Monkeypox,caused by the monkeypox virus(MPXV),is a zoonotic infectious disease characterized clinically by fever,rash,and lymphadenopathy.In September 2024,the outbreak of a novel MPXV Clade Ib variant in the Democratic Republic of the Congo was designated by the World Health Organization as a public health emergency of international concern,highlighting deficiencies in current prevention and control systems.Although modified attenuated smallpox vaccines exhibit cross-protective efficacy against MPXV infection,their adverse effects still limit clinical applications.Further-more,the therapeutic efficacy of tecovirimat—the FDA emergency-authorized antiviral drug for Smallpox—is limited.Recent studies have shown that tecovirimat does not significantly improve lesion healing time or reduce overall mortality in patients infected with MPXV CladeⅠ.Monoclonal antibodies,which neutralize viral activity by targeting critical membrane proteins,have emerged as a pivotal strategy to overcome current therapeutic bottlenecks by integrating therapeutic,diagnostic and prophylactic functions.This article reviews the epidemiological and virological characteristics of MPXV,along with functional characteristics of MPXV major membrane proteins,including A29L,A35R,B6R,E8L,M1R and H3L,focusing on the research progress in monoclonal antibodies against these key targets.Their protective effects in vitro/in vivo are explored while such as strategies monoclonal antibody combina-tion therapy are recommended to enhance efficacy and overcome drug resistance.

Monkeypox,caused by the monkeypox virus(MPXV),is a zoonotic infectious disease characterized clinically by fever,rash,and lymphadenopathy.In September 2024,the outbreak of a novel MPXV Clade Ib variant in the Democratic Republic of the Congo was designated by the World Health Organization as a public health emergency of international concern,highlighting deficiencies in current prevention and control systems.Although modified attenuated smallpox vaccines exhibit cross-protective efficacy against MPXV infection,their adverse effects still limit clinical applications.Further-more,the therapeutic efficacy of tecovirimat—the FDA emergency-authorized antiviral drug for Smallpox—is limited.Recent studies have shown that tecovirimat does not significantly improve lesion healing time or reduce overall mortality in patients infected with MPXV CladeⅠ.Monoclonal antibodies,which neutralize viral activity by targeting critical membrane proteins,have emerged as a pivotal strategy to overcome current therapeutic bottlenecks by integrating therapeutic,diagnostic and prophylactic functions.This article reviews the epidemiological and virological characteristics of MPXV,along with functional characteristics of MPXV major membrane proteins,including A29L,A35R,B6R,E8L,M1R and H3L,focusing on the research progress in monoclonal antibodies against these key targets.Their protective effects in vitro/in vivo are explored while such as strategies monoclonal antibody combina-tion therapy are recommended to enhance efficacy and overcome drug resistance.

Objective To evaluate the sleep quality of patients with chronic kidney disease(CKD)and to explore the related factors of sleep disorder in patients with CKD.Methods The basic data of hospitalization patients with CKD without renal replacement therapy were prospectively collected,and the Pittsburgh sleep quality index(PSQI)scale was used to evaluate the sleep quality of patients.Patients with a PSQI score of≤5 were divided into the nor-mal sleep group,and patients with a PSQI score of>5 were divided into the sleep disorder group.Logistic regres-sion analysis was used to explore the related factors of sleep disorder in patients with CKD.Results A total of 189 patients with CKD who did not receive renal replacement therapy were included,including 114 males(60.3%)and 75 females(39.7%),aged 56.5±15.23 years.The PSQI score was7.00(5.00,8.00),there were 58 ca-ses in the normal sleep group and 131 cases in the sleep disorder group,and the prevalence of sleep disorder was as high as 69.3%.As the CKD stage progresses,the prevalence of sleep disorders gradually increases.There were differences between the sleep disorder group and the normal sleep group in subjective sleep quality,sleep latency,sleep duration,habitual sleep efficiency,sleep disorder superposition problems,and daytime dysfunction(P<0.05),while there was no statistically significant difference in the scores of sleep medication use.Retirement or unemployed(OR=6.509,95%CI:1.844-22.976)and women(OR=4.561,95%CI:1.241-16.767)were independent risk factors for sleep disorders,while eGFR(OR=0.960,95%CI:0.931-0.991)was a protective factor for sleep disorders,P<0.05.Conclusion The prevalence of sleep disorders in patients with chronic kidney disease without renal replacement therapy gradually increases with the decrease of eGFR and the increase of CKD stage,but they do not receive timely intervention with sleep improvement drugs.Clinicians need to focus on assess-ing sleep quality in women versus unemployed or retired patients with CKD.

