BACKGROUND: To date, results on relationship between CYP3A4 gene polymorphism were limited and inconclusive, and no study focused on the influence of CYP3A4 gene-obesity interaction on breast cancer risk, especially in Chinese women. The purpose of this study was to evaluate the impact of four single nucleotide polymorphisms (SNPs) of CYP3A4 gene, the SNP-SNP and gene-environment interactions on the susceptibility to breast cancer in Chinese women. METHODS: Logistic regression was used to explore the relationship between four SNPs of CYP3A4 gene and the risk of breast cancer. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best SNP-SNP and gene-abdominal obesity interaction combinations among four SNPs and abdominal obesity. Haplotype examination among 4 SNPs was conducted using the SHEsis web-based platform. RESULTS: Logistic regression analysis showed that carriers of rs2242480- T allele have significantly higher breast cancer risk, than those with rs2242480- CC genotype, adjusted OR (95%CI) was 1.68 (1.23-2.16) and 2.03 (1.53-2.58) for participants with CT genotype and TT genotype under additive model. We did not find any notable interactions between the four SNPs within the CYP3A4 gene. GMDR model found a significant association in a two-locus model involving rs2242480 and obesity, with a p-value of 0.018. Stratified analysis found that breast cancer risk was the highest in obese participants with rs2242480- CT or TT genotype, compared to those non-obese participants with rs2242480- CC genotype, OR (95%CI) was 3.02 (1.83-4.25). We found that all haplotype combinations were not correlated with breast cancer risk. CONCLUSIONS We found that the T allele of rs2242480 within the CYP3A4 gene and interaction between rs2242480 and obesity were associated with an increased risk of breast cancer. However, the results of this study were only applicable to the Han ethnic group and cannot be generalized to other ethnic groups in China, and more SNPs of CYP3A4 gene should been enrolled in the analysis in the future, to verify the results obtained in this study.
Adult ; Aged ; Female ; Humans ; Middle Aged ; Breast Neoplasms/etiology* ; China/epidemiology* ; Cytochrome P-450 CYP3A/metabolism* ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Haplotypes ; Obesity/epidemiology* ; Polymorphism, Single Nucleotide ; Risk Factors ; East Asian People

OBJECTIVE To introduce the Dutch system of pharmacy academic education， professional practice and continuing education， and provide new ideas for constructing a “demand-driven， industry-education integrated， and sustainably developing” Chinese-style pharmacy education system. METHODS Through literature and public data retrieval， as well as collection of field visit materials， the study systematically combed the stage characteristics， institutional design， and innovative practices of Dutch pharmacy education， extracted its features and advantages， and proposed suggestions for pharmacy education reform in China. RESULTS & CONCLUSIONS The Dutch pharmacy academic education system is characterized by stepped competency-based training， integrating basic theory with early clinical practice at the undergraduate level， emphasizing specialized division of labor and strengthening clinical competence at the master’s level， and promoting industry-university-research collaborative innovation at the doctoral level. The practice qualification certification and continuing education exhibit multi-dimensional synergy. Specifically， the practice qualification certification process adheres to the guiding principle of “evidence-based competency”， implementing an access system centered on competency assessment， which requires passing national examinations and registration. The continuing education for hospital pharmacists is guided by patient safety， while continuing education for community pharmacists and other pharmacists （such as industrial pharmacists， regulatory science pharmacists， etc.） is guided by the frameworks of “digital situational learning” and a “triple tracks encompassing industry， regulation， and emerging fields”， respectively. China may draw on the five-dimensional path of Dutch pharmacy education in “early integration， vertical coherence， unified standards， industry-university-research collaboration， and intelligent empowerment” to reform its pharmacy education in aspects such as curriculum design， credit systems， evaluation criteria， training models， and training methods， aiming to cultivate pharmacy professionals aligned with China’s practical E-mail：cqqianyan@hospital.cqmu.edu.cn requirements.

