Malignant pleural mesothelioma(MPM)is strongly associated with a history of asbestos exposure and is characterized by high malignancy,high mortality,and poor prognosis.Current treatments for MPM are limited and generally suboptimal,resulting in a median overall survival(OS)of approximately one year for MPM patients.However,advancements in treatment options,including surgery,radiotherapy,chemotherapy,immunotherapy and targeted therapy,have brought new hope to patients with MPM.For early-stage MPM patients categorized under the TNM staging system,surgical treatment is feasible and can improve survival rates and quality of life.However,there is still debate regarding the optimal surgical approach for MPM.In addition to surgery,radiotherapy plays a vital role in MPM treatment.It is often used as prophylactic treatment or for alleviating local symptoms in advanced stages.Radiotherapy can also serve as neoadjuvant or adjuvant therapy in surgical contexts.For patients experiencing local progression or isolated distant metastases after systemic treatment,radiotherapy is a viable option.The advent of advanced radiotherapy techniques,such as intensity-modulated radiotherapy(IMRT)and volumetric intensity-modulated arc therapy(VMAT),has significantly improved the precision and efficacy of radiotherapy while minimizing damage to healthy tissues.Furthermore,brachytherapy can relieve pain or act as a localized supplemental therapy.Chemotherapy remains the standard treatment for MPM.The combination of pemetrexed and platinum-based drugs is widely applied as first-line therapy and has been shown to significantly extend survival.However,commonly used second-line regimens often yield suboptimal results.In recent years,immunotherapy has developed rapidly.Dual immunotherapy with nivolumab and ipilimumab has demonstrated impressive clinical efficacy and safety.The combination of immunotherapy and chemotherapy has also notably extended patients'median survival.Multiple clinical trials have confirmed that this combination therapy benefits patients.Currently available targeted therapies for MPM primarily focus on anti-angiogenesis.Bevacizumab combined with chemotherapy has established its position as a first-line treatment.Research on ramucirumab and apatinib suggests that these drugs have certain efficacy and safety profiles.Beyond conventional treatment options,the UV1 cancer vaccine combined with dual immunotherapy offers new hope for patients.Chimeric antigen receptor T(CAR-T)cell therapy is an emerging treatment method being investigated in MPM patients,with phase Ⅰ clinical trials demonstrating good antitumor effects.Additionally,some antibody-drug conjugates are becoming therapeutic options for MPM through precise targeting.Tumor treating fields combined with chemotherapy has also shown efficacy in extending survival.Despite the increasing variety of treatment options for MPM,its diagnosis and treatment still face numerous challenges,including difficulties in early detection,treatment resistance,and a lack of large-scale evidence-based clinical studies.Future research should focus on improving early diagnosis rates,developing new treatment strategies,overcoming resistance,and advancing personalized therapy.Strengthening the integration of basic research and clinical trials will also be essential.Through multidisciplinary collaboration and continuous innovation,it is hoped that more effective and safer treatment options will become available,ultimately improving the prognosis of MPM patients.

Physiologically based pharmacokinet-ics(PBPK)model is a tool to simulate the process of drug absorption,distribution,metabolism and excretion in vivo.It is widely used in drug research and regulation.In the bioequivalence evaluation of generic drug consistency evaluation and drug pro-duction process change,the PBPK model can pro-vide a certain reference and theoretical support for the drug bioequivalence,thereby promoting safer and more economic drug clinical trials.In this pa-per,the application progress of PBPK model in bio-equivalence study will be reviewed in order to pro-vide support for clinical research on drugs in China.

