This study sought to evaluate the efficacy and safety of venetoclax (Ven) in combination with tyrosine kinase inhibitors (TKI) and reduced-dose chemotherapy for the treatment of patients with minimal residual disease (MRD) -positive and relapsed/refractory (R/R) Ph-positive acute lymphoblastic leukemia (Ph + ALL). A retrospective analysis was conducted on the clinical data of 13 patients with MRD-positive and relapsed Ph + ALL admitted between July 2015 and February 2024 at the Affiliated Cancer Hospital of Zhengzhou University. The cohort included seven males and six females, with a median age of 50 years (range: 37-71 years). Reinduction therapy consisted of Ven and TKI administration combined with reduced-dose chemotherapy. Among the 13 patients, 10 were MRD-positive, and three had R/R disease. Of the MRD-positive group, nine (90%) achieved complete molecular response (CMR), with a median time to response of 47 days (range: 30-80) ; one patient did not respond. Among the three patients who had R/R, two (66.6%) achieved complete remission, while one patient was nonresponsive. The median overall survival (OS) and relapse-free survival (RFS) time for the entire cohort were 21.5 months and 7 months, respectively. In patients who achieved CMR, the median OS and RFS time were 35 months and 34 months, respectively. Grade ≥3 hematologic adverse events occurred in five patients (38.4%) ; however, hematopoietic function recovered in all cases, and no grade ≥3 infections or organ-related adverse reactions were observed. These findings suggest that Ven combined with TKI and reduced-dose chemotherapy may be an effective and tolerable therapeutic strategy for MRD-positive and R/R Ph + ALL, particularly in significantly improving MRD clearance rates.

This study sought to evaluate the efficacy and safety of venetoclax (Ven) in combination with tyrosine kinase inhibitors (TKI) and reduced-dose chemotherapy for the treatment of patients with minimal residual disease (MRD) -positive and relapsed/refractory (R/R) Ph-positive acute lymphoblastic leukemia (Ph + ALL). A retrospective analysis was conducted on the clinical data of 13 patients with MRD-positive and relapsed Ph + ALL admitted between July 2015 and February 2024 at the Affiliated Cancer Hospital of Zhengzhou University. The cohort included seven males and six females, with a median age of 50 years (range: 37-71 years). Reinduction therapy consisted of Ven and TKI administration combined with reduced-dose chemotherapy. Among the 13 patients, 10 were MRD-positive, and three had R/R disease. Of the MRD-positive group, nine (90%) achieved complete molecular response (CMR), with a median time to response of 47 days (range: 30-80) ; one patient did not respond. Among the three patients who had R/R, two (66.6%) achieved complete remission, while one patient was nonresponsive. The median overall survival (OS) and relapse-free survival (RFS) time for the entire cohort were 21.5 months and 7 months, respectively. In patients who achieved CMR, the median OS and RFS time were 35 months and 34 months, respectively. Grade ≥3 hematologic adverse events occurred in five patients (38.4%) ; however, hematopoietic function recovered in all cases, and no grade ≥3 infections or organ-related adverse reactions were observed. These findings suggest that Ven combined with TKI and reduced-dose chemotherapy may be an effective and tolerable therapeutic strategy for MRD-positive and R/R Ph + ALL, particularly in significantly improving MRD clearance rates.

