A novel classification of posterior pelvic exenteration to assess prognosis in female patients with locally advanced primary rectal cancer: a retrospective cohort study from China PelvEx collaborative.

PURPOSE: Surgical techniques and the prognosis of posterior pelvic exenteration for locally advanced primary rectal cancer in female patients pose challenges that need to be addressed. Therefore, we investigated the short-term and survival outcomes of posterior pelvic exenteration in female patients using a novel Peking classification. METHODS: We retrospectively analysed a prospective database from China PelvEx Collaborative across three tertiary referral centres. A total of 172 patients who underwent combined resection for locally advanced primary rectal cancer were classified based on four subtypes (PPE-I [64/172], PPE-II [68/172], PPE-III [21/172], and PPE-IV [19/172]) according to the Peking classification; perioperative characteristics and short-term and oncological outcomes were analysed. RESULTS: Differences were significant among the four groups regarding colorectal reconstruction (p < 0.001), perineal reconstruction (p < 0.001), in-hospital complications (p < 0.05), and urinary retention (p < 0.05). The R0 resection rates for PPE-I, PPE-II, PPE-III, and PPE-IV were 90.6%, 89.7%, 90.5%, and 89.5%, respectively. The 5-year overall survival rates of the PPE-I, PPE-II, PPE-III, and PPE-IV groups were 73.4%, 68.8%, 54.7%, and 37.3%, respectively. Correspondingly, their 5-year disease-free survival rates were 76.0%, 62.5%, 57.7%, and 43.1%, respectively. Notably, the PPE-IV group demonstrated the lowest 5-year overall survival rate (p < 0.001) and 5-year disease-free survival rate (p < 0.001). CONCLUSION: The Peking classification can aid in determining suitable surgical techniques and conducting prognostic assessments in female patients with locally advanced primary rectal cancer.

Short- and long-term results of open vs laparoscopic multisegmental resection and anastomosis for synchronous colorectal cancer located in separate segments.

BACKGROUND: It remains unclear whether laparoscopic multisegmental resection and anastomosis (LMRA) is safe and advantageous over traditional open multisegmental resection and anastomosis (OMRA) for treating synchronous colorectal cancer (SCRC) located in separate segments. AIM: To compare the short-term efficacy and long-term prognosis of OMRA as well as LMRA for SCRC located in separate segments. METHODS: Patients with SCRC who underwent surgery between January 2010 and December 2021 at the Cancer Hospital, Chinese Academy of Medical Sciences and the Peking University First Hospital were retrospectively recruited. In accordance with the inclusion and exclusion criteria, 109 patients who received right hemicolectomy together with anterior resection of the rectum or right hemicolectomy and sigmoid colectomy were finally included in the study. Patients were divided into the LMRA and OMRA groups (n = 68 and 41, respectively) according to the surgical method used. The groups were compared regarding the surgical procedure's short-term efficacy and its effect on long-term patient survival. RESULTS: LMRA patients showed markedly less intraoperative blood loss than OMRA patients (100 vs 200 mL, P = 0.006). Compared to OMRA patients, LMRA patients exhibited markedly shorter postoperative first exhaust time (2 vs 3 d, P = 0.001), postoperative first fluid intake time (3 vs 4 d, P = 0.012), and postoperative hospital stay (9 vs 12 d, P = 0.002). The incidence of total postoperative complications (Clavien-Dindo grade: ≥ II) was 2.9% and 17.1% (P = 0.025) in the LMRA and OMRA groups, respectively, while the incidence of anastomotic leakage was 2.9% and 7.3% (P = 0.558) in the LMRA and OMRA groups, respectively. Furthermore, the LMRA group had a higher mean number of lymph nodes dissected than the OMRA group (45.2 vs 37.3, P = 0.020). The 5-year overall survival (OS) and disease-free survival (DFS) rates in OMRA patients were 82.9% and 78.3%, respectively, while these rates in LMRA patients were 78.2% and 72.8%, respectively. Multivariate prognostic analysis revealed that N stage [OS: HR hazard ratio (HR) = 10.161, P = 0.026; DFS: HR = 13.017, P = 0.013], but not the surgical method (LMRA/OMRA) (OS: HR = 0.834, P = 0.749; DFS: HR = 0.812, P = 0.712), was the independent influencing factor in the OS and DFS of patients with SCRC. CONCLUSION: LMRA is safe and feasible for patients with SCRC located in separate segments. Compared to OMRA, the LMRA approach has more advantages related to short-term efficacy.

