Objective:Exploring the effect of radiofrequency ablation treatment to restore sinus rhythm on the improvement of functional mitral regurgitation (FMR) and cardiac structure in patients with atrial fibrillation combined with moderate or severe FMR, compared with drug therapy alone.Methods:This retrospective cohort study consecutively enrolled patients diagnosed with persistent atrial fibrillation and moderate or severe FMR who were admitted to the Third Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2021. Forty-eight patients who were treated with radiofrequency ablation and maintained sinus rhythm were enrolled in the ablation group, and 63 patients who were treated with medication alone during the same period were in the medicine group. Patients in the ablation group and medicine group were matched in a 1∶1 ratio using a propensity score, and 41 patients were finally included in each of the 2 groups. All patients reexamined echocardiography after 3-month of treatment. The proportion of patients with FMR improvement and the differences in changes of cardiac structural and functional parameters were compared between groups.Results:After propensity score matching, the ablation group was aged (69.3±7.1) years with 21 males (51.2%) and the medicine group was aged (71.3±9.4) years with 21 males (51.2%). The echocardiography after 3-month of treatment showed the rate of FMR improvement was significantly higher in the ablation group than in the medicine group (19 (46.3%) vs. 33 (80.5%), P<0.001), and patients in the ablation group showed a significant decrease in FMR extent (Δmitral regurgitation area: (-1.30±2.64) cm 2 vs. (-3.55±2.50) cm 2, P<0.001), left atrial size (Δleft atrial diameter: (-0.17±3.78) mm vs. (-2.46±4.01) mm, P=0.009) and E/e′ (ΔE/e′:-2.54±7.34 vs.-6.34±7.08, P=0.021) compared with the medicine group. There was also a significant decrease in left ventricular size (Δleft ventricular end diastolic diameter: (-3.12±6.62) mm vs. (-0.73±3.62) mm, P=0.046) and significant increase in left ventricular ejection fraction (Δleft ventricular ejection fraction: (2.73±9.69) % vs. (-0.93±5.41) %, P=0.038) in ablation group. Conclusion:Performing radiofrequency ablation to restore sinus rhythm can effectively reduce the severity of mitral regurgitation and improve left atrial and left ventricular remodeling and cardiac function in patients with atrial fibrillation and FMR.

Objective:Hereditary neuropathy with liability to pressure palsy(HNPP)is a rare autosomal dominant peripheral neuropathy,usually caused by heterozygous deletion mutations in the peripheral myelin protein 22(PMP22)gene.This study aims to investigate the clinical and molecular genetic characteristics of HNPP. Methods:HNPP patients in the Department of Neurology at Third Xiangya Hospital of Central South University from 2009 to 2023 were included in this study.The general clinical data,nervous electrophysiological and molecular genetic examination results were collected and analyzed.Molecular genetic examination was to screen for deletion of PMP22 gene using multiplex ligation-dependent probe amplification(MLPA)after extracting genomic DNA from peripheral blood;and if no PMP22 deletion mutation was detected,next-generation sequencing was used to screen for PMP22 point mutations.The related literatures of HNPP were reviewed,and the clinical and molecular genetic characteristics of HNPP patients were analyzed. Results:A total of 34 HNPP patients from 24 unrelated Chinese Han families were included in this study,including 25 males and 9 females.The average age at illness onset was 22.0 years.Sixty-two point five percent of the families had a positive family history.Among them,30 patients had symptoms of peripheral nerve paralysis.Patients often presented with paroxysmal single limb weakness with(or)numbness(25/30),and some patients had paroxysmal unilateral recurrent laryngeal nerve(vagus nerve)paralysis(2/30).Physical examination revealed muscle weakness(23/29),hypoesthesia(9/29),weakened or absent ankle reflexes(20/29),distal limb muscle atrophy(8/29)and high arched feet(5/29).Most patients(26/30)could fully recover to normal after an acute attack.Thirty-one patients in our group underwent nervous electrophysiological examination,and showed multiple demyelinating peripheral neuropathies with both motor and sensory nerves involved.Most patients showed significantly prolonged distal motor latency(DML),mild to moderate nerve conduction velocity slowing,decreased amplitude of compound muscle action potential(CMAP)and sensory nerve action potential(SNAP),and sometimes with conduction block.Nerve motor conduction velocity was(48.5±5.5)m/s,and the CMAP amplitude was(8.4±5.1)mV.Nerve sensory conduction velocity was(37.4±10.5)m/s,and the SNAP amplitude was(14.4±15.2)μV.There were 24 families,23 of whom had the classical PMP22 deletion,the last one had a heterozygous pathogenic variant in the PMP22 gene sequence(c.434delT).By reviewing clinical data and genetic testing results of reported 1 734 HNPP families,we found that heterozygous deletion mutation of PMP22 was the most common pathogenic mutation of HNPP(93.4%).Other patients were caused by PMP22 small mutations(4.0%),PMP22 heterozygous gross deletions(0.6%),and PMP22 complex rearrangements(0.1%).Thirty-eight sorts of HNPP-related PMP22 small mutations was reported,including missense mutations(10/38),nonsense mutations(4/38),base deletion mutations(13/38),base insertion mutations(3/38),and shear site mutations(8/38).HNPP patients most often presented with episodic painless single nerve palsy.Common peroneal nerve,ulnar nerve,and brachial plexus nerve were the most common involved nerves,accounting for about 75%.Only eighteen patients with cranial nerve involved was reported. Conclusion:Heterozygous deletion mutation of PMP22 is the most common pathogenic mutation of HNPP.Patients is characterized by episodic and painless peripheral nerve paralysis,mainly involving common peroneal nerve,ulnar nerve,and other peripheral nerves.Nervous electrophysiological examination has high sensitivity and specificity for the diagnosis of HNPP,which is manifested by extensive demyelinating changes.For patients with suspected HNPP,nervous electrophysiological examination and PMP22-MLPA detection are preferred.Sanger sequencing or next generation sequencing can be considered to detect other mutations of PMP22.

