[The efficacy and safety of anlotinib combined with niraparib in treating patients with platinum-resistant recurrent ovarian cancer].

Objectives: To investigate the efficacy and safety of anlotinib combined with niraparib in treating patients with platinum-resistant ovarian cancer. Methods: Thirty-five patients with pathological confirmed platinum-resistant ovarian cancer who experienced progression after receiving at least two lines of standard treatment were eligible. All of them were treated with anlotinib combined with niraparib between September 2019 and October 2021. The primary endpoint was progression-free survival (PFS). The second endpoints included overall survival, objective response rate (ORR), disease control rate (DCR) and safety. Survival analysis was performed using the Kaplan-Meier method and Log-rank test, and influence factor analysis was performed using Cox proportional risk regression models. Results: The best overall response showed that partial response was observed in 14 patients, stable disease was noted within 13 patients, and progressive disease was found in 8 patients. Therefore, the ORR and DCR of these 35 patients were 40.0% (95% CI:22.9%-57.1%) and 77.1% (95% CI:62.9%-91.4%), respectively. The median follow-up duration was 18.9 months (6.9-32.2). The median PFS was 6.5 months (95% CI:5.35-7.66). Multivariate Cox regression analysis for PFS indicated that age, Eastern Cooperative Oncology Group performance status (ECOG PS) score, International Federation of Gynecology and Obstetrics (FIGO) stage, and BRCA mutation status were independent factors influencing PFS (P＜0.05). Additionally, the PFS in patients with BRCA mutation who have never received PARP inhibitor treatment was significantly longer than that in patients without BRCA mutation who have been exposed to prior PARPi treatment (15.0 vs 6.0 month, P=0.029). The most common treatment-related adverse reactions were fatigue (85.7%), hematologic toxic (85.7%) and hypertension (74.3%). There were no treatment-related deaths. Conclusion: Anlotinib combined with niraparib shows a promising efficacy and tolerable safety in platinum-resistant ROC patients.

[Comparison of maternal-fetal outcomes between laparoscopic cervicoisthmic cerclage and McDonald cerclage in women with cervical insufficiency].

Objective: To compare the maternal and fetal outcomes of women with cervical insufficiency (CI) undergoing McDonald cerclage (MC) and laparoscopic cervicoisthmic cerclage (LCC), so as to provide evidence for the selection of cerclage methods. Methods: A retrospective trial was carried out in the First Affiliated Hospital of Sun Yat-sen University from January 2010 to December 2020. A total of 221 women who underwent the prophylactic cerclage were divided into MC group (n=54), LCC with MC history group (n=28) and LCC without MC history group (n=129) by the mode of operation and whether the pregnant women who underwent LCC had MC history. General clinical data, pregnancy complications and pregnancy outcomes were compared between the three groups. Results: (1) General clinical data: the proportion of women accepted cervical cerclage during pregnancy in MC group, LCC with MC history group and LCC without MC history group were 100.0% (54/54), 7.1% (2/28) and 27.1% (35/129), respectively (P<0.001). The indications of the three groups showed statistical significance (P=0.003), and the main indication was the history of abortion in the second and third trimester [75.9% (41/54) vs 89.3% (25/28) vs 84.5% (109/129)]. (2) Pregnancy complications: the incidence of abnormal fetal position [7.8% (4/51) vs 17.4% (4/23) vs 19.8% (24/121)], placenta accrete [5.9% (3/51) vs 13.0% (3/23) vs 11.6% (14/121)], uterine rupture [0 vs 4.3% (1/23) vs 5.8% (7/121)] in the MC group were all lower than those in LCC with MC history and LCC without MC history groups. However, there were no statistical significances (all P>0.05). Intrauterine inflammation or chorioamnionitis [15.7% (8/51) vs 0 vs 0.8% (1/121)] and premature rupture of membrane [23.5% (12/51) vs 4.3% (1/23) vs 0] were both significantly higher in MC group than those in LCC with MC history and LCC without MC history groups (all P<0.001). (3) Pregnancy outcomes: the cesarean section rate was significantly lower in MC group (41.2%, 21/51) than that in LCC with MC history group (100.0%, 23/23) and LCC without MC history group (100.0%, 121/121; P<0.001). MC group was associated with lower expenditure than LCC with MC history and LCC without MC history groups (12 169 vs 26 438 vs 27 783 yuan, P<0.001). The success rates of live birth cerclage did not differ significantly in MC (94.4%, 51/54), LCC with MC history (82.1%, 23/28) and LCC without MC history (93.8%, 121/129) groups (χ2=5.649, P=0.059). There was no significant difference in neonatal intensive care unit occupancy, neonatal birth weight and neonatal asphyxia between the three groups (all P>0.05). Conclusions: Both LCC and MC are the treatment choice for women with CI, which may get similar liver birth. However, MC has the advantages of low cesarean section rate, economical and easy operation. Therefore, MC is recommended as the first choice for CI patients, and LCC is for women with failed MC.

