HLA-A2-restricted cytotoxic T lymphocyte epitopes from human hepsin as novel targets for prostate cancer immunotherapy.

Hepsin is a type II transmembrane serine protease that is overexpressed in prostate cancer, and it is associated with prostate cancer cellular migration and invasion. Therefore, HPN is a biomarker for prostate cancer. CD8(+) T cells play an important role in tumour immunity. This study predicted and identified HLA-A2-restricted cytotoxic T lymphocyte (CTL) epitopes in human hepsin protein. HLA-A2-restricted CTL epitopes were identified using the following four-step procedure: (1) a computer program generated predicted epitopes from the amino acid sequence of human hepsin; (2) an HLA-A2-binding assay detected the affinity of the predicted epitopes to the HLA-A2 molecule; (3) the primary T cell response against the predicted epitopes was stimulated in vitro; and (4) the induced CTLs towards different types of hepsin- or HLA-A2-expressing prostate cancer cells were detected. Five candidate peptides were identified. The effectors that were induced by human hepsin epitopes containing residues 229 to 237 (Hpn229; GLQLGVQAV), 268 to 276 (Hpn268; PLTEYIQPV) and 191 to 199 (Hpn199; SLLSGDWVL) effectively lysed LNCaP prostate cancer cells that were hepsin-positive and HLA-A2 matched. These peptide-specific CTLs did not lyse normal liver cells with low hepsin levels. Hpn229, Hpn268 and Hpn199 increased the frequency of IFN-γ-producing T cells compared with the negative peptide. These results suggest that the Hpn229, Hpn268 and Hpn199 epitopes are novel HLA-A2-restricted CTL epitopes that are capable of inducing hepsin-specific CTLs in vitro. Hpn229, Hpn268 and Hpn199 peptide-based vaccines may be useful for immunotherapy in patients with prostate cancer.

[Incidence and prognosis of olfactory and gustatory dysfunctions related to infection of SARS-CoV-2 Omicron strain: a national multi-center survey of 35 566 population].

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.

[Overview of characteristics and prevention and control status of foreigners living with HIV in China].

HIV infection among foreign personnel is one of the nonnegligible issues to control the epidemic of HIV/AIDS in China. It is necessary for HIV infection among foreign personnel to be taken effective measures in China. This paper consists of information about epidemic characteristics among foreign personnel with HIV in China, including influence on the overall infection, geographical distribution, and prevention status, referencing more effective AIDS knowledge and health education and behavior intervention.

[Analysis of factors related to the online social interaction and causal sexual behaviors among foreigners in Guangzhou].

Objective: To understand the social support, social network, and sexual behavior characteristics of foreigners living in Guangzhou, analyze factors relating to aspects of online social interactions and sexual behaviors of foreigners in Guangzhou, and provide references for targeted HIV intervention services for foreigners. Methods: A cross-sectional survey (both online and offline), among those who met the inclusion criteria was conducted between November 2019 and January 2020. Data were collected on demographics, social support, online social interactions, sexual behaviors, and so on. Statistics were compiled to analyze the factors that may influence casual sexual behaviors. Results: A total of 434 participants were included in the study (241 offline and 193 online). The majority of the participants were male 68.4% (297/434), age (31.0±8.8) years old, African 79.0% (343/434), business people 46.5% (202/434), students 48.2% (209/434), who have business partners and family members in China were 59.4% (258/434) and 28.1% (122/434) separately. They also had the following features: less than 10 close friends 57.1% (248/434); spend 1-3 hours on social applications per day 43.3% (188/434), had casual sexual behaviors in the last 3 months 15.2% (55/363). Multiple logistic regression model analysis showed that compared with those who used social applications for less than 1 hour per day, participants who used social applications for more than 6 hours per day were more likely to have casual sexual behaviors in the last 3 months (OR=3.63, 95%CI: 1.31-10.08). Conclusions: Participants who used social applications for a longer period every day were more likely to have casual sexual behaviors among foreigners in Guangzhou. Good use of social applications for health promotion and education of HIV can increase the health awareness of foreigners in China.

