<b>Objective:b> To investigate the feasibility and safety of modified interposed jejunal anastomosis following total laparoscopic proximal gastrectomy. <b>Methods:b> The modification in the digestive tract reconstruction involves transecting the small intestine 2-3 cm below the gastrojejunostomy site and relocating the enteroenterostomy cranially, based on the double-tract anastomosis technique. Specifically, the jejunum and its mesenteric vessels are transected 20-25 cm from the ligament of Treitz. An overlap anastomosis is performed between the esophagus and the distal jejunum, with the common opening closed using a 15 cm barbed suture in a buried manner. A side-to-side gastrojejunostomy is completed under natural anatomical alignment, and the common opening is closed similarly. A side-to-side anastomosis is then created between the small intestine approximately 10 cm below the gastrojejunal anastomosis and the small intestine distal to the ligament of Treitz. Finally, the small intestine is transected 2-3 cm below the gastrojejunal anastomosis without dividing the mesenteric vessels. <b>Results:b> From April to December 2024, a total of five patients with adenocarcinoma of the esophagogastric junction underwent modified interposed jejunum anastomosis following totally laparoscopic proximal gastrectomy at the Affiliated Tumor Hospital of Xinjiang Medical University. The median age of the group was 56 (53-74) years, including four males and one female, with a median body mass index of 24 (21-29) kg/m². Three cases were classified as Siewert type II and two as type III. All five patients successfully completed the totally laparoscopic proximal gastrectomy with modified interposed jejunum anastomosis. The median operative time was 215 (165-240) minutes, the digestive tract reconstruction time was 75 (65-93) minutes, and the intraoperative blood loss was 50 (30-100) ml. The median time to postoperative flatus was 71 (68-88) hours, with no severe complications occurring in any case. The median postoperative hospital stay was 8 (8-9) days. Within three months after surgery, none of the patients reported reflux symptoms such as acid regurgitation or heartburn. <b>Conclusions:b> Total laparoscopic modified interposed jejunal anastomosis is safe and feasible, with relatively simple operative steps. It effectively prevents reflux while ensuring the passage of food through the remnant stomach and duodenal loop.
Humans ; Gastrectomy/methods* ; Jejunum/surgery* ; Laparoscopy/methods* ; Anastomosis, Surgical/methods* ; Male ; Female ; Middle Aged ; Aged ; Stomach Neoplasms/surgery* ; Plastic Surgery Procedures/methods*

[摘 要] 目的：构建靶向CD38和CD138分子抗原的双靶点嵌合抗原受体基因修饰T淋巴细胞（CD38/CD138 CAR-T细胞），探讨其对多发性骨髓瘤（MM）细胞的体外杀伤作用。方法：利用CAR-T细胞技术，基于MM细胞高表达CD38和CD138抗原，分别构建靶向CD38、CD138的CD38 CAR-T与CD138 CAR-T细胞，以及同时靶向CD38与CD138的CD38/CD138 CAR-T细胞，实验分为未处理T、CD38 CAR-T、CD138 CAR-T和CD38/CD138 CAR-T细胞组。采用流式细胞术检测CAR-T细胞的表型，利用LDH释放法检测各种CAR-T细胞对MM细胞RPMI8226和U266的体外杀伤作用。结果：成功构建CD38 CAR-T、CD138 CAR-T和CD38/CD138 CAR-T细胞。CD38/CD138 CAR-T细胞倾向于向记忆表型分化，表达较高水平的增殖分子（CD25）、激活分子（CD27）和较低水平的耗竭分子（PD-1、CTLA-4、TIM-3）（均P < 0.001），而且CD38/CD138 CAR-T细胞不易于耗竭和衰老，且表达较低水平的r-H2AX、p-p53、p21和p16蛋白（均P < 0.01）。在不同效靶比条件下，CD38/CD138 CAR-T细胞较CD38 CAR-T、CD138 CAR-T细胞对RPMI8226和U266细胞具有更强的杀伤作用（均P < 0.001）。结论：靶向CD38和CD138治疗MM的CD38/CD138 CAR-T 细胞在体外具有较优表型及较强的抗肿瘤功能。

