Poor water solubility is the primary obstacle preventing the development of many pharmacologically active compounds into oral preparations. Self-nanoemulsifying drug delivery systems(SNEDDS) have become a widely used strategy to enhance the oral bioavailability of poorly soluble drugs by inducing a supersaturated state, thereby improving their apparent solubility and dissolution rate. However, the supersaturated solutions formed in SNEDDS are thermodynamically unstable systems with solubility levels exceeding the crystalline equilibrium solubility, making them prone to drug precipitation in the gastrointestinal tract and ultimately hindering drug absorption. Therefore, maintaining a stable supersaturated state is crucial for the effective delivery of poorly soluble drugs. Incorporating polymers as precipitation inhibitors(PPIs) into the formulation of supersaturated self-nanoemulsifying drug delivery systems(S-SNEDDS) can inhibit drug aggregation and crystallization, thus maintaining a stable supersaturated state. This has emerged as a novel preparation strategy and a key focus in SNEDDS research. This review explores the preparation design of SNEDDS and the technical challenges involved, with a particular focus on polymer-based S-SNEDDS for enhancing the solubility and oral bioavailability of poorly soluble drugs. It further elucidates the mechanisms by which polymers participate in transmembrane transport, summarizes the principles by which polymers sustain a supersaturated state, and discusses strategies for enhancing drug absorption. Altogether, this review provides a structured framework for the development of S-SNEDDS preparations with stable quality and reduced development risk, and offers a theoretical reference for the application of S-SNEDDS technology in improving the oral bioavailability of poorly soluble drugs.
Solubility ; Administration, Oral ; Polymers/chemistry* ; Drug Delivery Systems/methods* ; Humans ; Emulsions/chemistry* ; Biological Availability ; Animals ; Pharmaceutical Preparations/administration & dosage*

OBJECTIVE: Xuebijing injection has been recommended as a therapeutic approach for individuals with severe and critical COVID-19. This study aims to explore the correlation of neutrophil to lymphocyte platelet ratio (NLPR) with the severity and prognosis of COVID-19, and the effect of XBJ on the prognosis of patients with COVID-19 in different inflammatory states. METHODS: This was a retrospective study conducted at Wuhan Union Hospital in China. COVID-19 patients admitted between November 1, 2022 and February 1, 2023 were included. In predicting prognosis for individuals with COVID-19, new inflammatory indicators were used, and their prognostic value was assessed by using Cox regression models and receiver operating characteristic curves. Furthermore, a calculation was made to determine the cutoff value for NLPR. Relative risk and Cox regression models were used to examine the effects of Xuebijing injection on prognosis in patient cohorts that had been stratified by the NLPR cutoff. RESULTS: This research included 455 participants with COVID-19, with a mean age of 72 years. Several inflammatory indicators were found to be strongly correlated with prognosis, and NLPR shows the greatest predictive power. Patients with NLPR > 3.29 exhibited a mortality rate of 17.3%, which was 6.2 times higher than in patients with NLPR ≤ 3.29. Importantly, providing Xuebijing injection to patients with NLPR > 3.29 was associated with a lower risk of 60-day all-cause mortality. However, there was no discernible improvement in survival among patients with NLPR ≤ 3.29 who received Xuebijing injection. CONCLUSION NLPR is the most reliable inflammatory marker for predicting prognosis among individuals with COVID-19, and can accurately identify individuals who may benefit from Xuebijing injection. Please cite this article as: Liao M, Zhang LT, Bai LJ, Wang RY, Liu Y, Han J, Liu LH, Qi BL. Xuebijing injection reduces COVID-19 patients mortality as influenced by the neutrophil to lymphocyte platelet ratio. J Integr Med. 2025; 23(3): 282-288.
Humans ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Female ; Retrospective Studies ; Aged ; Neutrophils ; COVID-19 Drug Treatment ; COVID-19/blood* ; Middle Aged ; Prognosis ; Lymphocytes ; Blood Platelets ; Platelet Count ; SARS-CoV-2 ; Aged, 80 and over ; Adult

