To explore the potential of anti-programmed cell death ligand 1 (PD-L1) immunotherapy in giant congenital melanocytic nevus (GCMN) treatment.

GCMN cells were divided into four groups: GCMN group (GCMN cells alone), unactivated peripheral blood mononuclear cells (PBMC)+GCMN group (GCMN cells with unstimulated PBMCs), activated PBMC+GCMN group (GCMN cells with CD3/CD28 antibody-stimulated PBMCs), and activated PBMC+GCMN+PD-L1 inhibitor group (the activated PBMC +GCMN group treated with 10 μg·mL^-1 PD-L1 inhibitor atezolizumab). After 72 hours of culture, cell cytotoxicity and confluence were assessed. Cell viability was measured using the cell counting kit (CCK-8) assay, and apoptosis was evaluated via flow cytometry. Additionally, a humanized immune system was established in C-NKG severely immunodeficient mice by intraperitoneal injection of human PBMCs. A GCMN patient-derived xenograft (PDX) model was constructed in these humanized mice, divided into two groups: control group [phosphate buffer saline (PBS)] and experimental group (intraperitoneal injection of 10 mg·kg^-1 atezolizumab), administered every 3 days for 2 weeks, to evaluate in vivo efficacy.

Cell confluence rates for the GCMN, unactivated PBMC+GCMN, activated PBMC+GCMN, and activated PBMC+GCMN+PD-L1 inhibitor groups were (93.14±3.25)%, (85.29±2.40)%, (68.29±3.68)% and (22.55±4.28)%, respectively. Cell viability rates were (100.00±1.48)%, (80.35±2.60)%, (52.17±2.37)% and (15.61±1.82)%, respectively. Apoptotic cell proportions were (0.64±0.14)%, (9.32±0.91)%, (19.29±3.98)% and (28.43±0.33)%, respectively. Compared to the GCMN group, the activated PBMC+GCMN+PD-L1 inhibitor group showed statistically significant differences in all measured parameters (all P<0.05). In GCMN-PDX model, dermal cell density in experimental group and control group were (580±183) and (3 658±532) cells·mm^-2, respectively. And the difference of the above index between the two groups was statistically significant (all P<0.05).

This study demonstrates that PD-L1 inhibitors effectively target GCMN cells by activating the immune system, offering a promising new strategy for the clinical treatment of GCMN.

To investigate the effects of daptomycin (DAP) on the proliferation, apoptosis, and cell cycle of U266 [U266B1] human multiple myeloma cells (U266).

U266 cells were divided into the following groups: normal control group (NC group), DAP 20 μM group (DAP20), DAP 40 μM group (DAP40), DAP 80 μM group (DAP80), BZ 50 nM group (BZ50), and DAP 80 μM + BZ 50 nM group (DAP80+BZ50). U266 cells were treated with varying concentrations of DAP (0, 20, 40, and 80 μM), 50 nM bortezomib (BZ), and combination of DAP (80 μM) plus BZ (50 nM). Effects were assessed using cell counting kit-8 (CCK-8) assays, Western blotting (WB), flow cytometry, and quantitative real-time polymerase chain reaction (qPCR).

At 24 h post-treatment: Cell viability rates were recorded as (97.13±2.51)%, (96.80±3.44)%, (85.48±3.28)%, (81.56±2.09)%, (60.78±2.80)%, and (38.09±2.09)% for DAP alone (0-80 μM), BZ monotherapy, and combinatorial treatment, respectively. Early apoptotic cell proportions measured via flow cytometry showed values of (7.50±0.84)%, (8.20±1.41)%, (9.07±1.22)%, (13.14±2.27)%, (14.51±2.58)%, and (15.17±1.87)% across groups. Proportions of cells in G1 phase were determined to be (33.40±1.48)%, (33.03±2.49)%, (31.50±1.40)%, (38.59±1.54)%, (36.94±1.13)%, and (39.43±1.40)%. Relative expression levels of ribosomal protein S19 (RPS19) mRNA exhibited fold changes of 0.99±0.09, 1.00±0.14, 0.66±0.04, 0.61±0.06, 0.55±0.04, and 0.53±0.07, while corresponding protein levels via WB analysis were 1.08±0.05, 0.97±0.03, 0.90±0.02, 0.87±0.04, 0.89±0.04, and 0.57±0.03. Statistically significant differences (all P<0.001) were observed in BZ50, DAP80, and their combination compared to DAP 0 μM group.