Since May 2022, a severe global Mpox epidemic has underscored the urgent need for a preventative vaccine. On September 16, 2022, the mainland of China reported its first case of imported Mpox, which was subsequently followed by a significant rise in domestic infections commencing from June 2023. This alarming trend has escalated the likelihood of localized outbreaks and covert transmission, posing a heightened risk to public health. Notably, the United States, many European countries, and Japan have approved the use of smallpox vaccines for Mpox prevention and emergency vaccination post-exposure, based on their cross-protection efficacy. In recent years, virology research has broadened its scope to include investigations into various novel vaccine approaches, such as nucleic acid-based vaccines, protein subunit vaccines, and epitope peptide vaccines, and other related methodologies. This review offers a thorough examination of the current global landscape of Mpox prevalence, delves into the advancements in Mpox vaccine development, and highlights the progress achieved in Mpox vaccine research, serving as a valuable resource and providing technical insights essential for the effective prevention and control of Mpox.
Humans ; Vaccine Development ; Smallpox Vaccine ; Smallpox/epidemiology* ; Mpox, Monkeypox

Human alphaherpesvirus 2 (HSV-2) is the main pathogen resulting human genital herpes, which poses a major threat to the socio-economic development, while there is no effective vaccine. In this study, we developed a novel lipopolyplex (LPP)-delivered mRNA vaccine expressing the HSV-2 envelope glycoprotein gD and evaluated its immunogenicity in mice. The mRNA vaccine was prepared from the genetically modified gD mRNA synthesized in vitro combined with the LPP delivery platform and it was named gD-ORI mRNA. The expression of gD antigen in the mRNA vaccine was validated in vitro by Western blotting and indirect immunofluorescence assay, then the immune responses induced by this mRNA vaccine in mice were evaluated. The immunization with gD mRNA alone induced strong humoral and cellular immune responses in mice. Robust and long-lasting gD-specific IgG antibodies were detected in the mouse serum after booster immunization with gD-ORI mRNA. The immunized mice exhibited a Th1/Th2 balanced IgG response and robust neutralizing antibodies against HSV-2, and a clear dose-response relationship was observed. The gD-specific IgG antibodies were maintained in mice for a long time, up to 18 weeks post-booster immunization. At the same time, multifunctional gD-specific CD4⁺ and CD8⁺ T cells in vaccinated mice were detected by intracellular cytokine staining (ICS). This novel gD-expressing mRNA vaccine delivered by LPP induces strong and long-lasting immune responses in mice post booster immunization and has a promising prospect for development and application. This study provides scientific evidence and reference for the development of a new mRNA vaccine for HSV-2.
Animals ; Herpesvirus 2, Human/genetics* ; Viral Envelope Proteins/genetics* ; Mice ; Herpes Genitalis/immunology* ; RNA, Messenger/immunology* ; Female ; Mice, Inbred BALB C ; Antibodies, Viral/blood* ; mRNA Vaccines/immunology* ; Antibodies, Neutralizing/blood* ; Humans

Objective:To construct a novel respiratory syncytial virus (RSV) vaccine based on a recombinant influenza virus vector and evaluate its immune protective effects in mice.Methods:A recombinant H1N1 influenza A virus (IAV) expressing the extracellular domain (Gecto) of RSV A2 G protein was constructed and rescued, named as PR8NAGecto/WSN. After in vitro verification of the Gecto expression and PR8NAGecto/WSN growth kinetics, a single dose of PR8NAGecto/WSN was used to immunize BALB/c mice through intranasal administration to evaluate the efficacy of PR8NAGecto/WSN by assessing humoral (IgG, neutralizing antibody), mucosal (IgA) and cellular immunity (IFN-γ ELISPOT). Four weeks after immunization, the mice were challenged with RSV A2 or RSV B9320 to evaluate the protective effects of PR8NAGecto/WSN by analyzing mouse body weight changes, lung tissue virus titers and pathological changes. Results:A single-dose intranasal immunization with PR8NAGecto/WSN induced robust humoral, mucosal and cellular immunity in mice. Moreover, the mice in the immunized group had lower lung virus loads and mild lung pathological damages following the challenge with RSV A or RSV B subtype as compared with the control group.Conclusions:A single-dose intranasal immunization with PR8NAGecto/WSN induces robust immunity and provide protection against RSV A and B challenges in mice. This study provides new ideas and reference for the development of novel mucosal vaccines against RSV.