Objective:To explore the lag effect and correlation between daily average temperature and the incidence of other infectious diarrhea in Hebei Province.Methods:The data of meteorological factors (including temperature and average daily temperature) and the daily incidence of other infectious diarrhea in Zhangjiakou City, Chengde City, Tangshan City, Qinhuangdao City, Baoding City, Langfang City, Cangzhou City, Shijiazhuang City, Hengshui City, Xingtai City, and Handan City in Hebei Province from 2017 to 2020 were collected. Eleven prefecture-level cities were divided into four regions, including east, north, middle and south regions. Distributed lag non-linear model was applied to examine the non-linear associations and the lag effect of daily mean temperature on daily incidence of other infectious diarrhea. Meanwhile, the cold and hot effects were used to estinuate the lag-response relationship on the incidence of other infectious diarrhea.Results:A total of 231 008 cases of other infectious diarrhea were reported in Hebei Province. The seasonal distribution was obvious, showing a bimodal distribution of large peaks in summer and small peaks in winter. An inverse S-shaped association between average daily temperature and cumulative risk ratio ( RR) of other infectious diarrhea was observed in Hebei Province. Both high temperature (higher than 27.50 ℃) and low temperature (less than 13.67 ℃) could increase the risk of other infectious diarrhea. When the temperature was lower than 13.00 ℃, the lag time and RR had a U-shaped association (lag four to seven days, 23 to 30 days). Meanwhile, when it was higher than 13.00 ℃, it had an inverted U-shaped association (lag 5 to 21 days). A comparison of four regions of Hebei Province showed that the lag time from south to north was extended from six days to 30 days at low temperature effects with temperature P5=-7.24 ℃. When the temperature getting hot ( P95=28.25 ℃), the risk occurred at lag 0 days, and the lag time gradually got short from north to south. Thus, the high temperature effect reached maximum quickly with a relative short duration. Conclusions:The inverse S-shaped non-linear association between daily average temperature and the incidence of other infectious diarrhea in Hebei Province is observed. Both low temperature and high temperature are associated with increased risk of other infectious diarrhea. But the impact of low temperature is more notable, which has a relative long duration.

Objective:To understand the epidemic characteristics of influenza A (H1N1)pdm09 and hemagglutinin (HA) gene mutations in Hebei province from 2017 to 2020, in order to provide scientific basis for the prevention and control of influenza.Methods:The analysis was conducted on the data of Hebei province, which was down loaded from the Chinese National Influenza Surveillance Network from April 2017 to March 2020, and 37 influenza A (H1N1)pdm09 strains were selected for sequencing and evolutionary analysis of HA gene.Results:A total of 57 670 throat swabs from influenza like illness (ILI) patients in Hebei province were detected, and 8 569 samples were positive for the viral nucleic acid, with the positive rate of 14.86%, influenza A (H1N1)pdm09 accounted for 40.52% (3 472/8 569). The cases were detected throughout the whole 11 regions of Hebei province. All age groups were infected by influenza A (H1N1) virus, and the highest detection rate was in the 25- year age group, the peak detection rate was in winter and spring seasons. The HA genes of 37 strains of influenza A (H1N1) virus belong to 6B.1 branch, and the amino acid homology is from 97.31% to 100.00%. S74R, S164T, S183P and I295V were the major amino acid variation sites in 2017-2018 influenza season. S183P, H126Y, N129D, T185I, L233I and N260D were the major amino acid variation sites of epidemic strains in 2018-2019 influenza season. The variation sites of D187A and Q189E of epidemic strains were found in 2019-2020 influenza season.Conclusions:The prevalence of influenza A(H1N1) pdm09 in Hebei province has an obvious seasonality. The HA gene and its encoded amino acid have been mutating gradually. The strains which were isolated recently were clustered with the 2020-2021 season northern hemisphere vaccine strain A/Guangdong-Maonan/SWL1536/2019.