Objective:To investigate the application effects of nitrous oxide and oxygen mixed inhalation technology on analgesia and sedation during debridement and dressing change in children with moderate or severe burns.Methods:A retrospective non-randomized contemporary controlled study was conducted. From December 2019 to November 2021, 140 burn children with moderate or severe burns, aged 1 to 3 years, who met the inclusion criteria were admitted to Central Hospital Affiliated to Shandong First Medical University. During debridement and dressing change 3 to 14 days after injury, 42 children, including 23 males and 19 females, who received nurse-centered pain management mode and analgesia and sedation with nitrous oxide and oxygen mixed inhalation technology were included in nitrous oxide group (the dressing change process using the above-mentioned technology for the first time was selected for the follow-up study). Another 42 children, including 24 males and 18 females, were included in non-nitrous oxide group from 98 children who did not apply analgesia or sedation treatment during dressing change with stratified random sampling (one dressing change process was randomly selected for the follow-up study). The face, legs, activity, cry, and consolability scale and Ramsay sedation scale were used to evaluate the pain intensity and degree of sedation, respectively, at 30 minutes before dressing change (hereinafter referred to as before dressing change), immediately after debridement, and at 30 minutes after finishing dressing change (hereinafter referred to as after dressing change). After dressing change, the self-made satisfaction scale was used to evaluate the satisfaction degree of dressing change surgeons and guardians of children for analgesic effects during dressing change. The duration of dressing change and the healing time of deep partial-thickness burn wounds were recorded. The heart rate and percutaneous arterial oxygen saturation (SpO 2) before, during, and after dressing change and the occurrence of adverse events such as nausea and vomiting during dressing change were recorded. Data were statistically analyzed with Mann-Whitney U test, chi-square test, analysis of variance for repeated measurement, independent sample t test, and Bonferroni correction. Results:There were no significant differences in the score of pain intensity and score of sedation degree between children in two groups before and after dressing change ( P>0.05). Immediately after debridement, the score of pain intensity of children in nitrous oxide group was 2.5±0.7, which was significantly lower than 7.6±1.0 in non-nitrous oxide group ( t=-26.69, P<0.05); the score of sedation degree of children in nitrous oxide group was 1.83±0.38, which was significantly higher than 1.21±0.42 in non-nitrous oxide group ( t=7.15, P<0.05). After dressing change, the satisfaction degree scores of dressing change surgeons and guardians of children for analgesic effects during dressing change of children in nitrous oxide group were significantly higher than those in non-nitrous oxide group (with t values of 10.53 and 2.24, respectively, P<0.05). The dressing change duration of children in nitrous oxide group was significantly shorter than that in non-nitrous oxide group ( t=-5.33, P<0.05). The healing time of deep partial-thickness burn wounds in children between the two groups had no significant difference ( P>0.05). The heart rate of children in nitrous oxide group was significantly lower than that in non-nitrous oxide group during dressing change ( t=-12.40, P<0.05), while the SpO 2 was significantly higher than that in non-nitrous oxide group ( t=5.98, P<0.05). During dressing change, 2 children had nausea and 1 child had euphoria in nitrous oxide group, while heart rate of all children in non-nitrous oxide group continued to be higher than the normal range. Conclusions:In the process of debridement and dressing change in children with moderate or severe burns, the use of nurse-centered pain management mode and the standardized use of nitrous oxide and oxygen mixed inhalation technology can safely and effectively control pain and sedation.

Purpose: Cavernous nerve injury induced erectile dysfunction (ED) is a refractory complication with high incidence in person under radical prostatectomy. Studies have shown that relaxin-2 (RLX-2) plays a vital role of endothelial protection, vasodilation, anti-fibrosis and neuroprotection in a variety of diseases. However, whether penile cavernous erection can benefit from RLX-2 remains unknown. The purpose of the experiment was to explore the effects of RLX-2 on ED in the rat suffering with bilateral cavernous nerve injury (BCNI). Materials and Methods: The rats were divided into three groups: Sham group was underwent sham operation, BCNI+RLX group or BCNI group was underwent bilateral cavernous nerve crush and then randomly treated with RLX-2 (0.4 mg/kg/d) or saline by continuous administration using a subcutaneously implanted micro pump for 4 weeks respectively. Then, erectile function was evaluated by electrical stimulation of cavernous nerves. Cavernous nerves and penile tissues and were collected for histological evaluation. Results: Erectile function of rats with BCNI was partially improved after RLX-2 treatment. The BCNI group had lower expression of relaxin family peptide receptor (RXFP) 1, p-AKT/AKT, p-eNOS/eNOS ratios than sham operation rats, but RLX-2 could partially reversed these changes. Histologically, the BCNI+RLX group had a significant effect on preservation of neurofilament, neuronal glial antigen 2 of penile tissue and nNOS of cavernous nerves when compared with BCNI group. RLX-2 could inhibited the lever of BCNI induced corporal fibrosis and apoptosis via regulating TGFβ1-Smad2/3-CTGF pathway and the expression of Bax/Bcl-2 ratio, caspase3. Conclusions RLX-2 could improve erectile function of BCNI rats by protecting cavernous nerve and endothelial function and suppressing corporal fibrosis and apoptosis via RXFP1 and AKT/eNOS pathway. Our findings may provide a promising treatment for refractory BCNI induced ED.