[Objective] : To systematically evaluate the overall efficacy of external application of traditional Chinese medicine (EA-TCM) in combination with oral three-step analgesic ladder therapy for patients suffering from cancer-induced bone pain (CIBP). [Methods] : We conducted a literature search of randomized controlled trials on the combination of EA-TCM and three-step analgesic ladder therapy for CIBP across ten databases and two registration systems. It included four Chinese databases [Chinese Biomedical Literature Database (SinoMed), China National Knowledge Infrastructure (CNKI), Wanfang Database, and China Science and Technology Journal Database (VIP) ], six English databases (Scopus, Embase, Web of Science, PubMed, Cochrane Library, and OpenGrey), and two registration systems (Chinese Clinical Trial Registry and ClinicalTrials.gov). The timeframe for the literature search extended from the inception of each database to December 31, 2023. Meta-analysis was performed using RevMan (v5.4.1), and the outcome indicators (pain relief rate, analgesic duration, quality of life, pain intensity, breakthrough pain frequency, and adverse reactions) were graded using GRADE profiler (v3.6). [Results] : According to the established inclusion and exclusion criteria, a total of 43 studies was deemed eligible, involving 3 142 participants with CIBP. The results of meta-analysis showed that compared with oral three-step analgesic ladder therapy alone, the combined therapy of EA-TCM and three-step analgesic ladder has a significant improvement in pain relief rate [risk ratio (RR) = 1.32, 95% confidence interval (CI): 1.24 to 1.41, P < 0.000 01], analgesic duration [mean difference (MD) = 1.33, 95% CI: 0.97 to 1.69, P < 0.000 01], and quality of life (MD = 5.66, 95% CI: 4.88 to 6.44, P < 0.000 01). Furthermore, the combined therapy significantly reduced pain intensity (MD = – 1.00, 95% CI: – 1.19 to – 0.80, P < 0.000 01), breakthrough pain frequency (MD = – 0.43, 95% CI: – 0.51 to – 0.36, P < 0.000 01), and adverse reactions (RR = 0.60, 95% CI: 0.53 to 0.68, P < 0.000 01) in CIBP patients. Based on the GRADE assessment, the level of evidence varied from low to moderate. [Conclusion] EA-TCM combined with the three-step analgesic ladder therapy can effectively alleviate pain symptoms in patients with CIBP and improve their quality of life. Additionally, the EA-TCM can effectively reduce the incidence of adverse reactions associated with three-step analgesic therapy.

Objective To explore the construction of α-1,3-galactosyltransferase (GGTA1) gene-knockout (GTKO) Diannan miniature pigs and the kidney xenotransplantation from pigs to rhesus macaques, and to assess the effectiveness of GTKO pigs. Methods The GTKO Diannan miniature pigs were constructed using the CRISPR/Cas9 gene-editing system and somatic cell cloning technology. The phenotype of GTKO pigs was verified through polymerase chain reaction, Sanger sequencing and immunofluorescence staining. Flow cytometry was used to detect antigen-antibody (IgM) binding and complement-dependent cytotoxicity. Kidney xenotransplantation was performed from GTKO pigs to rhesus macaques. The humoral immunity, cellular immunity, coagulation and physiological indicators of the recipient monkeys were monitored. The function and pathological changes of the transplanted kidneys were analyzed using ultrasonography, hematoxylin-eosin staining, immunohistochemical staining and immunofluorescence staining. Results Single-guide RNA (sgRNA) targeting exon 4 of the GGTA1 gene in Diannan miniature pigs was designed. The pGL3-GGTA1-sgRNA1-GFP vector was transfected into fetal fibroblasts of Diannan miniature pigs. After puromycin selection, two cell clones, C59# and C89#, were identified as GGTA1 gene-knockout clones. These clones were expanded to form cell lines, which were used as donor cells for somatic cell nuclear transfer. The reconstructed embryos were transferred into the oviducts of trihybrid surrogate sows, resulting in 13 fetal pigs. Among them, fetuses F04 and F11 exhibited biallelic mutations in the GGTA1 gene, and F04 had a normal karyotype. Using this GTKO fetal pig for recloning and transferring the reconstructed embryos into the oviducts of trihybrid surrogate sows, seven surviving piglets were obtained, all of which did not express α-Gal epitope. The binding of IgM from the serum of rhesus monkey 20# to GTKO pig PBMC was reduced, and the survival rate of GTKO pig PBMC in the complement-dependent cytotoxicity assay was higher than that of wild-type pig. GTKO pig kidneys were harvested and perfused until completely white. After the left kidney of the recipient monkey was removed, the pig kidney was heterotopically transplanted. Following vascular anastomosis and blood flow restoration, the pig kidney rapidly turned pink without hyperacute rejection (HAR). Urine appeared in the ureter 6 minutes later, indicating successful kidney transplantation. The right kidney of the recipient was then removed. Seven days after transplantation, the transplanted kidney had good blood flow, the recipient monkey's serum creatinine level was stable, and serum potassium and cystatin C levels were effectively controlled, although they increased 10 days after transplantation. Seven days after transplantation, the levels of white blood cells, lymphocytes, monocytes and eosinophils in the recipient monkey increased, while platelet count and fibrinogen levels decreased. The activated partial thromboplastin time, thrombin time and prothrombin time remained relatively stable but later showed an upward trend. The recipient monkey survived for 10 days. At autopsy, the transplanted kidney was found to be congested, swollen and necrotic, with a small amount of IgG deposition in the renal tissue, and a large amount of IgM, complement C3c and C4d deposition, as well as CD68⁺ macrophage infiltration. Conclusions The kidneys of GTKO Diannan miniature pigs may maintain normal renal function for a certain period in rhesus macaques and effectively overcome HAR, confirming the effectiveness of GTKO pigs for xenotransplantation.