Objective:To understand the influence and lag effect of meteorological factors on the incidence of hand, foot and mouth disease (HFMD) in Shijiazhuang.Methods:The daily incidence data of HFMD in Shijiazhuang during 2017-2019 were collected from Chinese Information System for Disease Control and Prevention. The hourly meteorological data were collected form meteorological stations of Shijiazhuang of Chinese meteorological data network. The distributed lag nonlinear model was built for statistical analysis by software R 3.6.2.Results:When the daily average temperature was 15-26 ℃, the risk of incidence of HFMD increased at lag 3-6 days. However, the risk was highest when the temperature was 25 ℃ at lag 3 days ( RR=1.03,95% CI:1.00-1.06). When the daily average relative humidity was more than 80%, the risk of incidence of HFMD increased at lag 5-18 days. However, the risk was highest at lag 9 days ( RR=1.04, 95% CI: 1.02-1.06).When the daily average air pressure ranged from 999 hPa to 1 007 hPa, the risk of incidence of HFMD increased at lag 5-8 days. However, the risk was highest at lag 6 days ( RR=1.01, 95% CI: 1.00-1.02).When the daily average precipitation ranged from 15 to 32 mm, the risk of incidence of HFMD increased at lag 3-18 days. However, the risk was highest at lag 6 days ( RR=1.11, 95% CI: 1.02-1.19). Conclusions:Meteorological factors increased the risk of incidence of HFMD such as higher daily average temperature (15-26 ℃), higher daily average humidity (>80%), lower daily average air pressure (999-1 007 hPa) and higher daily average precipitation (15-32 mm) in Shijiazhuang during 2017-2019. They were all correlated with the incidence of HFMD with certain lag days. It is suggested to use these meteorological indicators for the early warning of HFMD.

Objective:To understand the epidemiological characteristics of influenza in Hebei Province from 2018 to 2019, and to analyze the characteristics and variation of hemagglutinin(HA) gene of influenza B-Victoria(BV) strains.Methods:Throat swab specimens of influenza-like cases within 3 days of fever were collected from 28 sentinel hospitals in Hebei province, meanwhile, The surveillance data was collected by the Chinese National Influenza Surveillance Network from April 2018 to March 2019, Throat swab specimens were collected from patients with influenza-like symptoms in sentinel hospitals, and tested by RT-PCR and virus isolation. 14 influenza B-Victoria strains from different regions were selected to sequence HA gene, Phylogenetic tree and the molecular characteristics were analyzed by DNASTAR 7.0 and Mega-X software.Results:From 2018 to 2019, A total of 99 266 cases of influenza-like illness (ILI) were detected from 4 689 103 cases by 28 influenza sentinel hospitals in Hebei Province, the visit percentage of ILI was 2.12%. During the period, 18 730 samples were detected, and 2 752(14.69%) samples were positive tested by RT-PCR, the peak was in the third week of 2019(44.92%), In the early stage of epidemic season, Influenza A(H1N1)pdm09 virus was the main type, while BV virus was the main type in the late stage. HA gene sequence analysis showed that the 14 BV viruses belonged to 162-164 amino acid deletion strains, the amino acid homology between HA sequences was 97.16%-100.00%, and 97.16%-98.95% compared with the vaccine strain B/Colorado/06/2017 recommended by WHO. Compared with the vaccine strains, 14 strains involved 11 amino acid site mutations.Conclusion:Influenza was prevalent in winter and spring in Hebei province from 2018 to 2019, Multiple mutations in antigenic sites of BV viruses might be related to the outbreaks.

