OBJECTIVE To explore the practice and application effect of lean Six Sigma （LSS） management in the cost- benefit management of PIVAS operation in a tertiary comprehensive hospital （hereinafter referred to as “S Hospital”）， providing reference for the operation and management of PIVAS in hospitals. METHODS The five steps （define， measure， analyze， improve and control， i.e. DMAIC） of LSS management were implemented for PIVAS operation cost-benefit of S Hospital， and lean management was implemented for its cost-benefit management elements （human resource cost， medical and health material cost， and all-in-one parenteral nutrition preparation income）. Several intervention measures including personnel training and performance assessment， refined management system of consumables， and doctor’s advice package of full parenteral nutrition were developed. Finally， the overall improvement effect was evaluated by the total benefit， total cost and net benefit of PIVAS. The effects of human resource allocation optimization and improvement were evaluated by the work efficiency， work quality， job satisfaction， turnover rate and accumulated rest days. The effects of consumables cost management were evaluated by the amount of medical and health materials cost. The improvement effects of all-in-one parenteral nutrition preparation income were evaluated by the profit amount， quantity and the proportion of single bottle of parenteral nutrition. RESULTS After implementing DMAIC in S Hospital， the total benefit of PIVAS was increased from （471 366.50±9 201.5） yuan/month to （479 679.50±14 320.14） yuan/month （P＞ 0.05）， the total cost was decreased from （305 878.88±3 201.75） yuan/month to （294 610.59±5 007.33） yuan/month （P＜0.05）， and the net benefit of PIVAS was increased by 11.83% compared with that before the improvement. The work efficiency， work quality and job satisfaction of employees were significantly improved， the accumulated rest days were significantly reduced， and the turnover rate of third-party employees was reduced from 15.0% before the improvement to 7.5% after the improvement. The cost of medical and health materials significantly decreased from （67 826.42±2 812.76） yuan/month before improvement to （56 384.33±4 607.67） yuan/month after improvement （P＜0.05）. The quantity of all-in-one parenteral nutrition was significantly increased from （1 263.75±135.83） group/month before improvement to （2 061.25±89.04） group/month after improvement （P＜0.05）， and the proportion of users of single bottle of parenteral nutrition in total users decreased from 93.25% before improvement to 58.75% after improvement. The profit of all-in-one parenteral nutrition was 63.18% higher than that before implementing DMAIC. CONCLUSIONS The implementation of PIVAS operation cost-benefit management based on DMAIC is conducive to strengthening the cost control of PIVAS and promoting the healthy development of PIVAS.

ObjectiveTo investigate the chemical constituents of Chuanxiong Rhizoma-Paeoniae Radix Rubra（CRPRR） that cross the blood-brain barrier in rats with ischemic stroke， their brain-protective effects， and their impact on inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） based on ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） and pharmacodynamic experiments. MethodsA focal cerebral ischemia-reperfusion injury model was established in rats via the middle cerebral artery occlusion/reperfusion （MCAO/R） method using intraluminal suture. Neurological function was evaluated using behavioral scoring. UPLC-Q-TOF-MS was employed to identify the chemical constituents of CRPRR that crossed the blood-brain barrier and entered the cerebrospinal fluid in MCAO/R model rats. Male Sprague-Dawley rats were randomly divided into six groups： sham operation group， model group， low-， medium-， and high-dose CRPRR groups （1.35， 2.7， 5.4 g·kg^-1， respectively）， and an edaravone group （5 mg·kg^-1）， with 12 rats in each group. The sham and model groups received normal saline， while the treatment groups received the respective doses of CRPRR once daily by gavage for three consecutive weeks. The brain-protective effects of CRPRR were assessed using the Longa five-point scoring method， open field test， Morris water maze， 