Objective To understand the surveillance situation of poliovirus in Guangzhou from 2011 to 2024, and to further strengthen polio surveillance and ensure the continued maintenance of a polio-free status. Methods An analysis was conducted on the discovery and investigation results of six cases of vaccine-derived poliovirus (VDPV) detected in Guangzhou. Results A total of 6 VDPV incidents were reported in Guangzhou from 2011 to June 2024, among which 5 incidents were from sewage sample testing in the Liede Sewage Treatment Plant in Guangzhou, all of which were confirmed as VDPV, with 1 for type I, 1 for type II, and 3 for type III. In addition, one confirmed HFMD case was identified as a type VDPV II carrier. No presence of any wild poliovirus (WPV), VDPV cases, or circulating VDPV (cVDPV) was reported. Conclusion Guangzhou City has maintained a high level of vigilance and effectiveness in the monitoring and prevention of polio. Continuously strengthening the construction of the polio monitoring network, optimizing vaccination strategies, and comprehensively improving public health awareness are still the focus of the prevention and control work in the future.

Objective To develop GTKO (α-1,3-galactosyltransferase gene-knockout, GTKO)/hCD55 (human CD55) gene-edited xenotransplant donor pigs and verify their function. Methods In this study, CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated nuclease 9), PiggyBac transposon technology and somatic cell nuclear transfer technology were used to construct GTKO/hCD55 gene-edited Diannan miniature pigs. The phenotype and function of GTKO/hCD55 pigs were analyzed by Sanger sequencing, real-time fluorescence quantitative PCR, flow cytometry, immunofluorescence, bisulfite sequencing, antigen-antibody binding assays, and complement-dependent cytotoxicity assays. Results After transfection of PX458 and PiggyBac gene editing vectors into wild-type fetal pig fibroblasts, 48 single-cell colonies were obtained through puromycin drug screening. Two single-cell colonies were selected for somatic cell nuclear transfer, resulting in two fetal pigs at 33 days of gestation. The GGTA1(α-1,3-galactosyltransferase) genotypes of fetal pig F01 were -17 bp and wild type (WT), while the GGTA1 genotypes of fetal pig F02 were -26 bp/+2 bp and -3 bp. The hCD55 mRNA expression levels of both fetal pigs were significantly higher than those of WT pigs (P＜0.01). The fetal pig F02 was selected as the donor cell source for recloning, 11 surviving piglets were obtained, all identified as GTKO/hCD55 gene-edited pigs. These pigs showed absence of α-Gal antigen expression, but weak or no expression of hCD55 was observed. Methylation analysis of the hCD55 gene's CpG island showed hypermethylation in kidney tissue lacking hCD55 expression, whereas it was not methylated or partially methylated in kidney tissue expressing hCD55. Moreover, codon optimization of the CpG island of the hCD55 gene to reduce CG content could achieve stable expression of the hCD55 gene. In addition, antigen-antibody binding experiment showed that the amount of human IgM binding to GTKO/hCD55 gene-edited pig fibroblasts was significantly lower than that of WT pigs (P＜0.01). Complement-dependent cytotoxicity experiment showed that the survival rate of fibroblasts in GTKO/hCD55 pigs was significantly higher than that in WT pigs (P＜0.01). Conclusion This study demonstrates the successful generation of GTKO/hCD55 gene-edited xenotransplant donor pigs. Methylation-induced gene silencing of the hCD55 gene can be effectively avoided by reducing the CG content of the CpG island through codon optimization. This study provides a reference for the development of xenotransplant donor pigs and guides subsequent research on xenotransplantation.

