Disitamab Vedotin Alone or in Combination With Immune Checkpoint Inhibitors in Bladder-Sparing Treatment of Muscle-Invasive Bladder Cancer: A Real-World Study.

PURPOSE: To evaluate the efficacy and safety of a novel humanized anti-HER2 antibody, RC48-ADC (Disitamab vedotin, DV), the combination of RC48-ADC with PD-1 inhibitors was used to treat muscle-invasive bladder cancer (MIBC). This combination therapy has potential applications in both bladder preservation and neoadjuvant therapy for MIBC. METHODS: Patients with MIBC underwent transurethral resection of bladder tumors followed by RC48-ADC alone or in combination with PD-1 inhibitors. Radiological and endoscopic evaluations were conducted 3 months later. The primary endpoint was objective response rate (ORR), with secondary endpoints including complete response rate (CR), partial response rate (PR), and bladder preservation rate. Treatment safety was assessed according to RECIST v1.1 criteria. RESULTS: Eleven patients were enrolled, with a median follow-up of 19.0 months. Nine patients achieved objective response, including 6 CR and 3 PR cases. The pathological ORR was 81.8%. Eight patients continued combined treatment after 3 months, maintaining a 72.7% bladder preservation rate at 16 months. One elderly patient progressed from ypT2N0M0 to ypT3N0M0 and underwent radical cystectomy but had no recurrence or metastasis 12 months postoperation. All patients reported varying degrees of treatment-related adverse reactions, which were largely manageable. CONCLUSION: The combination of RC48-ADC and PD-1 inhibitors proves to be a viable and safe option for bladder-sparing therapy, particularly for T2-stage MIBC patients who are ineligible for surgery and chemotherapy. This approach offers a promising new direction for bladder preservation or neoadjuvant therapy in MIBC patients.

Robot-assisted single-port retroperitoneal partial nephrectomy with a novel purpose-built single-port robotic system with deformable surgical instruments.

OBJECTIVE: To investigate the safety and feasibility of using a novel purpose-built single-port robotic system (the SHURUI Robotic Surgical System) with deformable surgical instruments to perform retroperitoneal single-port partial nephrectomy. MATERIALS AND METHODS: A prospective study was conducted to recruit patients with a single renal tumor no more than 4 cm. Robot-assisted single-port partial nephrectomy was performed by using the novel purpose-built single-port robotic system with deformable surgical instruments. Patients' demographics, tumor characteristics, and perioperative parameters were recorded and analyzed. RESULTS: Sixteen patients were recruited to the study. The median tumor size was 2.0 cm (IQR: 1.2-2.4 cm). The median R.E.N.A.L score was 6 (IQR: 4-4.5). In 3 cases, pure single-port surgery was carried out, and all the assistance was through the robotic port. Median docking time was 15.5 min (IQR: 14.25-22.25 min). Median operating time was 148.5 min (IQR: 178-238.5 min). Median console time was 107 min (IQR: 92.75-149.75 min). Median warm ischemic time was 26.5 min (IQR: 24.5-30 min). Median blood loss was 17.5 ml (IQR: 10-50 ml). CONCLUSIONS: Retroperitoneal partial nephrectomy can be safely performed with this novel purpose-built single-port robotic system (SHURUI) with deformable surgical instruments. Further studies are needed to fully evaluate the role of this new platform.

Pelvic drain placement after robot-assisted radical prostatectomy: meta-analysis.

