Objective To investigate the value of L3 skeletal muscle index(L3-SMI)combined with interleukin-6(IL-6)and activin A in predicting early-stage pancreatic cancer cachexia.Methods A total of 74 patients with pancreatic cancer who were diagnosed in Hebei Medical University Forth Hospital from July 2020 to July 2023 were enrolled,and according to the presence or absence of cachexia after admission,the patient were divided into cachexia group with 58 patients and non-cachexia group with 16 patients.The levels of L3-SMI,IL-6,and activin A were observed within 48 hours after admission.The independent-samples t test was used for comparison of normally distributed continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.A multivariate Logistic regression analysis was used to investigate the influencing factors for pancreatic cancer cachexia;the receiver operating characteristic(ROC)curve was used to analyze the value of L3-SMI,IL-6,and activin A alone or in combination in predicting pancreatic cancer cachexia,and the Z test was used for comparison of the area under the ROC curve(AUC).Results Compared with the non-cachexia group,the cachexia group had a significantly higher level of L3-SMI and significantly lower serum levels of IL-6 and activin A(t=8.649,3.049,and 8.100,all P＜0.05).The multivariate logistic analysis showed that L3-SMI(odds ratio[OR]=0.266,95%confidence interval[CI]:0.103-0.683,P＜0.05),serum IL-6(OR=4.158,95%CI:1.368-12.333,P＜0.05),and activin A(OR=5.124,95%CI:1.550-16.939,P＜0.05)were influencing factors for pancreatic cancer cachexia.L3-SMI,IL-6,and activin A alone had a significantly lower AUC than the combination of the three indicators in predicting pancreatic cancer cachexia(0.851/0.752/0.791 vs 0.946,Z=-2.841,-2.552,and-2.647,all P＜0.001),and the combination of the three indicators had the highest sensitivity(90.9%),specificity(87.8%)and Youden index(0.788).Conclusion L3-SMI combined with serum IL-6 and activin A has a good value in predicting early-stage pancreatic cancer cachexia.

Objective:To summarize the genetic and phenotypic features of MORC family CW-type zinc finger 2 (MORC2) gene-related neuropathy in Chinese patients. Methods:The clinical and whole exome sequencing data of MORC2 gene-related neuropathy families with a definitive genetic diagnosis were collected from the Third Xiangya Hospital of Central South University between 2010 and 2023. Literature involving Chinese families with MORC2 gene-related neuropathy was extensively reviewed to provide a comprehensive summary of the genetic and phenotypic spectrum of the disease. Results:A total of 10 families with MORC2 gene-related neuropathy were identified and analyzed. Six different heterozygous pathogenic variants in the MORC2 gene were observed among these families, including the novel variant c.1330G>C (p.G444R) that had not been previously reported. Six families presented as axonal Charcot-Marie-Tooth disease caused by variants in the MORC2 gene (CMT2Z) phenotype with childhood or adult onset, and carried variants c.754C>T (p.R252W), c.1199A>G (p.Q400R), c.1330G>C (p.G444R), or c.1396G>A (p. D466N); 3 families manifested as severe spinal muscular atrophy (SMA)-like phenotype with infantile onset, all carried c.260C>T (p.S87L); 1 family carried c.1181A>G (p.Y394C), presented as DIGFAN syndrome phenotype with infantile onset combined with mental and motor retardation. Systematic review showed 8 Chinese families carried pathogenic variants of the MORC2 gene, among which 5 families were associated with the CMT2Z phenotype, carrying c.754C>T (p.R252W), c.1079A>G (p.E360G), c.1220G>A (p.C407Y), or c.1397A>G (p.D466G); 1 family was associated with SMA-like phenotype, carrying c.260C>T (p.S87L); and 2 families were associated with DIGFAN syndrome, carrying c.79G>A (p.E27K) and c.292G>A (p.G98R). Conclusions:A novel pathogenic variant c.1330G>C (p.G444R) of the MORC2 gene associated with the CMT2 phenotype is reported. Eleven pathogenic variants of the MORC2 gene have been reported in the Chinese patients to date, and c.754C>T(p.R252W) may be the most common. Patients with MORC2 gene-related neuropathy carrying different variants present with significant clinical heterogeneity, manifesting as CMT2Z, early-onset severe SMA-like myasthenia, or DIGFAN syndrome.