Objective:To explore the effects of the intervention of ginger baixiao moxibustion combined with probiotics on immune function, liver and kidney function of colorectal cancer patients after surgery, so as to provide a theoretical basis for clinical intervention methods to promote postoperative rehabilitation of patients.Methods:This study was a randomized controlled trial, and 180 patients with colorectal cancer radical resection from the Cancer Hospital of Guangxi Medical University were randomly divided into 4 groups, namely control group, probiotic group, ginger baixiao moxibustion group, and combination group, with 45 cases in each group. The control group was given routine nursing before and after surgery. In the probiotic group, probiotics were used for 3 d in routine preoperative care and 4 d from the first day after surgery. The preoperative routine care of the ginger baixiao moxibustion group was supplemented by ginger baixiao moxibustion for 3 d, and the intervention was carried out on the first day after surgery for 4 d. The combined group was treated with probiotics before and after surgery, and the specific intervention methods were the same as those of the probiotics group and the ginger baixiao moxibustion group. The differences in postoperative immune function, liver and kidney function and and other indexes among the four groups were compared.Results:Forty-five cases were ultimately selected from each of the 4 groups. There were 31 males and 14 females, aged (56.67 ± 10.13) years old in the control group. There were 27 males and 18 females, aged (55.33 ± 13.02) years old in the probiotic group. There were 20 males and 25 females, aged (57.87 ± 12.43) years old in the ginger baixiao moxibustion group. There were 26 males and 19 females, aged (57.67 ± 11.63) years old in the combination group. The IgA at 5 d after the operation in the control group, the probiotic group, the ginger baixiao moxibustion group and the combined group were (1.46 ± 0.42), (1.71 ± 0.49), (1.72 ± 0.58), (1.97 ± 0.72) g/L, and the IgM were (0.96 ± 0.20), (1.13 ± 0.33), (1.11 ± 0.35), (1.18 ± 0.52) g/L, and the IgG were (8.45 ± 1.68), (9.57 ± 1.71), (9.41 ± 2.14), (10.40 ± 2.16) g/L, and the differences among the four groups were statistically significant ( F=6.20, 10.64, 7.69, all P<0.05). The CD3 + values at 5 d after the operation in the control group, the probiotic group, the ginger baixiao moxibustion group and the combined group were 0.616 ± 0.094, 0.671 ± 0.101, 0.653 ± 0.119, 0.723 ± 0.091, and CD4 + were 0.408 ± 0.060, 0.444 ± 0.063, 0.441 ± 0.103, 0.483 ± 0.069, and CD4 +/CD8 + were 2.173 ± 0.715, 2.367 ± 0.963, 2.204 ± 1.137, 2.803 ± 1.064, and the differences among the four groups were statistically significant ( F=8.58, 7.43, 3.93, all P<0.05). The alanine aminotransferases at 5 d after the operation in the control group, the probiotic group, the ginger baixiao moxibustion group and the combined group were (16.22 ± 11.56), (15.87 ± 10.69), (12.91 ± 7.45), (11.31 ± 8.31) U/L, and the aspartate aminotransferases were (26.13 ± 7.97), (25.84 ± 7.89), (25.67 ± 10.85), (21.84 ± 5.51) U/L, and the differences among the four groups were statistically significant ( F=2.71, 2.70, both P<0.05). Conclusions:The combination of ginger baixiao moxibustion and probiotics intervention can effectively improve the immune function of colorectal cancer patients after surgery, and improve the liver function and other indexes of patients to a certain extent, so as to benefit patients.

