OBJECTIVE To explore the mechanism of improvement effect of Chanbao zhichuang suppository （CBZCS） on hemorrhoids in rats through network pharmacology and metabolomics. METHODS A hemorrhoid model was established by subcutaneous injection of rhododendron oil to induce anal swelling. SD rats were divided into blank group （NC group， 0.32 g/kg vaseline）， model group （Model group， 0.32 g/kg vaseline）， CBZCS low-， medium-， and high-dose groups （CBZCS-L， CBZCS- M， CBZCS-H groups， with dosages of 0.16， 0.32， and 0.64 g/kg respectively）， and Mayinglong musk hemorrhoids suppository group （Positive group， 0.32 g/kg）， with 9 rats in each group. Anal administration was performed at 6， 12， 24， 48， and 72 hours after modeling. After the last administration， the pathological changes of the anal tissues in rats were observed， and the serum levels of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in rats were detected. Differential metabolite analysis and enrichment analysis were conducted by metabolomics methods， and the target proteins of CBZCS in treating hemorrhoids were obtained by network pharmacology. The core metabolic pathways were screened by interaction and enrichment analysis of differential metabolites and proteins， and the core proteins were experimentally verified. RESULTS Compared with the NC group， the anal tissues of the Model group showed obvious lesions， and the levels of IL-6 and TNF- α in the serum were significantly increased （P＜0.05）； compared with the Model group， the pathological damage of the anal tissues in the treatment groups was alleviated to varying degrees， and serum levels of IL-6 in CBZCS-H group， CBZCS-M group， and Positive group as well as serum levels of TNF-α in CBZCS-H group were significantly reduced （P＜0.05）. The metabolomics results showed that 34 differential metabolites were screened from the anal tissues of rats， and 22 of them showed a return after CBZCS administration. The differential metabolites mainly enriched in arachidonic acid metabolism， histidine metabolism， and glycerophospholipid metabolism. Through the network pharmacology， 138 intersection genes of CBZCS against hemorrhoids were determined. The analysis results showed that differential metabolites and target proteins were mainly enriched in the arachidonic acid metabolism pathway， and the regulation of this pathway might be related to cyclooxygenase-2 （COX-2）， Myc proto-oncogene protein （c-MYC）， cytochrome P450 1B1 （CYP1B1）， interleukin-1β （IL-1β）， and IL-6 protein expression. The experimental verification results showed that the expression levels of key proteins （COX-2， c-MYC， CYP1B1， IL-6， IL-1β） in the anal tissues of the Model group were significantly higher than those in the NC group （P＜0.05）， and the levels of the above proteins in the anal tissues of CBZCS-H group and Positive group were significantly lower than those in the Model group （P＜0.05）. CONCLUSIONS The mechanism of CBZCS in treating hemorrhoids may be to inhibit the expression of COX-2， c-MYC and CYP1B1 proteins， thereby inhibiting arachidonic acid metabolism and reducing the release of inflammatory factors IL-6 and IL-1β.

Aim To investigate the regulatory and an-ti-tumour effects of baicalein on mouse hepatocellular carcinoma cells and mouse macrophage co-cultures.Methods In vitro experiments,mouse hepatocellular carcinoma cell H22 and mouse macrophage RAW264.7 were randomly divided into a blank group and different concentrations of gradient administration group(5,10,20,40,80 mg·L-1),and the cell activity was detec-ted by CCK-8 assay;the two kinds of cells were co-cultured in Transwell chambers of 6-well plates for 48 h,and were randomly divided into the blank,model,and low,medium,and high baicalin groups(10,20,40 mg·L-1).Cell scratch and invasion assays,ELISA kits were used to detect TNF-α and IL-10 factor levels,and Western blot was used to determine the lev-els of CCNA2 and related proteins.The levels of TNF-α and IL-10 were detected by ELISA kits,and the ex-pression levels of CCNA2 and related proteins were de-tected by Western blot.In vivo experiments,H22 sub-cutaneous tumour model was established and randomly divided into the blank,positive,model and drug-ad-ministered groups.Mouse spleen,thymus and tumour indices were counted,and immunohistochemistry and Western blot were employed to detect the expression levels of CCNA2 and macrophage-related indexes in tumour tissues.Results Different doses of baicalein had a significant inhibitory effect on H22 and no signif-icant cytotoxicity on M0-type RAW264.7;the mor-phology of M0-type RAW264.7 cells was changed after co-culture,TNF-α was elevated and IL-10 was re-duced in the baicalein group;the results of the cell scratch assay and invasion assay found that baicalein inhibited M2-type macrophage invasion and metastasis;Arg1,p-p38/p38,p-stat3/stat3,N-cadherin,CCNA2 decreased significantly and Inos and E-cadherin in-creased significantly in the baicalein group;CCNA2,CD206 expression decreased significantly and CD86 expression increased significantly in the administered group.Conclusions Baicalein reverses M2-type mac-rophage polarisation and pro-carcinogenic functions and inhibits M2-type macrophage migration and invasion by modulating M2-type macrophage-related signalling pathways.

