[Research progress on drug resistance of anti-varicella-zoster virus drugs].

Varicella-zoster virus (VZV) causes chickenpox when it first infects humans, and the virus may reactivate in adulthood and cause herpes zoster (HZ). Broad-spectrum antiviral drugs are one of the treatments for varicella and herpes zoster, but the emergence of drug resistance poses many challenges to this treatment and increases the burden of disease on patients. This paper discusses the resistance mechanisms, resistance sites and resistance detection methods of anti-VZV drugs in order to help further research on new anti-VZV targets, new drugs and monitoring of resistance to existing drugs.

[Clinical research progress of human respiratory syncytial virus vaccine].

Human respiratory syncytial virus (HRSV) is one of the main pathogen causing severe acute lower respiratory tract infections in infants and the elderly, with high incidence rate and mortality worldwide. Vaccine is one of the important measure to prevent infection, transmission and severe disease of HRSV, but currently there is no officially approved preventive vaccine for prevention of HRSV in the world. This paper reviews and analyzes the current research and development progress of HRSV vaccine, summarizes the design routes of different types of HRSV preventive vaccines, and discusses the difficulties and challenges in vaccine research and development, in order to provide reference for the research and development of HRSV vaccine and the development of clinical trials.

[Research progress on the burden of respiratory syncytial virus infection in the elderly].

Human Respiratory Syncytial Virus (HRSV) is a serious threat to the population health. The elderly are one of the susceptible populations. The prevalence of HRSV in the elderly is generally higher than that in other age groups except children, which has gradually attracted attention in recent years. This paper reviewed the prevalence, common complications and major complications of HRSV in the elderly, briefly expounded the economic burden of HRSV infection, and proposed that attention should be paid to the disease burden of the elderly after HRSV infection, timely treat common complications, so as to reduce the occurrence of adverse survival outcomes and provide scientific evidence for the prevention and control of HRSV infection in the elderly.

[Genetic analysis of varicella-zoster virus in patients with viral anterior uveitis].

Objective: To analyze the intraocular varicella-zoster virus (VZV) infection and genetic characteristics in patients clinically diagnosed with viral anterior uveitis. Methods: A total of 83 aqueous humor samples were collected from patients clinically diagnosed with viral anterior uveitis infection in China from June 2018 to July 2019. The positive samples infected with VZV were screened by real time polymerase chain reaction, and the single nucleotide polymorphisms on the open reading frames 22, 38 and 62 of the positive samples were amplified and analyzed. According to the gene characteristics of the amplified target fragment, the vaccine strain and wild strain (8 vaccine strains and the rest were wild strains) were identified to determine the genotype. Results: There were 83 patients (31 females and 52 males) with viral uveitis infection, whose mean age was 51.0 (45.5, 61.0) (range: 15-83) years,, and, of which 57.8% (48 cases) were infected with viral uveitis over 50 years of age. None of the patients had a history of varicella or herpes zoster vaccination. Of the samples of 83 patients infected with viral uveitis, 57 (68.6%) were positive for VZV. Among them, 14 were successfully amplified to obtain the target fragment gene sequences, all of which were wild strains by analysis, and belonged to Clade2 of genotype, which was the same as the VZV vaccine strain types infected by varicella and herpes zoster patients in China. Conclusion: From 2018 to 2019, VZV infection in Chinese patients with viral anterior uveitis was a wild strain, and the genotype belonged to Clade2 as the vaccine strain, which was the same as the main epidemic genotype of VZV infection in Chinese patients with varicella and herpes zoster.

[Characterization analysis of gM, gL genes of varicella zoster virus in six provinces of China].