Objective To explore the application value of a novel portable endoscope to perform upper gastrointestinal tract examinations in primary medical units.Methods A total of 532 subjects receiving portable endoscope examination were enrolled for analysis.The primary outcome was the success rate of operation.The secondary outcomes were the operation time,examination results,polyp removal and biopsy pathology results,and the subjective evaluation.Results In 532 cases,2 were withdrawn midway after the endoscope was inserted into the esophagus due to the patients'inability to tolerate the examination.Additionally,6 cases did not undergo examination of the descending part of the duodenum because of serious reactions during the procedure.Ultimately,524 cases successfully completed the upper gastrointestinal examination,and the success rate was 98.5％.The average examination time was(4.7±1.8)min,and the average time for disposal sheath wearing and removing was(4.2±1.4)min.The most common lesions were chronic non-atrophic gastritis(85.1％,451/530),reflux esophagitis(14.7％,78/530)and bile reflux(14.0％,74/530).A total of 10 cases of polyp removal were completed,and the polyp removal rate was 71.4％(10/14).Biopsy pathological diagnosis was completed in 44 cases,and the biopsy rate was 8.3％(44/530).The main discomfort symptoms during the examination were nausea(53.6％,285/532),vomiting(51.1％,272/532),and sore throat(38.5％,205/532),the main discomfort symptoms after the examination were sore throat(27.8％,148/532),nausea(19.5％,104/532),and vomiting(14.7％,78/532).No serious adverse events such as gastrointestinal bleeding,perforation,cardiac or pulmonary complications occurred.Conclusion The novel portable endoscope can safely and effectively complete the diagnosis and treatment of upper gastrointestinal diseases in primary medical units,while saving the decontamination process.However,the incidence of discomfort is high during examinations.Further optimization of the operation methods is needed.

Objective To investigate whether there exist differences in the improvement of left ventricular diastolic function between angiotensin receptor-neprilysin inhibitor(ARNI)and angiotensin-converting enzyme inhibitor(ACEI)/angiotensin receptor blocker(ARB)in patients with hypertensive heart disease(HHD).Methods A retrospective cohort study was conducted on the HHD patients admitted in Department of Cardiovascular Diseases of our hospital from January 2021 to December 2024.The general information,echocardiographic parameters before and after treatment,and results of routine tests were collected.Finally,517 HHD patients were subjected,including 117 receiving ARNI treatment(ARNI group)and 400 getting ACEI/ARB treatment(ACEI/ARB group).A 1∶1 propensity score matching(PSM)was performed with a caliper value of 0.02,resulting in 89 matched cases for each group.Electrocardiography was performed to assess left ventricular diastolic dysfunction(LVDD),with various parameters,including left atrial volume index,early diastolic peak velocity at the interventricular septal portion of mitral annulus(septal e'),early diastolic peak velocity at the lateral wall portion of mitral annulus(lateral e'),tricuspid regurgitation velocity,and E/e'.These parameters were followed up and reassessed during the treatment period.Kaplan-Meier survival curve was plotted to compare the incidence of LVDD between the 2 groups.Multivariable logistic regression model was employed to identify the risk factors contributing to LVDD.Results The median follow-up time was 412(309,736)d in the whole cohort,and was 409(300,729)d for the patients after PSM.Kaplan-Meier survival analysis demonstrated that the incidence of LVDD was lower in the ARNI group than the ACEI/ARB group both before and after PSM(P<0.05).After treatment,the ARNI group obtained lower lateral e'[8.00(7.00,9.40)vs 9.00(7.10,10.30)cm/s,P<0.001],thinner left ventricular posterior wall thickness[12.20(10.80,12.80)vs 12.30(11.20,12.90)mm,P<0.048]when compared with the ACEI/ARB group.After adjusting for confounding factors,multivariable logistic regression analysis revealed that advanced age(OR=1.082,P<0.001),increased systolic blood pressure(OR=1.009,P=0.005),thicker left ventricular posterior wall thickness(OR=1.462,P<0.001),left atrial enlargement(OR=1.081,P<0.001),and use of calcium channel blocker(OR=1.548,P=0.006)were independent risk factors for LVDD,and positively correlated with the risk of LVDD.While,male(OR=0.709,P=0.043)and BMI(OR=0.933,P=0.006)were protective factors,which were negatively correlated with LVDD risk.Conclusion In HHD patients,ARNI is superior to ACEI/ARB in reducing the incidence of LVDD.