BACKGROUND: It is not clear whether the routine placement of a pelvic drain after robot-assisted radical prostatectomy is a necessity. The aim of this study was to investigate this through a meta-analysis of RCTs and non-randomized studies. METHODS: A search was performed in PubMed/MEDLINE, Embase, the Cochrane Library, and the Web of Science, up to 9 March 2023, for clinical trials comparing no drain with pelvic drain placement for patients with prostate cancer after robot-assisted radical prostatectomy. Two researchers independently conducted literature screening, data extraction, and quality assessment. A random-effect model was assumed for all analyses. The Cochrane Collaboration's risk-of-bias tool was used to evaluate the methodological quality of RCTs and, for non-randomized studies, the ROBINS-I tool was used (where ROBINS-I stands for Risk Of Bias In Non-randomized Studies - of Interventions). This meta-analysis was prospectively registered in PROSPERO, the international prospective register of systematic reviews (CRD42023406429). RESULTS: A total of six studies with 1480 patients were included in the meta-analysis. Both the meta-analysis of RCTs and the meta-analysis of non-randomized studies showed that patients without drains had a similar estimated blood loss (mean difference 40.49 ml, 95% c.i. -59.75 to 140.74 ml, P = 0.430, and mean difference -14.20 ml, 95% c.i. -32.26 to 3.87 ml, P = 0.120 respectively), overall complication rate (OR 0.60, 95% c.i. 0.35 to 1.04, P = 0.070, and OR 0.90, 95% c.i. 0.59 to 1.39, P = 0.640 respectively), Clavien-Dindo grade I-II complication rate (OR 0.62, 95% c.i. 0.34 to 1.13, P = 0.120, and OR 0.83, 95% c.i. 0.28 to 2.51, P = 0.750 respectively), Clavien-Dindo grade III-V complication rate (OR 0.60, 95% c.i. 0.10 to 3.69, P = 0.590, and OR 0.92, 95% c.i. 0.25 to 3.39, P = 0.900 respectively), and duration of hospital stay (mean difference -0.08 days, 95% c.i. -0.45 to 0.29 days, P = 0.670, and mean difference -0.64 days, 95% c.i. -2.67 to 1.39 days, P = 0.540 respectively) compared with routinely drained patients. Meta-analysis of non-randomized studies revealed that the duration of operation for patients without drains was shorter than that for patients with drains (mean difference -34.88 min, 95% c.i. -43.58 to -26.18 min, P < 0.001), but the meta-analysis of RCTs indicated that there was no significant difference between the two groups (mean difference -7.64 min, 95% c.i. -15.61 to 0.32 min, P = 0.060). CONCLUSION: The intraoperative and postoperative outcomes of patients without drains were not inferior to those of patients with drains. In selected patients, pelvic drains can be omitted after robot-assisted radical prostatectomy.

Analyze and simulate an individualized nutritional computing system for multidisciplinary teams in nutritional support therapy.

To explore the efficiency of nutritional support therapy . Pharmacists led the construction of an individualized nutritional computing system and were involved in the process of treatment. After obtaining relevant professional knowledge and instruction on how to operate the system, MDT members intervened in the incorrect treatment process during nutritional support therapy. The Department of Radiation Oncology and the Intensive Care Unit (ICU) were selected as pilot departments to compare and analyze the rationality of nutrition risk screening and the use of enteral nutrition (EN) and parenteral nutrition (PN) in treatment before and after intervention. The individualized nutritional computing system significantly improved work efficiency, promoted nutrition risk screening, and saved 10-15 minutes in the treatment of each patient. After intervention in the Department of Radiation Oncology, the use rate of Total Nutrient Admixture (TNA) increased by 7.17%, and the single-bottle infusion rate of PN preparation decreased by 17.94% in patients at risk of malnutrition. The use rate of EN and single-bottle infusion rate of PN preparation in patients without risk of malnutrition decreased by 15.17% and 20.81%, respectively. Overall, 98.75% of ICU patients were at risk of malnutrition. The use rates of EN and TNA increased by 12.79% and 12.14%, respectively, and the single-bottle infusion rate of PN preparation decreased by 10.06%. Streamlined and mobile MDT, the use of an individualized nutritional computing system, and the effective work of pharmacists in the process significantly improved the efficiency and rationality of nutritional support therapy .

Extraperitoneal tissue retraction technique: An effective assistant of extraperitoneal pure single-port robotic-assisted radical prostatectomy with the da Vinci Si surgical system.