DAP may exert its inhibitory effect on U266 cell proliferation and promote apoptosis by downregulating the expression of RPS19. This study provides a potential therapeutic drug for the treatment of multiple myeloma.

To study the in vitro and in vivo pharmacodynamics of dirozalkib.

Prepare dirozalkib solutions with concentrations ranging from 3.81×10^-3 to 1 000.00 nmol·L^-1. The activities of dirozalkib against kinases anaplastic lymphoma kinase (ALK), ALK-L1196M, and ALK-G1202R were evaluated using the Mobility Shift Assay and Radioisotope Filter Binding methods. The inhibitory effect of dirozalkib on cell proliferation was evaluated using the CellTiter-Glo assay in multiple Ba/F3 cell lines transfected with EML4-ALK fusion genes and drug-resistant mutants, at concentrations ranging from 1.53×10^-2 to 1 000.00 nmol·L^-1. Ba/F3-EML4-ALK-L1196M (crizotinib-resistant) cells were subcutaneously inoculated in NOD SCID mice. The tumor-bearing mice were randomly divided into blank group (solvent control), experimental group (50 mg·kg^-1 dirozalkib), control group (50 mg·kg^-1 crizotinib), each group consisted of 9 mice. The mice were gavage once a day, continuous administration over a 14-day period. BALB/c nude mice were used to establish a human lung cancer tumor tissue-derived LU-01-0319R (crizotinib-resistant) patient-derived tumor xenograft (PDX) model. The tumor-bearing mice were randomly divided into blank group (solvent control), experimental group (24 mg·kg^-1 dirozalkib), control group (24 mg·kg^-1 crizotinib), each group consisted of 9 mice. The mice were gavage once a day, continuous administration over a 21-day period. Human lung cancer H228-luc cells were intracranially inoculated in BALB/c nude mice. The tumor-bearing mice were randomly divided into blank group (solvent control), experimental group (100 mg·kg^-1 dirozalkib), control group (100 mg·kg^-1 crizotinib), each group consisted of 9 mice. The mice were gavage once a day, continuous administration over a 14-day period. Assessed the anti-tumor efficacy of dirozalkib.

Dirozalkib significantly inhibited the kinase activities of ALK, ALK-L1196M, and ALK-G1202R [50% inhibiting concentration (IC₅₀) <1.0 nmol·L^-1]. In cells, dirozalkib exhibited significant proliferation inhibitory activity against NCI-H3122 cells harboring EML4-ALK fusion (IC₅₀ = 3.00 nmol·L^-1). Additionally, it demonstrated potent inhibitory activity against multiple cell lines with EML4-ALK fusion and drug-resistant mutants of crizotinib and second-generation ALK inhibitors (IC₅₀: 1.92-62.85 nmol·L^-1). In the crizotinib-resistant Ba/F3-EML4-ALK-L1196M xenograft model, dirozalkib at a dose of 50 mg·kg^-1 had a significant anti-tumor effect, with a relative tumor proliferation rate of 6.14%. In the LU-01-0319R human lung cancer xenograft model (crizotinib-resistant PDX model), the 24 mg·kg^-1 dirozalkib also had a significant tumor inhibitory effect, with a relative tumor proliferation rate of 13.19%. For the H228-luc human lung cancer intracranial inoculation model, dirozalkib at 100 mg·kg^-1 could significantly inhibit tumor growth [BLI value was (569.34±153.65) × 10⁵ photons·s^-1]and could significantly prolong the survival time of the animals.

Dirozalkib effectively inhibits ALK and various resistance mutations associated with first- and second-generation ALK-TKIs, and shows significant antitumor activity in multiple tumor models, including intracranial implantation models.