Objective:To understand the epidemiological characteristics of influenza in Hebei Province from 2018 to 2019, and to analyze the characteristics and variation of hemagglutinin(HA) gene of influenza B-Victoria(BV) strains.Methods:Throat swab specimens of influenza-like cases within 3 days of fever were collected from 28 sentinel hospitals in Hebei province, meanwhile, The surveillance data was collected by the Chinese National Influenza Surveillance Network from April 2018 to March 2019, Throat swab specimens were collected from patients with influenza-like symptoms in sentinel hospitals, and tested by RT-PCR and virus isolation. 14 influenza B-Victoria strains from different regions were selected to sequence HA gene, Phylogenetic tree and the molecular characteristics were analyzed by DNASTAR 7.0 and Mega-X software.Results:From 2018 to 2019, A total of 99 266 cases of influenza-like illness (ILI) were detected from 4 689 103 cases by 28 influenza sentinel hospitals in Hebei Province, the visit percentage of ILI was 2.12%. During the period, 18 730 samples were detected, and 2 752(14.69%) samples were positive tested by RT-PCR, the peak was in the third week of 2019(44.92%), In the early stage of epidemic season, Influenza A(H1N1)pdm09 virus was the main type, while BV virus was the main type in the late stage. HA gene sequence analysis showed that the 14 BV viruses belonged to 162-164 amino acid deletion strains, the amino acid homology between HA sequences was 97.16%-100.00%, and 97.16%-98.95% compared with the vaccine strain B/Colorado/06/2017 recommended by WHO. Compared with the vaccine strains, 14 strains involved 11 amino acid site mutations.Conclusion:Influenza was prevalent in winter and spring in Hebei province from 2018 to 2019, Multiple mutations in antigenic sites of BV viruses might be related to the outbreaks.

Objective:To report the genetic and clinical features of sorbitol dehydrogenase (SORD) gene-related Charcot-Marie-Tooth disease (CMT) in Chinese population.Methods:Fifty-seven undiagnosed sporadic or autosomal recessive (AR) inherited CMT2 families were collected from the Department of Neurology of the Third Xiangya Hospital from 2009 through 2018 .Polymerase chain reaction combined with Sanger sequencing were used to detect the mutations of SORD gene, and the relative clinical features were summarized. Results:The homozygous SORD gene hot spot mutation c.757delG (p. Ala253GlnfsTer27) was detected in four sporadic patients, accounting for about 7% of the total. Two patients with CMT2 phenotype were characterized by progressive lower limb weakness and atrophy with electromyogram changes of axonal degeneration in both motor and sensory nerves. Two patients with distal hereditary motor neuropathy (dHMN) phenotype exhibited progressive lower limb weakness and atrophy with electromyogram changes of axonal degeneration in motor nerves only. The age of onset was between five and 16 years, and the CMT neuropathy score was 2-9.Conclusions:The homozygous hot spot mutation of SORD gene (c.757delG, p.Ala253GlnfsTer27), and related childhood or adolescence onset, mildly affected CMT2/dHMN phenotypes are firstly reported in Chinese population. SORD gene-related CMT might be the most common subtype of AR-CMT2.

Dengue viruses(DENV) are seriously affected by cell autophagy in intracellular replication,transmission between host,and the pathogenic mechanism.Here,the latest research progress of complex interplay between DENV and cell autophagy were reviewed in this paper.Autophagy,a cellular procedural protein degradation pathway generally possessed by all eukaryotes plays a key role in response to outside pressure and maintaining cellular homeostasis.This catabolic pathway also promotes cell survival against the invasion of pathogens such as various viruses.However,autophagy plays an opposite role in the replication of DENV.Autophagy not only provides a replication site for viruses to replicate,but also provides a source of energy for this process.Cell autophagy also participates in the pathogenesis of some DENV infection.In short,autophagy contributes to the replication of DENV.

Objective:To understand the epidemiological characteristics of cases with severe and fatal hand, foot, and mouth disease (HFMD) caused by other enterovirus in Hebei province, 2013-2017. Genetic characteristics of the main pathogen cosackie virus A6 (CoxA6) were also analyzed to further clarifying the characteristics and rules of genetic evolution on this virus.Methods:Descriptive epidemiological methods were used to analyze the distribution of severe and fatal cases with HFMD caused by other enterovirus in Hebei, 2013-2017. The VP1 sequences of CoxA6 were phylogenetically analyzed, using the Mega 5.2 software package.Results:A total of 86 severe and fatal cases with HFMD caused by other enterovirus were reported, accounting for 1.12%, comparing to all the HFMD caused by other enterovirus. Cases began to rise in April, and peaked in May-July. 65.12% of the cases occurred in children between 1 and 5 years old. The sex ratio between male and female was 1.39∶1. A total of 93.02% of the cases were children outside the child care settings. A total of 39 positive strains were identified, with positive isolation rate as 45.35%. Phylogenetic analysis on the VP1 sequences of CoxA6 strains in this study revealed that CoxA6 strains belonged to sub-genotypes D3a and D3b.Conclusions:Severe and fatal HFMD cases that caused by other enterovirus in Hebei province was with seasonal feature, consistent with the overall trend of this disease, 2013-2017. No new evolutionary branch appeared in the CoxA6 strain.