Objective: The limitations of tissue retraction and the amount of surgical working space have a great impact on extraperitoneal single-port robotic-assisted radical prostatectomy (sp-RARP) with the multiport robotic surgical system. We used an extraperitoneal tissue retraction technique to achieve tissue exposure and working space expansion. This study evaluated the safety, feasibility, and efficacy of the extraperitoneal tissue retraction technique in extraperitoneal pure sp-RARP with the da Vinci Si surgical system. Methods: Data from 42 patients were analyzed retrospectively from December 2018 to February 2020. The extraperitoneal tissue retraction technique was not used in 20 patients (group I) and was used in 22 patients (group II). Preoperative, intraoperative, and postoperative data were collected. The oncological and functional data during late follow-up were recorded. Results: All patients successfully underwent extraperitoneal pure sp-RARP. No patients required conversion to a multiport surgery or placement of additional assistant ports. The two groups were similar regarding baseline features. The median operation time in group I was significantly longer than that in group II (P < 0.001). The estimated blood loss volume in group I was significantly higher than that in group II (P < 0.001). There were no serious complications in either group. There were four cases of peritoneal tears in group I and none in group II (P = 0.043). The surgical margin and lymph nodes were negative in both groups. The oncological and functional outcomes were similar between the two groups 6 months after the procedure. Conclusions: The extraperitoneal tissue retraction technique is safe and feasible. The technique promotes tissue exposure and expands the surgical working space, which is important for achieving extraperitoneal pure sp-RARP with the da Vinci Si surgical system, especially for beginners. The short-term oncological and functional outcomes were within acceptable ranges. The long-term effects of this technique need further evaluation.

A comparison of perioperative outcomes between extraperitoneal robotic single-port and multiport radical prostatectomy with the da Vinci Si Surgical System.

To evaluate outcomes between extraperitoneal robotic single-port radical prostatectomy (epR-spRP) and extraperitoneal robotic multiport radical prostatectomy (epR-mpRP) performed with the da Vinci Si Surgical System, comparison was performed between 30 single-port (SP group) and 26 multiport (MP group) cases. Comparisons included operative time, estimated blood loss (EBL), hospital stay, peritoneal violation, pain scores, scar satisfaction, continence, and erectile function. The median operation time and EBL were not different between the two groups. In the SP group, the median operation time of the first 10 patients was obviously longer than that of the latter 20 patients (P < 0.001). The median postoperative hospital stay in the SP group was shorter than that in the MP group (P < 0.001). The rate of peritoneal damage in the SP group was less than that in the MP group (P = 0.017). The pain score and overall need for pain medications in the SP group were lower than those in the MP group (P < 0.001 and P = 0.015, respectively). Patients in the SP group were more satisfied with their scars than those in the MP group 3 months postoperatively (P = 0.007). At 3 months, the cancer control, recovery of erectile function, and urinary continence rates were similar between the two groups. It is safe and feasible to perform epR-spRP using the da Vinci Si surgical system. Therefore, epR-spRP can be a treatment option for localized prostate cancer. Although epR-spRP still has a learning curve, it has advantages for postoperative pain and self-assessed cosmesis. In the absence of the single-port robotic surgery platform, we can still provide minimally invasive surgery for patients.

Pure retroperitoneoscopic extravesical standardized seeable (PRESS) excision of distal ureter and bladder cuff in radical nephroureterectomy: step-by-step technique.

BACKGROUND: Concerns have been raised regarding the management of bladder cuff with these minimally invasive approaches. The aim of this study was to describe a modified radical nephroureterectomy (RNU) with pure retroperitoneoscopic extravesical standardized seeable (PRESS) bladder cuff excision (BCE) and to assess its outcomes based on a novel concept of intraoperative "trifecta." METHODS: Twenty-four patients with upper urinary tract urothelial carcinoma underwent retroperitoneoscopic RNU from August 2017 to August 2019. A modified RNU with PRESS BCE and lymph node dissection (LND) was performed. Descriptive analysis of patients' characteristics, surgical technique, perioperative outcomes, and follow-up data was performed. BCE trifecta was defined as en-bloc excision, mucosa-to-mucosa reliable closure and no urine spillage. RESULTS: In 23 out of 24 cases (95.8%) the procedure was successfully completed. One patient was converted to open distal ureterectomy with a Gibson incision due to peritoneum rupture during dissection of the distal ureter. BCE trifecta was achieved in 95.7% (22/23) cases of all patients finished with PRESS technique. Median OT was 260 min (IQR: 220-305) with median EBL of 100 mL (IQR: 100-250). Median OT for distal ureterectomy was 52 min (IQR: 40-69). No positive surgical margin occurred. Median postoperative hospital stay was 6 d (IQR: 5-7). Median follow-up time was 7 mo (IQR: 5-17). One patient (4.3%) experienced bladder recurrence and no patient developed distant metastasis or died of the disease. CONCLUSIONS: Herein, we demonstrate a standardized retroperitoneoscopic RNU technique that is safe and reproducible, enabling the visual confirmation of complete BCE and facilitating LND. BCE trifecta should be a routine goal in minimally invasive RNU. Prospective comparison with the standard open surgical technique is warranted.