2，3，5-triphenyltetrazolium chloride （TTC） staining， hematoxylin and eosin （HE） staining， and transmission electron microscopy. ResultsNine chemical constituents were identified in the cerebrospinal fluid containing CRPRR， namely paeoniflorin， senkyunolide F， senkyunolide G， paeonimetabolin Ⅰ， paeoniflorin derivative， senkyunolide H， benzoylpaeoniflorin， senkyunolide A， and ligustilide. Animal experiment results showed that compared with the sham operation group， the model group exhibited disordered neuronal arrangement， severe vacuolation， nuclear pyknosis， and evident mitochondrial swelling. Chromatin aggregation and peripheralization were also observed. Neurological scores and the number of crossings in the central region were significantly increased （P<0.01）， while platform crossings were significantly decreased （P<0.01）， and clear infarct areas were present （P<0.01）. Serum levels and protein expression of TNF-α， IL-1β， and IL-18 were significantly elevated （P<0.01）. Compared with the model group， all dose groups of CRPRR showed marked improvement in neuronal morphology which was close to the normal level， with mitochondrial swelling alleviated and chromatin distribution more uniform. The medium- and high-dose groups significantly reduced neurological scores （P<0.01）， while the low-， medium-， and high-dose groups significantly reduced the number of central crossings （P<0.01） and infarct volume （P<0.01）， and decreased TNF-α， IL-1β， and IL-18 levels （P<0.05， P<0.01） compared with the model group. Furthermore， the medium- and high-dose groups significantly reduced TNF-α protein expression （P<0.05，P<0.01）， and the high-dose group significantly reduced IL-1β and IL-18 protein expression （P<0.01）. ConclusionThis study confirmed that CRPRR improves neurological function and alleviates brain tissue damage in MCAO/R rats. Its mechanism may be associated with the downregulation of inflammatory factors TNF-α， IL-1β， and IL-18， as well as the presence of nine active chemical constituents in cerebrospinal fluid， namely paeoniflorin， senkyunolide F， senkyunolide G， paeonimetabolin Ⅰ， paeoniflorin derivative， senkyunolide H， benzoylpaeoniflorin， senkyunolide A， and ligustilide， which are closely related to their brain-protective effects.

ObjectiveTo investigate the chemical constituents of Chuanxiong Rhizoma-Paeoniae Radix Rubra（CRPRR） that cross the blood-brain barrier in rats with ischemic stroke， their brain-protective effects， and their impact on inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） based on ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） and pharmacodynamic experiments. MethodsA focal cerebral ischemia-reperfusion injury model was established in rats via the middle cerebral artery occlusion/reperfusion （MCAO/R） method using intraluminal suture. Neurological function was evaluated using behavioral scoring. UPLC-Q-TOF-MS was employed to identify the chemical constituents of CRPRR that crossed the blood-brain barrier and entered the cerebrospinal fluid in MCAO/R model rats. Male Sprague-Dawley rats were randomly divided into six groups： sham operation group， model group， low-， medium-， and high-dose CRPRR groups （1.35， 2.7， 5.4 g·kg^-1， respectively）， and an edaravone group （5 mg·kg^-1）， with 12 rats in each group. The sham and model groups received normal saline， while the treatment groups received the respective doses of CRPRR once daily by gavage for three consecutive weeks. The brain-protective effects of CRPRR were assessed using the Longa five-point scoring method， open field test， Morris water maze， 2，3，5-triphenyltetrazolium chloride （TTC） staining， hematoxylin and eosin （HE） staining， and transmission electron microscopy. ResultsNine chemical constituents were identified in the cerebrospinal fluid containing CRPRR， namely paeoniflorin， senkyunolide F， senkyunolide G， paeonimetabolin Ⅰ， paeoniflorin derivative， senkyunolide H， benzoylpaeoniflorin， senkyunolide A， and ligustilide. Animal experiment results showed that compared with the sham operation group， the model group exhibited disordered neuronal arrangement， severe vacuolation， nuclear pyknosis， and evident mitochondrial swelling. Chromatin aggregation and peripheralization were also