Comprehensive evaluation of inactivated SARS-CoV-2 vaccination on sperm parameters and sex hormones.

Background: The inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine has made significant contributions to fighting the epidemic in the past three years. However, the rapid development and application raised concerns about its safety in reproductive health, especially after several studies had observed a decrease in semen parameters following two doses of mRNA SARS-CoV-2 vaccination. Thus, it is necessary to comprehensively evaluate the effect of inactivated SARS-CoV-2 vaccine on male fertility. Methods: A retrospective cohort study was conducted in the Center for Reproductive Medicine of the Affiliated Hospital of Jining Medical University between July 2021 and March 2023. A total of 409 men with different vaccination status and no history of SARS-CoV-2 infection were included in this study. Their sex hormone levels and semen parameters were evaluated and compared separately. Results: The levels of FSH and PRL in one-dose vaccinated group were higher than other groups, while there were no significant changes in other sex hormone levels between the control and inactivated SARS-CoV-2 vaccinated groups. Most semen parameters such as volume, sperm concentration, total sperm count, progressive motility and normal forms were similar before and after vaccination with any single dose or combination of doses (all P > 0.05). Nevertheless, the total motility was significantly decreased after receiving the 1 + 2 doses of vaccine compared to before vaccination (46.90 ± 2.40% vs. 58.62 ± 2.51%; P = 0.001). Fortunately, this parameter was still within the normal range. Conclusion: Our study demonstrated that any single dose or different combined doses of inactivated SARS-CoV-2 vaccination was not detrimental to male fertility. This information could reassure men who want to conceive after vaccination and be incorporated into future fertility recommendations.

Vaccine inequity-induced COVID-19 dilemma: Time to sober up.

OBJECTIVE: The aim of the study was to discuss the catastrophic consequences of inequitable vaccine distribution and analyze the main challenges to address it, helping to guide efforts to address inequities in vaccine coverage. METHODS: All published papers written in English were searched through PubMed, Web of Science, and Google Scholar with the combination of relevant terms of COVID-19 vaccine inequity. RESULTS: In this paper, we first outlined the scope of inequitable vaccine distribution and identify its truly catastrophic consequences. Next, from the perspectives of political will, free markets, and profit-driven enterprises based on patent and intellectual property protection, we analyzed in depth the root causes of why this phenomenon is so difficult to combat. In addition, some specific and crucial solutions that should be undertaken in the long term were also put forward in order to provide a useful reference for the authorities, stakeholders, and researchers involved in addressing this worldwide crisis and the next one. CONCLUSIONS: Achieving COVID-19 vaccine equity faces funding gaps, vaccine nationalism, and barriers to access to intellectual property and technology. Thus, the scope of global vaccine inequity is immense, and its repercussions will continue to be felt worldwide, especially among the world's most vulnerable residents, both adults and children. Beyond fundamental issues, the growing vaccine hesitancy and unreliable distribution in low-income countries must be addressed.

Reflections on the dynamic zero-COVID policy in China.

The coronavirus disease 2019 (COVID-19) pandemic has posed a serious threat to global healthcare and economy. In order to curb its spread, China adopted the dynamic zero-COVID policy, aiming to diagnose and isolate cases and close contacts as soon as possible. However, there is a controversy about the impact of isolation measures on social order, including the economy, personal employment and public mental health. Therefore, this review discusses and analyzes in detail the advantages and challenges of implementing dynamic zero-COVID policy. Although this public health policy might cause a shock to the economy in the short term, China still achieved a continued healthy economic performance with stable unemployment and strong export growth. Moreover, the rates of infection and mortality in China were lower than those in the United States and the European Union. However, due to the high transmissibility and low pathogenicity of the Omicron variant and prolonged lockdown-induced psychological damage, people questioned the effectiveness and necessity of this policy. Now that China has adjusted its policy in a timely manner, but many problems still remain unsolved. Some practical suggestions in terms of mental health, vaccine development, drugs supply, and economic recovery are put forward at the end of our paper to minimize negative impacts and provide a reference for future efforts.

Comprehensive evaluation of the effect of inactivated SARS-CoV-2 vaccination on female fertility: A retrospective cohort study.

Fear of possible negative effects of coronavirus disease 2019 (COVID-19) vaccine on fertility is the main reason for vaccine hesitancy among the public especially women of childbearing age. Despite the high coverage of COVID-19 vaccination in China, more scientific evidence is still needed to address their concerns and guide fertility counseling and management in the future. Herein, we performed a retrospective cohort study at a single large center for reproductive medicine in China between August 2020 and May 2023. Patients aged 20-42 years with no history of laboratory-confirmed COVID-19 were included and categorized into different groups according to their vaccination status. The serum sex hormone levels, anti-Müllerian hormone concentrations, embryo quality, and pregnancy outcomes were evaluated and compared among them. We found there were no significant differences in the concentrations of follicle-stimulating hormone, luteinizing hormone and progesterone between the unvaccinated, first-dose, second-dose, and booster vaccinated groups. However, the estradiol showed a highly significant increase in the one-dose vaccinated group compared with its levels in other groups. Among unvaccinated and either vaccinated patients, anti-Müllerian hormone levels were comparable (p = 0.139). The number of oocytes retrieved, fertilization rate and good-quality embryo rate were all similar between each group of in vitro fertilization and intracytoplasmic sperm injection. No significant differences were observed regarding other laboratory parameters. Moreover, the vaccination status of infertile couples did not exert any adverse effect on the pregnancy outcomes in all assisted reproductive technologies cycles. In short, we comprehensively evaluated the reproductive safety of inactivated severe acute respiratory syndrome coronavirus 2 vaccine and found any dose of vaccination wouldn't negatively affect female fertility parameters such as sex hormone levels and ovarian reserve. Moreover, this is the first study to complete the live birth follow-up of the cohort after receiving inactivated severe acute respiratory syndrome coronavirus 2 vaccine, further dispelling the misconception and providing reassurance for decision-making by clinicians.