[Analysis on influencing factors on HIV testing behaviors in some foreigners in Guangzhou].

Objective: To analyze the influencing factors of HIV testing behavior among foreigners in Guangzhou, and provide a reference for promoting HIV testing and intervention services in foreigners. Methods: A cross-sectional survey was conducted from November 2019 to January 2020 among 230 eligible foreigners selected in Guangzhou through convenient sampling method in the form of one-to-one questionnaire interview, HIV testing behaviors and related influencing factors were described and analyzed with χ(2) test and multivariate logistic regression model. Results: A total of 230 foreigners were included in the study, in whom 156 were males (67.8%), 217 were from Africa (94.3%), 138 (60.0%) were with education level of university and above, 169 (73.5%) were in business, 47 (20.4%) were students, 132 (57.4%) had cumulative residence >12 months in Guangzhou and 113 (49.1%) had health examination in China in the past 6 months. In these foreigners, the rate of AIDS-related knowledge awareness was 76.0%, the proportion of condom use in the last sex was 39.6%(89/225) and 47.8%(110/230) received HIV tests in the past 3 months. Multivariate logistic regression analysis showed, the influencing factors of HIV testing behavior in the past 3 months included cumulative residence ≤12 months (compared with cumulative residence >12 months, OR=3.12, 95%CI: 1.49-6.56), health examination in China in the past 6 months (compared to those who had not, OR=2.53, 95%CI: 1.17-5.48), awareness of HIV testing and consulting service in Guangzhou (compared with those who had no awareness, OR=3.65, 95%CI: 1.71-7.78). Conclusions: Some foreigners in Guangzhou had relatively low rates of HIV testing and condom use. Those who pay attention to their own health status and know well about HIV testing and consulting services are more likely to receive HIV testing, foreigners in Guangzhou should be encouraged to receive HIV testing. Their self-testing awareness should be improved.

[Effect of comprehensive AIDS intervention among men aged 50 or over who had non-marital sexual behavior].

Objective: To evaluate the effectiveness of AIDS intervention programs on men aged 50 or over and having had non-marital sexual behavior. Methods: A community-based intervention/experimental and based on individual level study was adopted. Stratified sampling method was used. 12 townships/streets in Fuyang district of Hangzhou were identified as intervention or control group (six research sites each). All of the subjects in the township (street) were included. The inclusion criteria of study objects would include men aged 50 or older who reported having unmarried sex in the last year. Estimated sample size was 290, with each 145 in the intervention group and the control group. All the intervention group participants were provided with a total of 4 intervention-related items (knowledge and education on AIDS prevention, information radiation and behavioral change, broadcast expert lectures), every 3 months, for 12 month, the main evaluation indicators would include: incidence of non-marital sex and commercial sex in the last year, condom use when having non-marital sex in the last episode. Results: A total of 312 subjects were recruited. 300 of them completed the baseline study while 284 of them completed the follow-up survey. Among the subjects who had undergone the baseline study, the average age was (65.58±7.89), 71.33% were married or cohabiting with someone, 52.00% having had primary school education. After the implementation of intervention programs, the incidence of non-marital sex dropped to 59.42% (82/138) and the incidence of commercial sex dropped from 79.73% (118/148) to 55.07% (76/138). Condom use rate in the last non-marital sexual contact increased from 19.59% (29/148) to 51.22% (42/82). In the control group, the incidence of non-marital sex in the year before dropped to 74.66% (109/146) and the incidence of commercial sex dropped from 91.45% (139/152) to 72.60% (106/146). Rates of condom use during the last non-marital sexual contact dropped from 32.89% (50/152) to 31.19% (34/109). Statistically, there were significant differences appeared between the two groups on the incidence of non-marital sex in the past year (χ(2)=7.48, P=0.008), the incidence of commercial sex in the last year (χ(2)=9.47, P=0.003) and the rate of condom use in the last sex experience (χ(2)=7.83, P=0.007). Conclusions: Results from this intervention study showed that: in the intervention group, both the incidence rates of non-marital or commercial sex had reduced, together with the increase of condom use in non-marital sex in the last sexual experience. Intervention strategies that involving knowledge and education on AIDS prevention, information radiation and behavioral change, broadcasting lectures by experts etc. were all proved effective.