observed. Neurological scores and the number of crossings in the central region were significantly increased （P<0.01）， while platform crossings were significantly decreased （P<0.01）， and clear infarct areas were present （P<0.01）. Serum levels and protein expression of TNF-α， IL-1β， and IL-18 were significantly elevated （P<0.01）. Compared with the model group， all dose groups of CRPRR showed marked improvement in neuronal morphology which was close to the normal level， with mitochondrial swelling alleviated and chromatin distribution more uniform. The medium- and high-dose groups significantly reduced neurological scores （P<0.01）， while the low-， medium-， and high-dose groups significantly reduced the number of central crossings （P<0.01） and infarct volume （P<0.01）， and decreased TNF-α， IL-1β， and IL-18 levels （P<0.05， P<0.01） compared with the model group. Furthermore， the medium- and high-dose groups significantly reduced TNF-α protein expression （P<0.05，P<0.01）， and the high-dose group significantly reduced IL-1β and IL-18 protein expression （P<0.01）. ConclusionThis study confirmed that CRPRR improves neurological function and alleviates brain tissue damage in MCAO/R rats. Its mechanism may be associated with the downregulation of inflammatory factors TNF-α， IL-1β， and IL-18， as well as the presence of nine active chemical constituents in cerebrospinal fluid， namely paeoniflorin， senkyunolide F， senkyunolide G， paeonimetabolin Ⅰ， paeoniflorin derivative， senkyunolide H， benzoylpaeoniflorin， senkyunolide A， and ligustilide， which are closely related to their brain-protective effects.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

AIM: To evaluate the safety and efficacy of allogeneic intrastromal lenticule implantation combined with corneal collagen cross-linking(CXL)in patients with moderate to advanced keratoconus.METHODS: A retrospective case series analysis was conducted. A total of 19 patients(20 eyes)with moderate to advanced keratoconus who underwent combined allogeneic intrastromal lenticule implantation and CXL at the Jinan Mingshui Eye Hospital from June 2021 to December 2023 were included. The uncorrected distance visual acuity(UCVA), thinnest corneal thickness, central corneal epithelial thickness, anterior corneal flat keratometry(Kf), steep keratometry(Ks), and mean keratometry(Km), as well as the first applanation time(A1T), the first applanation length(A1L), the velocity during the first applanation moment(VIN), the second applanation time(A2T), the second applanation length(A2L), the velocity during the second applanation moment(VOUT), highest concavity time(HCT), highest concavity radius(HCR), peak distance(PD), deformation amplitude(DA), stiffness parameter at first applanation(SP-A1), integrated radius(IR), central corneal thickness(CCT), intraocular pressure(IOP), corneal thickness-corrected IOP, biomechanically intraocular pressure IOP(bIOP), and corneal thickness variation rate(ARTH)were compared between the two groups before surgery and at 1 wk, 1, 3 and 6 mo after surgery.RESULTS: All patients successfully completed the surgery without any intraoperative complications. No significant differences were observed between pre-operative and post-operative measurements for UCVA or the corneal biomechanical parameters, including A1L, A2L, PD, A1T, A2T, VIN, VOUT, DA, IOP, and bIOP(all P>0.05). Significant differences were found between pre-operative and post-operative values for corneal thinnest point thickness, central corneal epithelial thickness, Kf, Ks, Km, and the corneal biomechanical parameters, including HCT, HCR, SP-A1, ARTH, IR, and CCT(all P<0.05). The anterior corneal curvature demonstrated an initial increase followed by a decrease post-operatively. Furthermore, significant differences were observed between pre-operative and post-operative values for HCT, HCR, SP-A1, ARTH, IR, and CCT(all P<0.005).CONCLUSION: Allogenic intrastromal lenticule implantation combined with corneal collagen cross-linking demonstrates favorable safety and stability in treating moderate-to-advanced keratoconus. This combined procedure effectively increases corneal thickness and rigidity, resulting in corneas that are more resistant to deformation postoperatively.