Adolescent idiopathic scoliosis(AIS)is a complex three-dimensional deformity involving coronal,sagittal,and axial planes,with a prevalence that should not be overlooked.With advancements in technology and in-depth research,an increasing number of hospitals and physicians are exploring standardized diagnostic and treatment approaches for AIS.Comprehensive and in-depth understanding is required for AIS,including its etiology,screening and diagnosis,classification,assessment and examination,treatment options,exploration of current focus,and evaluation of quality of life.Such understanding ensures that the diagnostic and treatment are scientific,standardized,and timely.Based on the principles of evidence-based medicine,a consensus on the diagnosis and treatment of AIS is reached after multiple discussions among spinal surgery experts,aiming to provide reference and guidance for clinical practice.

Physiologically based pharmacokinet-ics(PBPK)model is a tool to simulate the process of drug absorption,distribution,metabolism and excretion in vivo.It is widely used in drug research and regulation.In the bioequivalence evaluation of generic drug consistency evaluation and drug pro-duction process change,the PBPK model can pro-vide a certain reference and theoretical support for the drug bioequivalence,thereby promoting safer and more economic drug clinical trials.In this pa-per,the application progress of PBPK model in bio-equivalence study will be reviewed in order to pro-vide support for clinical research on drugs in China.

Objective:To analyze and compare the reporting data of adverse events following immunization (AEFI) of influenza vaccines in Fujian Province from 2019 to 2023.Methods:Using the National Immunization Program Information Management System, the AEFI reports and vaccination data of influenza vaccines in Fujian Province from 2019 to 2023 were collected, and the reporting rates and clinical characteristics of AEFI of 6 types of influenza vaccines were compared. The 6 types of vaccines in the analysis were as follows: trivalent inactivated influenza vaccines (IIV3) for 6-35 months old people, IIV3 for ≥3 years old people, trivalent live attenuated nasal spray vaccine (LAIV3) for 3-17 years old people, quadrivalent inactivated influenza vaccines (IIV4) for 6-35 months old people, IIV4 for ≥6 months old people, and IIV4 for ≥3 years old people.Results:From 2019 to 2023, a total of 87 687.21 million doses of influenza vaccine were vaccinated in Fujian Province, and 510 cases of AEFI were reported, with a reporting rates of 5.82 per 100 000 doses. Among the 510 cases, 443 (86.86%) were general reactions, 56 (10.98%) were abnormal reactions, 1 (0.20%) was psychogenic reactions, and 10 (1.96%) were coincidence. There were no reports of vaccination accidents and vaccine quality accidents. The reporting rates of AEFI were relatively higher in 2019 and 2020 (18.38 and 18.00 per 100 000 doses, respectively), and lower in 2021, 2022 and 2023 (8.91, 10.68 and 2.30 per 100 000 doses, respectively); the differences were statistically significant (all P<0.05). The differences of reporting rates of AEFI between IIV3 for 6-35 months old people and IIV4 for 6-35 months old people, the injectable vaccines and nasal spray vaccines were not statistically significant. However, the reporting rates of overall AEFI, general reactions and abnormal reactions of IIV3 for ≥3 years old people were all higher than those of IIV4 for ≥3 years old people (7.77 per 100 000 doses vs. 3.88 per 100 000 doses, 6.18 per 100 000 doses vs. 3.59 per 100 000 doses, 1.41 per 100 000 doses vs. 0.19 per 100 000 doses). The reporting rates of overall AEFI and general reaction of IIV3 for 6-35 months old people were both higher than those of IIV3 for ≥3 years old (16.47 per 100 000 doses vs. 7.77 per 100 000 doses, 13.05 per 100 000 doses vs. 6.18 per 100 000 doses), and the differences were statistially significant (all P<0.05). The reporting rates of general abnormal reactions of IIV4 for 6-35 months old and ≥ 6 months old people were both higher than those of IIV4 for ≥3 years old people (14.73 per 100 000 doses and 9.52 per 100 000 doses vs. 3.88 per 100 000 doses); the reporting rates of general reactions and abnormal reactions of IIV4 for ≥6 months old people were both higher than those of IIV4 for ≥3 years old people (12.94 per 100 000 doses vs. 3.59 per 100 000 doses, 1.34 per 100 000 doses vs. 0.19 per 100 000 doses), the differences were statistcially significant (all P<0.05). In terms of clinical features, the reporting rates of fever (37.6-38.5 ℃ and ≥ 38.5 ℃), local redness and swelling (diameter 2.6-5.0 cm), and local induration (diameter ≤2.5 cm and 2.6-5.0 cm) after vaccination of IIV3 for ≥3 years old people were higher than those of IIV4 for ≥ 3 years old people (1.41 per 100 000 doses vs. 0.64 per 100 000 doses, 3.00 per 100 000 doses vs. 1.16 per 100 000 doses); the reporting rates of allergic rash and angioedema of IIV3 for ≥ 3 years old people were higher than those of IIV4 for ≥3 years old people (0.53 per 100 000 doses vs. 0.12 per 100 000 doses, 0.35 per 100 000 doses vs. 0); the differences were statistically significant (all P<0.016 7). Conclusions:The reporting rates of AEFI for influenza vaccines in Fujian Province from 2019 to 2023 was showing a downward trend. The AEFI was mainly general reactions. The reporting rates of AEFI were different among different influenza vaccines, but the overall safety was good.