Background: and Purpose Posterior cerebral artery occlusion (PCAo) can cause long-term disability, yet randomized controlled trials to guide optimal reperfusion strategy are lacking. We compared the outcomes of PCAo patients treated with endovascular thrombectomy (EVT) with or without intravenous thrombolysis (IVT) to patients treated with IVT alone. Methods: From the multicenter retrospective Posterior cerebraL ArTery Occlusion (PLATO) registry, we included patients with isolated PCAo treated with reperfusion therapy within 24 hours of onset between January 2015 and August 2022. The primary outcome was the distribution of the modified Rankin Scale (mRS) at 3 months. Other outcomes comprised 3-month excellent (mRS 0–1) and independent outcome (mRS 0–2), early neurological improvement (ENI), mortality, and symptomatic intracranial hemorrhage (sICH). The treatments were compared using inverse probability weighted regression adjustment. Results: Among 724 patients, 400 received EVT+/-IVT and 324 IVT alone (median age 74 years, 57.7% men). The median National Institutes of Health Stroke Scale score on admission was 7, and the occluded segment was P1 (43.9%), P2 (48.3%), P3–P4 (6.1%), bilateral (1.0%), or fetal posterior cerebral artery (0.7%). Compared to IVT alone, EVT+/-IVT was not associated with improved functional outcome (adjusted common odds ratio [OR] 1.07, 95% confidence interval [CI] 0.79–1.43). EVT increased the odds for ENI (adjusted OR [aOR] 1.49, 95% CI 1.05–2.12), sICH (aOR 2.87, 95% CI 1.23–6.72), and mortality (aOR 1.77, 95% CI 1.07–2.95). Conclusion Despite higher odds for early improvement, EVT+/-IVT did not affect functional outcome compared to IVT alone after PCAo. This may be driven by the increased risk of sICH and mortality after EVT.

Due to the limitations of current anti-HBV therapies, the HBV core (HBc or HBcAg) protein assembly modulators (CpAMs) are believed to be potential anti-HBV agents. Therefore, discovering safe and efficient CpAMs is of great value. In this study, we established a HiBiT-based high-throughput screening system targeting HBc and screened novel CpAMs from an in-house marine chemicals library. A novel lead compound <b>8ab>, a derivative of the marine natural product naamidine J, has been successfully screened for potential anti-HBV activity. Bioactivity-driven synthesis was then conducted, and the structure‒activity relationship was analyzed, resulting in the discovery of the most effective compound <b>11ab> (IC₅₀ = 0.24 μmol/L). Furthermore, <b>11ab> was found to significantly inhibit HBV replication in multiple cell models and exhibit a synergistic effect with tenofovir disoproxil fumarate (TDF) and IFNa2 in vitro for anti-HBV activity. Treatment with <b>11ab> in a hydrodynamic-injection mouse model demonstrated significant anti-HBV activity without apparent hepatotoxicity. These findings suggest that the naamidine J derivative <b>11ab> could be used as the HBV core protein assembly modulator to develop safe and effective anti-HBV therapies.

Methods: In retrospectively collected data, 149 patients who underwent single-level ACDF for degenerative disease were enrolled and divided into non-plating (n=66) and plating (n=83). Interspinous motion (ISM) at the arthrodesis segment, Numeric Rating Scale (NRS) for neck pain, and Neck Disability Index (NDI) were serially evaluated at 3, 6, and 12 months postoperatively. Predictable factors for fusion, including age, sex, plating, diabetes, smoking, and type of grafts, were investigated, and fusion was defined as ISM <1 mm. Results: In both groups, ISM was the highest at 3 months and gradually decreased thereafter, and the plating group showed significantly lower serial ISM than the non-plating group at 12 months. The plating group had lower NRS and NDI scores than the nonplating group at 12 months, and the difference in the NRS scores was statistically significant, particularly at 3 and 6 months, although that of the NDI scores was not. In a multivariate analysis, plating was the most powerful predictor for fusion. Conclusions Plating significantly decreases the serial ISM compared with non-plating in single-level ACDF, and such decreased motion is correlated with decreased neck pain until 12 months postoperatively, particularly at 3 and 6 months. Given that plating was the most predictive factor for fusion, we recommend plating even in single-level ACDF for better early clinical outcomes.

The present study aimed to assess the molecular profiles of subepithelial connective tissue grafts (CTGs) obtained at different locations and depths in the human palate. Sixty-four CTGs belonging to anterior deep (AD), anterior superficial (AS), posterior deep (PD), and posterior superficial (PS) groups were subjected to RNA-Sequencing and their transcriptomes were analyzed computationally. Functional correlations characterizing the CTG groups were validated by cell biological experiments using primary human palatal fibroblasts (HPFs) extracted from the CTGs. A clearly more pronounced location-dependent than depth-dependent difference between the grafts, with a minimal number of genes (4) showing no dependence on the location, was revealed. Epithelial, endothelial, and monocytic cell migration was strongly (P < 0.001) potentiated by AD- and PS-HPFs. Moreover, significantly increased expression of genes encoding C-C and C-X-C motif chemokine ligands as well as significantly (P < 0.01) activated p38 signaling suggested immunomodulatory phenotype for AD- and PS-HPFs. Increased growth factor gene expression and significantly activated (P < 0.001) Erk and Akt signaling in HPFs originating from A-CTGs implied their involvement in cell survival, proliferation, and motility. Prominent collagen-rich expression profile contributing to high mechanical stability, increased osteogenesis-related gene expression, and strongly activated (P < 0.001) Smad1/5/8 signaling characterized HPFs originating from P-CTGs. The present data indicate that in humans, differences between palatal CTGs harvested from different locations and depths appear to be location- rather than depth-dependent. Our findings provide the basis for future personalization of the therapeutic strategy by selecting an optimal graft type depending on the clinical indications.
Humans ; Connective Tissue/transplantation* ; Palate ; Collagen ; Fibroblasts ; Signal Transduction

