BACKGROUND: Poly adenosine-diphosphate-ribose polymerase (PARP) inhibitors (PARPi) have been approved to act as first-line maintenance (FL-M) therapy and as platinum-sensitive recurrent maintenance (PSR-M) therapy for ovarian cancer in China for >5 years. Herein, we have analyzed the clinical-application characteristics of olaparib and niraparib in ovarian cancer-maintenance therapy in a real-world setting to strengthen our understanding and promote their rational usage. METHODS: A retrospective chart review identified patients with newly diagnosed or platinum-sensitive recurrent ovarian cancer, who received olaparib or niraparib as maintenance therapy at Sichuan Cancer Hospital between August 1, 2018, and December 31, 2021. Patient medical records were reviewed. We grouped and analyzed patients based on the type of PARPi they used (the olaparib group and the niraparib group) and the line of PARPi maintenance therapy (the FL-M setting and the PSR-M setting). The primary endpoint was the 24-month progression-free survival (PFS) rate. RESULTS: In total, 131 patients (olaparib: n = 67, 51.1%; niraparib: n = 64, 48.9%) were enrolled. Breast cancer susceptibility genes ( BRCA ) mutations ( BRCA m) were significantly less common in the niraparib group than in the olaparib group [9.4% (6/64) vs . 62.7% (42/67), P <0.001], especially in the FL-M setting [10.4% (5/48) vs . 91.4% (32/35), P <0.001]. The 24-month progression-free survival (PFS) rates in the FL-M and PSR-M settings were 60.4% and 45.7%, respectively. In patients with BRCA m, the 24-month PFS rates in the FL-M and PSR-M settings were 62.2% and 72.7%, respectively. CONCLUSIONS Olaparib and niraparib were effective in patients with ovarian cancer without any new safety signals except for skin pigmentation. In patients with BRCA m, the 24-month PFS of the PARPi used in the PSR-M setting was even higher than that used in the FL-M setting.
Humans ; Female ; Ovarian Neoplasms/drug therapy* ; Piperazines/therapeutic use* ; Middle Aged ; Retrospective Studies ; Phthalazines/therapeutic use* ; Piperidines/therapeutic use* ; Indazoles/therapeutic use* ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use* ; Adult ; Aged ; China ; Neoplasm Recurrence, Local/drug therapy* ; Progression-Free Survival

Probiotics have shown excellent application prospects in preventing and treating many diseases. However, their sensitivity to the harsh environment in vivo always leads to a massive loss of viability and insufficient therapeutic effect. Fortunately, modified probiotics have emerged and provide multiple possibilities for their use in various diseases. Modification not only endows probiotics with extra capacity to resist severe environments but also gives them exogenous characteristics, such as prolonged retention time and improved therapeutic effects. Modified probiotics could combine with other therapies, which has opened up new avenues to enhance the efficacy of probiotic-based therapy. In this review, we have summarized the current physicochemical and biological modification strategies of probiotics. In addition, the progress of research on probiotic-based combination therapy has also been extensively reviewed, which contributes to the enhanced delivery of probiotics or other active constituents and provides new ideas for disease treatment, bioimaging, and diagnosis.