Quercetin attenuates diabetic neuropathic pain by inhibiting mTOR/p70S6K pathway-mediated changes of synaptic morphology and synaptic protein levels in spinal dorsal horn of db/db mice.

Numerous studies indicate that the changes of synaptic morphology and synaptic protein levels in spinal dorsal horn neurons contributes to the development and maintenance of neuropathic pain. Quercetin, a bioflavonoid compound, has been shown to have analgesic effect in several pain models. However, the underlying mechanism for quercetin to allieviate pain is unclear. Therefore, in this study, we observed the effect of quercetin on diabetic neuropathic pain in db/db mice and explored the underlying mechanisms. Our results showed that chronic quercetin treatment alleviated thermal hyperalgesia in db/db mice. Moreover, quercetin administration significantly reduced the total dendritic length, the number of dendritic branches, and the dendritic spine density in the spinal dorsal horn neurons of db/db mice. Meanwhile, the up-regulated expressions of synaptic plasticity-associated proteins postsynaptic density protein 95 (PSD-95) and synaptophysin in spinal dorsal horn of db/db mice were decreased by quercetin treatment. In addition, quercetin treatment reduced the phosphorylated levels of mammalian target of rapamycin (mTOR) and p70 ribosomal S6 kinase (p70S6K) in spinal dorsal horn of db/db mice. These results demonstrate that quercetin may alleviate diabetic neuropathic pain by inhibiting mTOR/p70S6K pathway-mediated changes of synaptic morphology and synaptic protein levels in spinal dorsal horn neurons of db/db mice. These findings suggest that quercetin may be a promising therapeutic drug in neuropathic pain.

Clinical outcomes of 168 Chinese patients after local surgery for bone metastases arising from advanced renal cell carcinoma.

BACKGROUND: The effectiveness of local surgery for bone metastases (BM) arising from renal cell carcinoma (RCC) remains uncertain. Herein, the authors performed what to the best of their knowledge is the first investigation of the outcomes of Chinese patients with RCC and BM. METHODS: Data were collected for 168 patients with RCC and BM who were treated at Changzheng Hospital in Shanghai, China, between March 2009 and December 2018. All patients underwent local surgery for BM arising from RCC. Overall survival (OS) was defined as the interval between the date of local surgery and death or last follow-up and was estimated using the Kaplan-Meier method. Univariate and multivariable Cox proportional hazards analyses were used to identify significant prognostic factors. RESULTS: The median OS in the study cohort was 43 months (range, 0-113 months). The 1-year, 3-year, and 5-year survival rates after surgery were 77.4%, 55.9%, and 31.8%, respectively. Univariate analyses demonstrated significant survival differences associated with sex (P = .003), the number of preoperative metastatic sites (BM alone or BM with concomitant metastasis; P < .001), and the number of BM (single or multiple; P = .008). OS also did not appear to differ regardless of whether the patients received postsurgical targeted therapy. Multivariable Cox regression demonstrated that the following characteristics were independent predictors of OS: the number of preoperative metastatic sites, International Metastatic Renal Cell Carcinoma Database Consortium risk score, and Memorial Sloan Kettering Cancer Center score. CONCLUSIONS: Careful patient selection for local surgery is of paramount importance. The prognoses of patients in the Memorial Sloan Kettering Cancer Center-based and International Metastatic Renal Cell Carcinoma Database Consortium-based poor-risk groups were much worse than those of the intermediate-risk groups. In current clinical practice, "stratified treatment" can be performed according to these criteria.

Overexpression of grapevine VvNAC08 enhances drought tolerance in transgenic Arabidopsis.

