Although olaparib has demonstrated substantial clinical benefits as maintenance therapy in BRCA mutation-carrying women with newly diagnosed advanced ovarian cancer, its effectiveness in patients without BRCA mutations remains poorly investigated. This study aims to provide the first evidence on the efficacy of mono-olaparib maintenance therapy in such context. Using real-world data from 11 high-volume tertiary care centers in China, a retrospective cohort study was conducted to assess the efficacy and safety of olaparib as first-line maintenance therapy in patients with BRCA wild-type ovarian cancer. The primary objective was 1-year progression-free survival rate. Safety was also evaluated. Fifty patients with a median age of 54 years were included, and all of them tested negative for BRCA mutations but positive for homologous recombination deficiency (HRD). The 1-year PFS rate was 75.2% (95% CI, 63.4 to 89.2), and the median PFS was 21.0 months (95% CI, 13.8 to 28.2). All the patients received olaparib at a starting dose of 300 mg twice daily, and none experienced serious adverse events (AEs). Eight (16%) patients had dose adjustment, but none discontinued olaparib treatment due to AEs. We provide the first evidence that mono-olaparib could be a safe and effective maintenance treatment option for patients newly diagnosed with HRD-positive/BRCA wild-type ovarian cancer.
Humans ; Female ; Phthalazines/adverse effects* ; Piperazines/administration & dosage* ; Middle Aged ; Ovarian Neoplasms/genetics* ; Retrospective Studies ; Adult ; Aged ; Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage* ; China ; Maintenance Chemotherapy ; BRCA2 Protein/genetics* ; Antineoplastic Agents/adverse effects* ; Progression-Free Survival ; BRCA1 Protein/genetics*

Background:Antibiotics can reduce the efficacy of immunotherapy for melanoma,non-small cell lung cancer and renal cell carcinoma by altering the intestinal microbiome,but their effect in the treatment of gastrointestinal cancer is unclear.Aims:To investigate the prognostic effect of antibiotics on PD-1/PD-L1 inhibitors in the treatment of colorectal cancer(CRC)patients.Methods:The clinicopathological data of 95 patients diagnosed with CRC and treated with immune checkpoint inhibitors(ICIs)from December 2018 to May 2022 at Renmin Hospital of Wuhan University were retrospectively analyzed,and the patients were divided into antibiotic group and control group according to whether antibiotics were used.Risk factors of progression free survival(PFS)and overall survival(OS)were analyzed by univariate and multivariate analysis.Results:Among the 95 patients with CRC,64 were male and 31 were female.The mean age was(60.46±11.82)years.PFS(10.9 months vs.24.8 months,P=0.032)and OS(14.5 months vs.35.5 months,P=0.008)were significantly decreased in antibiotic group than in control group,and one-year survival rate was 56.5%and 78.7%,respectively.Multivariate analysis showed that tumor location and antibiotic use were independent risk factors of PFS(P<0.05),while tumor location,antibiotic use and no radical surgery were independent risk factors of OS(P<0.05).Univariate and multivariate analyses showed that antibiotic administration route,dose were not risk factors of PFS(P>0.05);univariate analysis showed that antibiotic administration route was correlated with OS(P=0.045),however,multivariate analysis showed that antibiotic administration route,infection location were not risk factors of OS(P>0.05).Conclusions:Tumors located in colon and antibiotics applied within 30 days before and after the first dose of ICIs can shorten PFS and OS in CRC patients,while radical surgery can prolong the OS of CRC patients.

One of the distinct hallmarks of cancer cells is aerobic glycolysis (Warburg effect). Lactate dehydrogenase A (LDHA) is thought to play a key role in aerobic glycolysis and has been extensively studied, while lactate dehydrogenase C (LDHC), an isoform of LDHA, has received much less attention. Here we showed that human LDHC was significantly expressed in lung cancer tissues, overexpression of Ldhc in mice could promote tumor growth, and knock-down of LDHC could inhibit the proliferation of lung cancer A549 cells. We solved the first crystal structure of human LDHC4 and found that the active-site loop of LDHC4 adopted a distinct conformation compared to LDHA4 and lactate dehydrogenase B4 (LDHB4). Moreover, we found that (ethylamino) (oxo)acetic acid shows about 10 times selective inhibition against LDHC4 over LDHA4 and LDHB4. Our studies suggest that LDHC4 is a potential target for anticancer drug discovery and (ethylamino) (oxo)acetic acid provides a good start to develop lead compounds for selective drugs targeting LDHC4.