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 analyze the main syndrome types, medication rules, and core prescription characteristics of traditional Chinese medicine (TCM) in the treatment of metabolism-associated fatty liver disease (MAFLD), and to predict the anti-MAFLD mechanism of core formula, so as to provide references for the clinical application of TCM and the development of new drugs. [Methods] Literature research on TCM in treating MAFLD was retrieved from China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang Database since the establishment of the database to July 2022. Excel 2019 and Chinese Medicine Inheritance Computing Platform (V3.0) were used for frequency analysis, association rule analysis, and cluster analysis of effective prescriptions. The key components, targets, and action pathways of anti-MAFLD core formulas were predicted by network pharmacology. Finally, the interactions between the obtained core components and their core targets were verified reversely by molecular docking technology. [Results] A total of 218 articles were screened and selected, including 352 prescriptions, involving 270 traditional Chinese herbs. The drugs were used a total of 3 901 times, and a total of 10 915 cases were collected, among which the prevalence rate was higher in males. The main types of TCM syndrome included intermingled phlegm and blood stasis syndrome, liver depression and spleen deficiency syndrome, and damp-heat in liver and gallbladder syndrome, among which Shanzha (Crataegi Fructus), Danshen (Salviae Miltiorrhizae Radix et Rhizoma), Fuling (Poria), Zexie (Alismatis Rhizoma), Chaihu (Bupleuri Radix), and Baizhu (Atractylodis Macrocephalae Rhizoma) were the most frequently used. The properties of Chinese medicine primarily encompassed thermal characteristics, with a predominant emphasis on cold and warm; the flavors of herbs were predominantly characterized by bitterness and sweetness, while the majority exhibited tropism towards the spleen and liver meridians. The drugs were primarily classified based on their efficacy in tonifying deficiencies, promoting diuresis and moistening, enhancing blood circulation and removing blood stasisheat-clearing, etc. The association rules were employed to derive a set of 20 core drug pairs, while cluster analysis was utilized to identify three distinct groups of core drug combinations. Network pharmacological showed that the main components of the core formula “Shanzha (Crataegi Fructus) - Danshen (Salviae Miltiorrhizae Radix et Rhizoma) - Zexie (Alismatis Rhizoma) - Chaihu (Bupleuri Radix) - Fuling (Poria)” in the treatment of MAFLD were quercetin, apigenin, puerarin, luteolin, ursolic acid, kaempferol, tanshinone IIA, emodin, paeonol, etc., which involved RAC-alpha serine/threonine-protein kinase 1 (AKT1), cellular tumor antigen p53 (TP53), interleukin (IL)-6, IL-1β, signal transducer and activator of transcription 3 (STAT3), epidermal growth factor receptor (EGFR), peroxisome proliferative activated receptor gamma (PPARG), and other key targets. The molecular docking results showed that the core components had good binding to lipid and atherosclerosis, and phosphatidylinositol 3 kinase (PI3K)/AKT signaling pathway-associated proteins. [Conclusion] The main principles of TCM for the treatment of MAFLD involve soothing the liver and strengthening the spleen, eliminating phlegm and dampness, clearing heat and dampness, as well as promoting blood circulation and removing blood stasis. The core formula may exert anti-MAFLD effects mediated through multiple components, targets, and signaling pathways. This study establishes a theoretical foundation for the clinical application of TCM in the treatment of MAFLD, and serves as a reference for further exploration of new drugs against MAFLD.

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 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 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 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.