[An overview on the opioid substitution therapy service model].

When facing the worldwide abuse of opioid substance, one of the effective responses is opioid substitution therapy (OST). However, different OST service patterns may affect the therapeutic outcome. Using the System Engineering Initiative for Patient Safety (SEIPS) model, we can analyze the factors that affecting the outcomes of patients from the perspective work system. In this paper, SEIPS model is used to describe the existing OST service model. According to the operation mechanism of the methadone maintenance treatment in China and the existing OST service model, some suggestions are put forward to carry out effective OST service in the country.

[Current situation on new psychoactive substances abuse among methadone maintenance treatment patients in China].

Methadone maintenance treatment (MMT) greatly contributed to the successful outcomes of prevention and control on both AIDS and drug abuse in China. However, the features on drug abuse changed in the past decades, and the prevalence of new psychoactive substances abuse potentially somehow offset the achievement of MMT. This paper concised the information on research and surveys of this issue that targeting on the current situation, characteristics, related factors and relevant public health problem on new psychoactive substances abuse, among patients who have been on MMT, in China.

[New psychoactive substances abuse among patients with access to methadone maintenance treatment in Jiangsu province: a case-control study].

Objective: To explore the reasons and factors associated with new psychoactive substances abuse among patients with access to methadone maintenance treatment (MMT). Methods: A well-developed questionnaire and urine tests were used to collect information about demographic characteristics, condition of MMT and drug abuse, family and social support of MMT clients. A 1∶1 matched case-control study was conducted, and conditional logistic regression model was used to identify factors associated with new psychoactive substances abuse. Results: A total of 212 (106 pairs) clients receiving MMT were recruited, and most of them were males (78.3%, 166/212), married or cohabitant (48.6%, 103/212) and unemployed (63.2%, 134/212). The average age of the clients was (45.1±7.2) years. The main types of abused new psychoactive substances were benzodiazepine (62.3%, 66/106) and methamphetamine (39.6%, 42/106). The proportion of abusing multi new psychoactive substances was 8.5% (9/106). Results from multivariate conditional logistic regression analysis indicated that using opioid drug during the past 6 months of MMT treatment might increase the risk of abusing new psychoactive substances (OR=3.25, 95%CI: 1.35-7.79), benzodiazepine (OR=3.25, 95%CI: 1.11- 9.47) and methamphetamine (OR=13.31, 95%CI: 1.12-158.01). Moreover, MMT for more than9 years reduced the risk of abuse of new psychoactive substances (OR=0.03, 95%CI: 0.01-0.21), benzodiazepine (OR=0.02, 95%CI: 0.00-0.36) and methamphetamine (OR=0.02, 95%CI: 0.00-0.69). Conclusion: Less new psychoactive substances abuse might be associated with longer duration of MMT treatment. And inappropriate support from family and friends might increase the risk of abusing new psychoactive substances in MMT clients, especially in clients who used opioid.

[Quality of network direct reporting of information about intervention service in population at high risk for HIV infection in China, 2013-2014].