Objective:To observe the analgesic effect of local anesthesia combined with nerve block anesthesia on golden microneedles for improving facial aging.Methods:Between December 2018 and December 2019 in Burn and Plastic Surgery of Nanchong Central Hospital, sixty female patients (between 30 and 58 years old, with an average of 45.2 years old) with natural facial skin aging were randomly divided into two groups: Group A: surface anesthesia group (30 cases); Group B: local anesthesia combined with nerve block anesthesia (30 cases). Intraoperative and postoperative pain scores, length of operation, and incidence of adverse reactions were compared between groups A and B.Results:Pain score during surgery was (6.90±0.96) points in Group A, (3.63±0.72) points in Group B. The difference between the two groups was statistically significant ( t=14.93, P<0.05); Pain score at 30 minutes after operation was (2.03±0.62) in Group A, (0.77±0.73) in Group B, the difference between the two groups was statistically significant ( t=7.28, P<0.05). There was no statistically significant difference between the two groups in the pain score at 24 hours after operation ( P>0.05); The operation process in group B was simplified, and the treatment time was significantly shortened. The difference between the two groups was statistically significant ( t=17.93, P<0.05). Conclusions:The method of local anesthesia combined with nerve block anesthesia is used in the treatment of gold microneedles to improve the analgesic effect in facial aging, which significantly shortens the treatment time and has fewer adverse reactions. This method is worth popularizing.

Objective To analyze clinical characteristics of severe community-acquired pneumonia during pregnancy and its outcomes, and to explore the relevant risk factors. Methods From September 2012 to September 2017,324 398 pregnancies admitted in 7 tertiary hospitals were included. Clinical data of 33 cases of pregnancies with severe community-acquired pneumonia(severe pneumonia group)and 214 cases of pregnancies with common community-acquired pneumonia (control group) were reviewed retrospectively, including the clinical information, manifestations, laboratory examinations and pregnancy outcomes. Relevant risk factors were analyzed by multivariate logistic regression analysis. Results (1) General data: pregnancies with severe community-acquired pneumonia accounted for 0.010%(33/324 398) of hospitalized pregnancies, the gestational age of two groups were(28±8)and(23±8)weeks, body mass index were(21.7±2.1)and(25.5±3.4)kg/m2, rate of low income were 54.5%(18/33)and 31.8%(68/214), respectively. The differences between two groups were all statistically significant(all P<0.05). No significant differences were found in age, pregnancy and parity times, rate of main pregnant complications such as diabetes and hypertension, educational level, asthma and onset seasons between two groups(all P>0.05). (2)Clinical data: the severe pneumonia group had significantly higher incidence of fever [100.0%(33/33)vs 75.2%(161/214)], shortness of breath(90.9% vs 16.8%)compared with the control group(all P<0.05).The median peripheral leukocytes counts were 12.3×109/L and 10.2×109/L, the hemoglobin level were(84±18) and(107±14)g/L,the albumin level were(26±4)and(37±3)g/L, the median serum urea nitrogen level were 3.7 and 2.4 mmol/L,the serum creatinine level were(72±25)and(45±11)μmol/L, respectively in two groups. The differences were all statistically significant (all P<0.05). No significantly statistical differences were found in coagulation indicator and cardiac function between two groups(all P>0.05).(3) Treatments: in severe pneumonia group, 12 patients(36.4%,12/33)needed invasive mechanical ventilation, 9 patients(27.3%,9/33)needed non-invasive mechanical ventilation, average time of mechanical ventilation was(7±4)days;8 patients(24.2%,8/33)with septic shock needed vasoactive drugs. However, there was no patient in control group needing mechanical ventilation and vasoactive drugs.(4)Pregnant outcomes: one patient(3.0%,1/33)died in the severe pneumonia group, while no death occurred in the control group. The hospital stay between two groups were(15.1±4.1)and(7.0±1.9)days, the rates of abortion and stillbirth between two groups were 42.4%(14/33)and 3.3%(7/214), the rates of premature were 10/19 and 6.3% (13/207), the rates of cesarean were 15/19 and 43.0%(89/207), the rates of low birth weight newborn were 17/19 and 14.0%(29/207), the rates of infected newborn were 15/19 and 10.1%(21/207), the birth weights were(2 165±681)and(3 102±400)g, respectively. The differences between two groups were all statistically significant(all P<0.05).(5)Multivariate logistic regression analysis demonstrated that anemia, low body mass index, hypoproteinemia were risk factors for severe pneumonia in pregnancy(all P<0.05). Conclusions Pregnancy with severe community-acquired pneumonia may be complicated by multiple organ dysfunctions, lead to adverse outcomes. Anemia, malnutrition are risk factors for pregnancy with severe pneumonia. Active and effective treatment may improve its prognosis.

Objective: To evaluate whether the self-designed single-channel intracavitary applicator yields equivalent clinical efficacy and safety to the standard Fletcher-type three-channel applicator in the high-dose-rate (HDR) brachytherapy for uterine cervical cancer. Methods: From December 2011 to April 2017, patients initially diagnosed with cervical cancer were randomly assigned into the external beam radiotherapy (EBRT)+ single-channel intracavitary applicator group (the patent single-channel group) and EBRT+ the Fletcher applicator group. Whole pelvis irradiation was delivered with 6-MV photons via a four-field box variant or anterior and posterior parallel fields. Five to six fractions of intracavitary brachytherapy were performed at a dose of 7 Gy at point A once a week after 30 Gy (BED at point A: 80-90 Gy). Chemotherapy was given with intravenous injection of cisplatin at a dose of 40 mg/m² once weekly during EBRT.Clinical efficacy and safety were evaluated after the treatment. Results: In total, 150 eligible cases were assigned into the Fletcher applicator group and 149 cases into the patent single-channel group. The short-term clinical efficacy and acute toxicity did not significantly differ between two groups. The response rate was 94.0% in the Fletcher group, and 94.7% in the patent single-channel group. In the Fletcher applicator group, 76(50.7%) patients developed ≥ grade 3 hematologic toxicity and 61(40.9%) in the patent group (P=0.195). Conclusions: The self-designed patent single-channel intracavitary applicator yields equivalent clinical efficacy and safety (acute toxicity) to the standard Fletcher-type three-channel applicator in the HDR brachytherapy for uterine cervical cancer. Clincal Trial Registration Chinese Clinical Trial Registry (ChiCTR-TRC-12002321).