To analyze the preventive effect of potassium citrate sustained-release tablets on stent mural calculi after ureteral lithotripsy for upper urinary tract calculi and influence on urinary calcium ion and urinary oxalic acid concentration.

The patients with upper urinary tract calculi who underwent ureteral lithotripsy were randomly divided into control group and treatment group. Both groups of patients received routine dietary guidance and health education after surgery. The control group received routine anti-infection, pain relief and stone removal treatment after surgery, while the treatment group received oral potassium citrate sustained-release tablets on the basis of the control group after surgery (1.08 g per time, 3 times a day) continuously until the ureteral stent tube was removed. The ureteral stent tube was removed at 4 or 8 weeks after surgery based on the patient’s recovery status, and the occurrence of stent mural calculi was observed, and 24-hour urine samples were collected from patients during follow-up at 4 weeks after surgery to detect urine pH, levels of uric acid, oxalic acid and citric acid and concentrations of calcium and phosphorus ions. The differences in occurrence of ureteral stent calculi and urine detection indicators were compared between the two groups.

In treatment group, 42 cases were enrolled but 2 cases were lost to follow-up, and 40 cases were finally included for statistical analysis. In control group, 43 patients were included but 3 patients were lost to follow-up, thus 40 patients were enrolled for statistical analysis. Ureteral stents were removed at 4 weeks or 8 weeks after surgery in both groups. The treatment group had a total of 64 ureteral stent tubes retained, and the incidence rate of stent mural calculi was 1.56% (1 case/64 cases). The control group had a total of 62 ureteral stent tubes retained, and the incidence rate of stent mural calculi was 11.29% (7 cases/62 cases, P<0.05). At 4 weeks after surgery, the calcium ion concentrations in treatment group and control group were (2.63±0.66) and (3.45±1.02) mmol·L^-1, oxalic acid levels were (0.41±0.04) and (0.52±0.07) mmol·L^-1, phosphorus ion concentrations were (12.36±2.38) and (16.01±2.16) mmol·L^-1, uric acid levels were (2.02±0.17) and (2.43±0.23) mmol·L^-1, urine pH values were 6.85±0.34 and 6.24±0.34, urine citric acid levels were (1.61±0.22) and (1.39±0.17) mmol·L^-1, respectively (all P<0.05). The adverse drug reactions in treatment group during medication included nausea and diarrhea, with a total incidence rate of 10.00% (4 cases/40 cases). No adverse drug reactions were observed in the control group.

Potassium citrate sustained-release tablets can reduce the incidence rate of stent mural calculi after ureteral lithotripsy for upper urinary tract calculi, and lower the concentrations of urinary calcium ion and oxalic acid.

To observe the clinical efficacy and safety of ferulic acid piperazine tablets combined with continuous renal replacement therapy in the treatment of children with acute renal failure.

Children with acute renal failure were randomly divided into control group and treatment group. Both groups were given basic treatment, based on which, the control group was given continuous renal replacement therapy; the treatment group was given piperazine ferulate tablets 100 mg per time, orally, tid, on the basis of control group. Two groups were treated for 2 weeks. The clinical efficacy, renal function, levels of renal injury markers and safety were compared between the two groups.

Treatment group was enrolled 85 cases, 2 cases dropped out, and 83 cases were finally included in the statistical analysis. Control group was enrolled 84 cases, 3 cases dropped out, and 81 cases were finally included in the statistical analysis. After treatment, the total effective rates of treatment and control groups were 92.77% (77 cases/83 cases) and 81.48% (66 cases / 81 cases) with statistically significant difference (P<0.05). After treatment, the serum creatinine levels of treatment and control groups were (120.35±17.12) and (148.12±20.03) μmoL·L^-1; the blood urea nitrogen levels were (12.29±2.14) and (15.64±3.01) μmoL·L^-1; the β2-microglobulin levels were (1.87±0.25) and (2.14±0.39) mg·L^-1; the 24-h urinary protein quantification were (0.94±0.31) and (1.24±0.47) g·24 h^-1; N-acetyl-β-D-glucosidase contents were (17.03±2.98) and (20.36±3.51) U·L^-1; the renal injury molecule 1 contents were (1.62±0.27) and (2.09±0.32) μg·L^-1; the neutrophil gelatinase-associated lipid transport protein contents were (50.36±8.13) and (59.23±10.14) μg·L^-1, respectively, and the differences were all statistically significant (all P<0.05). The adverse drug reactions of treatment group were nausea, vomiting and abdominal distension, while those in the control group were dizziness, nausea and vomiting. The total incidences of adverse drug reactions in the treatment and control groups were 7.23% and 4.94% without significant difference (P>0.05).