Indolylarylsulfones (IASs) are classical HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with a unique scaffold and possess potent antiviral activity. To address the high cytotoxicity and improve safety profiles of IASs, we introduced various sulfonamide groups linked by alkyl diamine chain to explore the entrance channel of non-nucleoside inhibitors binding pocket. 48 compounds were designed and synthesized to evaluate their anti-HIV-1 activities and reverse transcriptase inhibition activities. Especially, compound R₁₀L₄ was endowed with significant inhibitory activity towards wild-type HIV-1 (EC_50(WT) = 0.007 μmol/L, SI = 30,930) as well as a panel of single-mutant strains exemplified by L100I (EC₅₀ = 0.017 μmol/L, SI = 13,055), E138K (EC₅₀ = 0.017 μmol/L, SI = 13,123) and Y181C (EC₅₀ = 0.045 μmol/L, SI = 4753) which were superior to Nevirapine and Etravirine. Notably, R₁₀L₄ was characterized with significantly reduced cytotoxicity (CC₅₀ = 216.51 μmol/L) and showed no remarkable in vivo toxic effects (acute and subacute toxicity). Moreover, the computer-based docking study was also employed to characterize the binding mode between R₁₀L₄ and HIV-1 RT. Additionally, R₁₀L₄ presented an acceptable pharmacokinetic profile. Collectively, these results deliver precious insights for next optimization and indicate that the sulfonamide IAS derivatives are promising NNRTIs for further development.

[摘 要] 目的：探讨碱性核蛋白1（BNC1）对食管鳞状细胞癌（ESCC）细胞增殖、迁移、侵袭、细胞周期和凋亡的影响及其作用机制。方法：通过qPCR法检测ESCC细胞和正常食管上皮细胞中BNC1 mRNA的表达水平，免疫组织化学染色法检测10例ESCC患者癌及癌旁组织中BNC1的蛋白表达水平。利用siRNA敲低BNC1在KYSE-150和KYSE-30细胞中的表达，CCK-8法、划痕愈合实验、Transwell实验和流式细胞术检测BNC1对细胞增殖、迁移、侵袭、细胞周期和凋亡等的影响。通过CHIP-seq实验和GEPIA在线网站数据分析并结合敲低BNC1后的转录组测序数据分析筛选BNC1调控的下游靶基因，qPCR法验证BNC1敲低后靶基因的表达变化，并用双荧光素酶报告基因实验验证BNC1对靶基因的调控作用。结果：BNC1 mRNA和蛋白水平在ESCC组织中较癌旁组织高表达（均P<0.01）。敲低BNC1可明显抑制KYSE-150、KYSE-30细胞的增殖、迁移和侵袭能力（P<0.05或P<0.01），将细胞阻滞于G1期并促进细胞的凋亡（均P<0.01）。CHIP-seq实验结果和在线网站GEPIA数据分析结合敲低BNC1后的转录组测序数据显示，G蛋白通路抑制因子1（GPS1）可能为BNC1正向调控的致癌靶基因。qPCR法和双荧光素酶报告基因实验结果显示，BNC1对GPS1有调控作用（P<0.01）。结论：BNC1在ESCC组织和细胞中高表达，干扰BNC1可显著抑制ESCC细胞的增殖、迁移和侵袭能力，阻滞细胞于G1期并促进细胞凋亡，其机制可能是BNC1通过靶向GPS1调控ESCC细胞的恶性生物学行为。