NAC [No apical meristem (NAM), Arabidopsis transcription activation factor (ATAF), Cup-shaped cotyledon (CUC)] transcription factors (TFs) play an important role in plant growth and response to various environmental stress. Drought stress is the primary factor limiting the growth and fruit quality of grapevines worldwide. However, the biological function of the NAC family members in grapevine is not clear. In this study, we reported that VvNAC08, a novel NAC transcription factor gene, was expressed after drought, salicylic acid (SA) and abscisic acid (ABA), jasmonic acid (JA) and melatonin (MT) treatments in grapevine. VvNAC08 was expressed in various tissues. The open reading frame (ORF) of VvNAC08 was 792 bp, encoding 263 amino acids. The VvNAC08 protein could bind to NACRS [CGTA/CACG] in yeast. When subjected to drought and dehydration stress, VvNAC08-overexpression (OE) Arabidopsis had a higher survival rate and a lower water loss rate than wild type (WT) plants. Under drought conditions, transgenic Arabidopsis overexpressing VvNAC08 had a lower malondialdehyde (MDA), H2O2 contents, but a higher peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT) activities as well as more proline content. Moreover, the expressions of marker genes, including ABI5, AREB1, COR15A, COR47, P5CS, RD22, and RD29A, were up-regulated in VvNAC08-overexpression lines when subjected to drought treatments. The results suggest that the transgenic Arabidopsis overexpressing VvNAC08 enhances resistance to drought while up-regulating the expressions of ABA- and stress-related genes.

Anti-tumor activity and mechanism of oligoclonal hepatocellular carcinoma tumor-infiltrating lymphocytes in vivo and in vitro.

Objective: To explore a method for culturing hepatocellular carcinoma and tumor-infiltrating lymphocytes (HCC-TIL) and investigate the mechanism of TIL in killing tumors. Methods: The distribution of regulatory T cells (Treg) in HCC was detected by immunohistochemistry. Conventional TIL and oligoclonal TIL were isolated by the traditional method of enzyme digestion combined with mechanical treatment for whole HCC and micro HCC tissue block culturing method. MTT was used to compare the killing activity of TIL. Flow cytometry was used to analyze the proportion of CD8+ T cells and Treg cells in TIL. Tumor-bearing mice were established, and TIL adoptive immunotherapy was performed. Results: Treg cells were mainly distributed in the stroma of HCC. In vitro experiments showed oligoclonal TIL had higher cytotoxicity to tumor cells which negatively correlated with the proportion of Treg cells. In vivo experiments showed oligoclonal TIL had a higher anti-tumor effect. IFN-γ in peripheral blood and the positive rate of intratumoral lymphocytic infiltration in oligoclonal TIL group were both higher. TGF-ß and IL-10 in peripheral blood and the positive rate of intratumoral FoxP3 and IL-17 were both lower than those in conventional TIL group. Conclusion: The oligoclonal TIL culture method could obtain TIL with higher purity, and cytotoxicity to tumor cells was associated with Treg cells. The oligoclonal TIL had cytotoxicity to autologous HCC cells and significant inhibitory effect on the growth of transplanted tumors. The mechanism might be associated with the inhibition of Treg cells proliferation, increase of IFN-γ secretion, and decrease of TGF-ß, IL-10, and IL-17 secretion.

Sirtuin 1 alleviates diabetic neuropathic pain by regulating synaptic plasticity of spinal dorsal horn neurons.

Accumulating evidence has demonstrated that the enhanced synaptic plasticity of nociceptive interneurons in the spinal dorsal horn is the basis of central sensitization in neuropathic pain. Our previous results demonstrated that sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, alleviates neuropathic pain in type 2 diabetes mellitus rats. SIRT1 has also been reported to regulate synaptic plasticity in different brain neurons. However, the role of SIRT1 in synaptic plasticity of spinal dorsal horn neurons remains unknown. In this study, we found that in the spinal dorsal horn of diabetic neuropathic pain (DNP) rats and db/db mice, decreased SIRT1 expression was accompanied by enhanced structural synaptic plasticity. The levels of postsynaptic density protein 95 (PSD-95), growth-associated protein 43 (GAP43), and synaptophysin increased in the spinal dorsal horn of DNP rats and db/db mice and in high glucose-cultured primary spinal neurons. Upregulation of spinal SIRT1 by SIRT1 activator SRT1720 relieved pain behavior, inhibited the enhanced structural synaptic plasticity in rats and db/db mice with DNP, and decreased the levels of synapse-associated proteins in DNP rats, db/db mice, and high glucose-cultured spinal neurons. SIRT1-shRNA induced pain behavior and enhanced structural synaptic plasticity in normal rats and increased synapse-associated proteins levels in normal rats and spinal neurons. Intrathecal injection of AAV-Cre-EGFP into SIRT1 mice also induced pain behavior and enhanced synaptic plasticity of the spinal dorsal horn neurons. These results suggest that SIRT1 plays an important role in the progression of DNP by regulating synaptic plasticity of spinal dorsal horn neurons.