Objective To explore planning effect of AI-HIP assisted surgical planning system in primary unilateral total hip arthroplasty(THA)and its influence on clinical outcomes.Methods A retrospective analysis was conducted on clinical data of 36 patients who underwent their first unilateral THA from March 2022 to November 2022 and continuously used AI-HIP system(AI-HIP group),including 16 males and 20 females,aged from 43 to 81 years old with an average of(62.2±10.9)years old.According to the matching principle,36 patients who were planned by the traditional template method at the same period were selected as the control group,including 16 males and 20 females,aged from 40 to 80 years old with an average of(60.9±12.1)years old.The accuracy between two groups of prostheses were compared,as well as the combined eccentricity difference between preoperative planning and postoperative practice,lower limb length difference,osteotomy height from the upper edge of the lesser trochanter and top shoulder distance to evaluate planning effect.Harris score and visual analogue scale(VAS)were used to evaluate clinical efficacy.Results Both groups were followed up for 12 to 18 months with an average of(14.5±2.1)months.The complete accuracy and approximate accuracy of acetabular cup and femoral stalk prosthesis in AI-HIP group were 72.2％,100％,58.3％,88.9％,respectively,which were better than 44.4％,83.3％,33.3％,66.7％in control group(P＜0.05).There was no statistical significance in planning of femoral head prosthesis size(P＞0.05).The actual combined eccentricity difference and combined eccentricity difference(practical-planning)in Al-HIP group were 1.0(0.2,2.4)mm and 1.1(-2.1,3.2)mm,respectively;which were better than 3.0(1.4,4.9)mm and 3.5(-1.6,6.5)mm in control group(P＜0.05).There was no significant difference between two groups in actual osteotomy height of the upper margin of the lesser trochanter(P＞0.05).In AI-HIP group,the actual difference of lower extremity length after surgery,the difference of lower extremity length(practical-planning),osteotomy height from the upper margin of lesser trochanter(practical-planning),actual topshoulder distance after surgery,and topshoulder distance(practical-planning)were 1.5(0.2,2.8),1.1(-0.3,2.2),2.1(-2.3,4.1),(15.3±4.1),2.2(-4.8,0.3)mm,respectively;which were better than control group of 2.6(1.3,4.1),2.5(0.3,3.8),5.8(-2.4,7.7),(13.0±4.3),-5.7(-9.4,-2.2)mm(P＜0.05).At final follow-up,there were no significant differences in Harris scores of pain,function,deformity,total scores and VAS between two groups(P＞0.05).The range of motion score was 4.8±0.6 in AI-HIP group,which was higher than that in control group(4.4±0.8)(P＜0.05).Conclusion Compared with traditional template planning,AI-HIP assisted surgical planning system has good accuracy in predicting the prosthetic size of the acetabular cup and femoral stalk,restor-ing joint eccentricity,planning lower limb length,osteotomy height and top shoulder distance on the first unilateral THA,and the clinical follow-up effect is satisfactory.

Objective To retrieve,evaluate and summarize the best evidence on the management of ocular complications in intensive care patients ventilated in prone position,and to provide references for clinical practice.Methods Evidence on management of ocular complications in intensive care patients ventilated in prone position was systemically retrieved in the guideline websites,professional association websites and databases,such as the BMJ Best Practice,UpToDate,Cochrane Library,Joanna Briggs Institute,PubMed,Web of Science,Science Direct,Embase,CNKI,Wanfang and other databases,including guidelines,clinical decisions,evidence summaries,expert consensuses,group standards,systematic reviews and scoping reviews,published from January 2013 to June 2023.The guidelines were individually evaluated by 4 researchers,and the remaining literature was individually evaluated by 2 researchers.The literature that met the criteria was extracted and graded.Results A total of 15 articles were involved,including 6 guidelines,2 clinical decisions,2 evidence summaries,3 systematic reviews,1 scoping review and 1 group standard.Finally,6 evidence topics and 16 pieces of best evidence were formed,including organization and training,risk identification,eye assessment,eye protection,position management and regular observation.Conclusion This study summarized the best evidence on the management of ocular complications in intensive care patients ventilated in prone position.In the application,the best evidence should be selected according to the clinical situation,so as to reduce the incidence of ocular complications and improve the quality of life of patients.