OBJECTIVE: To investigate the expression and clinicopathological significance of the cell cycle regulators cyclin E, cyclin D1, p21, p16 in laryngeal carcinogenesis tissus. METHOD: The expression of cell cycle regulators were detected by flow cytometry method in 23 cases of polyps of vocal cord, 69 cases of laryngeal precancerous change and 33 cases of laryngeal squamous cell carcinoma (LSCC), which tissue was paraffin embedded, sliced, dewaxed, and prepared into the cell suspension, then fluorescently labeled by cyclin E, cyclin D1, p21 and p16. RESULT: In polyps of vocal cord, laryngeal precancerous change and LSCC, The positive expression rate of cyclin E and cyclin D1 were respectively 13.04%, 20.29D, 42.420 and 26.09%, 43.48% and 93.94%. The positive expression rate of p16 and p21 were respectively 61.90%, 40.98%, 14.28% and 47.62%, 23.81%, 26.23%. Those showed the positive expression rate of cyclin D1, cyclin E gradually decreased from vocal cord polyps, laryngeal precancerous change to LSCC, (P < 0.05, P < 0.01), while the positive expression rate of p21 and p16 gradually decreased (P < 0.01). CONCLUSION The abnormal expression of cell cycle regulatory factors is the molecular events of laryngeal carcinoma. High expression of positive regulatory factors cyclin D1 and cyclin E, and low expression of negative regulatory factors p16 and p21, which showed the imbalance of multiple positive and negative regulatory factors related with cell cycle play an important role in the occurrence of laryngeal cancer.
Adult ; Cyclin D1 ; metabolism ; Cyclin E ; metabolism ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Female ; Flow Cytometry ; Humans ; Laryngeal Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Oncogene Proteins ; metabolism

【Objective】To establish a simple method for preparing tissue chip.【Methods】One hundred and thirty mammary cancer and intestinal cancer specimens were fixed by formaldehyde(40?g/L) and embedded by wax,and then were made into routine tissue slices and stained by haematoxylin and eosin(HE).Wax slices with tissue chip were prepared by fixing a tissue slice(0.1 cm in diameter)into the hole(0.2 cm in diameter and 2～4mm in depth) of a blank wax slice and were sliced into 4?m-thick slices.The tissue chips were mounted on the slide and stained by immunohistochemistry after treatment.【Results】A slide held 45 tissue chips and 130 specimens could be all detected only on 3 slides,which saved time and the amount of reagent.The immunohistochemical results showed that the positive location was accurate and the background was clear.【Conclusion】This method for preparing tissue chip is simple and effective,and can save the amount of reagent.It is easy for the comparative and separated detection of specimens.

OBJECTIVETo investigate the molecular biological mechanism of endothelial cell proliferation induced by bFGF.

METHODSCultured rat myocardial microvascular endothelial cells were stimulated with bFGF of various concentrations. By northern blot analysis, the levels of c-myc mRNA expression were detected.

RESULTSThe expression of c-myc mRNA in the bFGF-treated groups increased (P < 0.05) with a dose- and stimulating time-dependent manner. The c-myc mRNA expression reached to a peak level at 2 hours.

CONCLUSIONSC-myc expression may be an important component in controlling the transit of cells through the cell cycle.

Animals ; Cell Division ; drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Endothelium, Vascular ; cytology ; drug effects ; metabolism ; Fibroblast Growth Factor 2 ; pharmacology ; Gene Expression Regulation ; drug effects ; Genes, myc ; genetics ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Time Factors

OBJECTIVETo investigate the roles of microfilaments in the expression of collagenase and TIMP-1 in normal and hypertrophic scar.

METHODSCell culture and Northern blot hybridization methods were used in this study.

RESULTSAfter the disruption of microfilaments with cytochalasin B, mRNA contents of collagenase and TIMP-1 both increased significantly in normal and hypertrophic scar fibroblasts.

CONCLUSIONThe result suggest that the microfilament cytoskeleton may regulate the synthesis and degradation of ECM, which may be a mechanism of gene regulation during wound healing.

Actin Cytoskeleton ; physiology ; Cells, Cultured ; Collagenases ; genetics ; Fibroblasts ; metabolism ; Humans ; RNA, Messenger ; analysis ; Tissue Inhibitor of Metalloproteinase-1 ; genetics ; Wound Healing ; physiology