Efficacy of neoadjuvant immunotherapy in advanced colorectal cancer: a meta-analysis of cross-sectional studies.

BACKGROUND: Although neoadjuvant immunotherapy is being widely studied, there is no consensus on its efficacy in microsatellite-stable (MSS) or mismatch repair proficient (pMMR) colorectal cancer (CRC). This meta-analysis aimed to evaluate studies on neoadjuvant immunotherapy for advanced CRC to assess its efficacy and provide new clinical guidelines. METHODS: We searched literature databases to identify studies that assessed the efficacy of neoadjuvant immunotherapy in advanced CRC. The outcomes evaluated were pathological complete response (pCR), major pathological response (MPR), R0 resection, and anal preservation rates. Heterogeneity among the included studies was assessed by sensitivity analysis, and publication bias was evaluated using Begg and Egger tests. RESULTS: Eleven articles were included in the analysis. The pCR, MPR, R0 resection, and anal preservation rates reported in these studies were 39 and 49, 97, and 76%, respectively. The MSI-H and MSS groups had pooled pCR rates of 70 and 24%, respectively. The pCR rates for the induction, consolidation, and concurrent immuno-chemoradiotherapy (CRT) subgroups were 43, 33, and 27%, respectively, and those for the single and double immunotherapy subgroups were 34 and 40%, respectively. CONCLUSION: Neoadjuvant immunotherapy combined with CRT is effective in treating MSI-H/dMMR advanced CRC. It could also be a new first-line therapeutic option for MSS/pMMR advanced CRC.

Efficacy and safety of anti-PD-1/PD-L1 therapy in the treatment of advanced colorectal cancer: a meta-analysis.

BACKGROUND: Immune checkpoint inhibitors have shown promise in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) advanced colorectal cancer (CRC) immunotherapy, and many clinical trials have been conducted. OBJECTIVE: To evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in advanced CRC. METHOD: PubMed, Web of Science, Embase, and The Cochrane Library were searched for relevant studies up to September 2021. A retrospective cross-sectional data analysis was performed and Stata 16 software was used for analyses. RESULTS: Sixteen studies including 1503 patients were analyzed. The objective response rate (ORR) of anti-PD-1/PD-L1 was 23% (95% CI 0.14, 0.31); the overall 1-year survival rate (OSR) was 57% (95% CI 0.42, 0.73). The ORR of MSI-H/dMMR advanced CRC was 37% (95% CI 0.25, 0.48) and that of microsatellite stable/mismatch repair proficient (MSS/pMMR) disease was 11% (95% CI 0.06, 0.16). The ORR was 42% in the BRAF mutant subgroup and 19% in the RAS mutant group. The ORR was 14% in the PD-L1 ( +) subgroup and 32% in the PD-L1(-) subgroup. The rate of adverse effects was 85% (95% CI 0.80, 0.91). CONCLUSION: Anti-PD-1/PD-L1 therapy in MSI-H/dMMR advanced CRC was associated with improved survival. Anti PD-1/PD-L1 combined with antiangiogenic drugs, targeted agents, or chemotherapy might be effective in MSS mCRC. Immunotherapy was effective for the BRAF mutant and KRAS/NRAS(RAS) mutant CRC. Low expression of PD-L1 was a potential predictive marker for positive response and outcome. The high incidence of adverse events at 85% was worthy of further investigation. Further analysis with a higher number of high-quality studies is needed to verify the conclusions.

Morphology and statistics of wide-spectrum speckles.

Although the theory of scattered speckles was initially established via idealization of treating the incident light as monochromatic, phenomenon and regulations of wide-spectrum speckles are yet urgent to be studied, with immense growing applications of broadband source such as femtosecond laser, light-emitting-diode and sunlight illumination. Here we quantitatively analyze the morphology and statistics of speckles produced by a point-like source with wide-spectrum, using a phase plate model to describe the scattering layer. Due to differences in induced phase related to wavelength, wide-spectrum speckle patterns appear radial divergence in intensity distribution, as well as in visibility of both speckles and that of the second-order coherence. This is significantly different from the translation-invariance of monochromatic speckles. The spatially-varying morphology and statistics of the speckles contain spatial and spectral information of the incidence, thus can be used as an indicator to achieve optical metrology or sensing with a wide-spectrum source in the scattering environment.

