Neoadjuvant combination of pazopanib or axitinib and programmed cell death protein-1-activated dendritic cell-cytokine-induced killer cells immunotherapy may facilitate surgery in patients with renal cell carcinoma

BackgroundRadical/cytoreductive nephrectomy or nephron-sparing surgery may be thought to be not safe or unfeasible in some renal cell carcinoma (RCC) patients in which tumor is locally advanced or highly complicated. Neoadjuvant therapy may reduce the volume of the tumor, thus facilitates surgery. The aim the study is to evaluate the efficacy and safety of neoadjuvant combination of pazopanib or axitinib and PD-1-activated dendritic cell-cytokine-induced killer (PD-1/DC-CIK) cell immunotherapy in those patients.MethodsData from 16 RCC patients who received neoadjuvant pazopanib (Group P, n=9) or axitinib (Group A, n=7) plus PD-1/DC-CIK cells immunotherapy were reviewed retrospectively. A total of 9 participants that were potential candidates for radical/cytoreductive nephrectomy (RN/CN) had locally advanced tumor and 5 participants with partial nephrectomy (PN) absolute indications had highly complicated tumors. The efficacy outcomes were based on volume changes of the primary tumor, lymph nodes, and tumor thrombus in 13 participants with complete computed tomography (CT) imaging. The treatment-related toxicities and surgical complications were also reported.ResultsWith a median of 2.1 months treatment, the overall volume of the tumors decreased by a median of 42.30% [interquartile range (IQR): 19.37–66.78%]. Specifically, the median reduction of tumor volume was 88.77 and 15.50 cm³ in group P and group A, respectively (P=0.014). However, participants in Group P were more likely to experience grade 3 or 4 treatment-related adverse events (AEs) than those in Group A (44.4% vs. 0). Finally, all participants were candidates for appropriate surgery after neoadjuvant therapy (as assessed by the surgeon), and 10 participants accepted surgery, including 5 PN, 4 RN/CN, and 1 lymph node dissection. A solitary participant had Clavien grade IV acute renal failure required dialysis and another had grade II lymphatic leakage.ConclusionsNeoadjuvant combination of pazopanib or axitinib and PD-1/DC-CIK cells immunotherapy was well-tolerated and could effectively reduce the volume of tumors in locally advanced or highly complicated RCC patients.     

Genomic annotation and molecular evolution of monkeypox virus outbreak in 2022

Monkeypox virus (MPXV) has generally circulated in West and Central Africa since its emergence. Recently, sporadic MPXV infections in several nonendemic countries have attracted widespread attention. Here, we conducted a systematic analysis of the recent outbreak of MPXV-2022, including its genomic annotation and molecular evolution. The phylogenetic analysis indicated that the MPXV-2022 strains belong to the same lineage of the MPXV strain isolated in 2018. However, compared with the MPXV strain in 2018, in total 46 new consensus mutations were observed in the MPXV-2022 strains, including 24 nonsynonymous mutations. By assigning mutations to 187 proteins encoded by the MPXV genome, we found that 10 proteins in the MPXV are more prone to mutation, including D2L-like, OPG023, OPG047, OPG071, OPG105, OPG109, A27L-like, OPG153, OPG188, and OPG210 proteins. In the MPXV-2022 strains, four and three nucleotide substitutions are observed in OPG105 and OPG210, respectively. Overall, our studies illustrated the genome evolution of the ongoing MPXV outbreak and pointed out novel mutations as a reference for further studies.     

THE OPERATIVE TREATMENT OF SPINAL FRACTURE-DISLOCATION WITHOUT NEUROLOGIC DEFICITS

Objective. To evaluate the results of operative treatment of spinal fracture-dislocation without neumlogic deficits. Metods. Eighteen patients with spinal fracture-dislocation were neurologically intact at the time of injury, and all were treated operatively. The fracture sites were:8 cases in cervical spine, 3 cases in thoracic spine, and 7 cases in lumbar spine. Eight patients with cervical injuries had variant degrees of forward slide and kyphotic deformity. Of the 10 thoracic and lumbar fractures, one had lateral dislocation, 4 cases with kyphotic deformities, 5 cases withspinal canal compromise averaged 50% (ranging from 40% to 70% ).Results. The aveiage period of follow-up was 4.4 years with a range of 11 months to 13 years. All the patients returned to full-time work. No patient developed neurologic deterioration. Kyphotic deformity was corrected in the 4 cases, and no progressive kyphosis was noted. There was no operation-related complication. The averaged post-opera-five hospitalization time was 13 days. Conclusions. Despite the rare incidence of spinal fracture-dislocation without neurologic deficits, we suggested that kind of fracture be considered unstable fracture because of its potential risk of delayed neurologic deterioration and kyphotic deformity, and be treated operatively to restore the sagittal alignment and the stability of the spine.     