Objective To investigate the relationship between serum T cell immunoglobulin mucin mole-cule-3(TIM-3)and netrin-1(NTN-1)levels and the risk of recurrence of B-cell acute lymphoblastic leukemia(B-ALL).Methods A total of 60 children with B-ALL were selected from January 1,2021 to January 1,2023.According to the expression of fusion gene,the children were divided into fusion gene positive group(26 ca-ses)and fusion gene negative group(34 cases).The blood routine,inflammatory factor levels,TIM-3 and its ligand galectin-9(Gal-9),NTN-1 and its downstream protein phosphorylated protein kinase B(pAKT)and protein kinase B(AKT)levels were compared between the negative fusion gene group and the positive fusion gene group at admission.The patients were followed up for 1 year and the recurrence of B-ALL was counted.The difference of serum TIM-3 and NTN-1 levels between the children with recurrence and those without re-currence was compared,and the correlation between the levels of TIM-3 and NTN-1 and recurrence was ana-lyzed.Results Compared with before treatment,the levels of TIM-3 and Gal-9 in both groups decreased after treatment,and the differences were statistically significant(P＜0.05).Compared with before treatment,the levels of TIM-3 and Gal-9 in both groups were decreased after treatment,and the differences were statistically significant(P＜0.05).The levels of NTN-1 and pAKT in fusion gene positive group were significantly higher than those in fusion gene negative group,with statistical significance(P＜0.05),but there was no statistical significance in AKT comparison(P＞0.05).In the follow-up period,there were 9 cases(34.61％)of recur-rence in the fusion gene positive group and 2 cases(5.88％)in the fusion gene negative group.The recurrence rate in the fusion gene positive group was higher than that in the fusion gene negative group,and the differ-ence was statistically significant(P＜0.05).The levels of TIM-3 and NTN-1 in recurrent children were sig-nificantly higher than those in non-recurrent children,and the difference was statistically significant(P＜0.05).Multiple Logistic regression analysis showed that TIM-3 and NTN-1 were independent risk factors af-fecting the prognosis of children(P＜0.05).Serum TIM-3 and NTN-1 levels were positively correlated with the risk of recurrence of B-ALL(r=0.445,0.437,P＜0.05).Conclusion The levels of TIM-3 and NTN-1 are different in different types of B-ALL,which can reflect the risk of recurrence of B-ALL,and it is recom-mended to pay close attention to them.

Objective To evaluate the clinical efficacy of acupuncture at Four Gates(bilateral LI4 and LR3)and other acupoints in treating postoperative pain after laparoscopic inguinal hernia repair and to explore its potential mechanism of action.Methods Sixty patients who underwent tension-free laparoscopic inguinal hernia repair at the Third Affiliated Hospital of Guangzhou University of Chinese Medicine between June 2024 and January 2025 and developed postoperative pain were enrolled.They were randomly divided into an observation group(n=30)and a control group(n=30)using a random number table.The control group received standard postoperative care,while the observation group received additional acupuncture at Four Gates and other acupoints(administered at 0 hour and 24 hours postoperatively).Clinical efficacy was assessed after 24 hours.Changes in the Numerical Rating Scale(NRS)for pain and the Bruggrmann Comfort Scale(BCS)were recorded.Serum levels of white blood cells(WBC),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),and cortisol(COR)were compared before and after treatment.Safety and adverse reactions were also evaluated.Results(1)After 4 hours and 24 hours of treatment,the NRS scores in the observation group were significantly improved(P＜0.05).Additionally,the observation group showed a significantly greater improvement in NRS scores than the control group during the same period,with statistically significant differences(P＜0.05).(2)After 4 hours and 24 hours of treatment,the BCS scores of both groups of patients were significantly improved(P＜0.05).The observation group showed a significantly greater improvement in BCS scores than the control group,with statistically significant differences(P＜0.05).(3)After treatment,the levels of WBC,CRP,and ESR in the observation group were significantly lower than those in the control group(P＜0.05).There was no statistically significant difference in COR levels between the two groups(P＞0.05).After treatment,the WBC levels in the observation group were slightly lower than before treatment,but the difference was not statistically significant(P＞0.05),while the WBC levels in the control group were significantly higher than before treatment(P＜0.05).(4)The overall response rate in the observation group was 96.70％(29/30),while that in the control group was 56.77％(17/30).The efficacy of the observation group was superior to that of the control group,with a statistically significant difference(P＜0.05).(5)No significant adverse reactions occurred in either the observation group or the control group.There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Acupuncture at Four Gates and other acupoints significantly alleviates postoperative pain,enhances patient comfort,and demonstrates excellent clinical efficacy with high safety.The treatment modulates postoperative WBC,CRP,ESR,and COR levels,suggesting systemic anti-inflammatory and stress-regulatory effects.