A feed-forward loop between nuclear translocation of CXCR4 and HIF-1α promotes renal cell carcinoma metastasis.

CXC chemokine receptor 4 (CXCR4) has been suggested to play a critical role in cancer metastasis. Some studies have described CXCR4 nuclear localization in metastatic lesions of renal cell carcinoma (RCC), which has been suggested to be correlated with cancer metastasis. However, the underlying mechanism and clinical significance of CXCR4 nuclear localization remains unknown. Here, we show that CXCR4 nuclear localization is more likely to occur in RCC tissues, especially in metastases, and is associated with poor prognosis. CXCR4 nuclear localization requires its nuclear localization sequence (NLS, residues 146-RPRK-149). After the mutation of NLS in CXCR4, CXCR4 nuclear localization in RCC cells is lost. Nuclear localization of CXCR4 promoted RCC tumorigenicity both in vitro and in vivo. Mechanistically, we found that CXCR4 and hypoxia-inducible factor-1α (HIF-1α) colocalized in RCC cells and interacted with each other. Moreover, CXCR4 nuclear localization promoted nuclear accumulation of HIF-1α, thereby promoting the expression of genes downstream of HIF-1α. Reciprocally, nuclear HIF-1α promoted CXCR4 transcription, thus forming a feed-forward loop. Subcellular CXCR4 and HIF-1α expression levels were independent adverse prognostic factors and could be combined with TNM stage to generate a predictive nomogram of the clinical outcome of patients with RCC. Therefore, our findings indicate that CXCR4 nuclear translocation plays a critical role in RCC metastasis and may serve as a prognostic biomarker and potential therapeutic target.

Optimal Design of Wavelength Selective Thermal Emitter for Thermophotovoltaic Applications.

We theoretically and numerically demonstrate optimal design of wavelength selective thermal emitter using one-dimensional (1D) and two-dimensional (2D) metal-dielectric gratings for thermophotovoltaic (TPV) applications. Proposed design consists of tungsten (W) and silicon dioxide (SiO2) gratings which can withstand high temperatures. Radiative properties of 1D grating were calculated using a numerical method, while effective medium approximation was used for 2D gratings. Optimal designs were obtained such that output power is maximum for GaSb photovoltaic (PV) cell at emitter temperature of 1500 K and radiated energy for longer wavelengths is limited to a low value. A constrained optimization was performed using genetic algorithm (GA) to arrive at optimal design.

Changes of serum alpha-fetoprotein and alpha-fetoprotein-L3 after hepatectomy for hepatocellular carcinoma: prognostic significance.

BACKGROUND: Alpha-fetoprotein (AFP) is the most established tumor marker of hepatocellular carcinoma (HCC), but one of its limitations is non-specificity. Many studies have demonstrated that alpha-fetoprotein-L3 (AFP-L3) is more specific than AFP in the early diagnosis and prognosis of HCC. However, there is a lack of knowledge about the post-hepatectomy profiles of serum AFP and AFP-L3 values in HCC patients. To identify the profiles after surgical resection of HCC, we analyzed the correlation between the profiles and postoperative HCC recurrence or survival, and evaluated their utility in predicting postoperative therapeutic efficacy and prognosis. METHODS: From August 2003 to December 2004, 318 patients with positive serum AFP who had received surgical resections were enrolled in this study. Preoperative and postoperative serum AFP and AFP-L3 levels were measured simultaneously and regularly, and their postoperative profiles during a long-term follow-up were recorded and summarized. RESULTS: A high ratio of AFP-L3 to total AFP was shown to correlate with pathologic features of aggressiveness. The overall 1-, 3-, and 5-year recurrence rates of the whole series were 28%, 57%, and 84%, and the overall survival rates were 86%, 61%, and 33%, respectively. The changes of serum AFP and AFP-L3 after hepatectomy for HCC were classified into 3 groups (group A: AFP-L3 undetectable; group B: AFP-L3 <10%; and group C: AFP-L3 >10%). Patients with positive postoperative AFP-L3 had significantly earlier recurrence than those with negative results. The overall survival was significantly shorter in the positive groups than in the groups negative for postoperative AFP-L3. CONCLUSION: Post-hepatectomy changes in serum AFP and AFP-L3 levels occurred in three distinct patterns, which were closely correlated with HCC recurrence and patient survival with different prognostic values.