Using combined Lactobacillus and quorum quenching enzyme supplementation as an antibiotic alternative to improve broiler growth performance, antioxidative status, immune response, and gut microbiota.

To seek viable alternatives to antibiotics, we determined the combinatorial effects of Lactobacillus and a quorum quenching enzyme (QQE) on broiler growth performance, antioxidant capacity, immune responses, and cecal microbial populations. In total, 360 one-day-old male broilers (Ross 308) were randomly allotted to 3 dietary treatments, with 12 replicate pens/treatment and 10 birds/replicate pen. Dietary treatments lasted 42 d and comprised: corn-soybean meal basal diet (control group, CON); control plus antibiotic growth promoter supplement group (AGP); and control plus Lactobacillus and QQE supplement group (LQ). Dietary LQ supplementation significantly increased final body weight (BW) and average daily gain (ADG) when compared with CON and AGP groups between 22 and 42 d and 1 to 42 d (P < 0.05). No significant differences were observed for serum superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels between treatments (P > 0.05). A higher concentration of total antioxidant capacity (T-AOC) was observed on d 42 in the LQ group (P = 0.06). Feeding LQ significantly increased serum immunoglobulins (IgA and IgG) levels when compared with other treatments (P < 0.05). A statistical trend was also observed for increased cecal butyrate levels (P = 0.06) in the LQ group. Bacterial α-diversity was unaffected by dietary treatments (P > 0.05). However, from principal component analysis (PCoA), the microbial community structure was different between the LQ and AGP groups. Diet supplemented with LQ significantly (P < 0.05) decreased the relative abundance of Synergistota and Proteobacteria and significantly (P < 0.05) increased the proportion of Ruminococcaceae and Faecalibacterium. Thus, supplemental LQ improved growth performance, immune status, and modulated intestinal microbial communities in broilers. We provide a new perceptive on antibiotic substitutes in the poultry industry.

[Investigation of pregestational diabetes mellitus in 15 hospitals in Guangdong province].

Objective: To investigate the morbidity, diagnostic profile and perinatal outcome of pregestational diabetes mellitus (PGDM) in 15 hospitals in Guangdong province. Methods: A total of 41 338 women delivered in the 15 hospitals during the 6 months, 195 women with PGDM (PGDM group) and 195 women with normal glucose test result (control group) were recruited from these tertiary hospitals in Guangdong province from January 2016 to June 2016. The morbidity and diagnostic profile of PGDM were analyzed. The complications during pregnancy and perinatal outcomes were compared between the two groups. In the PGDM group, pregnancy outcomes were analyzed in women who used insulin treatment (n=91) and women who did not (n=104). Results: (1) The incidence of PGDM was 0.472%(195/41 338). Diabetes mellitus were diagnosed in 59 women (30.3%, 59/195) before pregnancy, and 136 women (69.7%,136/195) were diagnosed as PGDM after conceptions. Forty-six women (33.8%) were diagnosed by fasting glucose and glycohemoglobin (HbA1c) screening. (2) The maternal age, pre-pregnancy body mass index (BMI) , prenatal BMI, percentage of family history of diabetes, incidence of macrosomia, concentration of low density lipoprotein were significantly higher in PGDM group than those in control group (all P<0.05). Women in PGDM group had significantly higher HbA1c concentration ((6.3±1.3)% vs (5.2±0.4)%) , fasting glucose [(6.3±2.3) vs (4.8±1.1) mmol/L], oral glucose tolerance test (OGTT) -1 h glucose ((12.6±2.9) vs (7.1±1.3) mmol/L) and OGTT-2 h glucose [(12.0±3.0) vs (6.4±1.0) mmol/L] than those in control group (P<0.01). (3) The morbidity of preterm births was significantly higher (11.3% vs 1.0%, P<0.01), and the gestational age at delivery in PGDM group was significantly smaller [(37.6±2.3) vs (39.2±1.2) weeks, P<0.01]. Cesarean delivery rate in the PGDM group (70.8% vs 29.7%) was significantly higher than the control group (P<0.01). There was significantly difference between PGDM group and control in the neonatal male/female ratio (98/97 vs 111/84, P=0.033). The neonatal birth weight in PGDM group was significantly higher ((3 159±700) vs (3 451±423) g, P<0.01) . And the incidence of neonatal hypoglycemia in the PGDM group was higher than the control group (7.7% vs 2.6%, P=0.036). (4) In the PGDM group, women who were treated with insulin had a smaller gestational age at delivery [(36.9±2.9) vs (37.9±2.5) weeks, P<0.01], and the neonates had a higher neonatal ICU (NICU) admission rate (24.2% vs 9.6%, P<0.01). Conclusions: The morbidity of PGDM in the 15 hospitals in Guangdong province is 0.472%. The majority of PGDM was diagnosed during pregnancy; HbA1c and fasting glucose are reliable parameters for PGDM screening. Women with PGDM have obvious family history of diabetes and repeated pregnancy may accelerate the process of diabetes mellitus. Women with PGDM have higher risk for preterm delivery and neonatal hypoglycemia. Unsatisfied glucose control followed by insulin treatment may increase the need for NICU admission.