Objective: To analyze the genetic characterization of glycoprotein M(gM.),glycoprotein L(gL) of varicella zoster virus. Methods: According to the program of "Ministry of Science and Technology of China" , Based on the 12 suspected VZV patients monitored in Beijing (1 case), Shanghai (5 cases), Jilin (2 cases), Qinghai (1 case), Guangdong (2 case) and Sichuan (case) in 2007-2015. A total of 12 Vesicle fluid and throat swab samples were collected. Positive samples were identified by Agarose gel electrophoresis and two glycoprotein genes were amplified by polymerase chain reaction (PCR). Nucleotide sequences were determined and analyzed by PCR amplification of VZV positive specimens V-OKA-BK of the domestic varicella attenuated live vaccine and the Varilrix-1 of the imported attenuated live vaccine. Nucleotide sequences of VZV positive specimens, vaccine strains (V-OKA-BK, varilrix-1) and GenBank foreign wild strains (41 strains), parent strains (P-oka), vaccine strains (V-oka, Varilrix, Varivax) were compared using BioEdit and MEGA 5.0. Results: 12 specimens were VZV positive. Compared with the vaccine strains and the parent strains, the GM gene of 1 positive specimen had radical mutation at 86686 sites, which resulted in amino acid mutation, 5 positive specimens had base mutation at 87844 sites, and 30 strains of foreign wild strains had the same variation at 87 844 sites. 1 positive specimens of gL gene in 101245 sites had base mutation, and led to amino acid mutation, 6 positive specimens at 101624, 101625, 101626 sites had base of loss and the foreign wild strains in these 3 sites had the same variation. Compared with the vaccine strains, the nucleotide and amino acid homology of gM of 12 VZV positive specimens were 99.2%-100% and 98.2%-100%, respectively, and gL of those were 99.3%-100% and 98.6%-100%, respectively. Compared with 41 strains of foreign wild strains, homology of gM's nucleotides and amino acid were 99.3%-100% and 98.5%-100%, respectively; 99.1%-100% and 98.6%-100% for gL. The results of phylogenetic analysis showed that 7 VZV positive samples were on the same branch with 4 vaccine strains and p-oka strain. Based on gL, 12 VZV positive samples were on the same branch as the vaccine strains and p-oka strain. Conclusion: This study demonstrates that the genes of gM, gL are highly conserved and remain stable immunogen, which may be involved in the attenuation of VZV and need to be further researched.

[Genetic characterization of varicella zoster virus in Jilin province in 2014, China].

OBJECTIVE: To clarify the genotype of wild-type strains of varicella zoster virus (VZV) in Jilin province in 2014, and to discriminate between v-Oka vaccine strains and wild-type strains. METHODS: Vesicle fluid and throat swab samples were collected from 13 individuals with suspected VZV in Jilin province from January to December 2014. Viral DNA was extracted, the fragments of 15 open reading fragments (ORFs) were amplified by polymerase chain reaction (PCR), and viral genotypes were determined by single nucleotide polymorphisms (SNP). PCR restriction fragment length polymorphism (RFLP) was used to distinguish between wild-type strains and v-Oka vaccine strains. The results were analyzed with MEGA5 software, using the VZV reference strain sequences from GenBank. RESULTS: The 13 suspected samples included 5 males and 8 females, aged 11-27 years (mean: (16.69±5.48) years). Sampling was performed on days 0 to 3 of suspected infection. VZV strains were detected in 8 samples, all belonging to Clade 2. There was a synonymous mutation (T>C) in SNP18082 compared with the v-Oka vaccine strain. Analysis of PCR-RFLPs showed that all 8 positive samples were wild-type strains (PstⅠ(+)BglⅠ(+)SmaⅠ(-)). CONCLUSIONS: The study revealed that the VZV strains circulating in Jilin province in 2014 were wild-type strains belonging to Clade 2.

c-Met and RON expression levels in endometrial adenocarcinoma tissue and their relationship with prognosis.

OBJECTIVE: To investigate the potential relevance of c-Met and RON gene expression in patients with adenocarcinoma of the endometrium and analyze the relationships among the c-Met and RON expression, clinicopathological characteristics, and patient survival. MATERIALS AND METHODS: The study included 60 cases diagnosed with endometrial adenocarcinoma with more than five-years follow-up. Total RNA from formalin-fixed paraffin-embedded tissues of 60 adenocarcinomas of the endometrium and normal endometrium tissues were isolated for c-Met and RON quantitative analysis by real-time real-time polymerase chain reaction (RT-PCR). RESULTS: The c-Met and RON expression in endometrial adenocarcinoma was significantly higher than that in normal endometrial tissues (p < 0.01), with average up-regulated levels of 3.94 ± 1.88 and 2.74 ± 0.88, respectively. Moreover, high c-Met expression was significantly correlated with the histological stage (p = 0.017), and high RON expression was related to histological stage (p = 0.035), muscle invasion (p = 0.006), and lymph node metastasis (p = 0.018). Multivariate Cox regression analysis revealed that the co-expression of c-Met and RON was an independent prognostic factor for adenocarcinoma of the endometrium and was significantly associated with decreased overall survival (HR = 3.571, p = 0.014). CONCLUSION: The co-expression of c-Met and RON is associated with a poor prognosis in endometrial adenocarcinoma and is an independent prognostic marker for endometrioid adenocarcinoma.

