The mechanism of Tibetan medicine Zuotangkaca pills (ZTKCW) for the treatment of hypertension was explored by network pharmacology and in vivo experiments. 68 active ingredients of ZTKCW and 518 drug-disease targets were screened by network pharmacology. Eight core components of ZTKCW (vasicolinone, luteolin, (–)-isocorypalmine, esculetin, liquiritigenin, etc.) and eight key targets (AKT1, TNF, IL6, and STAT3, etc.) were screened by network topology analysis. KEGG enrichment analysis showed that the core targets were mainly enriched in lipids and atherosclerosis, JAK/STAT, and inflammation-related pathways. An in vivo experiment was conducted using spontaneously hypertensive rats (SHR), which were gavaged with ZTKCW at doses of 0.41, 0.82, and 1.64 g/kg for 12 weeks, respectively. The results showed that ZTKCW at a dose of 1.64 g/kg significantly reduced both systolic and diastolic pressure in SHR rats and decreased the phosphorylation levels of AKT1, PI3K, STAT3, and JAK2 in the thoracic aorta and heart tissues. This study demonstrates that ZTKCW may exert its antihypertensive effects through PI3K/AKT and JAK2/STAT3 pathways, providing some insights and a theoretical basis for the use of ZTKCW in hypertension.

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

Objective:To explore the diagnostic value of preoperative diffusion weighted imaging (DWI) histogram parameters in the depth of invasion of early rectal cancer.Methods:A total of 180 patients with early rectal cancer admitted to 904th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army from August 2020 to August 2024 were selected as the study objects. Patients were divided into intramucosal cancer group ( n=102) and submucosal cancer group ( n=78) according to the depth of tumor invasion. The general data of the two groups were compared. The intraclass correlation coefficient (ICC) was used to analyze the consistency of DWI histogram parameters extracted by the two radiologists, and the differences between the two groups were compared. Receiver operator characteristic (ROC) curve was used to analyze the predictive value of each parameter to the depth of tumor invasion. Multivariate logistic regression was used to analyze the independent influencing factors of invasion depth, and a predictive model was constructed. The ROC curve was drawn to analyze the predictive value of the model for tumor invasion depth, and the Hosmer-Lemeshow test was used to analyze the goodness of fit of the model. Results:There were statistically significant differences in age ( t=8.15, P<0.001), maximum tumor diameter ( χ2=29.29, P<0.001), endoscopic type ( χ2=20.96, P<0.001), histological type ( χ2=24.93, P<0.001) and differentiation degree ( χ2=73.35, P<0.001) between intramucosal cancer group and submucosal cancer group. The mean, variance, skewness, kurtosis, the 1 st, 10 th, 50 th, 90 th, and 99 th percentiles of the histogram parameters of DWI had good consistency (all ICC>0.75). There were statistically significant differences in the mean ( t=5.69, P<0.001), variance ( t=9.75, P<0.001), skewness ( t=10.88, P<0.001), kurtosis ( t=10.06, P<0.001), the 1 st percentile ( t=3.43, P<0.001), 10 th percentile ( t=3.59, P<0.001), 50 th percentile ( t=9.97, P<0.001), 90 th percentile ( t=4.63, P<0.001), and 99 th percentile ( t=2.44, P=0.016) of the DWI histogram parameters between the intramucosal cancer group and the submucosal cancer group. ROC curve analysis results showed that mean [area under the curve (AUC) =0.77], variance (AUC=0.88), skewness (AUC=0.88), kurtosis (AUC=0.78), 50 th percentile (AUC=0.86) and 90 th percentile (AUC=0.82) had certain diagnostic value for submucous cancer. Multivariate analysis showed that age ( OR=9.98, 95% CI: 1.10-90.70, P=0.041), maximum tumor diameter ( OR=7.36, 95% CI: 1.08-50.23, P=0.042), and differentiation degree ( OR=19.88, 95% CI: 1.21-327.92, P=0.037), variance ( OR=16.24, 95% CI: 2.26-116.68, P=0.006), skewness ( OR=21.13, 95% CI: 2.80-59.61, P=0.003), 1 st percentile ( OR=9.78, 95% CI: 1.17-81.76, P=0.035) were independent factors in predicting tumor invasion depth in patients with early rectal cancer. The predictive model based on the above indicators was logit ( P) =1.51+2.30×age+2.00×maximum tumor diameter+2.99×differentiation degree+2.79×variance+3.05×skewness+ 2.28×the 1 st percentile. ROC curve analysis showed that the predictive model had an AUC of 0.97 (95% CI: 0.95-0.99) for judging the occurrence of submucosal cancer in patients with early rectal cancer, the sensitivity was 0.95, and the specificity was 0.88. The Hosmer-Lemeshow test results showed that the goodness of fit of the model was ideal ( P=0.823) . Conclusions:Age, maximum tumor diameter, differentiation degree, variance, skewness, and the 1 st percentile are independent factors in predicting tumor invasion depth in patients with early rectal cancer. The predictive model constructed based on these factors can effectively predict the risk of submucosal cancer in patients with early rectal cancer.