Objective:To evaluate the short-term efficacy and safety of a preoperative combination of programmed cell death protein-1 (PD-1) inhibitor with either oxaliplatin + capecitabine (CapeOx) or oxaliplatin + tegafur gimeracil oteracil potassium (SOX) in the treatment of locally advanced immunotherapy-sensitive gastric cancer (LAGC) or adenocarcinoma of the esophagogastric junction (AEG).Methods:The cohort of this retrospective descriptive case series comprised patients with LAGC or AEG whose cancers had been determined to be immunotherapy- sensitive by endoscopic biopsy before treatment in the Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital and Institute from 1 August 1 2021 to 31 January 2024. Patients with any one of the following three characteristics were immunotherapy-sensitive: (i) PD-L1 combined positive score (CPS) ≥5; (ii) microsatellite instability-high (MSI-H) / mismatch repair deficiency (dMMR); or (iii) Epstein-Barr virus-encoded RNA (EBER) positivity. All study patients received PD-1 inhibitors combined with CapeOx or SOX as a neoadjuvant or conversion treatment strategy before surgery. Patients with immune system diseases, distant metastases, or human epidermal growth factor receptor 2 positivity were excluded. Factors analyzed included pathological complete response, clinical complete response, major pathological response, R0 resection rate, surgical conversion rate, and safety of the treatment, including immune-related adverse events (irAEs) and surgical complications.Results:The study cohort comprised 39 patients (28 men and 11 women) of median age 62 (range 44–79) years. After the above-described preoperative treatment, radical resection of the 14 tumors that were initially considered unresectable was achieved (surgical conversion rate: 14/14). Twenty-three of the remaining 25 patients underwent radical resection. The last two patients achieved clinical complete responses and opted for a "non-surgical strategy" (watch and wait). Overall, 37 patients (94.9%) underwent radical resection, with an R0 resection rate of 100% (37/37), pathological complete response rate of 48.6% (18/37), and major pathological response rate of 62.2% (23/37). Of the 24 patients with CPS ≥ 5 (non-MSI-H/dMMR and non-EBER positive), 11 achieved pathological complete responses and one with CPS=95 achieved a clinical complete response. Of the eight patients with MSI-H/dMMR, six achieved pathological complete responses and one a clinical complete response. Of the seven patients with EBER positivity, one achieved a pathological complete response. After excluding patients with major pathological complete responses, there was a statistically significant difference in CPS scores between preoperative biopsy specimens and postoperative surgical specimens in 13 patients (7.769±5.570 vs. 15.538±16.870, t=2.287, P=0.041). All patients tolerated preoperative immunotherapy well; nine patients (9/39, 23.1%) had Grade I–II irAEs. There were no Grade III–IV irAEs. The five patients with pyloric obstruction before treatment tolerated normal diets after treatment. The incidence of postoperative complications among all patients who underwent surgery was 18.9% (7/37), including one case of Grade IIIA anastomotic leakage, one of Grade IIIA intestinal obstruction, one of Grade II abdominal hemorrhage, two of Grade II abdominal infection, one of Grade I intestinal obstruction. Additionally, one patient developed COVID-19 postoperatively. All patients recovered with symptomatic treatment. Conclusion:We found that preoperative treatment of patients with LAGC or AEG of one of three types (CPS≥5, dMMR+MSI-H, and EBER positivity) with a PD-1 inhibitor combined with CapeOx or SOX chemotherapy achieved promising effectiveness and safety, with high surgical conversion, R0 resection, and complete response rates.