Objective:To investigate the association of serum apolipoprotein A1 (Apo-A1) and tumor abnormal protein (TAP) with recurrence risk after transurethral resection of bladder tumor (TURBT) in patients with bladder cancer.Methods:The data of 120 patients with bladder cancer who received TURBT treatment and were followed up in Xi′an Daxing Hospital from April 2018 to April 2021 were retrospectively collected. According to the recurrence data after 3 years of follow-up, the patients were divided into recurrence group (29 cases) and non-recurrence group (91 cases). Baseline data, serum Apo-A1, TAP levels and other laboratory indicators at the last preoperative examination were collected and compared between the two groups. Cox regression analysis was performed to determine the association of serum Apo-A1, TAP with recurrence in these patients after TURBT. The dose-response relationship between serum Apo-A1, TAP and risk of recurrence after TURBT in patients with bladder cancer was analyzed by restricted cubic spline method. The interaction of serum Apo-A1 and TAP on recurrence after TURBT in patients with bladder cancer was analyzed.Results:During the follow-up period of 3 years, the disease recurred in 29 patients, with recurrence time from 16 to 33 months, and with the median recurrence time of 25.00 (20.50, 29.50) months. The proportion of tumor TNM stageⅡ, tumor pathological grade G 2, non intravesical bacillus Calmette-Guérin perfusion after operation and serum Apo-A1, TAP, nuclear matrix protein 22, bladder tumor antigen levels in the recurrence group were higher than those in the non-occurrence group: 72.41% (21/29) vs. 50.55% (46/91), 34.48% (10/29) vs. 14.29% (13/91), 31.03% (9/29) vs. 12.09% (11/91), (29.45 ± 4.78) μg/L vs. (24.81 ± 4.25) μg/L, (165.37 ± 10.28) μm 2 vs. (156.33 ± 9.92) μm 2, (31.11 ± 5.21) μg/L vs. (28.29 ± 5.13) μg/L, (27.93 ± 4.18) μg/L vs. (25.57 ± 4.95) μg/L, and the differences were statistically significant ( P<0.05). Cox regression analysis showed that the recurrence after TURBT was related to the levels of serum Apo-A1, TAP and nuclear matrix protein 22 ( P<0.05). The results of restricted cubic spline analysis showed that there was a linear dose-response relationship between serum Apo-A1, TAP levels and the risk of recurrence after TURBT in patients with bladder cancer ( P<0.05). When serum Apo-A1≥25.50 μg/L and TAP≥159.20 μm 2, the risk of postoperative recurrence increased with the increase of their expression. There was a positive interaction between serum Apo-A1 and TAP on the recurrence after TURBT in patients with bladder cancer. The risk of recurrence in patients with high expression of both was 25.25 times that of patients with low expression of both, and the synergistic effect was 1.521 times that of the sum of the effects of the two alone. In the risk of tumor recurrence, 32.95% was caused by the interaction between the two. Conclusions:The risk of recurrence after TURBT in patients with bladder cancer may be related to the levels of serum Apo-A1 and TAP. Increase of the two levels may be a risk factor for postoperative recurrence, and there is a significant dose-response relationship between the two, and there is a positive interaction with tumor recurrence.