Purpose: Various types of trauma can cause retinal hemorrhages in children, including accidental and nonaccidental head trauma. We used animal eyes and a finite element model of the eye to examine stress patterns produced during purely linear and angular accelerations, along with stresses attained during simulated repetitive shaking of an infant. Methods: Using sheep and primate eyes, sclerotomy windows were created by removing the sclera, choroid, and retinal pigment epithelium to expose the retina. A nanofiber square was glued to a 5 mm2 area of retina. The square was pulled and separated from vitreous while force was measured. A finite element model of the pediatric eye was used to computationally measure tension stresses during shaking. Results: In both sheep and primate eyes, tension stress required for separation of retina from vitreous range from 1 to 5 kPa. Tension stress generated at the vitreoretinal interface predicted by the computer simulation ranged from 3 to 16 kPa during a cycle of shaking. Linear acceleration generated lower tension stress than angular acceleration. Angular acceleration generated maximal tension stress along the retinal vasculature. Linear acceleration produced more diffuse force distribution centered at the poster pole. Conclusions The finite element model predicted that tension stress attained at the retina during forcible shaking of an eye can exceed the minimum threshold needed to produce vitreoretinal separation as measured in animal eyes. Furthermore, the results show that movements that involve significant angular acceleration produce strong stresses localized along the vasculature, whereas linear acceleration produces weaker, more diffuse stress centered towards the posterior pole of the eye.

<b>Backgroundb> Some studies have shown that PM_2.5 exposure is closely related to central nervous system diseases that lead to cognitive dysfunction and change the composition of intestinal flora. However, there are few studies on the role of intestinal flora in PM_2.5-induced depression- and anxiety-like behaviors in mice. <b>Objectiveb> To observe the effects of PM_2.5 exposure on depression- and anxiety-like behaviors and the composition of intestinal flora in mice, and to explore the role of intestinal flora in regulating 5-hydroxytryptamine (5-HT) in depression- and anxiety-like behaviors in mice exposed to PM_2.5. <b>Methodsb> Eight-week-old male SPF C57BL/6J mice were randomly divided into control group (NS group), probiotic group (LGG group), PM_2.5 group (PM group), and combined exposure group (PML group), 6 mice in each group. Mice in the PM group and the PML group were exposed to PM_2.5 in a dynamic exposure cabinet for 6 h per day, 6 d a week for 7 consecutive weeks, and the PM_2.5 concentrations were approximately 8 times higher than the outdoor concentration. The LGG group and the PML group were orally administered with Lactobacillus rhamnosus while the NS group and the PM group were orally administered with the same amount of saline. Elevated plus maze test and open field test were used to detect depression and anxiety in mice. Fecal samples of mice were collected to evaluate intestinal flora abundance, diversity, and structure between groups using high-throughput sequencing of 16S rRNA. ELISA was employed to detect the levels of 5-HT in serum and hippocampus. Spearman correlation was used to analyze the correlations of differential intestinal flora with 5-HT level in hippocampus and depression- and anxiety-like behavior indicators in mice. <b>Resultsb> The percentage of open-arm entry [M(P₂₅, P₇₅)] in the PM group was 0.0% (0.0%, 33.3%), lower than those in the NS group [47.7% (25.0%, 50.8%) ] and the PML group [46.9% (40.0%, 50.0%)], and the differences were statistically significant (P<0.05). The total travelled distance and the time spent in central area (\begin{document}$\bar x \pm s $\end{document}) in the PM group were (2.01±0.90) m and (10.31±1.99) s respectively, shorter than those of the NS group [(3.80±0.89) m, (14.47±3.07) s], the total travelled distance in the PML group [(2.73±1.12) m] was shorter than those of the NS group and the LGG group [(4.21±1.08) m], and the differences were statistically significant (P<0.05). Compared to the NS group, the Simpson index of the PM group significantly increased (P<0.05). Compared to the LGG group, the Simpson index of the PML group significantly decreased (P<0.05). The results of Beta diversity analysis showed that there were differences in the composition of intestinal flora among the four groups of mice. Compared with the NS group and the LGG group, the abundances of Erysipelotrichaceae and Dubosiella in the PM group and the PML group increased, while the abundances of Prevotellaceae_UCG-001 decreased, and the differences were statistically significant (P<0.05). In hippocampus, the level of 5-HT in the PM group [(135.02±10.31) μg·g⁻¹] was lower than those in the NS group [(178.77±43.15) μg·g⁻¹] and the LGG group [(224.85±22.98) μg·g⁻¹], and the level of 5-HT in the PML group [(161.27±15.81) μg·g⁻¹] was lower than that in the LGG group (P<0.05). 5-HT level in hippocampus was significantly positively correlated with the relative abundance of Prevotellaceae_UCG-001 (r=0.6090, P=0.012). The percentage of open-arm entry was significantly negatively correlated with the relative abundance of Dubosiella (r=−0.4630, P=0.023). <b>Conclusionb> Atmospheric PM_2.5 exposure may cause depression- and anxiety-like behaviors in mice. The observed behavior dysfunction may be associated with the changes in diversity and relative abundance of intestinal flora as well as the decrease of 5-HT level. Such depression- and anxiety-like behaviors are alleviated after adding probiotics.