[Genetic characterization of varicella-zoster virus in people aged 20 years and under in Yichang City of Hubei Province, 2019-2020].

Objective: To analyze the genetic characteristics of varicella-zoster virus (VZV) in people aged 20 years and under in Yichang City of Hubei Province from 2019 to 2020. Methods: Based on the Yichang Health Big Data Platform, we investigated cases 20 and under clinically diagnosed as herpes zoster in three hospitals from March 2019 to September 2020. Collecting vesicle fluid and throat swab samples of the cases and completing questionnaires to obtain basic information. Real-time fluorescent quantitative PCR was used for positive identification of the virus. PCR amplification of VZV's open reading frame (ORF) and sequencing of the products to determine the VZV genotype. Analyze mutations at some specific single nucleotide polymorphism (SNP) sites. Results: Among 46 cases of herpes zoster, the male to female ratio was 1.3∶1 (26∶20) and the age ranged from 7 to 20 years old. Fifteen cases had been vaccinated against varicella, including 13 and 2 cases of 1 and 2 doses, respectively. VZV strains were detected in 34 samples (73.91%), all belonging to Clade 2. Phylogenetic tree analysis of the nucleotide of ORF22 showed, compared with Clade 2 referenced strains, the sequence matching degree of nucleotide for all 34 samples was 99.0% to 100.0%. Conclusion: The main VZV strain causing herpes zoster in people aged 20 years and under in Yichang from 2019 to 2020 was Clade 2.

Lung cancer patients with a previous extra-pulmonary malignancy should not be considered homogeneous: a clinicopathological analysis of 3530 surgical cases.

BACKGROUND: Lung cancer patients with a previous extra-pulmonary malignancy have been widely discussed for their postoperative prognosis. Still, whether different types of previous extra-pulmonary malignancy confer different clinicopathological features and outcomes of lung cancer patients deserves further investigation. METHODS: The medical records of patients undergoing operation for pulmonary malignancy were retrospectively reviewed. After identifying primary lung cancer out of pulmonary metastasis in patients with a history of previous extra-pulmonary malignancy, clinicopathological parameters and postoperative prognosis were compared between lung cancer patients without and with different types of previous extra-pulmonary malignancy. RESULTS: Approximately, 5.0% lung cancer patients undergoing surgery had a previous extra-pulmonary malignancy. Prior breast cancer (20%) and colorectal cancer (16%) formed the majority of these previous extra-pulmonary malignancies. Many clinicopathological features such as reason for visit, tumor size and histological subtype were significantly different between lung cancer patients without and with different types of previous extra-pulmonary malignancy (P < 0.05). Lung cancer patients with a previous occurrence of breast cancer were the most different type from patients without a previous extra-pulmonary malignancy in clinicopathological features (P < 0.05). The postoperative overall survival was not significantly different between lung cancer patients without and with different types of previous extra-pulmonary malignancy (P > 0.05). CONCLUSION: Previous extra-pulmonary malignancy was confirmed to be harmless to postoperative prognosis of lung cancer patients. Lung cancer patients with a previous extra-pulmonary malignancy, especially with a previous occurrence of breast cancer, were highly heterogeneous in clinicopathological features. These findings implied there might be a unique etiology existing in lung cancer following a previous occurrence of breast cancer.

Simultaneous effects of surface spins: rarely large coercivity, high remanence magnetization and jumps in the hysteresis loops observed in CoFe2O4 nanoparticles.