Objective To explore the differences in positive psychological resources among elementary and secondary school students with and without non-suicidal self-injury(NSSI)behaviors.Methods Between September and October 2023,the assessment data of 56 870 students aged 9 to 18 years in Chengdu,Sichuan Province were collected.The R software package was used to evaluate the network structure and symptom centrality,and the global strength and structural differences of the networks of students with and without NSSI behaviors in elementary,junior high,and senior high schools were compared.Results The prevalence of NSSI among elementary and secondary school students stands at 12.21%.Specifically,it peaks in junior high school students,reaching 14.22%,followed by that in senior middle school students at 13.66%,and is lowest in elementary school students at 10.17%.Regarding the network structure in elementary school students,irrespective of the presence or absence of NSSI behavior,subjective support exhibits the strongest network strength,and family functioning demonstrates the highest closeness centrality.Among junior high school students without NSSI behaviors,the strongest network strength was observed in subjective support,whereas for those with NSSI behaviors,self-esteem showed the strongest network strength.In addition,subjective support exhibited the highest closeness centrality in both groups.In senior high school students,self-esteem was the factor with the strongest network strength for students with or without NSSI behaviors.For senior high school students without NSSI,subjective support had the highest closeness centrality,while for those with NSSI,expressive suppression showed the highest closeness centrality.The edge weights differed significantly among elementary school students in family functioning-self-esteem(E=0.093)and family functioning-objective support(E=0.087).For junior high school students,significant differences were found in objective support-subjective support(E=0.131)and family functioning-impulse control(E=0.109).Among senior high school students,significant differences were observed in impulse control-family function(E=0.133)and subjective support-utilization of support(E=0.130)(P<0.05).Conclusion Excessive family involvement in elementary school students and expressive suppression in senior high school students may be important influencing factors for NSSI behaviors.The lack of social support has a greater impact on junior and senior high school students.The strength of the connection among subjective support,objective support,and utilization of support is an important indicator.

Objective To investigate the effects of estrogen signaling on T-cell recruitment and polarization in acutely injured skeletal muscle.Methods One hundred C57BL/6 male mice,one hundred and eighty C57BL/6 female mice were selected.Twenty-five female mice were ovariectomized(OVX)and 10 male mice were taken as the sham-operated(sham).Then,cardiotoxin(CTX)induced tibialis anterior(TA)injury for preparing mice myoinjury model.Subcutaneous injection of 17β-estradiol(E2)or estrogen receptor antagonist 4-hydroxytamoxifen(4-OHT)was performed.A total of 140 mice(70 males and 70 females)were divided into four group including:PBS-male,CTX-male,PBS-female,and CTX-female.Serum estradiol(E2)levels were measured by ELISA,and muscle injury models were validated via HE staining.Subsequently,20 male and 20 female mice were selected for immunofluorescence(IF)and Real-time PCR to assess estrogen receptors(ER)expression in injured muscle tissue.Further,10 male and 40 female mice were allocated into five experimental groups,including CTX,CTX+E2,CTX+4-OHT,CTX+OVX,CTX+sham.HE staining and IF were performed to evaluate inflammatory infiltration in the injured muscle.Additionally,50 female mice were divided into CTX and CTX+OVX groups,and IF combined with flow cytometry were used to analyze T-cell phenotypes and muscle fiber regeneration in the injured muscle.Results In vivo,serum E2 and myofiber ERβ increased post-injury in mice of both sexes,significantly higher in females.Compared to the control group,E2 alleviated inflammation,OVX exacerbated inflammation,increased CD4+T-cell infiltration,elevated T helper 1 cell(Th1)response,decreased regulatory T cells(Tregs),impaired regeneration.In vitro,IFN-γ/LPS significantly upregulated ERβ in myotubes.Conclusion Estrogen signaling critically regulates muscle inflammation.Estrogen deficiency(OVX)delays repair of skeletal muscle by promoting Th1 response and suppressing Tregs function.