Objective:To analyze the characteristics and prognosis of visual field of Leber hereditary optic neuropathy (LHON) with G11778A mutation.Methods:A retrospective clinical study. Twenty-two (44 eyes) of LHON patients diagnosed with G11778A site mutation by mt-DNA examination from May 2008 to February 2018 in Ophthalmology Department of Dongfang Hospital of Beijing University of Chinese Medicine, were enrolled in this study. All patients underwent best corrected visual acuity (BCVA), visual field and optical coherence tomography (OCT). The BCVA examination was performed using the international standard visual acuity chart, which was converted into logarithm of the minimum angle of resolution (logMAR) BCVA for record. The thickness of the retinal nerve fiber layer (RNFL) in the 200μm×200μm annular region 1.73 mm outside the optic disc was measured by OCT. At least 7 visual field examinations were performed within one month before and after 2, 4, 8, 12, 18, 24 and 30 months of the course of disease by using Octopus 101 perimetry. Among 44 eyes, 27 eyes were detected with G2 procedure (G2 group) and 17 eyes were detected with LVC procedure (LVC group). The mean field defect (MD) and mean optical sensitivity (MS) were used as the main outcome indexes. According to the onset age, the patients were further divided into the ≤14 years old group and>14 years old group. There was a significant difference in initial logMAR BCVA between the G2 group and LVC group ( t=4.994, P=0.000), but there was no significant difference in gender ( χ2=1.896, P=0.169) and age ( t=0.337, P=0.708) between the two groups. Independent sample t test was used for comparison between groups, paired t test was used for comparison within groups, and one-way analysis of variance was used for comparison between groups. The statistical data were compared by χ2 test. Results:In the G2 group, the MD value of the subgroup of children (≤14 years old) decreased gradually during the follow-up period, and the MD value since 18 months after onset was significantly lower than the value of 2 months after onset ( t=3.813, 4.590, 5.033; P=0.002, 0.001, 0.000). No obvious visual field index changes were seen in other subgroups ( P>0.05). The central scotoma was the most common type of visual field defect in the early stage, and the diffuse defect was the most common type of visual field defect in the late stage. There was a significant difference in the types of visual field distribution between the early and late stage in G2 group ( χ2=17.414, P=0.015). There was no significant difference in the type of visual field distribution between the early and late stage in LVC group ( χ2=4.541, P=0.474). The MD value in the G2 group remained stable within 8 months after onset, but significantly improved after 18 months after onset ( t=2.100, 3.217, 3.566; P=0.046, 0.003, 0.001). The MS in the LVC group did not significantly improve during follow-up ( P>0.05). The average visual acuity of the G2 group was significantly improved from 12 months ( t=3.039, 3.678, 4.264, 5.078; P=0.008, 0.002, 0.001, 0.000). The visual acuity of the eyes in the G2 group was better than that of the LVC group during all follow-up periods ( P≤0.05). The RNFL thickness of all patients continued to decrease after onset, but the RNFL thickness was significantly higher at 4, 8, 18, 24, 30 months in the G2 group than those in the LVC group ( t=2.471, 2.269, 2.474, 2.509, 2.782; P=0.018, 0.028, 0.017, 0.016, 0.008). Conclusions:The main types of visual field defect of LHON with G11778A mutation are the central scotoma in the early stage, while the diffuse defect and central scotoma are both very common in the later stage. The visual field of LHON patients examined by G2 procedure is significantly improved during the follow-up, as well as the visual acuity improved significantly, and the visual field improvement in younger cases (≤14 years old) is better than that of older cases (>14 years old), but the visual field of the LVC procedure cases did not improve during follow-up.

Objective: To analyze the effects of twirling reinforcing and reducing manipulations on protein expres-sion in parietal cortex of spontaneously hypertensive rats (SHRs), and elucidate the main mechanisms and differences between two manipulations in hypertension treatment. Methods: Rats were randomly divided into the control, model, twirling reinforcing manipulation (TRFM), and twirling reducing manipulation (TRDM) groups. The control and model groups received catch and fixation stimulations once a day for 14 days. The TRFM and TRDM groups were intervened once a day for 20 min for 14 days. On days 0, 2, 6, 10, and 14 after acupuncture, rat systolic blood pressures (SBPs) were measured. Differential protein (DP) expression in the rat parietal cortices was detected. Thereafter, GO functional significance and KEGG pathway enrichment analyses were performed. Results: Compared with the model group, SBP of rats in the TRDM and TRFM groups decreased on days 6 and 10 of acupuncture, respectively (P=.009; P<.001). Moreover, SBP of the TRDM group was signif-icantly lower than that of the TRFM group on days 10 and 14 of acupuncture (P = .015; P = .013). Compared with control group, 601 and 1040 DPs were up-and downregulated, respectively, in the model group. Compared with model group, 44 and 28 up-and downregulated DPs were expressed, respectively, in the TRFM group. Compared with model group, expression of 616 and 427 up-and downregulated DPs, respectively, was found in the TRDM group. After combining the results of GO and KEGG enrichment analyses, five and one pathways were found to be related to the central antihypertensive mechanism of the parietal cortex during twirling reducing and reinforcing manipulations, respectively. Conclusion: TRDM showed a more effective antihypertensive effect on SHRs than TRFM; this antihy-pertensive effect was related to the regulation of different proteins and their biological functions.