Metered-dose inhaler efficiency enhancement: a case study and novel design.

The efficiency of the metered-dose inhaler (MDI) is a critical issue in aerosol medicine because it deals with delivering a life-saving medication to patients with various lung diseases. Mouthpiece diameter, air flow rate, and entrance angle are among many parameters that influence the MDI penetration efficiency. It is well known that inertial impaction accounts for the massive aerosol deposition in the oral airway. In this study, the authors present a novel simple modification of the inhaler mouthpiece using a wire-based jet depressor to reduce the inertial impaction of aerosols. A 0.5 mm diameter wire is placed inside the MDI mouthpiece at a distance of 2 mm in front of the MDI nozzle. Two mouthpieces were modified and employed in the experiments (16 and 20 mm). The penetration efficiencies are measured and the results of the modified mouthpiece are compared with the conventional mouthpiece. The experiments are conducted at three different air flow rates (30, 60, and 90 L/min) and five entrance/spray angles (0 degrees, 10 degrees, 20 degrees, 30 degrees, and 40 degrees). The results show that the new modified mouthpiece has higher aerosol penetration efficiency than the ones with the conventional mouthpiece. A second type of experiment is conducted to evaluate the relative strength of the aerosol impaction.

Balloon-based in vitro MDI aerosol deposition experiments on the effects of mouthpiece diameter.

For this article, we studied the effects of mouthpiece diameter and flow rate on aerosol penetration efficiency for metered-dose inhaler (MDI) applications. Measurements show that increasing the mouthpiece diameter has a moderate and positive influence on the particle penetration efficiency of the MDI. The particle penetration efficiency increases monotonically with the increase of the mouthpiece diameter from 16 mm to 20 mm. Second, the experiments show that airflow rate has an apparent and significant effect on particles deposition in the oral airway. The reduction of the airflow rate from 90 L/min to 30 L/min tripled the penetration efficiency of the MDI. A new experimental system has been employed to measure the particles deposition in the human airways. Expansion balloons were used to induce airflow as well as to collect the penetrated particles through an airway cast. The potential advantages of the balloon-based experimental system are simplicity, accuracy, and cost-effectiveness.

Fine particle deposition within human nasal airways.

An original mathematical model describing particle diffusion in human nasal passages is presented. A unique feature of the model is that it combines effects of both turbulent and laminar flows. To account for turbulence, concentration equations written in cylindrical coordinates are first simplified by a scaling technique and then solved analytically based on momentum/mass transfer analogy. To describe laminar motion, the work of Martonen et al. (1995a) is modified for application to nasal passages. The predictions of the new model agree well with particle deposition data from experiments using human replica nasal casts over a wide range of flow rates (4-30 L/min) and particle sizes (0.001-0.1 micro m). The results of our study suggest that a complex fluid dynamics situation involving a natural transition from laminar to turbulent motion may exist within human nasal passages during inspiration. The model may be used to predict deposition efficiencies of inhaled particles for inhalation toxicology (e.g., the risk assessment of air pollutants) and aerosol therapy (e.g., the treatment of lung diseases) applications.

Flow simulation in the human upper respiratory tract.

Computer simulations of airflow patterns within the human upper respiratory tract (URT) are presented. The URT model includes airways of the head (nasal and oral), throat (pharyngeal and laryngeal), and lungs (trachea and main bronchi). The head and throat morphology was based on a cast of a medical school teaching model; tracheobronchial airways were defined mathematically. A body-fitted three-dimensional curvilinear grid system and a multiblock method were employed to graphically represent the surface geometries of the respective airways and to generate the corresponding mesh for computational fluid dynamics simulations. Our results suggest that for a prescribed phase of breath (i.e., inspiration or expiration), convective respiratory airflow patterns are highly dependent on flow rate values. Moreover, velocity profiles were quite different during inhalation and exhalation, both in terms of the sizes, strengths, and locations of localized features such as recirculation zones and air jets. Pressure losses during inhalation were 30-35% higher than for exhalation and were proportional to the square of the flow rate. Because particles are entrained and transported within airstreams, these results may have important applications to the targeted delivery of inhaled drugs.