Tumor budding as a predictor for prognosis and therapeutic response in gastric cancer: A mini review.

In recent years, the role of tumor budding in gastric cancer has received increased attention across a number of disciplines. Several studies have found associations between tumor budding and the prediction of lymph node metastasis in early gastric cancer, prognosis of advanced gastric cancer, predictors of therapeutic response to immune checkpoint inhibitors, such as microsatellite instability (MSI), and therapeutic targets of molecular targeted therapy, such as human epidermal growth factor receptor 2 (HER-2). Therefore, tumor budding is a major element in the formulation of risk stratification and precision medicine strategies for patients with gastric cancer.

Enhancing robustness of ghost imaging against environment noise via cross-correlation in time domain.

Research towards practical applications of ghost imaging attracts more and more attention in recent years. Signal-to-noise ratio (SNR) of bucket results thus quality of images can be greatly affected by environmental noise, such as strong background light. We introduce temporal cross-correlation into typical ghost imaging to improve SNR of bucket value, taking temporal profile of illumination pulses as a prior information. Experimental results at sunny noontime verified our method, with the imaging quality greatly improved for the object at a distance of 1.3km. We also show the possibility of 3-dimensional imaging, experimentally.

[Effects of ceruloplasmin/PTEN on histone modifications induced by silica].

OBJECTIVE: To explore the roles of ceruloplasmin (Cp) in histone modifications in human embryonic lung fibroblasts (HELFs) induced silica and the effects of phosphatase and tension homolog deleted on chromosome ten (PTEN) in this process. METHODS: HELFs were exposed to different concentrations of silica (50, 100, 200 microg/ ml) or Cp (10, 20, 30 microg/ml) for 24 h, and the level of protein lysine acetylation, of histone H2, H3 and H4 acetylation and histone H3 methylation were checked by werstern blot assay. HELFs and cells transfected with PTEN shRNA (PT) were treated with 200 microg/ml silica for 1 h, then added 30 microg/ml Cp for 24 h. Acetylation levels of protein lysine, histone H2, H3, H4 and methylation level of histone H3 were detected by werstern blot assay. RESULTS: Silica could induce the high level of protein lysine acetylation and acetyl-histone H2B (lys5/12), acetyl-histone H3 (lys9/14), acetyl-histone H4 (lys12) and the low level of methyl-histone (arg2), which could be reversed by Cp, in no exception for acetyl-histone H2B (lys5/12). Cp couldn't reverse histone modifications induced by silica when inhibited PTEN. CONCLUSION: Cp could reverse silica-induced the change of histone acetylation and histone methylation, and PTEN involved in this process.

[Roles of p53 in the interaction of p21 and cell cycle proteins induced by benzo [a] pyrene].

OBJECTIVE: To investigate the roles of p53 in the interaction of p21, cyclin D1 and CDK4 in human embryonic lung fibroblasts (HELFs) induced by benzo (a) pyrene. METHODS: p53-H group (cells transfected with p53 small interference RNA plasmid, p53 siRNA) and HELF/CMV group (cells transfected with CMV vector) were treated with 2 micromol/L B [a] P for 24 h, and HELF/CMV + PFT-alpha group (HELF/CMV cells were treated with p53 chemical inhibitor, Pifithrin-alpha) was treated with 2 micromol/L B [a] P and 20 micromol/L PFT-alpha for 24 h. The above three groups set up control groups, respectively. Western blot assay was used to check the levels of p53, phosphorylated p53 at 20 site (p53-ser20), p21, cyclin D1 and CDK4. Immunoprecipitation assay was used to investigate the roles of p53 in the interaction of p21, cyclin D1 and CDK4. RESULTS: After inhibition of p53 using PFT-alpha or siRNA, the high levels of p53, p53-ser 20 and p21 induced by B [a] P were markedly decreased. The change of cyclin D1 level was not obsevered and the level CDK4 was free of B [a] P. The combination of p21 and CDK 4 was increased after HELFs exposed to B [a] P, which can not be observed after inhibition p53. The combination of p21 and cyclin D1 was increased with or without the expression of p53 after HELFs exposed to B [a] P. The combination of cyclin D1 and CDK 4 was not affected by B [a] P. CONCLUSION: p53 can affect the combination of p21 and CDK4 in HELFs induced by B [a] P.