Objective:To investigate the incidence of port-site metastasis (PSM) after laparoscopic surgery in patients with epithelial ovarian cancer and prognostic factors influencing outcomes in those with abdominal wall PSM.Methods:Clinicopathological and follow-up data of 22 ovarian epithelial cancer patients diagnosed with abdominal wall PSM after laparoscopic surgery, who were treated in the Sichuan Cancer Hospital between May 2014 and July 2023, were retrospectively collected. A retrospective analysis of PSM characteristics and prognostic factors influencing outcomes, was conducted in these patients.Results:(1) Between May 2014 and July 2023, a total of 369 ovarian cancer patients with a history of laparoscopic surgery performed at other hospitals were admitted. Among them, 24 cases (6.5%, 24/369) were diagnosed with tumor lesions at the abdominal wall port sites via postoperative pathological examination, with a median interval time of 25.5 days (interquartile range: 19.5, 32.0 days) after laparoscopic surgery. Of these, 22 cases with complete clinicopathological and follow-up data were included in this study. (2) The age of the 22 PSM patients was (53.0±8.6) years, and the median follow-up time was 37.6 months (24.7, 63.4 months). Surgical-pathological staging revealed stage Ⅰ-Ⅱ disease in 4 cases and stage Ⅲ-Ⅳ disease in 18 cases. Histopathological differentiation included 5 cases of well-to-moderately differentiated tumors and 17 cases of poorly differentiated tumors. Pathological subtypes comprised 11 cases of high-grade serous adenocarcinoma, 5 cases of low-grade serous adenocarcinoma, and 6 cases of clear cell carcinoma or cystadenocarcinoma. Lymph node status was as follows: negative for lymph node metastasis ( n=16), positive ( n=5), and no lymphadenectomy performed ( n=1). Postoperative residual disease was categorized as no macroscopic residual disease ( n=13), residual disease ≤1 cm ( n=7), and residual disease >1 cm ( n=2). (3) Following secondary cytoreductive surgery combined with postoperative adjuvant therapy, the median progression-free survival and overall survival (OS) time of the patients were 8.8 months (4.6, 14.3 months) and 27.7 months (15.5, 38.4 months), respectively. Univariate Cox regression analysis demonstrated that surgical-pathological stage, histopathological differentiation grade, and lymph node metastasis status were significantly associated with OS time in patients with abdominal wall PSM (all P<0.05). In contrast, age, Eastern Cooperative Oncology Group performance status score, histopathological subtype, preoperative serum cancer antigen 125 level, presence of residual lesions after surgery and poly adenosine diphosphate ribose polymerase inhibitor usage showed no significant correlation with OS time (all P>0.05). Multivariate Cox regression analysis identified surgical-pathological stage ( HR=4.579，95% CI：1.111-18.866； P=0.035) and histopathological differentiation grade ( HR=5.307，95% CI：1.042-27.031； P=0.045) as independent risk factors for OS time in PSM patients. Conclusion:Abdominal wall PSM following laparoscopic surgery for epithelial ovarian cancer maybe adversely affect patient prognosis, particularly in cases with advanced stage and poorly differentiated tumors, which warrants significant clinical attention.

Objective:To investigate the incidence of port-site metastasis (PSM) after laparoscopic surgery in patients with epithelial ovarian cancer and prognostic factors influencing outcomes in those with abdominal wall PSM.Methods:Clinicopathological and follow-up data of 22 ovarian epithelial cancer patients diagnosed with abdominal wall PSM after laparoscopic surgery, who were treated in the Sichuan Cancer Hospital between May 2014 and July 2023, were retrospectively collected. A retrospective analysis of PSM characteristics and prognostic factors influencing outcomes, was conducted in these patients.Results:(1) Between May 2014 and July 2023, a total of 369 ovarian cancer patients with a history of laparoscopic surgery performed at other hospitals were admitted. Among them, 24 cases (6.5%, 24/369) were diagnosed with tumor lesions at the abdominal wall port sites via postoperative pathological examination, with a median interval time of 25.5 days (interquartile range: 19.5, 32.0 days) after laparoscopic surgery. Of these, 22 cases with complete clinicopathological and follow-up data were included in this study. (2) The age of the 22 PSM patients was (53.0±8.6) years, and the median follow-up time was 37.6 months (24.7, 63.4 months). Surgical-pathological staging revealed stage Ⅰ-Ⅱ disease in 4 cases and stage Ⅲ-Ⅳ disease in 18 cases. Histopathological differentiation included 5 cases of well-to-moderately differentiated tumors and 17 cases of poorly differentiated tumors. Pathological subtypes comprised 11 cases of high-grade serous adenocarcinoma, 5 cases of low-grade serous adenocarcinoma, and 6 cases of clear cell carcinoma or cystadenocarcinoma. Lymph node status was as follows: negative for lymph node metastasis ( n=16), positive ( n=5), and no lymphadenectomy performed ( n=1). Postoperative residual disease was categorized as no macroscopic residual disease ( n=13), residual disease ≤1 cm ( n=7), and residual disease >1 cm ( n=2). (3) Following secondary cytoreductive surgery combined with postoperative adjuvant therapy, the median progression-free survival and overall survival (OS) time of the patients were 8.8 months (4.6, 14.3 months) and 27.7 months (15.5, 38.4 months), respectively. Univariate Cox regression analysis demonstrated that surgical-pathological stage, histopathological differentiation grade, and lymph node metastasis status were significantly associated with OS time in patients with abdominal wall PSM (all P<0.05). In contrast, age, Eastern Cooperative Oncology Group performance status score, histopathological subtype, preoperative serum cancer antigen 125 level, presence of residual lesions after surgery and poly adenosine diphosphate ribose polymerase inhibitor usage showed no significant correlation with OS time (all P>0.05). Multivariate Cox regression analysis identified surgical-pathological stage ( HR=4.579，95% CI：1.111-18.866； P=0.035) and histopathological differentiation grade ( HR=5.307，95% CI：1.042-27.031； P=0.045) as independent risk factors for OS time in PSM patients. Conclusion:Abdominal wall PSM following laparoscopic surgery for epithelial ovarian cancer maybe adversely affect patient prognosis, particularly in cases with advanced stage and poorly differentiated tumors, which warrants significant clinical attention.

