillance system maintained by the Tianjin Centers for Disease Control and Prevention (CDC), and the population data of permanent Tianjin residents were from Tianjin Municipal Public Security Bureau. Liver cancer mortality, years of life lost (YLL), years lived with disability (YLD), and disability adjusted life years (DALY) were calculated using the cause of death surveillance data collected by Tianjin Centers for Disease Control and Prevention. The distributions of these data among residents of different sexes, ages, and regions were analyzed. Segi's world standard population was used for standardization. Joinpoint regression was used for trend analysis on the mortality rate of liver cancer and the disease burden.Results:The liver cancer mortality rate in Tianjin decreased by 46.75% from 1999 to 2021, with distinct phased characteristics. From 1999 to 2010, the age-sex-standardized mortality rate (SMR) decreased from 12.62/100 000 to 11.64/100 000 with an annual percent change (APC) of -1.32% ( P=0.003). From 2010 to 2021, the SMR decreased from 11.64/100 000 to 6.72/100 000 (APC=-3.89%, P＜0.001). The age-sex-standardized DALY rates(SDR) decreased by 50.63% from 1999 to 2021, also with distinct phased characteristics. From 1999 to 2010, the SDR decreased from 388.67/100 000 to 349.38/100 000 (APC=-1.35%, P=0.002). From 2010 to 2021, the SDR decreased from 349.38/100 000 to 191.88/100 000 (APC=-4.43%, P＜0.001). The liver cancer mortality rate declined most rapidly in the age group under 45 years; the APC for those under 35 years was -5.07% ( P＜0.001), and for those aged 35-44 years, the APC was 0.63% ( P=0.707) and -8.21% ( P＜0.001) before and after 2007, respectively. Both SMR and SDR were significantly higher in males than in females ( P＜0.01). Both SMR and SDR were significantly higher in urban areas than in rural areas from 1999 to 2007 ( P＜0.05), but they became similar after 2008. Liver cancer DALY are predominantly YLL, accounting for 99%. The median age of liver cancer deaths in Tianjin during 1999-2021 was 64-68 years old, with males lower than females ( P＜0.05), and rural areas lower than urban areas ( P＜0.05), generally showing an increasing trend (1999-2014: APC=0.11%, P=0.047; 2014-2021: APC=0.51%, P=0.005). Conclusions:Liver cancer mortality rate and disease burden decreased from 1999 to 2021 in Tianjin, with an especially accelerated decline after 2010. Further efforts to reduce liver cancer mortality in Tianjin are needed, and special attention should be focused on the elderly, male, and rural residents.

Objective:To analyze the clinical and genetic characteristics of three Chinese pedigrees affected with Genetic epilepsy with febrile seizures plus (GEFS+ ).Methods:Three GEFS+ probands and their pedigree members presented at the Children′s Hospital of Zhengzhou University from January 2020 to December 2021 were selected as the study subjects. Clinical data of the pedigrees were collected. Whole exome sequencing was carried out for the probands, and Sanger sequencing was used to verify the candidate variants.Results:Proband 1 was a 3-year-and-2-month-old male with febrile seizure plus. His father, two aunts, grandmother, aunt grandmother, uncle grandfather, and paternal great-grandmother also had onset of febrile seizures at 1 ~ 2 years of age with remission before 6 years old. Proband 2 was a 1-year-and-4-month-old male with complex febrile seizure. His mother, maternal uncle, and maternal grandmother also had febrile seizures before 5 ~ 6 years of age. Proband 3 was a 3-year-and-11-month-old male with febrile seizure plus. His father and grandfather also had febrile seizures plus with remission at 7 ~ 8 years of age. Genetic testing revealed that proband 1 had harbored a paternally derived heterozygous SCN1A: c. 1613T>C variant, proband 2 had harbored a maternally derived heterozygous SCN1A: c. 2804A>G variant, and proband 3 had harbored a paternally derived heterozygous SCN1A: c. 1271T>C variant. All of the three variants were predicted as likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (PM1+ PM2_Supporting+ PP1+ PP3+ PP4). Conclusion:The c. 1613T>C, c. 2804A>G and c. 1271T>C variants probably underlay the pathogenesis of GEFS+ in these pedigrees.

Objective:This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients.Methods:Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy.Results:A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P＜0.001). Conclusions:Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.

Objective:To explore the trends and distribution of liver cancer between sexes, ages, and urban-rural areas in Tianjin, China from 1999 to 2021, and provide data for targeted prevention and control strategies of liver cancer in Tianjin.Methods:Liver cancer mortality data of Tianjin during 1999-2021 were from the Tianjin population based mortality surveillance system maintained by the Tianjin Centers for Disease Control and Prevention (CDC), and the population data of permanent Tianjin residents were from Tianjin Municipal Public Security Bureau. Liver cancer mortality, years of life lost (YLL), years lived with disability (YLD), and disability adjusted life years (DALY) were calculated using the cause of death surveillance data collected by Tianjin Centers for Disease Control and Prevention. The distributions of these data among residents of different sexes, ages, and regions were analyzed. Segi's world standard population was used for standardization. Joinpoint regression was used for trend analysis on the mortality rate of liver cancer and the disease burden.Results:The liver cancer mortality rate in Tianjin decreased by 46.75% from 1999 to 2021, with distinct phased characteristics. From 1999 to 2010, the age-sex-standardized mortality rate (SMR) decreased from 12.62/100 000 to 11.64/100 000 with an annual percent change (APC) of -1.32% ( P=0.003). From 2010 to 2021, the SMR decreased from 11.64/100 000 to 6.72/100 000 (APC=-3.89%, P＜0.001). The age-sex-standardized DALY rates(SDR) decreased by 50.63% from 1999 to 2021, also with distinct phased characteristics. From 1999 to 2010, the SDR decreased from 388.67/100 000 to 349.38/100 000 (APC=-1.35%, P=0.002). From 2010 to 2021, the SDR decreased from 349.38/100 000 to 191.88/100 000 (APC=-4.43%, P＜0.001). The liver cancer mortality rate declined most rapidly in the age group under 45 years; the APC for those under 35 years was -5.07% ( P＜0.001), and for those aged 35-44 years, the APC was 0.63% ( P=0.707) and -8.21% ( P＜0.001) before and after 2007, respectively. Both SMR and SDR were significantly higher in males than in females ( P＜0.01). Both SMR and SDR were significantly higher in urban areas than in rural areas from 1999 to 2007 ( P＜0.05), but they became similar after 2008. Liver cancer DALY are predominantly YLL, accounting for 99%. The median age of liver cancer deaths in Tianjin during 1999-2021 was 64-68 years old, with males lower than females ( P＜0.05), and rural areas lower than urban areas ( P＜0.05), generally showing an increasing trend (1999-2014: APC=0.11%, P=0.047; 2014-2021: APC=0.51%, P=0.005). Conclusions:Liver cancer mortality rate and disease burden decreased from 1999 to 2021 in Tianjin, with an especially accelerated decline after 2010. Further efforts to reduce liver cancer mortality in Tianjin are needed, and special attention should be focused on the elderly, male, and rural residents.