[Roles of ceruloplasmin in silica-induced JNK/ERK/AP-1 cell signaling pathway change].

OBJECTIVE: To investigate the roles of ceruloplasmin (Cp) in JNK/ERK/ AP-1 cell signaling pathway change in human embryonic lung fibroblasts (HELFs) induced by silica. METHODS: Cp stimulated HELFs in different time points (before 1 h, accompanied with or after 1 h of silica-adding). HELFs were divided into these groups: control group, silica(100 microg/ml for 24 h) group, Cp (30 microg/ml for 24 h) group and silica plus Cp (100 microg/ml silica plus 30 microg/ml Cp) group. DN-JNK cells and DN-ERK cells (cells were transfected with dominant negative mutant plasmid) contained these groups: control group, silica group, silica plus Cp group. MTT assay was used to detect the effects of Cp on silica-induced cell proliferation. Western blot assay was performed to detect the levels of JNK, ERK, c-Jun, c-Fos and their phosphorylated levels. RESULTS: Cp promoted cell proliferation induced by silica when silica stimulated HELFs 1 h then adding to Cp. Cp significantly increased silica-induced the high levels of JNK, ERK and phosphorylated JNK (p-JNK), p-ERK, p-c-Jun and p-c-fos protein. After inhibition of JNK or ERK, silica-and-Cp-induced cell proliferation was markedly decreased. When suppressing JNK protein, the increased levels of p-JNK, p-c-Jun and p-c-fos protein was not observed. The high levels of p-ERK, p-c-Jun and p-c-fos protein were decreased when inhibiting ERK protein. CONCLUSION: Cp could further strengthen silica-induced cell proliferation by JNK/c-Jun/c-Fos and ERK/c-Jun cell signaling pathway.

[The effects of ceruloplasmin in PI3K/PTEN cell signaling pathway change induced by silica].

OBJECTIVE: To investigate the roles of ceruloplasmin (Cp) in PI3K/PTEN cell signaling pathway change in human embryonic lung fibroblasts (HELFs) induced by silica. METHODS: HELFs transfected with pGenesil1.1 plasmid and pGenesil1.1 with PTEN shRNA (PT) plasmid were successfully established. 100 µg/ml silica and different concentrations of Cp (10, 20, 30 µg/ml) were used in this experiment and Cp were treated cells after exposed to silica for 1h. Three different cell lines (including HELFs, PT and cells were transfected with p85 dominant negative mutant plasmid (DN-p85)) were divided into control groups, silica groups and silica+different concentrations of Cp groups. MTT assay was used to detect the effects of Cp on silica-induced cell proliferation after inhibiting PTEN and p85. When suppressing the expression of PTEN and p85, western blot assay was performed to detect the levels of p85, p110, AKT308, AKT473 and ERK, JNK and their phosphorylated levels. RESULTS: After inhibition of PTEN, the high levels of p85 induced by 100 µg/ml silica with 30 µg/ml Cp were markedly decreased (P<0.05). When suppressing p85, the increased cell proliferation was not observed. And the high levels of AKT308, AKT473, ERK and phosphorylated JNK and ERK stimulated by 100 µg/ml silica with 30 µg/ml Cp were decrease (P < 0.05). CONCLUSION: Cp could further strengthened silica-induced cell proliferation by PI3K/AKT/MAPK cell signaling pathway, of which the level of p85 was regulated by PTEN.

[Influence of serum from rats with scald on the cytoskeleton of colonic smooth muscle cells of rats].