Objective:To explore the radiological damage to cells induced by the delayed particles of 9C-ions for heavy ion therapy, as well as the microdosimetric distribution and biological effects of these particles on a single model of V79 Chinese hamster lung cells. Methods:The Monte Carlo program was employed to simulate the endonuclear absorbed doses of α particles with various energies (3-10 MeV) transported in cells (cell radius RC = 10 μm, nucleus radius RN = 5 μm). Then, the result were compared with the S values ( SN←N, SN←Cy, and SN←CS) derived using the medical internal radiation dose (MIRD) method to demonstrate the feasibility of Monte Carlo simulations. Finally, the energy deposition of the delayed particles of 9C-ions generated at three sites (i.e., on the surface and in the cytoplasm and nucleus of the V79 cell model) during their transport in targets was simulated, and the result ing cell surviving fraction was analyzed. Results:Monte Carlo and MIRD method yielded differences in S values of 1.91%-4.95% for SN←N (nucleus to nucleus), 1.48%-5.11% for SN←Cy (cytoplasm to nucleus), and -1.99% to 0.80% for SN←CS(surface to nucleus), indicating highly consistent S values derived using both method(differences < 6%). When a 9C-ion decayed on the surface of the V79 cell model and the produced secondary particles entered the cell, the average endonuclear absorbed dose was 10 -2 Gy orders of magnitude, with a cell surviving fraction of about 88%. In the case where decay occurred in the cytoplasm, the cell surviving fraction was about 80%. However, when the 9C ion decayed in the nucleus, α particles had short ranges and deposited most of their energy in the cell (mean endonuclear absorbed dose: 0.1 Gy). In this case, severe cell damage was induced, with the cell surviving fraction reducing to about 53%. Conclusions:9C-ions emit secondary charged particles due to decay, among which α particles cause great damage to cells when entering the nucleus and trigger evident biological effects.

Objective:To investigate the correlations of urinary adverse reactions with dose to the bladder and urethra during external pelvic irradiation for locally advanced cervical cancer.Methods:This study retrospectively collected relevant dosimetric parameters and urinary symptoms, such as frequent, urgent, and painful urination, from locally advanced cervical cancer patients treated with external pelvic irradiation in the Department of Oncology, Affiliated Hospital of Guizhou Medical University. The dosimetric parameters examined in this study included the maximum, minimum, and mean doses to bladder and urethra (i.e., Dmax, Dmin and Dmean), mean doses received in an area of 0.1, 1, and 2 cm 3 around the planning target volume, D0.1 cm 3, D1 cm 3, D2 cm 3, and percentages of irradiated volumes in the whole organ volume under doses of 5, 10, 15, 20, 25, 30, 35, 40, 45, 50 Gy, V5 Gy, V10 Gy, V15 Gy, V20 Gy, V25 Gy, V30 Gy, V35 Gy, V40 Gy, V45 Gy, V50 Gy. Then the correlations between urinary symptoms and these dosimetric parameters were analyzed using the independent-sample t-test and the Logistic regression model. Results:The median volumes of bladder and urethra were 294.8 and 4.71 cm 3, respectively. Patients were divided into two groups based on the median division. The univariate analysis showed that urethral Dmax, Dmin, Dmean, V5 Gy, V10 Gy, V15Gy, V20 Gy, V25 Gy, V30 Gy, V35 Gy, V40 Gy, V45 Gy and V50 Gy correlated with urinary complications ( t = 14.30, 21.65, 32.19, 33.36, 16.62, 17.91, 21.52, 20.11, 12.27, 37.25, 30.18, 36.24 and 21.98, P<0.05). The multivariate analysis further indicates that urethral D2 cm 3, V20 Gy, V40 Gy and Bladder V40 Gy, D1 cm 3, D2 cm 3 were independent predictors of grade 2 urinary adverse reactions ( P<0.05). Conclusions:This study reported the correlations of relevant dosimetric parameters of urethra with urinary toxicity during external pelvic irradiation. It holds that urethral D2 cm 3, V20 Gy and V40 Gy should be restricted to minimize the risks of grade 2 urinary complications.