Comparison of Chinese and Western rifapentines and improvement of bioavailability by prior taking of various meals

Bioavailability was measured by rifapentine (RPE) serum concentrations and by the urinary ratio between RPE and creatinine, in specimens obtained 4-50 h after 600 mg RPE preceded by food. The bioavailabilities of RPEs manufactured in China and by a Western manufacturer were similar after a standard English breakfast, and serum concentrations were also similar to those obtained in an earlier Italian study following a complex meal. Although absorption of RPE was unsatisfactory after lipid-rich biscuits or shortbread, absorption after egges and toast was excellent and was nearly as good after a fast-food sandwich. The urinary measure of bioavailability at 26 h appeared as efficient as peak serum estimations at 6, 8 and 26 h. Fast-food sandwiches are being taken before RPE in a current clinical trial of Chinese RPE in Hong Kong.     

小鼠颗粒子宫腺细胞的组织学与超微结构的研究

对昆明种小鼠颗粒子宫腺细胞（ＧＭＧ细胞）进行光镜及电镜观察,结果显示：ＧＭＧ细胞以其胞浆中含耐淀粉酶消化的ＰＡＳ阳性颗粒为特点,而该种颗粒在电镜下为带有帽状结构的膜包颗粒。ＧＭＧ细胞有特殊的形态,其出现和消失与妊娠过程同步。     

N-端融合蛋白对重组HBeAg抗原性的影响

目的　研究 Ｎ－ 末端融合蛋白对大肠杆菌中表达的 Ｈ Ｂｅ Ａｇ 抗原性的影响。方法　用 Ｐ Ｃ Ｒ 法,从抗－ Ｈ Ｂｃ（ ＋ ） 血清标本中获得 Ｈ Ｂ Ｖ Ｐｒｅ ｃ － ｃ 基因片段,将其插入质粒 Ｔｒｃ９９ Ａ,重组成亚克隆 Ｐ Ｈ Ｂ Ｉ。以 Ｐ Ｈ Ｂ Ｉ为模板,扩增获得编码乙肝病毒核心蛋白１ ～１４０ 氨基酸的基因片段,加上终止信号,分别插入质粒ｐ Ｇ Ｅ Ｘ－ ２ Ｔ 和 Ｔｒｃ９９ Ａ 中,各自转化后,以 Ｉ Ｐ Ｔ Ｇ 诱导,大肠杆菌表达插入基因。以 Ｅ Ｌ Ｉ Ｓ Ａ 和 Ｓ Ｄ Ｓ－ Ｐ Ａ Ｇ Ｅ 方法测定表达产物的分子量和 Ｈ Ｂｅ Ａｇ 、 Ｈ Ｂｃ Ａｇ 滴度。结果　在 Ｉ Ｐ Ｔ Ｇ 诱导下,大肠杆菌中分别表达 Ｎ－ 端融合的 Ｇ Ｓ Ｔ－ Ｈ Ｂｅ Ａｇ 融合蛋白和非融合 Ｈ Ｂｅ Ａｇ 蛋白。分子量各为４１０００ Ｄ 和１５０００ Ｄ。培养裂解物经 Ｅ Ｌ Ｉ Ｓ Ａ 测定,融合蛋白 Ｈ Ｂｅ Ａｇ ： Ｈ Ｂｃ Ａｇ 的滴度比为２５６ ：１ ,非融合蛋白为１６ ：１ 。结论　 Ｎ－ 端融合蛋白 Ｇ Ｓ Ｔ－ Ｈ Ｂｅ Ａｇ 抗原性更接近血清 Ｈ Ｂｅ Ａｇ 。