Objective:To investigate the effects of anterolateral femoral perforator flaps pedicled with oblique branch of lateral circumflex femoral artery and carrying fascia lata in repairing destructive wounds and rebuilding function of hands or feet.Methods:This study was a retrospective observational study. From January 2022 to March 2023, 16 patients with destructive wounds in hands or feet combined with extensor tendon defects who met the inclusion criteria were admitted to Suzhou Ruihua Orthopedic Hospital, including 12 males and 4 females, aged 3 to 63 years. The wounds were located on the hands in 12 cases and on the feet in 4 cases. The number of defective extensor tendon ranged one to five, and the length of the defect ranged from 2.5 to 6.0 cm. The wound area was 11.0 cm×5.5 cm to 29.0 cm×9.5 cm after debridement. The wounds were repaired with anterolateral femoral perforator flaps pedicled with oblique branch of lateral circumflex femoral artery and carrying fascia lata, and the flap area was 12.0 cm×6.5 cm to 30.0 cm×11.0 cm. The fascia lata was used to repair the extensor tendon defects, and the harvesting area of fascia lata was 8.0 cm×3.0 cm to 12.0 cm×8.0 cm. The wounds in flap donor areas in 15 patients were sutured directly, and the wound in flap donor area in 1 patient was covered with medium-thickness skin graft from lower abdomen. The survival of flaps and the wound healing in donor and recipient areas of flaps were observed within 1 week after operation. The number of patients who underwent thinning and plastic surgery or tenolysis was recorded during postoperative follow-up. At the last follow-up, the recovery of sensory function of the transplanted flaps on hands or feet was evaluated, the efficacy of flap repair was evaluated according to the comprehensive flap evaluation scale, and the function of hands was evaluated according to the trial standards for evaluation of partial function of upper extremity by the Hand Surgery Society of Chinese Medical Association. The following two indexes were compared, including the measured total active motion of the injured fingers and the foot function assessed using Maryland foot function scale between before surgery and at the last follow-up.Results:Arterial crisis occurred in flaps in 2 patients after operation, and the flaps survived after timely exploration; the flaps in the rest patients survived well after operation. No obvious scar hyperplasia or ulceration was observed in donor and recipient areas of flaps after operation. All patients were followed up for 8 to 16 months, of which 6 patients underwent flap thinning and plastic surgery 6 to 7 months after operation, and 4 patients underwent tenolysis 3 to 6 months after operation. At the last follow-up, the recovery of sensory function of flaps reached S1 level in 5 cases and S2 level in 11 cases, and the two-point discrimination only had 1 point. The efficacy of flap repair scored 80 to 91, which were evaluated as excellent in 5 cases, good in 9 cases, and acceptable in 2 cases. The hand function was evaluated as excellent in 5 cases, good in 5 cases, and acceptable in 2 cases. The active extension function of the injured finger/toe was reconstructed successfully, and the total active motion of the injured finger was (225±22)° at the last follow-up, which was significantly higher than (117±20)° before surgery ( t=119.59, P<0.05); the foot function score was 86±7 at the last follow-up, which was significantly higher than 29±7 before surgery ( t=222.68, P<0.05), and the foot function was evaluated as excellent in 2 cases, good in 1 case, and acceptable in 1 case. Conclusions:The operation of harvesting the anterolateral femoral perforator flap pedicled with oblique branch of lateral circumflex femoral artery is relatively simple. After the wounds on hands or feet being repaired with the flaps, the appearance and function are good, with no obvious scar hyperplasia in donor and recipient areas of flaps. The fascia lata carried by the flap can repair the extensor tendon defect at the same time and improve the movement of the finger/toe.