Objective:To analyze the clinical characteristics of long-term survival patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy combined with primary tumor radiotherapy, and to establish a Nomogram prognostic model, aiming to provide a certain reference for making a decision about the treatment of advanced NSCLC.Methods:A retrospective analysis was made on the data of 260 NSCLC patients who participated in two prospective clinical studies from January 2003 to May 2012 and the data of 138 NSCLC patients admitted to the Affiliated Cancer Hospital of Guizhou Medical University from January 2014 to August 2020. The former 260 cases were used as a training set and the latter 138 cases were used as the validation set. The overall survival (OS) of ≥ 18 months was defined as long-term survival (LTS). The clinical characteristics of LTS patients were compared with those with OS less than 18 months. The clinical characteristics and treatment-related parameters between the two types of patients were compared using the χ2 test. A multivariate analysis was made using logistic regression, and a nomogram model was built using RStudio. Results:The median OS of the training set was 13.4 months (95% CI: 11.9-14.9), with 1-, 2-, and 3-year OS rates of 55.4%, 19.1%, and 11.9%, respectively. In the training set, 87 cases had LTS and were classified as the LTS group, while 173 cases had OS less than 18 months and were classified as the non-LTS group. The univariate analysis showed that the prognostic factors affecting LST included the KPS score, T status, the number of metastatic organs, the number of metastatic lesions, brain metastasis, bone metastasis, the number of chemotherapy cycles, the biologically effective dose (BED) to the primary tumor, hemoglobin level, platelet count, plasma D-dimer, fibrinogen level, lactate dehydrogenase, and lung immune prognostic index (LIPI; χ2=4.72-12.63, P < 0.05). The multivariable analysis showed that the independent prognostic factors of LTS included a number of chemotherapy cycles ≥ 4, BED ≥ 70 Gy, platelets ≤ 220×10 9/L, D-dimer ≤ 0.5 mg/L, and a good LIPI score ( P= 0.002, 0.036, 0.005, 0.008, and 0.002). A nomogram model was established using the meaningful parameters obtained in the multivariable analysis, determining that the training and validation sets had a consistency index (C-index) of 0.750 and 0.727, respectively. As shown by the analytical result of the corrected curves, for the advanced NSCLC patients treated with thoracic radiotherapy, their LTS probability predicted using the nomogram prognostic model was highly consistent with their actual LTS probability. Both the analytical result of the receiver operating characteristic (ROC) curves and the decision curve analysis (DCA) result showed that the composite prediction model was more beneficial than a single prediction model. Conclusions:For patients with advanced NSCLC treated with thoracic radiotherapy, the independent prognostic factors of LTS included the number of chemotherapy cycles, BED, platelet count, pre-chemotherapy D-dimer, and LIPI score. The Nomogram prognostic model built based on these prognostic factors is a convenient, intuitive, and personalized prediction model used to screen patients who can benefit from thoracic radiotherapy.

Objective:To retrospectively analyze the clinical efficacy and safety of three-dimensional radiotherapy for the primary tumors in patients with stage Ⅳ non-small cell lung cancer complicated with malignant pleural effusion (MPE-NSCLC).Methods:A total of 198 patients who were initially pathologically diagnosed with MPE-NSCLC from January 2007 to April 2018 were enrolled and divided into the untreated group ( n=45), drug group ( n=57) and radiotherapy group ( n=96), respectively. The short-term efficacy, overall survival (OS) and adverse events in the drug and radiotherapy groups were analyzed. The OS rate was analyzed by Kaplan-Meier method and log-rank test. Clinical prognosis was evaluated by multivariate Cox′s regression model. Results:In the radiotherapy group, the objective response rate and non-response rate was 54% and 46%, significantly better than 25% and 75% in the drug group ( P=0.007). In the radiotherapy group, the 1-, 2-, 3-, 5-year OS and median survival was 47%, 18%, 6%, 1% and 12 months, remarkably higher than 15%, 3%, 2%, 0% and 5 months in the drug group, respectively (all P<0.001). Multivariate Cox′s regression analysis showed that radiotherapy for the primary tumors was an independent prognostic factor to prolong the OS ( P<0.001). Radiotherapy at a dose of ≥63 Gy and 4-6 cycles of chemotherapy tended to prolong the OS ( P=0.063 and 0.071). The OS of patients with EGFR mutation receiving radiotherapy combined with molecular target therapy was significantly better than that of those with unknown EGFR status treated with radiotherapy and chemotherapy ( P=0.007). Addition of radiotherapy for the primary tumors did not significantly increase the incidence of adverse events ( P>0.05). Conclusion:Addition of three-dimensional radiotherapy for the primary tumors in MPE-NSCLC patients may prolong the OS and yield tolerable adverse events.