Well-dispersed uniform cobalt ferrite nanoparticles were synthesized by thermal decomposition of a metal-organic salt in organic solvent with a high boiling point. Some of the nanoparticles were diluted in a SiO2 matrix and then the undiluted and diluted samples were characterized and their magnetic behavior explored. The undiluted and diluted samples exhibited maximum coercivity Hc of 23,817 and 15,056 Oe at 10 K, respectively, which are the highest values reported to date, and the corresponding ratios of remanence (Mr) to saturation (Ms) magnetization (Mr/Ms) were as high as 0.85 and 0.76, respectively. Interestingly, the magnetic properties of the samples changed at 200 K, which was observed in magnetic hysteresis M(H) loops and zero-field cooling curves as well as the temperature dependence of Hc, Mr/Ms, anisotropy, dipolar field, and the magnetic grain size. Below 200 K, both samples have large effective anisotropy, which arises from the surface spins, resulting in large Hc and Mr/Ms. Above 200 K, the effective anisotropy decreases because there is no contribution from surface spins, while the dipolar interaction increases, resulting in small Hc and Mr/Ms. Our results indicate that strong anisotropy and weak dipolar interaction tend to increase Hc and Mr/Ms, and also clarify that the jumps around H = 0 in M(H) loops can be attributed to the reorientation of surface spins. This work exposes the underlying mechanism in nanoscale magnetic systems, which should lead to improved magnetic performance.

Immunization of mice with ultraviolet-irradiated Schistosoma mansoni cercariae: a re-evaluation.

Mice immunized by percutaneous exposure to ultraviolet-irradiated Schistosoma mansoni cercariae developed levels of resistance to subsequent S. mansoni infection comparable to those induced by gamma-irradiated cercariae (50-70% reduction in adult worm burden). Cercariae treated with ultraviolet doses ranging from one to three times the minimum dose required to prevent long-term survival induced the highest levels of resistance.

Vaccination against bovine schistosomiasis japonica with highly X-irradiated schistosomula.

Cercariae of the Chinese mainland strain of Schistosoma japonicum were used. Eighteen cattle, divided into six groups of three each, were immunized with schistosomula transformed from cercariae exposed to three different doses of X-irradiation (24, 36, and 48 kR). The immunization was given either once, twice, or thrice, and the number of immunizing schistosomula was 10,000 or more in each immunization. The immunized cattle were challenged with 500 normal cercariae. Five native cattle were similarly infected with normal cercariae as controls. All cattle were killed 32-33 days after challenge or infection, and the worms were obtained by perfusion. The mean worm reduction in the 18 experimental animals varied from 42.1 to 96.0%. The mean percent worm reduction of the six experimental groups varied from 54.8 to 87.1. The reduction was greater with increasing numbers of immunizations, and was higher in the groups immunized with schistosomula exposed to 36 kR than in those exposed to 24 or 48 kR. Statistical analyses showed that all immunized groups yielded significantly fewer worms than controls. However, the three doses of X-irradiation (24, 36, and 48 kR) had no significant effect for a fixed number of immunizations (1, 2, or 3). The means for both two and three immunizations were significantly different from the mean for one immunization, although they were not significantly different from each other.

Vaccination of bovines against schistosomiasis japonica with highly irradiated schistosomula in China.

Vaccination of Chinese bovines (cattle and buffaloes) against schistosomiasis japonica with 36 kR gamma-irradiated schistosomula was done for laboratory challenge and for field trials in China. Altogether, 61 bovines were used. All experimental animals were vaccinated 2-3 times with 10,000 irradiated schistosomula per time. For the laboratory challenge, all experimental and control cattle were challenged with 500 normal cercariae and each buffalo, with 2,000 cercariae. The laboratory-challenged bovines were killed after 54-57 days of challenge; the bovines for the field trial in the lightly endemic area, after 5 months in the field; and the bovines for the field trial in the heavily endemic area, after 58-63 days. When the animals were killed, the number of mature worms in the vaccinated (experimental) and non-vaccinated (control) animals was recorded and the percentage of worm reduction in each group was calculated. The first group, consisting of three vaccinated and three non-vaccinated cattle, was given a laboratory challenge; the worm reduction was 71.6%. The second group, consisting of two vaccinated and three non-vaccinated buffaloes, was also given a laboratory challenge; the worm reduction was 74.4%. The third group, consisting of seven vaccinated and eight non-vaccinated buffaloes, was utilized in a field trial in a lightly endemic area; the worm reduction was 75.6%. The fourth group, consisting of eight vaccinated and nine non-vaccinated cattle, and the fifth group, consisting of nine vaccinated and nine non-vaccinated buffaloes, were pastured in a heavily endemic area. The worm reduction was 65.1% in the fourth group and 75.7% in the fifth group.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect of scopolamine and picrotoxin on the learning-dependent long-term synaptic potentiation].