Objective: To determine the contribution of follow-up formula (FUF) to the nutrient intake of 7-24-month-old infants and young children. Methods: The cluster random sampling method and the convenience sampling method were used in combination, and geographic and economic factors were taken into consideration. Four areas of China (Beijing, Hebei, Guangxi, Guangdong) were selected, with 120 infants chosen from each of these areas (half of which were 7-12 months old, and half were 13-24 months old). A dietary survey was completed by a continuous 24-hour weighing method over two days. Questionnaires were completed by their caregivers which included weighing the FUF and supplementary food given to the infant, and recording the frequency of breast feeding and any supplementary nutrients. A total of 518 questionnaires were distributed, and 472 questionnaires qualified for inclusion. Nutrient intake was calculated using the China food composition, infant formula food nutrient content and infant nutrition supplement brand-label information databases, and then the nutrient intake proportion (the percentage of estimated energy requirement (EER%), recommended nutrient intake (RNI%) or adequate intake (AI%)), and the contribution rate of FUF were analyzed. Results: A total of 472 infants were investigated (227 infants aged 7-12 months old, 245 infants aged 13-24 months old). The findings revealed that the median energy intake of 7- 12-month-old and 13- 24-month-old infants were 2 530.08 kJ and 3 445.48 kJ, respectively, which accounted for 85.18% and 94.14% of EER, respectively; and the median intake of protein reached 91.50% and 105.88% of their RNI/AI, respectively. For micronutrients, the median intake of vitamin B₁, vitamin B₂, niacin, vitamin E, potassium, zinc and manganese in 7- 12-month-old infants and vitamin B₂, vitamin E, potassium, magnesium, iron and manganese in 13-24-month-old children accounted for 82.00% and 114.29% of RNI/AI (RNI%/AI%), respectively. The intake of vitamin B₆, iron and selenium in 7-12-month-old infants and vitamin B₁, vitamin B₆, vitamin C, calcium and selenium in 13-24-month-old children was less than 80% RNI/AI. Furthermore, some nutrients showed higher intake levels, such as vitamin A, calcium, phosphorus and magnesium in 7-12-month-old infants and vitamin A and phosphorus in 13-24-month-old children, which were higher than 130% RNI/AI. In total, 40.53% (92) of infants aged 7-12 months and 52.65% (129) of children aged 13- 24 months were fed FUF as part of their diet, and its contribution rate to macronutrients was 29.69% for carbohydrates and 51.77% for fats, and to micronutrients was 2.04% for manganese and 74.24% for vitamin C. Conclusion FUF contributes to the nutrient intake of infants and young children aged from 7-24 months old at different rates depending on the macronutrient or micronutrient analyzed.

Population pharmacokinetics of vancomycin (VAN) in the Chinese patients was described by using nonlinear mixed-effects modeling (NONMEM). 619 VAN serum concentrations data from 260 patients including 177 males and 83 females were collected separately from two centers. A one-compartment model was used to describe this sparse data. No significant difference was observed between two center datasets by introducing SID covariate. The final model was as CL= (θ (base0+ θ(max) x(1 -e(-θ(Age)(Age/72) and V = θ x θ (Age)(Age/72). The creatinine clearance (CL(Cr)) and Age were identified as the most significant covariate in the final model. Typical values of clearance (CL) and volume of distribution (V) in the final model were 2.91 L x h(-1) and 54.76 L, respectively. Internal model validation by Bootstrap and NPDE were performed to evaluate the robustness and prediction of the final model. The median and 95% confidence intervals for the final model parameters were based on 1000 Bootstraps. External model evaluation was conducted using an independent dataset that consisted of 34 patients to predict model performance. Pharmacodynamic assessment for VAN by AUC (0-24 h) to MIC ratios of over 400 was considered to be the best to predict treatment outcomes for patients. AUC (0-24 h) was calculated by clearance based on the above population model. The results indicate that the conventional dosing regimen probably being suboptimal concentrations in aged patients. The approach via population pharmacokinetic of VAN combined with the relationship of MIC, Age, CL(Cr) and AUC(0-24 h)/MIC can predict the rational dose for attaining efficacy.