The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new drugs.Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors,however,not much is known about the influence of phenformin on OSCC cells.We found that phenformin suppresses OSCC cell proliferation,and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro.RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4(DNA damage inducible transcript 4)and NIBAN1(niban apoptosis regulator 1).We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy.Further,the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4(activation transcription factor 4),which was induced by phenformin treatment in OSCC cells.Mechanistically,these results revealed that phenformin triggers endoplasmic reticulum(ER)stress to activate PERK(protein kinase R-like ER kinase),which phosphorylates the transitional initial factor eIF2,and the increased phosphorylation of eIF2 leads to the increased translation of ATF4.In summary,we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth.Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.

Objective To compare the condition and prognosis of systemic lupus erythematosus(SLE)between children and adults.Methods A total of 196 patients diagnosed as SLE in Wuxi Children's Hospital and Wuxi People's Hospital from January 2015 to December 2021 were enrolled.They were assigned to children group(n=67)on adult group(n=129).Clinical characteristics and laboratory data of the patients at the onset of the disease and data during follow-up were recorded and compared between the two groups.Results The incidence of infection,the rate of kidney involvement,the number of organs involved,and the positive rate of anti-nucleosome antibody at onset in the children group were higher than those in the adult group(P<0.05).The SLE disease activity index and the average daily dose of glucocorticoid of the children group were significantly higher than those of the adult group at onset,1-month of follow-up,6-month of follow-up,and 1-year of follow-up(P<0.05).The results of Eysenck personality questionnaire showed that the children group had lower score of E scale and higher score of N scale than the adult group(both P<0.05).Conclusion There are certain differences in clinical manifestations between children and adults with SLE.Children have higher SLE activity and need longer recovery time than adults.It is essential to strengthen the monitoring of glucocorticoid side effects and psychological issues in children with SLE during follow-up.

BACKGROUND: After the treatment of osteoporotic vertebral compression fractures with bone cement implantation,deteriorative osteoporosis and the distance augment between bone cement and bones result in a decrease in bone cement-bone interface compression strength and torsion strength, and then the bone cement tends to displace, which is easy to cause a secondary vertebral fracture.OBJECTIVE: To investigate the clinical efficacy of bone cement implantation via three approaches on osteoporotic vertebral compression fractures.METHODS: Sixty patients with single osteoporotic vertebral compression fracture were treated with vertebroplasty,percutaneous kyphoplasty or fraction cement vertebroplasty. All data were collected to analyze the correlation between the bone cement morphology and treatment method, and to detect the visual analogue scale, Oswestry disability index,Cobb angle and incidence of secondary vertebral fractures.RESULTS AND CONCLUSION: The visual analogue scale scores, Oswestry disability index, and Cobb angle in thethree groups were significantly improved after treatment (P < 0.05). All above indicators showed no significant difference among groups at each time point after treatment, suggesting that these three kinds of treatments exert the same effects on pain relief, functional recovery, preventing the vertebral height loss and maintaining spinal mechanical properties.Bone cement displacement and secondary vertebral fracture occurred after clotted cement implantation. Therefore,mixed and trabecular-shaped grafts are preferred, aiming to achieve good long-term treatment outcomes in osteoporotic vertebral compression fractures.