BACKGROUND:There are many treatment methods for knee osteoarthritis,among which electroacupuncture,as an important non-drug treatment,is effective in the treatment of knee osteoarthritis,but its exact mechanism is not clear. OBJECTIVE:Effect of electroacupuncture on the expression of p53 and P21 in articular cartilage and subchondral bone of aged rats with knee osteoarthritis. METHODS:Eight 6-month-old male Sprague-Dawley rats were included in the young group and sixteen 24-month-old male Sprague-Dawley rats were randomly divided into old group(n=8)and electroacupuncture group(n=8).The rats in the electroacupuncture group received electroacupuncture stimulation once a day,5 days a week,for 8 continuous weeks,and the other two groups did not do any treatment.Eight weeks later,the level of type Ⅱ collagen C-terminal peptide in peripheral blood was detected by ELISA,the morphology of left knee cartilage and subchondral bone was observed by safranin O-fast green staining,the degree of knee cartilage degeneration was evaluated by modified Mankin's score,the microstructure of left knee cartilage and subchondral bone was detected by micro-CT,and the expression levels of matrix metalloproteinase 13,P53,P21 Mrna and protein were detected by RT-PCR and western blot respectively. RESULTS AND CONCLUSION:Compared with the young group,the level of C-terminal peptide of type Ⅱ collagen in the peripheral blood was increased in the old group(P<0.05).The micro-CT results showed that the bone volume fraction,bone mineral density and the number of bone trabeculae were decreased in the old group compared with the young group(P<0.05),while the trabecular separation increased(P<0.05).Safranin O-fast green staining showed that in the old group,the surface layer of cartilage was uneven with fissures,the morphology of chondrocytes was irregular and stained unevenly,the boundary between the cartilage and subchondral bone was blurred,and the matrix loss was serious.The Mankin's score was higher in the old group than the young group(P<0.05).The expression of matrix metalloproteinase 13,P53,P21 at Mrna and protein levels increased in the old group compared with the young group(P<0.05).Compared with the old group,electroacupuncture decreased the level of C-terminal peptide of type Ⅱ collagen(P<0.05),increased the bone volume fraction,bone mineral density and the number of bone trabeculae(P<0.05),and decreased the trabecular separation(P<0.05).Safranin O-fast green staining showed that in the electroacupuncture group,the surface of cartilage was smooth and red staining was uniform,and the cell morphology and structure were between the young group and the old group.Following electroacupuncture treatment,the Mankin's score(P<0.05),matrix metalloproteinase 13 and P21 Mrna expression(P<0.05),and matrix metalloproteinase 13 and P53 protein expression decreased(P<0.05),while there was a decreasing trend of P53 Mrna and P21 protein expression,but with no statistical significance(P>0.05).To conclude,electroacupuncture may delay articular cartilage degeneration and subchondral osteoporosis in aged rats by inhibiting the expression of P53 and P21,so as to protect joints and delay joint aging.

Objective To investigate the clinical outcomes of cranioplasty with polyether ether ketone(PEEK)or titanium after large craniectomy in patients.Methods Clinical data of 150 patients undergoing skull repair due to large frontotemporal skull defect in our hospital from April 2018 to June 2022 were retrospectively analyzed,and they were divided into titanium mesh group and PEEK group according to different repair materials.The conditions of surgical site infection,bleeding,subcutaneous effusion,seizure,implant rupture or exposure in the two groups were compared.Results In the PEEK group,96.3％of patients needed to implant the repair material under the temporal muscle,which was significantly higher than that in the titanium mesh group(78.1％)(P＜0.05).There were no significant differences in postoperative complications including infection,bleeding,seizure,implant rupture or leakage between the two groups(P＞0.05).However,the incidence of postoperative subcutaneous effusion in PEEK group was higher than that in titanium mesh group(14.8％VS4.2％,P＜0.05),and the difference was statistically significant.Conclusion Both titanium and PEEK can be used in cranioplasty for patients with large frontotemporal cranial defects.Subcutaneous effusion is common in patients underwent cranioplasty with PEEK postoperatively,which needs to be paid more attention.