5-HMF attenuates striatum oxidative damage via Nrf2/ARE signaling pathway following transient global cerebral ischemia.

Recent studies have shown 5-hydroxymethyl-2-furfural (5-HMF) has favorable biological effects, and its neuroprotection in a variety of neurological diseases has been noted. Our previous study showed that treatment of 5-HMF led to protection against permanent global cerebral ischemia. However, the underlying mechanisms in cerebral ischemic injury are not fully understood. This study was conducted to investigate the neuroprotective effect of 5-HMF and elucidate the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway mechanism in the striatum after transient global cerebral ischemia. C57BL/6 mice were subjected to bilateral common carotid artery occlusion for 20 min and sacrificed 24 h after reperfusion. 5-HMF (12 mg/kg) or an equal volume of vehicle was intraperitoneally injected 30 min before ischemia and 5 min after the onset of reperfusion. At 24 h after reperfusion, neurological function was evaluated by neurological disability status scale, locomotor activity test and inclined beam walking test. Histological injury of the striatum was observed by cresyl violet staining and terminal deoxynucleotidyl transferase (TdT)-mediated dNTP nick end labeling (TUNEL) staining. Oxidative stress was evaluated by the carbonyl groups introduced into proteins, and malondialdehyde (MDA) levels. An enzyme-linked immunosorbent assay (ELISA)-based measurement was used to detect Nrf2 DNA binding activity. Nrf2 and its downstream ARE pathway protein expression such as heme oxygenase-1, NAD (P)H:quinone oxidoreductase 1, glutamate-cysteine ligase catalytic subunit and glutamate-cysteine ligase modulatory subunit were detected by western blot. Our results showed that 5-HMF treatment significantly ameliorated neurological deficits, reduced brain water content, attenuated striatum neuronal damage, decreased the carbonyl groups and MDA levels, and activated Nrf2/ARE signaling pathway. Taken together, these results demonstrated that 5-HMF exerted significant antioxidant and neuroprotective effects following transient cerebral ischemia, possibly through the activation of the Nrf2/ARE signaling pathway.

Inhibition of RhoA expression by adenovirus-mediated siRNA combined with TNF-α induced apoptosis of hepatocarcinoma cells.

Tumor necrosis factor-alpha (TNF-α) has been used as an effective treatment for Hepatocellular Carcinoma, however, inducing tumor cell apoptosis by TNF-α alone is still unsatisfactory. RhoA is highly expressed in hepatocarcinoma cells and can be activated by TNF-α. The activation of RhoA directly leads to a poor prognosis of HCC. Therefore, we propose to investigate the therapeutic effect of TNF-α together with RhoA siRNA. RhoA inhibition was accomplished by constructing a recombinant adenovirus that can efficiently express RhoA siRNA in HepG2 cells. The recombinant adenovirus AdshRNA-RhoA and AdU6-control were generated by adenovirus-mediated siRNA expression system. The inhibition effects were detected by RT-PCR in addition to immunoblot to quantify the decreased levels of RhoA expression, and the therapeutic effect for HCC was demonstrated by the proliferation and apoptosis ratios of HepG2 cells. The inhibition effects of RhoA by AdshRNA-RhoA were significant at both mRNA and protein levels: the transcription of RhoA mRNA decreased by 74.46%, and the expression of protein decreased by 76.48%. The proliferation rate of HepG2 cells detected by MTT showed that a treatment of AdshRNA-RhoA and TNF-α together could strengthen the suppression ability of TNF-α to HepG2 cells, resulting in approximately 14.2% more than those treated with only TNF-α. FCA and TUNEL assays results revealed that the combined treatment can induce apoptosis in approximately 52.14%-65% of the HepG2 cells, whereas this ratio in the TNF-α-alone group was only 21.91%-32%. Our results showed that AdshRNA-RhoA can efficiently enhance the TNF-α-induced apoptosis of hepatocarcinoma cells. This method might be a useful therapeutic route in HCC and other tumors.

Overexpression of C35 in breast carcinomas is associated with tumor progression and lymphnode metastasis.

To investigate C35 protein expression in breast carcinoma and to investigate its clinicopathological significance, a total of 68 cases of breast carcinoma and 20 cases of normal breast tissue samples were obtained from the clinic. Protein expression of C35, ER, PR and HER-2 were determined using immunohistochemistry. The correlations between C35 expression and clinicopathological parameters were analyzed on the basis of individual clinicopathologic records. Overexpression of C35 was detected in 56 of 68 (82.35%) breast carcinoma samples and only 3 of 20 (15%) normal breast tissue samples, and frequency of C35 expression was significantly associated with clinical Tumor Node Metastasis staging and Scarff-Bloom-Richardson grade (p < 0.05), but was not related to patients age, menstrual status and tumor diameter. C35 expression was positively related with the expression of HER-2 (r = 0.207), whereas negatively related with the expression of ER and PR. Further, C35 was prevalent in all four molecular subtypes of breast carcinoma with no significant difference of expression frequency. However, they have significant differences in lymphatic metastasis cases compared to the non-metastasis cases (p < 0.05). Since C35 protein was extensively expressed in all stages of breast carcinoma, and was closely associated with tumor progression and lymph node metastasis, it might be used as a reliable biomarker or therapeutic target for diagnosis and treatment.