[Comparison of efficacy and safety between domestic immune checkpoint inhibitors and pembrolizumab in the treatment of driver gene-negative advanced non-small cell lung cancer].

Objective: To compare the efficacy and safety of domestic immune checkpoint inhibitors and pembrolizumab in the treatment of driver gene-negative advanced non-small cell lung cancer. Methods: A retrospective analysis was conducted on the data of 1 241 patients with driver gene-negative, unresectable stage ⅢB to Ⅳ non-small cell lung cancer who were treated at the Hunan Cancer Hospital from January 1, 2017 to October 1, 2022. All patients received monotherapy or combination therapy with domestic immune checkpoint inhibitors or pembrolizumab. Among the 1 241 patients, there were 1 066 males and 175 females, with an age range of 14 to 84 years and a median age of 62 years. Among them, 67 patients received monotherapy with domestic immune checkpoint inhibitors, 695 patients received combination therapy with domestic immune checkpoint inhibitors, 102 patients received monotherapy with pembrolizumab, and 377 patients received combination therapy with pembrolizumab. The efficacy and safety of domestic immune checkpoint inhibitors and pembrolizumab monotherapy or combination therapy were compared. Results: In the immune checkpoint inhibitor monotherapy group, the objective response rate (ORR) using domestic immune checkpoint inhibitors and pembrolizumab was 43.3%(29/67) and 44.1%(45/102), respectively, and the disease control rate (DCR) was 79.1%(53/67) and 84.3%(86/102), respectively, with no statistically significant differences (both P>0.05). In the immune combination therapy group, the ORR using domestic immune checkpoint inhibitors and pembrolizumab was 60.9%(423/695) and 62.9%(237/377), respectively, and the DCR was 92.9%(646/695) and 91.0%(343/377), respectively, with no statistically significant differences (both P>0.05). In the immune checkpoint inhibitor monotherapy group, the median progression-free survival (PFS) using domestic immune checkpoint inhibitors and pembrolizumab was 9.0 (95%CI: 3.0-15.0) months and 7.4 (95%CI: 4.8-9.8) months, respectively, with no statistically significant differences (P=0.660). The median overall survival (OS) was 27.0 (95%CI: 25.0-29.0) months and 22.0 (95%CI: 17.1-26.9) months, respectively, with no statistically significant differences (P=0.673). In the immune combination therapy group, the median PFS using domestic immune checkpoint inhibitors and pembrolizumab was 9.0 (95%CI: 8.2-9.8) months and 10.5 (95%CI: 9.0-12.0) months, respectively, with no statistically significant differences (P=0.186). The median OS was 24.0 (95%CI: 19.1-28.9) months and 26.0 (95%CI: 21.3-30.7) months, respectively, with no statistically significant differences (P=0.359). The incidence of grade 1-2 reactive capillary proliferation of the skin in the domestic immune checkpoint inhibitor group and pembrolizumab group was 14.0% (107/762) and 0, respectively. The incidence of grade≥3 reactive capillary proliferation of the skin was 1.0% (7/762) and 0, respectively, with statistically significant differences (both P<0.05). No statistically significant differences were observed in other adverse reactions (all P>0.05). Conclusions: The efficacy of domestically produced immune checkpoint inhibitors is comparable to that of pembrolizumab in the treatment of driver gene-negative advanced non-small cell lung cancer. There is little difference in safety, except for the specific difference in domestically produced immune checkpoint inhibitor, which has a unique risk of reactive cutaneous capillary endothelial proliferation.

[Two complementary dominant genes controlling apomixis in genus Citrus and poncirus].