Objective: To analyze the problems in the network direct reporting of information about intervention service conducted in population at high risk for HIV infection in China during 2013-2014, and provide evidence for the improvement of the network direct reporting of the intervention information. Methods: The wrong records of the intervention service in population at high-risk were collected from national AIDS prevention and treatment information system. The wrong records, including those found at county (district) level and those found at state level, were analyzed with descriptive statistical method. Results: A total of 1 066 wrong records were found during 2013-2014, and average annual wrong record rate was <0.1%. Up to 71.3% (760/1 066) of wrong records occurred in the first half year. The wrong records in eastern, central and western areas accounted for 14.9% (159/1 066), 22.6% (241/1 066) and 62.5% (666/1 066) of the total respectively. More wrong records were found in the intervention information for men who have sex with men and injecting drug users than in those for female sex workers. Among the total wrong records, 86.4% (921/1 066) were found at county level and 13.6% (145/1 066) were found at state level. The wrong records were mainly"annual number of persons receiving the first HIV test"and"annual number of persons covered by intervention". Common causes of wrong records were underreporting and delay, staff fault, miscalculation and misunderstanding. Conclusion: In general, the wrong record rate in intervention information for population at high risk for HIV infection reported directly through network was low in China. It is necessary to strengthen the recording of the intervention service, the quality control of statistics and network direct reporting and staff training to improve the quality of reported data of intervention service.

Cardioprotection mediated by urocortin is dependent on PKCepsilon activation.

Urocortin (Ucn) is an endogenous cardioprotective agent that protects against the damaging effects of ischemia and reperfusion injury in vitro and in vivo. We have found that the mechanism of action of Ucn involves both acute activation of specific target molecules, and using Affymetrix (Santa Clara, CA) gene chip technology, altered gene expression of different end effector molecules. Here, from our gene chip data, we show that after a 24 h exposure to Ucn, there was a specific increase in mRNA and protein levels of the protein kinase C epsilon (PKCepsilon) isozyme in primary rat cardiomyocytes compared with untreated cells and in the Langendorff perfused ex vivo heart. Furthermore, a short 10 min exposure of these cells to Ucn caused a specific translocation/activation of PKCepsilon in vitro and in the Langendorff perfused ex vivo heart. The importance of the PKCepsilon isozyme in cardioprotection and its relationship to cardioprotection produced by Ucn was assessed using PKCepsilon-specific inhibitor peptides. The inhibitor peptide, when introduced into cardiomyocytes, caused an increase in apoptotic cell death compared with control peptide after ischemia and reperfusion. When the inhibitor peptide was present with Ucn, the cardioprotective effect of Ucn was lost. This loss of cardioprotection by Ucn was also seen in whole hearts from PKCepsilon knockout mice. These findings indicate that the cardioprotective effect of Ucn is dependent upon PKCepsilon.

[Overdose of heroin and influencing factors in intravenous drug users in parts of Yunnan].

OBJECTIVE: To assess the prevalence of overdose of heroin and risk factors in intravenous drug users(IDUs)in Yunnan Province. METHODS: During July-August of 2015, IDUs were recruited from four methadone maintenance treatment(MMT)clinics and two compulsory drug rehabilitation centers in Honghe and Dehong prefectures, Yunnan province. The information about IDUs ' demographic characteristics and drug use history, overdose of heroin in previous12 months and the latest overdose of heroin were collected through face to face questionnaire survey. The factors associated with overdose of heroin were evaluated with logistic regression models. RESULTS: Of the 340 IDUs surveyed, 85.3%(290/340)were males, the mean age was 37.7±8.7 years, 65.6%(223/340)were Han ethnicity, and 49.4%(167/338)were HIV positive, 22.6%(77/340)reported having used club-related drugs(such as ephedrine, methamphetamine, benzodiazepines and ketamine)in the previous 12 months. Of the 340 IDUs, 41.8%(142/340)had at least one overdose of heroin in their lifetime(median: 3 overdoses)and 15.6%(53/340)had at least one overdose of heroin(median : 1 overdose use)in previous 12 months. The mean age of the 53 IDUs was(36.7 ± 8.4)years, and 83.0%(44/53)of them were males, the average drug use history was(16.5 ± 7.6)years. Dosage increase(26.4%, 14/53)and multidrug use(28.3%, 15/53)were the main causes for overdose of heroin. Multiple logistic regression analysis indicated that methadone maintenance treatment during the past year(OR=0.534, 95%CI: 0.290-0.980)was independently associated with decreased risk of overdose of heroin, needle sharing in the past 6 months(OR=2.735, 95%CI: 1.383-5.407)and being forced to receive drug rehabilitation for less than one year(OR=2.881, 95% CI: 1.226-6.767)were independently associated with increased risk of overdose of heroin. CONCLUSION: Overdose of heroin is common among IDUs in Yunnan. It is necessary to encourage IDUs to receive MMT and strengthen the health education about the prevention of overdose of heroin, especially before they leave drug rehabilitation centers. And it is important to establish a referral mechanism from drug rehabilitation center to MMT clinic for drug users.