OBJECTIVE To innovatively apply the pre-intelligent precision dosing and verification system （hereinafter referred to as “the system”）， and to provide a reference for the high-level “intelligent” transformation of inpatient pharmacy. METHODS The limitations of the triple-serial dispensing mode， which comprised the automatic medicine packaging machine （ATC）， intelligent tablet dispensing table （ITDT） and medication detection machine （MDM）， were analyzed. The application of the system and the adoption of the barcode scanning verification method optimized the pre-dosing management， whole-tablet drug dispensing process and ATC temporary dosing management. The comparative analysis was conducted to assess dosing time， labor cost and packaging error of the eight-month period， before and after the system application. RESULTS The triple-serial dispensing mode had a weak ability to avoid error risks in the manual dosing stage， and also had errors in the verification stage. Through the innovative application system， the pre-dosing management had been upgraded， the whole-tablet drug dispensing process had been optimized， and the ATC temporary dosing management had been improved. The average time required for each drug for pre-dosing， whole-tablet drug dispensing and ATC temporary dosing was significantly shortened after the application of the system， compared with before the application of the system （P＜0.001）. The number of pharmacists was reduced from two to one. The error rate of ATC decreased significantly from 0.220‰ to 0.029‰ （P＜0.001）. Specifically， the rate of pharmacist-related errors （pre-dosing error， ITDT dosing error， and ATC temporary dosing error） decreased from 0.116‰ to 0.001‰ （P＜0.001）， and machine-related errors decreased from 0.096‰ to 0.023‰ （P＜0.001）. CONCLUSIONS This innovative integration mode greatly improves the working efficiency and quality of inpatient pharmacy. It enhances refined management of drug expiration and inventory， saves time and labor costs， improves the accuracy of drug dispensing， and ensures patient medication safety.

Objective: To explore the correlation between blind box consumption and non-suicidal self-injury(NSSI) among middle school students, so as to provide new theoretical insights for the prevention of NSSI. Methods: Using stratified random cluster sampling method, 2 807 middle school students aged 11-19 years old were selected from Hunan and Gansu provinces from November 2024 to March 2025. The blind box consumption questionnaire and Functional Assessment of Self mutilation Scale were administered to collect data on students blind box consumption frequency, as well as NSSI behavior. The χ 2 test was used to compare differences in the distribution of NSSI across different groups. Multivariate Logistic regression analysis was performed to infer the correlation and gender differences. Results: A total of 15.3% of middle school students reported having at least one NSSI incident in the past year, among which the reported rates of occasional NSSI (1-4 times) and repeated NSSI (≥5 times) were 5.5% and 9.8% respectively. The results of univariate analysis showed that there was statistically significant different in NSSI distribution among groups with different blind box consumption frequencies ( χ 2=55.72, P <0.05). After adjusting for confounding factors such as age, gender, school stage, family type, discipline style, pocket money, impulsiveness and emotion management, the results of multiple Logistic regression models showed that compared with the group without blind box consumption, the risks of "occasional NSSI" and "repeated NSSI" were higher in the group with blind box consumption ( OR =1.54, 1.66), and the frequency of blind box consumption(continous variable) was positively correlated with the risks of "occasional NSSI" and "repeated NSSI" among middle school students ( OR =1.26, 1.34)(all P <0.05).After gender stratification, the consumption behavior of blind boxes and the frequency of blind box consumption (continuous variable) of boys and girls were associated with "repeated NSSI"(boys: OR =1.61, 1.32, girls: OR =1.65, 1.35), and only in the male group was a correlation between blind box consumption and "occasional NSSI" observed ( OR =2.27) (all P <0.05). Conclusion Blind box consumption may be related to NSSI among middle school students, and there are gender differences in its correlation with NSSI among middle school students.