Objective To investigate the effect of quercetin on paraptosis induced by low-concentration hydrogen peroxide(H2O2)in human lens epithelial cells(LECs).Methods The human lens epithelial cell line SRA01/04 was cul-tured in vitro and randomly divided into the following groups:control group,H2O2 group(50 μmol·L-1 H2O2),and H2O2+Quercetin group(50 μmol·L-1 H2O2 and 20 μmol·L-1 quercetin).The area and number of endoplasmic reticulum vacuoles in the cells were observed using transmission electron microscopy and super-resolution laser confocal microscopy.Intracellular reactive oxygen species(ROS)levels were detected using the DCFH-DA fluorescent probe.Western blot was performed to detect the expression levels of the following proteins:insulin-like growth factor 1 receptor(IGF1R),phos-phorylated IGF1R(p-IGF1R),ALG-2-interacting protein X(ALIX),glucose-regulated protein 78(GRP78),extracellular signal-regulated kinase(ERK),phosphorylated ERK(p-ERK),P38,and phosphorylated P38(p-P38).Additionally,len-ses from 8-week-old Sprague-Dawley rats were subjected to ex vivo culture and divided into the normal group,the H2O2 treatment group(50 μmol·L-1 H2O2),and the combination treatment group(50 μmol·L-1 H2O2 and 20 μmol·L-1 quer-cetin).The degree of lens opacity was observed under a stereomicroscope,and the area of lens opacity was quantified.The ultrastructure of the endoplasmic reticulum in the rat LECs was observed by transmission electron microscopy.Western blot was used to detect the expression levels of the aforementioned proteins in the rat LECs.Results Compared with the control group,the H2O2 group exhibited significant increases in the area and number of endoplasmic reticulum vacuoles,ROS levels,and the relative protein expression levels of p-IGF1R,p-ERK,p-P38,and GRP78,while the relative expression of ALIX protein was decreased(all P＜0.001).Compared with the H2 O2 group,the H2O2+quercetin group showed signifi-cant reductions in the area and number of endoplasmic reticulum vacuoles,ROS levels,and the relative expression levels of p-IGF1R,p-ERK,p-P38,and GRP78,while the relative expression of ALIX protein was increased(all P＜0.01).In the ex vivo cultured rat lens model,compared with the normal group,the H2O2 group displayed a significant increase in lens opac-ity area,expanded endoplasmic reticulum area in LECs,elevated relative expression levels of p-IGF1R,p-ERK,p-P38,and GRP78 proteins,and decreased ALIX expression(all P＜0.000 1).In contrast,the combination treatment group showed significantly reduced lens opacity area,decreased endoplasmic reticulum area in LECs,lower relative expression of p-IGF1R,p-ERK,p-P38,and GRP78,and increased ALIX expression compared to the H2O2 group(all P＜0.01).Conclu-sion Quercetin inhibits activation of the IGF1R/MAPK signaling pathway and alleviates endoplasmic reticulum stress,thereby effectively attenuating paraptosis in lens epithelial cells.These findings provide a novel strategy for the prevention and treatment of early age-related cataract.

Objective To investigate the effect of continuous theta burst stimulation-intermittent theta burst stimulation(cTBS-iT-BS)priming protocols with different time intervals on the plasticity of primary motor cortex(M1).Methods A total of 39 healthy young adults were recruited from Changzhou De'an Hospital from March to August,2024.Participants received cTBS-iTBS priming protocols with intervals of 5 minutes,10 minutes and 15 minutes using a randomized crossover design.Motor-evoked potential(MEP)amplitudes in M1 were recorded at baseline(before intervention)and 0 minute,10 minutes,20 minutes and 30 minutes after intervention.Results The main effects of stimulation protocol(F=19.761,P<0.001)and measurement time(F=10.224,P<0.001)were significant.At each time point after intervention,the MEP amplitude was significantly higher under the 10-minute interval than under the 5-minute and 15-minute intervals(t>3.010,P<0.05).Conclusion The 10-minute interval of cTBS-iTBS is more effective on M1 plasticity.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective:To evaluate the efficacy of ultrasound-guided median interspinous in-plane approach to subarachnoid puncture in obese pregnant patients.Methods:This study was a randomized controlled trial. Eighty obese parturients who underwent elective cesarean section from March 2022 to January 2024 in our hospital were divided into 2 groups( n=40 each) by the random number table method: median interspinous in-plane approach group(group M) and paramedian interlaminar in-plane approach group(group P). After successful puncture, 0.5% ropivacaine 15 mg(3 ml) was intrathecally injected in both groups. The first-attempt success of puncture, the number of puncture attempts, operation time, the total success of puncture, and the visibility scores of the anterior and posterior union, positioning structure(lamina in group P, spinous process in group M) and puncture needle under ultrasound were recorded. Results:Compared with group P, the visibility score of positioning structure under ultrasound was significantly increased, the success rate of puncture at the first attempt was increased, the number of puncture attempts was decreased, the operation time was shortened, the total success rate of puncture was increased( P<0.05), and no significant change was found in the visibility scores of the anterior and posterior union and puncture needle in group M( P>0.05). Conclusions:For obese pregnant patients, the ultrasound-guided median interspinous in-plane approach can accurately and quickly perform subarachnoid puncture, which has more advantages than the traditional paramedian interlaminar in-plane approach.