The purpose of this study was to investigate the effects of microinjection of scopolamine, a M-cholinergic antagonist and picrotoxin, a GABA-ergic antagonist into the rat hippocampal CA3 area on the learning-dependent long-term potentiation (LDLTP) during the establishment, extinction and re-establishment of conditioned drinking response. Following stimulation of the perforant path, field potentials of hippocampal CA3 of freely moving rats were recorded. The results were as follows: the synaptic efficacy and the development of LDLTP in hippocampal CA3 were depressed significantly by scopolamine, but the extinction of LDLTP was accelerated. Picrotoxin significantly enhanced synaptic efficacy and facilitated the development of LDLTP, but it depressed the extinction of LDLTP. Meanwhile, the establishment or extinction of drinking conditioning was correspondingly depressed or accelerated. Moreover, the development of LDLTP and its extinction preceded the development and extinction of drinking conditioning. The results provide further evidence indicating that LDLTP might be one of the neuronal mechanisms underlying behavioral learning and memory. Moreover, it seems that M-cholinergic receptors and GABA-ergic receptors in rat hippocampal CA3 area are involved in the development and retention of LDLTP.

[The learning dependent long-term synaptic potentiation in the rat hippocampal CA3 region].

The purpose of this study is to investigate the changes of synaptic efficacy in the rat hippocampal CA3 region during establishment, extinction and re-establishment of conditioned drink response by means of implanted electrodes and behavioral observation. The monosynaptic population excitatory postsynaptic potential (EPSPs) and population spike (PS) elicited by stimulating the perforant path were recorded. The results showed that the long-term potentiation (LTP) in the hippocampal CA3 region appeared with the establishment of conditioned response, the LTP extinguished with experimental extinction of conditioned response and reappeared during the re-establishment of conditioned response. Moreover, both maximal level of LTP and its complete extinction preceded those of conditioned behavior, suggesting that the LTP was learning-dependent. In addition, the enhanced PS was not presented immediately after behavioral training, and developed within subsequent 24 h, with a maximum at the 4th hour. The magnitude of conditioned response depended on the level of LTP. A cross-correlation analysis of the slopes of PS and EPSPs indicated that the changes of PS were caused by alterations of synaptic transmission. These results suggest that the learning-dependent LTP might be one of the neuronal substrates underlying behavioral learning and memory.

[Role of N-methyl-D-aspartate receptor in the maintenance of learning-dependent long-term potentiation in rat hippocampal CA3 area].

The effect of microinjection of 2-amino-5-phosphonovaleric acid (APV), a selective NMDA receptor antagonist, into the rat hippocampal CA3 area on the synaptic efficacy and related conditioned behavior during the acquisition and consolidation of discrimination learning behavior was examined. The results showed: (1) After population spike (PS) amplitude had just increased to the maximum through training i.e. learning-dependent LTP had just formed, APV 1 microliter (2 mmol/L) was injected into CA3 area, then the rats were trained during the time of efficacy of the drug in every experimental block. The result demonstrated that the PS amplitude could not be maintained at the highest level but decreased to the pre-experiment level after 8 blocks. Correct response percentage of rats could not be consolidated with further training but decreased to less than 10%. (2) After the PS amplitude had kept up at the highest level, APV 1 microliter (2 mmol/L) was injected into CA3 area, then the rats were trained during the time of efficacy of the drug in every experimental block, in which case the PS amplitude also could not be maintained at the highest level but decreased to the pre-experiment level after 14 blocks. Correlatively, when the correct response percentage of rats decreased gradually to less than 10%, the conditioned response of the animals extinguished, but its extinction speed was slower than it was in result (1). These results suggest that the NMDA receptor in CA3 area plays an important role in the maintenance of the learning-dependent long-term potentiation.