Apomixis is very common in Citrus genus and its related genus. Two monoembryonic tangerine varieties (C. reticulata Blanco) Clementine and Wilking were used as seed parents to cross with four polyembryonic orange varieties [C. sinensis (L.) Osbeck]. Both sexual and apomictic progenies were found in each F1 population with different segregation ratios. In a total of 74 Wilking progenies, 23 were monoembryonic and 51 polyembryonic and the ratio of sexual and apomictic progenies was about 1:2 tested either in each individual cross or in the whole Wilking cross combionations. In Clementine progenies, 84 were monoembryonic and 71 polyembryonic and the ratio was about 1:1 tested either in each individual cross or in the whole Clementine cross combionations. According to the results together with other data published, a possible apomixis controlling mechanism was proposed, which involves two complementary dominant genes named as A1 and A2 that control apomixis in genus Citrus and Poncirus. Trees of genotype A1-A2-, except for homozygous of dominant gene A1 (which is lethal), can produce apomixis seeds. And those of other genotypes will produce sexual seeds. The segregation and recombination of these two genes accorded with Mendel's genetic laws. The proposed mechanism could explain genotypes controlling polyembryony-monoembryony existing both in nature species and artificial hybridization progenies as well as most of the known hybridization results.

Differential binding of triglyceride-rich lipoproteins to lipoprotein lipase.

In comparison to very low density lipoprotein (VLDL), chylomicrons are cleared quickly from plasma. However, small changes in fasting plasma VLDL concentration substantially delay postprandial chylomicron triglyceride clearance. We hypothesized that differential binding to lipoprotein lipase (LPL), the first step in the lipolytic pathway, might explain these otherwise paradoxical relationships. Competition binding assays of different lipoproteins were performed in a solid phase assay with purified bovine LPL at 4 degrees C. The results showed that chylomicrons, VLDL, and low density lipoprotein (LDL) were able to inhibit specific binding of (125)I-labeled VLDL to the same extent (85.1% +/- 13.1, 100% +/- 6.8, 90.7% +/- 23.2% inhibition, P = NS), but with markedly different efficiencies. The rank order of inhibition (K(i)) was chylomicrons (0.27 +/- 0.02 nm apoB) > VLDL (12.6 +/- 3.11 nm apoB) > LDL (34.8 +/- 11.1 nm apoB). By contrast, neither triglyceride (TG) liposomes, high density lipoprotein (HDL), nor LDL from patients with familial hypercholesterolemia were efficient at displacing the specific binding of (125)I-labeled VLDL to LPL (30%, 39%, and no displacement, respectively). Importantly, smaller hydrolyzed chylomicrons had less affinity than the larger chylomicrons (K(i) = 2.34 +/- 0.85 nm vs. 0.27 +/- 0.02 nm apoB respectively, P < 0.01). This was also true for hydrolyzed VLDL, although to a lesser extent. Chylomicrons from patients with LPL deficiency and VLDL from hypertriglyceridemic subjects were also studied. Taken together, our results indicate an inverse linear relationship between chylomicron size and K(i) whereas none was present for VLDL. We hypothesize that the differences in binding affinity demonstrated in vitro when considered with the differences in particle number observed in vivo may largely explain the paradoxes we set out to study.

[Effects of Andrographis paniculata component on nitric oxide, endothelin and lipid peroxidation in experimental atherosclerotic rabbits].

OBJECTIVE: To observe the effects of Andrographis Paniculata component (API0134) on nitric oxide (NO), endothelin (ET), cyclic guanosine monophosphate (cGMP), lipid peroxide (LPO) and superoxide dismutase (SOD) in experimental atherosclerotic rabbit. METHODS: An atherosclerotic rabbit model was established by feeding high cholesterol diet supplemented by bovine serum albumin injection bolus. The rabbits were randomly divided into the control, model, and API0134 treated group. Blood samples were collected before 4 weeks and 8 weeks after relevent treatment. RESULTS: Before 4 and after 8 weeks API0134 administration, compared with model group, the NO, cGMP and activity of SOD increased (P < 0.01), while LPO and ET decreased (P < 0.01). CONCLUSIONS: API0134 possesses the effects of antioxidation, preserving endothelial function, and maintaining the balance of NO/ET.

Effects of nifedipine on diastolic function in hypertensive patients--an echocardiographic study.

This study was undertaken to observe the changes in heart function and evaluate the effects of nifedipine on diastolic function in 70 patients with uncomplicated hypertension by M-mode and Doppler echocardiography. The results showed that diastolic abnormalities in hypertensive patients may precede systolic dysfunction and that nifedipine can improve diastolic function. It is easy and quick to estimate the diastolic function by measuring the EF slope, EA and EPSS, especially the E wave velocities. This method proved to be applicable to clinical practice.