Objective:To investigate the effect of a rapid rehabilitation nursing model under the theoretical framework of Rogers' Science of Unitary Human Beings in the postoperative care of children undergoing radical operation on Hirschsprung's disease.Methods:A total of 91 children with Hirschsprung's disease and their parents who underwent radical surgery at the Children's Hospital Affiliated to Zhengzhou University (Henan Children's Hospital, Zhengzhou Children's Hospital) between January 2022 and January 2024 were selected by convenience sampling. Using a computer-generated random number table, they were randomly divided into an intervention group ( n=46) and a control group ( n=45). The control group received routine surgical nursing, while the intervention group received a rapid rehabilitation nursing model based on Rogers' theoretical framework in addition to routine care. Postoperative pain stress, anorectal function, gastrointestinal functional recovery, and parental satisfaction were compared between the two groups. Results:On the third postoperative day, the intervention group had lower scores on the FLACC scale, better anorectal function, and shorter times to first bowel sound, first anal exhaust, and first defecation than the control group. The overall parental satisfaction rate in the intervention group was 86.96% (40/46), higher than 51.11% (23/45) in the control group, and the differences were statistically significant (all P<0.05) . Conclusions:The rapid rehabilitation nursing model under the theoretical framework of Rogers' Science of Unitary Human Beings showed significant effectiveness in children undergoing radical operation on Hirschsprung's disease. It reduced postoperative pain, promoted recovery of anorectal and gastrointestinal function, and improved parental satisfaction.

Objective To investigate the effect of quercetin on paraptosis induced by low-concentration hydrogen peroxide(H2O2)in human lens epithelial cells(LECs).Methods The human lens epithelial cell line SRA01/04 was cul-tured in vitro and randomly divided into the following groups:control group,H2O2 group(50 μmol·L-1 H2O2),and H2O2+Quercetin group(50 μmol·L-1 H2O2 and 20 μmol·L-1 quercetin).The area and number of endoplasmic reticulum vacuoles in the cells were observed using transmission electron microscopy and super-resolution laser confocal microscopy.Intracellular reactive oxygen species(ROS)levels were detected using the DCFH-DA fluorescent probe.Western blot was performed to detect the expression levels of the following proteins:insulin-like growth factor 1 receptor(IGF1R),phos-phorylated IGF1R(p-IGF1R),ALG-2-interacting protein X(ALIX),glucose-regulated protein 78(GRP78),extracellular signal-regulated kinase(ERK),phosphorylated ERK(p-ERK),P38,and phosphorylated P38(p-P38).Additionally,len-ses from 8-week-old Sprague-Dawley rats were subjected to ex vivo culture and divided into the normal group,the H2O2 treatment group(50 μmol·L-1 H2O2),and the combination treatment group(50 μmol·L-1 H2O2 and 20 μmol·L-1 quer-cetin).The degree of lens opacity was observed under a stereomicroscope,and the area of lens opacity was quantified.The ultrastructure of the endoplasmic reticulum in the rat LECs was observed by transmission electron microscopy.Western blot was used to detect the expression levels of the aforementioned proteins in the rat LECs.Results Compared with the control group,the H2O2 group exhibited significant increases in the area and number of endoplasmic reticulum vacuoles,ROS levels,and the relative protein expression levels of p-IGF1R,p-ERK,p-P38,and GRP78,while the relative expression of ALIX protein was decreased(all P＜0.001).Compared with the H2 O2 group,the H2O2+quercetin group showed signifi-cant reductions in the area and number of endoplasmic reticulum vacuoles,ROS levels,and the relative expression levels of p-IGF1R,p-ERK,p-P38,and GRP78,while the relative expression of ALIX protein was increased(all P＜0.01).In the ex vivo cultured rat lens model,compared with the normal group,the H2O2 group displayed a significant increase in lens opac-ity area,expanded endoplasmic reticulum area in LECs,elevated relative expression levels of p-IGF1R,p-ERK,p-P38,and GRP78 proteins,and decreased ALIX expression(all P＜0.000 1).In contrast,the combination treatment group showed significantly reduced lens opacity area,decreased endoplasmic reticulum area in LECs,lower relative expression of p-IGF1R,p-ERK,p-P38,and GRP78,and increased ALIX expression compared to the H2O2 group(all P＜0.01).Conclu-sion Quercetin inhibits activation of the IGF1R/MAPK signaling pathway and alleviates endoplasmic reticulum stress,thereby effectively attenuating paraptosis in lens epithelial cells.These findings provide a novel strategy for the prevention and treatment of early age-related cataract.