BACKGROUND: Iliac bones are common habitant parts in metastatic tumor of bone, and the affiliate cortex is easy to be penetrated into soft tissue blots. The irregular iliac shape and its complex surrounding tissues create the difficulties in puncture operations and cement perfusion.OBJECTIVE: To investigate the clinical outcomes of CT-guided versus DSA-guided puncture combined with bone cement perfusion for metastatic tumor to the ilium.METHODS: Sixty-four patients with metastatic tumor to the ilium udergoing bone cement perfusion were enrolled, and then divided into control and experimental groups (n=32 per group), followed by treated with DSA-guided percutaneous injection of bone cement, and CT-guided puncture, respectively. Subsequently, the diffuse distribution of bone cement was observed using CT. The success rate, leakage rate, Visual Analogue Scale scores and Oswestry Disability Index were compared between two groups.RESULTS AND CONCLUSION: (1) All patients received the surgery successfully, and bone cement leakage happened in two cases of control group and one case of experimental group. (1) The Visual Analog Scale and Oswestry Disability Index scores in the two groups were significantly better than those before treatment (P < 0.05), and the scores showed no significant differences between two groups (P > 0.05). (3) No difference was found in the pain relief and functional recovery between two groups. (4) To conclude, CT-guided treatment can achieve satisfactory outcomes for metastatic tumor to the ilium by bone cement infusion in appropriate time.

BACKGROUND:Vertebroplasty and kyphoplasty for osteoporotic vertebral compression fractures can result in many complications, such as bone cement leakage and adjacent-level fractures.
OBJECTIVE:To verify the possibility of biodegradable mesh-like microporous polymer bal oon for the treatment of osteoporotic vertebral compression fractures.
METHODS:Biodegradable mesh-like microporous P(DLLA-CL) bal oons were fabricated by electrospinning technique. Coated bal oons with the same specification was fabricated by coating P(DLLA-CL) onto the same mould. Morphology of the bal oons was observed by scanning electron microscopy. The bal oon leakage was observed by eyes after the injection of water or cement. The initial strength and stiffness were measured by a universal testing machine. The proliferation of MC3T3-E1 cel s on the bal oons was determined by laser confocal microscope and cel counting kit-8 assays. The biodegradation of bal oons in simulated body fluid, porcine pancreatic lipase, and fresh human serum was studied by residual weighing and scanning electron microscopy observation. Burst pressure of bal oons was measured after the bal oon was placed into a hole in the vertebral bone. For the in vitro calcium release tests, the bal oons were fil ed with calcium cement, tied, placed into 6atm ultrapure water, and then the calcium concentration was regularly determined.
RESULTS AND CONCLUSION:Mesh-like microporous bal oons presented with good fiber morphology, thickness distribution, and the presence of pores;on the coated bal oon surface, there was absence of specific morphology and porosity. Compared with the coated bal oon, the mesh-like microporous bal oon showed better mechanical properties, liquid permeability and burst pressure, to prevent leakage of bone cement and promote osteoblast adhesion and proliferation. In addition, the degradation of the mesh-like microporous bal oons was more uniform and stable than the coated bal oons, which may increase the calcium concentration in the injured vertebrae and wil be beneficial to the new bone growth and fracture healing.

BACKGROUND:Percutaneous vertebroplasty and percutaneous kyphoplasty have become the mainstream clinical methods for the treatment of vertebral compression fractures. However, both of them have several shortcomings such as bone cement leakage, spinal stenosis, nerve compression, pulmonary embolism and other issues. OBJECTIVE:To verify the possibility of bone filing mesh container prepared by polyethylene terephthalate for the treatment of vertebral compression fractures. METHODS:The biological properties of bone filing mesh container were examined according to GB/T16886. After sample aging test, the tensile properties of the aged samples and the fresh prepared samples were compared. The expansion and bone cement leakage were evaluated by injecting bone cement into the bone filing mesh container and measuring the pressure. The initial strength and stiffness of the fresh pig vertebrae with calcium phosphate cement injection or with bone filing mesh container filed with calcium phosphate cement were compared. The in vivo bone tissue growth was periodicaly observed after the lumbar vertebra of 4-month-old pigs was implanted with the bone filing mesh container that was then ful of bone cement. RESULTS AND CONCLUSION: The bone filing mesh container had good biocompatibility. Bone filing mesh containers after 2-year storage had the same tensile strength to the fresh bone filing mesh containers. At ambient conditions, after bone cement injection, bone filing mesh containers could be expanded at 5-10 atm and therefore could play the role of uplift; at 7-10 atm, bone cement could leak out from the bone filing mesh container and enter into the interspace between surrounding bone tissues, thus playing the role of adhesion and fixation. The vertebrae after bone cement injection with or without bone filing mesh containers had the same initial strength and stiffness and exhibited bigger initial strength and stiffness than untreated vertebrae. Thein vivo animal experiments proved that bone filing mesh container had no obvious effect on the vertebrae. These findings indicate that the bone filing mesh container can be used to restore the height and strength of the fractured vertebrae. Moreover, it may eliminate bone cement leakage and therefore increase the surgery safety.