Objective:To evaluate the short-term efficacy and safety of a preoperative combination of programmed cell death protein-1 (PD-1) inhibitor with either oxaliplatin + capecitabine (CapeOx) or oxaliplatin + tegafur gimeracil oteracil potassium (SOX) in the treatment of locally advanced immunotherapy-sensitive gastric cancer (LAGC) or adenocarcinoma of the esophagogastric junction (AEG).Methods:The cohort of this retrospective descriptive case series comprised patients with LAGC or AEG whose cancers had been determined to be immunotherapy- sensitive by endoscopic biopsy before treatment in the Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital and Institute from 1 August 1 2021 to 31 January 2024. Patients with any one of the following three characteristics were immunotherapy-sensitive: (i) PD-L1 combined positive score (CPS) ≥5; (ii) microsatellite instability-high (MSI-H) / mismatch repair deficiency (dMMR); or (iii) Epstein-Barr virus-encoded RNA (EBER) positivity. All study patients received PD-1 inhibitors combined with CapeOx or SOX as a neoadjuvant or conversion treatment strategy before surgery. Patients with immune system diseases, distant metastases, or human epidermal growth factor receptor 2 positivity were excluded. Factors analyzed included pathological complete response, clinical complete response, major pathological response, R0 resection rate, surgical conversion rate, and safety of the treatment, including immune-related adverse events (irAEs) and surgical complications.Results:The study cohort comprised 39 patients (28 men and 11 women) of median age 62 (range 44–79) years. After the above-described preoperative treatment, radical resection of the 14 tumors that were initially considered unresectable was achieved (surgical conversion rate: 14/14). Twenty-three of the remaining 25 patients underwent radical resection. The last two patients achieved clinical complete responses and opted for a "non-surgical strategy" (watch and wait). Overall, 37 patients (94.9%) underwent radical resection, with an R0 resection rate of 100% (37/37), pathological complete response rate of 48.6% (18/37), and major pathological response rate of 62.2% (23/37). Of the 24 patients with CPS ≥ 5 (non-MSI-H/dMMR and non-EBER positive), 11 achieved pathological complete responses and one with CPS=95 achieved a clinical complete response. Of the eight patients with MSI-H/dMMR, six achieved pathological complete responses and one a clinical complete response. Of the seven patients with EBER positivity, one achieved a pathological complete response. After excluding patients with major pathological complete responses, there was a statistically significant difference in CPS scores between preoperative biopsy specimens and postoperative surgical specimens in 13 patients (7.769±5.570 vs. 15.538±16.870, t=2.287, P=0.041). All patients tolerated preoperative immunotherapy well; nine patients (9/39, 23.1%) had Grade I–II irAEs. There were no Grade III–IV irAEs. The five patients with pyloric obstruction before treatment tolerated normal diets after treatment. The incidence of postoperative complications among all patients who underwent surgery was 18.9% (7/37), including one case of Grade IIIA anastomotic leakage, one of Grade IIIA intestinal obstruction, one of Grade II abdominal hemorrhage, two of Grade II abdominal infection, one of Grade I intestinal obstruction. Additionally, one patient developed COVID-19 postoperatively. All patients recovered with symptomatic treatment. Conclusion:We found that preoperative treatment of patients with LAGC or AEG of one of three types (CPS≥5, dMMR+MSI-H, and EBER positivity) with a PD-1 inhibitor combined with CapeOx or SOX chemotherapy achieved promising effectiveness and safety, with high surgical conversion, R0 resection, and complete response rates.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Quercetin (Que) is a flavonoid compound widely distributed in nature with various biological activities.Its anti-inflammatory effect plays a crucial role in many diseases,closely related to its regula-tion of histone post-translational modifications.However,there have been no detailed reports on the anti-inflammatory effects of quercetin regulating histone post-translational modifications.In this study,we first investigated the effect of quercetin on the M1 macrophages polarization.The results showed that quercetin can significantly down-regulate the levels of interleukin-1β(IL-1β) and interleukin-6 (IL-6 ) in M1 macrophages.Next,we used the super stable isotope labeling by amino acids in cell culture (super-SI-LAC) method derived from SILAC technology based on mass spectrometry to systematically analyze the post-translational modification levels of histone in macrophages treated with quercetin.A total of 30 his-tone modification sites were quantified,of which 12 histone lysine acetylation marks were significantly downregulated and 4 lysine methylation sites were upregulated (fold change>1.2,P<0.05),and some sites were verified by Western blot (WB),which was consistent with the mass spectrometry results.In conclusion,a comprehensive analysis of quercetin on regulating macrophage histone modifications in this study provides reliable data references and new insights for studying its anti-inflammatory mechanism.