OBJECTIVE: To study the influence of serum from scalded rats on the cytoskeleton of colonic smooth muscle cells (CSMC) of rats cultured in vitro, and to probe the possible mechanism of gastrointestinal motility disorder after burn. METHODS: CSMC isolated from healthy adult Wistar rat were cultured and divided into scald serum group (SS) and normal serum group (NS) according to the random number talbi. Two normal Wistar rats were used, one of which was inflicted with deep partial-thickness scald. Serum was obtained from blood collected from these two rats respectively and diluted to 20% in concentration. Serum from scald and normal rats were respectively added to the culture of CSMC in SS and NS groups. The expression of actin and the relative content of ß-tubulin in CSMC was respectively determined with flow cytometry and Western blot at post treatment hour (PTH) 1, 3, 6, and 12 (with 10 samples in each group at each time point). Data were processed with t test. RESULTS: Fluorescence intensity of actin in SS group at PTH 1, 3, 6, and 12 was respectively 59 ± 4, 26 ± 6, 39 ± 6, and 42 ± 6, all significantly lower than those in NS group (95 ± 10, 91 ± 10, 102 ± 9, and 97 ± 9, with t value respectively 10.528, 18.069, 18.748, 16.647, P < 0.05 or P < 0.01). In SS group, the fluorescence intensity decreased to the nadir at PTH 3, and then increased persistently at PTH 6 and 12. (2) Relative content of ß-tubulin in SS group at PTH 1, 3, 6, and 12 was respectively 14.44 ± 0.26, 8.61 ± 0.19, 11.76 ± 0.31, and 12.13 ± 0.29, all significantly less than those in NS group (22.37 ± 1.15, 21.87 ± 1.79, 23.24 ± 1.55, and 21.99 ± 2.02, with t value respectively 21.176, 23.365, 23.000, 15.273, P values all below 0.01). In SS group, the relative content of ß-tubulin decreased to the nadir at PTH 3 and increased slowly at PTH 6 and 12. CONCLUSIONS: The reduction of CMSC content which has the tendency of increasing later, can be attributed to the influence of scald serum in initial stage. This may be related to the tolerance and adaptation to scald serum and self-repair of CMSC.

[Clinical study on repair of burn wounds of degree II with recombinant human epidermal growth factor in elderly patients].

OBJECTIVE: To explore the therapeutic effect of recombinant human epidermal growth factor (rhEGF) for burn wounds of degree II in the elderly patients. METHODS: From February 2003 to October 2008, 80 patients with burn wounds of degree II were treated and randomly divided into two groups (n=40). In treatment group, there were 24 males and 16 females with an average age of 70 years (60-86 years), including 20 cases of superficial II degree and 20 cases of deep II degree. Burn wounds were caused by flame in 23 cases, by hot liquid in 16 cases, and by electricity in 1 case. The mean time from injury to hospitalization was (2.87 +/- 2.57) hours. The wounds were treated with silver sulfadiazine (SD-Ag) and rhEGF. In control group, there were 18 males and 22 females with an average age of 69 years (61-83 years), including 19 cases of superficial II degree and 21 cases of deep II degree. Burn wounds were caused by flame in 23 cases, by hot liquid in 14 cases, by electricity in 2 cases, and by chemistry in 1 case. The mean time from injury to hospitalization was (3.39 +/- 3.33) hours. The wounds were treated with SD-Ag. The dressing was changed every day until wounds healing. There were no significant differences in general data between two groups (P > 0.05). RESULTS: Wound did not heal in 1 case (deep II degree) of treatment group and in 5 cases (deep II degree) of control group over 40 days and free skin graft was used to repair wound. One case (superficial II degree) in control group gave up treatment. One case (deep II degree) died of pulmonary infection in treatment group. These cases were excluded and 72 cases were analysed. No other side reactions were observed in treatment group except for flash stabbing pain (4 cases) and pruritus (2 cases). Wound infection occurred in 5 cases of the control group and in 3 cases of the treatment group, and wound healed after symptomatic treatment. The healing time of burn wound was (14.30 +/- 1.26) days (superficial II degree) and (26.11 +/- 2.97) days (deep II degree) in the treatment group, was (16.22 +/- 1.40) days (superficial II degree) and (29.13 +/- 4.99) days (deep II degree) in control group, showing significant difference between two groups (P < 0.05). CONCLUSION: In combined treatment, rhEGF can promote the healing of burn wounds of degree II in the elderly patients.