Ferulic acid piperazine tablets combined with continuous renal replacement therapy have definitive clinical efficacy in the treatment of children with acute renal failure, which can significantly improve the renal function of children, reduce renal injury, without increasing the incidence of adverse drug reactions.

To observe the clinical efficacy and safety of zoledronic acid concentrate injection combined with alendronate sodium tablets in the treatment of elderly postmenopausal patients with type 2 diabetes mellitus (T2DM) complicated with osteoporosis (OP).

Elderly postmenopausal T2DM patients with OP were divided into control group and treatment group using random number table method. The control group was given oral alendronate sodium tablets, 10 mg per dose, once daily (qd), for a course of 1 year; the treatment group, based on the control group, received additional treatment with zoledronic acid concentrate injection, 5 mg per dose, once a year, via intravenous infusion, for a course of 1 year. The clinical efficacy, pain levels at different time points, bone density before and after treatment, bone metabolism indicators before and after treatment and safety were compared between two groups.

A total of 5 cases were lost during this study, with the final number of patients in the control and treatment groups being 38 cases and 42 cases, respectively. After treatment, the overall effective treatment rates were 84.21% (32 cases/38 cases) for the control group and 97.62% (41 cases /42 cases) for the treatment group, with statistically significant difference (P<0.05). The visual analogue scale (VAS) pain scores for the treatment group after 6 months and 1 year of treatment were (5.62±0.70) and (5.02±0.68) points, respectively, which were significantly lower than the control group’s (6.06±0.75) and (5.65±0.70) points. After 1 year of treatment, the bone density of the lumbar spine L_1-4 were (0.89±0.07) and (0.85±0.08) g·cm^-3 for the treatment and control groups, respectively; the femoral trochanter bone density were (0.78±0.08) and (0.73±0.09) g·cm^-3; the femoral neck bone density was (0.69±0.07) and (0.66±0.06) g·cm^-3; the bone density in the Ward triangle area were (0.79±0.08) and (0.73±0.10) g·cm^-3; the serum levels of type Ⅰ procollagen amino propeptide were (25.60±6.82) and (30.79±6.90) pg·mL^-1; the levels of bone-specific alkaline phosphatase (BALP) were (15.87±4.03) and (17.91±3.71) ng·mL^-1; the levels of Klotho protein were (885.20±32.60) and (810.76±33.15) pg·mL^-1; the levels of 25-hydroxyvitamin D [25-(OH)D] were (35.70±6.72) and (32.29±6.34) ng·mL^-1 for the treatment and control groups, respectively. The above indicators of the treatment group were statistically significantly different from those of the control group (all P<0.05). The main adverse drug reactions in the control group were mainly gastrointestinal discomfort and fatigue, while in the treatment group were mainly fever, muscle and bone pain, gastrointestinal discomfort and fatigue. The overall incidence of adverse drug reactions were 18.42% (7 cases/38 cases) in the control group and 21.43% (9 cases /42 cases) in the treatment group, with no statistically significant difference (P>0.05).

The combined treatment of zoledronic acid concentrate injection and alendronate sodium tablets in elderly postmenopausal T2DM patients with OP is obviously effective, capable of effectively alleviating pain, increasing bone density, raising serum Klotho and 25-(OH)D levels, and reducing BALP levels, with adverse drug reactions being controllable.