p16INK4A and p15INK4B gene deletions in primary leukemias.

The 9p21 locus has been deleted at a high frequency in a wide variety of tumors. Recently, two genes, p16INK4A and p15INK4B (also called MTS1 and MTS2), have been localized in close proximity at the 9p21 locus, encoding cyclin-dependent kinases 4/6 inhibitors of relative molecular mass 16 kD and 15 kD, respectively and also found to be deleted at a high frequency in tumor cell lines. We analyzed p16INK4A and p15INK4B genes in 178 cases of primary leukemias including 81 cases of chronic lymphocytic leukemia (CLL), seven of hairy cell leukemia (HCL), seven of chronic myelogenous leukemia (CML), 43 of acute myelogenous leukemia (AML), 27 of acute lymphoblastic leukemia (ALL), and 13 of myelodysplastic syndrome (MDS) by Southern blot analyses. The ALL cases showed a relatively high frequency of homozygous deletions (22%, 6 of 27) at the p16INK4A gene locus. Interestingly, of the six cases with p16INK4A homozygous deletions, only three showed homozygous deletions at the p15INK4B gene. In 81 CLL patients, we detected one homozygous and five heterozygous deletions at both the p16INK4A and p15INK4B genes and two heterozygous deletions at the p16INK4A gene alone. Deletion of these two genes in AML cases is relatively low (9%). We did not detect deletions in any of the MDS, HCL, and CML cases examined. Sequence analyses of p16INK4A gene of six CLL cases with heterozygous deletion at this locus showed a 27-bp deletion at the splice acceptor site of intron 1 in one case and changes in the coding sequence in three other cases. The data presented in this report showed that (1) p16INK4A and p15INK4B genes are preferentially deleted homozygously in ALL and heterozygously in CLL cases with frequent mutation in the second allele, and (2) p16INK4A gene appears to be more frequently deleted than p15INK4B gene.

Clinical measurement of antibodies against acetylcholine receptor (AchR), SOD and LPO in patients with myasthenia gravis (MG) before and after thymectomy.

The antibodies against acetylcholine receptor AchR and levels of SOD and LPO were measured in 11 patients with myasthenia gravis (MG), and the results were compared with normal controls and patients with diseases other than MG. The results showed that the antibodies against AchR were higher as compared with other groups before and after operation. The post-operative level of antibodies was obviously lower than the pre-operative value. An slight increase in SOD and significant decrease in mean value of LPO after surgery were noted. The possible mechanism was discussed.

Surgical treatment of myasthenia gravis and evaluation of its efficacy.

This paper reports 30 cases of myasthenia gravis (MG) treated by thymectomy from 1965 to 1990 in our hospital. Of all the 30 cases of MG, peripheral blood lymphocyte subpopulation was determined in 10, and anti-acetylcholine receptor antibody titer in 6, before and after operation. The results demonstrated the efficacy of thymectomy against MG. We considered that with application of hormone before and after operation to regulate immune function of the body, and/or with plasma exchange to remiss symptoms, all the patients with generalized MG may be indicated for treatment by thymectomy. Indication of treatment does not depend on age, sex and the course of the disease. But radical operation, proper anesthesia and appropriate use of antibiotics may ensure safety of the operation and its curative effect.