Aim To investigate the reversal effect of vatalanib, a novel kinase inhibitor, on multidrug re-sistance in cancer cells and its mechanism. Methods The cytotoxicity and reversal effects of vatalanib were evaluated in both resistant and sensitive tumor cell lines by MTS or SRB assays. The intracellular accumu-lation of fluorescence substrates ( Rh-123 , MX and ADR for P-gp, BCRP, MRP1, respectively) were ana-lysed by flow cytometry. Western blot or qRT-PCR was
used to determine the protein or mRNA expression lev-el of BCRP. The effect of vatalanib on ATPase activity of BCRP was determined using crude membranes pre-pared from HEK293/ABCG2 cells. Results Vata-lanib at the nontoxic dose ( 5 μmol · L-1 ) potentially reversed BCRP-mediated MDR in cancer cells, howev-er it had no effect on P-gp or MRP1 mediated MDR. Vatalanib did not alter the intracellular accumulation of MX in HEK 2 9 3 / ABCG 2 , and had no influence on the
BCRP-mediated drug efflux. The ATPase assay indica-ted that vatalanib may serve as a substrate of BCRP. Furthermore, vatalanib dramatically suppressed levels of both the protein and mRNA expression of BCRP in concentration-and time-dependent manners. However, reversal concentration of vatalanib had no influence on the total and phosphorylated forms of AKT and ERK1/
2 in resistant cancer cells. Conclusion Vatalanib could significantly reverse BCRP-mediated MDR with specificity, and its mechanism may correlate with the down-regulation levels of BCRP both mRNA and pro-tein in resistant cancer cells.

Objective To investigate the dosimetric influence of pure carbon fiber treatment tabletop of Elekta Precise new linear accelerator in radiotherapy.Methods Surface-axis distance (SAD) technology was employed for the measurement.Two groups of fields were set and both of them were SAD opposed portals ( one of them went through the tabletop,while the other did not).A PTW electrometer and a 0.6 cm3 Farmer ionization chamber were utilized for comparison measurement.Then dose attenuation of the main table board,extended body board,the extended board for head,neck and shoulders,and the joints of these boards were calculated.Results Under the energy of 6 MV,the dose attenuations of the following locations were:1.4％ - 7.2％ at the main treatment table board; 2.8％ - 38.7％,1.4％ -30.1％,1.5％ -20.8％ and 1.4％ - 11.2％,respectively at distances of 1,4,7 and 8 cm from the joint of the main table board ;0.5％ - 5.0％ at the extended body board; 4.7％ - 15.4％ at distance of 1cm from the joint of the extended body board; 0.5％ -3.3％ at the neck position of the extended board for head,neck and shoulders; 5.3％ - 16.7％ at the shoulder positions; and 6.8％ -30.4％ at the joint between the extended boards and the main table board.Conclusions The dose attenuations of the new linear accelerator pure carbon fiber treatment tabletop vary at different locations. Considerable higher attenuations are observed at the table board joints than other locations.

ObjectiveThis study evaluates the feasibility of intensity-modulated radiation therapy (IMRT) to treat patients with 1 -5 brain metastases from non-small cell lung cancer (NSCLC).Methods 30 IMRT patients with brain metastases for NSCLC studied retrospectively.Whole brain radiotherapy plus three-dimensional conformal radiotherapy (WBRT + 3DCRT) and WBRT plus stereotactic radiotherapy ( WBRT + SRT) plans were generated.Planning target volume ( PTV ) and organs at risk dose were measured and compared by dose volume histogram.Differences were analyzed in the three techniques by Wilcoxon Z -test.Results D99％ of the shoulder ( D99％-D90％ ) from IMRT were higher than from WBRT +3DCRT and WBRT+SRT in all cases.From D15％ of slope (D90％-D10％) to D5％ of tail (D10％ -D1％ ),IMRT were lower than WBRT + 3DCRT and WBRT + SRT ( Z =- 4.72,P =0.000 and Z =- 4.72,P =0.000).D10％ and D5％ of IMRT were (35.1 ±1.42) Gy and (37.7 ±2.91) Gy,WBRT +3DCRT were (36.5±2.86) Gy and ( 39.1 ± 3.56) Gy ;WBRT + SRT were (36.2 ± 2.57) Gy and ( 38.7 ± 3.67) Gy.IMRT vs WBRT+ 3DCRT and WBRT + SRT were significant ( Z=-3.18,-3.18,P=0.001,0.001 and Z=- 4.11,- 3.02,P =0.000,0.002) in 13 patients with 3 - 5 brain metastases.The total mean monitor units were 14756.3,9614.8 and 9043.2 for IMRT,WBRT +3DCRT and WBRT + SRT plans,respectively,with a 38.7％ reduction from IMRT to WBRT + SRT (Z =-4.78,-4.78,P =0.000,0.000).The brain doses around metastases were similar in the three techniques with 1 -2 metastases,but IMRT was the best with 3 -5 metastases.ConclusionsIMRT can advance brain metastases dose and improve the planning target minimum dose and spare the dose around brain metastases.Only IMRT is the best choice for just sparing the dose around brain metastases among 3 -5 brain metastases.