[Effects of 6-OHDA lesions of the bilateral dorsal noradrenergic bundle on learning-dependent long-term synaptic potentiation in dentate gyrus].

In the present study, the role of NE in learning-dependent long-term potentiation (LdLTP) was investigated by examining the effects of 6-hydroxydopamine (6-OHDA) lesion made in the bilateral dorsal noradrenergic bundle on the changes of synaptic efficacy in dentate gyrus (DG) and related conditioned response during drinking conditioning. Bilateral injection of 6-OHDA (12 micrograms/4 microliters) into the dorsal noradrenergic bundle caused a continuous decrease of the amplitude of population spike (PS) reaching a value of 50 +/- 6.3% and 28 +/- 6.4% respectively at the 6th and the 12th day after injection of the drug. During this period of 7 days, the LdLTP could not be produced in spite of 20 trainings per day for a total of 140 trials, and the conditioned drinking response could not be established. The above results indicate that normal levels of norepinephrine in the hippocampus are necessary to the establishment of LdLTP in the DG and suggest that the development of LdLTP in the DG may be modulated by the nucleus locus ceruleus via the dorsal noradrenergic bundle.

[Effect of electroshock on learning-dependent long-term potentiation in rat hippocampal CA3 area].

Population spikes were recorded from hippocampal CA3 of freely moving rats following stimulation of the perforant path. Six rats were trained to perform conditioned drinking behavior. (1) Animals were treated with electroshock in less than 15 minutes after daily training session for a period of 6 consecutive days. Synaptic efficacy did not increase and the conditioned response could not be established during the behavioral training in four rats, synaptic efficacy was increased, the long-term potentiation (LTP) appeared and the conditioned behavior was established in other two rats. (2) After consolidation of conditioned behavior, electroshock temporarily caused suppression of the learning-dependent LTP and the correlative conditioned response. Both LTP and the correlative conditioned response recovered in one to four hours after electroshock. In these cases, the maximal development of LTP preceded the development of conditioned behavior. The results indicated that the learning-dependent LTP might be one of the neural substrates underlying learning and memory.

[Changes of synaptic transmission efficiency in the MF-CA3 and PP-CA3 pathways of rat hippocampus during discrimination learning].

Electrophysiological and behavioral studies were performed in rat to investigate the changes of synaptic efficacy of the two inputs of hippocampal CA3 area [Mossy Fiber (MF) -CA3 and Perforant Path (PP) -CA3] during discrimination learning. The results showed that: (1) Amplitude of the population spike (PS) of both from MF-CA3 and PP-CA3 increased simultaneously with the establishment of conditioned response (CR) and both reached their maxima before CR reached the criterion of acquisition. (2) During natural extinction of CR, the amplitude of PS of both inputs decreased also simultaneously to their per-training level. These results indicated that the learning-dependent long-term potentiation (LTP) in both MF-CA3 and PP-CA3 inputs developed and extinguished synchronously, suggesting that the changes of synaptic efficacy of different inputs of hippocampal CA3 area coordinated during discrimination learning.

[Internal fixation for intertrochanteric fracture. Biomechanical study].

A Type IIIa intertrochanteric fracture was made on the preserved femurs of adult cadavers. The fracture was fixed by 4 methods: Percalcar Steinmann's pins, Knowle's pins, Nail plate and Angle plate. The loading limit of the fixations were 150, 140, 70 and 40 kg respectively. In fatigue test the loading ability of the percalcar Steinmann's pins were 4 times greater than that of Nail plate or Angle plate. In Nail plate and Angle plate. The pathological section of the upper femur showed the most bony destruction was at the trabecula beneath the lateral cortex, and in the percalcar Steinmann's, it was at the neck trabecula, where the cal car plays an important role in supporting the loading of the lowest pin. It was found that the level arm was shortened and the loading ability increased. As the direction of the lowest pin was nearly parallel to the loading axis of the hip. The calcar suffered less shearing force. These findings showed that the percalcar Steinmann's pins fixation is the best in these 4 methods.