[Adiponectin exerts antiproliferative effect on high glucose-induced BeWo cell proliferation in vitro].

OBJECTIVE: To determine the effects of adiponectin on high glucose induced BeWo cell proliferation in vitro. METHODS: BeWo cells were seeded in 96-well plates at the appropriate density. After treatments with high glucose (25 mmol/L), western blot analysis of cyclin D1 and a colorimetric assay (cell counting kit-8, CCK-8) were used to analyse BeWo cells' proliferation, and western blot was used to detect the expression of adiponectin. Moreover, we added adiponectin (20 µg/ml) in the culture medium and three methods were utilized for cell proliferation analysis: CCK-8, cell cycle analysis (by flow cytometry) and proliferating cell nuclear antigen (PCNA) immunocytochemical staining. RESULTS: Compared to BeWo cells cultured by normal glucose and high mannitol, the proliferation of BeWo cells treated by high glucose increased (P<0.05). Compared with BeWo cells cultured by high mannitol, the expression of adiponectin in BeWo cells treated by high glucose decreased. After added adiponectin in the culture medium, the proliferation of BeWo cells treated by adiponectin+high glucose decreased than that of cells treated by high glucose (0.770±0.050 versus 0.990±0.070, P<0.05); the proportion of G2+S phases of BeWo cells treated by adiponectin+high glucose decreased than that of cells treated by high glucose [(40.7±2.1)% versus (44.9± 3.9)%, P<0.05]; the rate of PCNA positive cell in BeWo cells treated by adiponectin+high glucose decreased than that of cells treated by high glucose [(28±5)% versus (44±5)%, P<0.05]. CONCLUSION: Adiponectin could inhibit proliferation of high glucose induced BeWo cells in vitro.

Plasma shock wave lithotripsy of gallstones in vitro. Animal experiments and clinical application.

It is sometimes very difficult to extract a huge impacted stone through the T-tube fistulous tract by conventional techniques with choledochoscope. To simplify the procedure, a lithotriptor PSW-G type using plasma shock wave to disintegrate the stone was designed. The efficacy to fragmentate stone was investigated both in vitro and in vivo. Stones can be shattered into pieces less than 3 mm in diameter in about 30 times of spark with lower energy ranging from 1.7-3.4 kV and 1-3 J. Animal experiments were carried out to prove the safety of the lithotriptor. There was neither interference with the cardiovascular and respiratory systems nor obvious damage to the adjacent tissue where plasma shock wave applied to break stones. Six patients with retained calculi impacted both in extra- and intra-hepatic duct were successfully treated by plasma shock wave lithotripsy. It appears very useful in dealing with a huge impacted stone in the biliary tract.

A retrospective study on diagnosis and treatment of severe acute pancreatitis.

Severe acute pancreatitis is highly controversial on its diagnostic criteria, the optimum time for surgery, the selection of surgical procedures, and the prevention and treatment of complications. We treated 40 patients with severe acute pancreatitis from July 1983 to July 1988. The comparison of clinical and laboratory data of severe acute pancreatitis and mild acute pancreatitis showed that in some patients neither Ranson's nor Bank's criteria are reliable in classifying or predicting the severity of the disease. The coexistence of acute peritonitis and bloody ascites with elevated amylase level is very helpful to identify the local conditions of pancreatic necrosis and hemorrhage. We suggest early operation (within 48 hours) be applied in severe acute pancreatitis. In our series, five types of surgical procedures were used. We consider that proper treatment of acute respiratory distress syndrome (ARDS) is most important in the management of severe pancreatitis.

Gallbladder mucin and cholesterol and pigment gallstone formation in hamsters.

We measured gallbladder mucin production by hamsters fed diets lithogenic for either cholesterol or pigment gallstones. In hamsters on the cholesterol stone diet, gallbladder production of 3H-glucosamine-labeled mucin was elevated two- and seven-fold after 1 and 3 weeks, respectively. After 1 week cholesterol crystals were seen in a mucus gel on the gallbladder surface. In hamsters on the pigment stone diet, gallbladder mucin production was significantly elevated after 1 and 3 weeks. The first precipitation of pigment crystals was in mucus in bile or on the gallbladder surface. Black pigment stones grew by agglomeration of pigment crystals enmeshed in mucus. In conclusion, gallbladder mucin production is increased before cholesterol or pigment stone formation, and the earliest deposition of crystals is in mucus in bile or on the gallbladder surface.