Objective:To investigate the influence of curative-intent resection with textbook outcomes of liver surgery (TOLS) on long-term prognosis of gallbladder carcinoma (GBC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 824 patients with GBC in the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, who were admitted to 15 medical centers from January 2014 to January 2021, were collected. There were 285 males and 539 females, aged (62±11)years. According to the evalua-tion criteria of TOLS, patients were divided into those who achieved TOLS and those who did not achieve TOLS. Measurement data with normal distribution were represented as Mean± SD, and com-parison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data were conduc-ted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX stepwise regression model with backward Wald method was used for univariate and multivariate analyses. Results:(1) Achievement of TOLS. Of the 824 patients undergoing curative-intent resection for GBC, there were 510 cases achieving TOLS and 314 cases not achieving TOLS. (2) Follow-up. Of the 824 patients undergoing curative-intent resection for GBC, after excluding 112 deaths within 90 days after discharge, 712 cases were included for the survival analysis. The median follow-up time, median overall survival time and 5-year overall survival rate of the 510 patients achieving TOLS were 22.1(11.4,30.1)months, 47.6(30.6,64.6)months and 47.5%. The median follow-up time, median overall survival time and 5-year overall survival rate of the 202 patients not achieving TOLS were 14.0(6.8,25.5)months, 24.3(20.0,28.6)months and 21.0%. There was a significant difference in overall survival between patients achieving TOLS and patients not achieving TOLS ( χ2=58.491, P<0.05). (3) Analysis of factors influencing prognosis of patients. Results of multivariate analysis showed that TOLS, carcinoembryonic antigen (CEA), CA19-9, poorly differentiation of tumor, T2 stage of eighth edition of American Joint Committee on Cancer (AJCC) staging, T3 and T4 stage of eighth edition of AJCC staging, N1 stage of the eighth edition of AJCC staging, N2 stage of the eighth edition of AJCC staging, adjuvant therapy were independent factors influencing overall survival time of patients undergoing curative-intent resection for GBC ( hazard ratio=0.452, 1.479, 1.373, 1.612, 1.455, 1.481, 1.835, 1.978, 0.538, 95% c onfidence interval as 0.352-0.581, 1.141-1.964, 1.052-1.791, 1.259-2.063, 1.102-1.920, 1.022-2.147, 1.380-2.441, 1.342-2.915, 0.382-0.758, P<0.05). Conclusion:Patients under-going curative-intent resection for GBC with TOLS can achieve better long-term prognosis.

Breast cancer remains a leading cause of mortality in women worldwide.Triple-negative breast cancer(TNBC)is a particularly aggressive subtype characterized by rapid progression,poor prognosis,and lack of clear therapeutic targets.In the clinic,delineation of tumor heterogeneity and development of effective drugs continue to pose considerable challenges.Within the scope of our study,high hetero-geneity inherent to breast cancer was uncovered based on the landscape constructed from both tumor and healthy breast tissue samples.Notably,TNBC exhibited significant specificity regarding cell prolif-eration,differentiation,and disease progression.Significant associations between tumor grade,prog-nosis,and TNBC oncogenes were established via pseudotime trajectory analysis.Consequently,we further performed comprehensive characterization of the TNBC microenvironment.A crucial epithelial subcluster,E8,was identified as highly malignant and strongly associated with tumor cell proliferation in TNBC.Additionally,epithelial-mesenchymal transition(EMT)-associated fibroblast and M2 macrophage subclusters exerted an influence on E8 through cellular interactions,contributing to tumor growth.Characteristic genes in these three cluster cells could therefore serve as potential therapeutic targets for TNBC.The collective findings provided valuable insights that assisted in the screening of a series of therapeutic drugs,such as pelitinib.We further confirmed the anti-cancer effect of pelitinib in an orthotopic 4T1 tumor-bearing mouse model.Overall,our study sheds light on the unique characteristics of TNBC at single-cell resolution and the crucial cell types associated with tumor cell proliferation that may serve as potent tools in the development of effective anti-cancer drugs.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate the evaluation efficacy and predictive prognostic value of alpha-fetoprotein (AFP) response in tyrosine kinase inhibitors (TKIs) in combination with PD-1 inhibitors (α-PD-1) for intermediate-to-advanced hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 205 patients with intermediate-to-advanced HCC who were admitted to 9 medical centers, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from March 2020 to July 2022 were collected. There were 178 males and 27 females, aged (52±12)years. Based on AFP response at 6-8 weeks after treatment, patients were divided into the AFP response group (AFP level decreased by ≥50% compared to baseline) and the AFP no response group (AFP level decreased by <50% compared to baseline). Observation indicators: (1) AFP response evaluation of anti-tumor efficacy; (2) comparison of patient prognosis; (3) analysis of factors affecting patient prognosis. Measurement data with normal distrubution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range) and M( Q1, Q3). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and the Log-Rank test was used for survival analysis. The COX proportional risk model was used for univariate analysis and the COX stepwise regression model was used for multivariate analysis. Results:(1) AFP response evaluation of anti-tumor efficacy. Before treatment, all 205 patients were positive of AFP, with a baseline AFP level of 1 560(219,3 400)μg/L. All 205 patients were treated with TKIs in combination with α-PD-1, and the AFP level was 776(66,2 000)μg/L after 6 to 8 weeks of treatment. Of the 205 patients, 88 cases were classified as AFP response and 117 cases were classified as AFP no response. According to the response evaluation criteria in solid tumors version 1.1, the objective response rate (ORR) and disease control rate (DCR) were 42.05%(37/88) and 94.32%(83/88) in patients of the AFP response group and 16.24% (19/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=16.846, 25.950, P<0.05). According to the modified response evaluation criteria in solid tumors, the ORR and DCR were 69.32% (61/88) and 94.32% (83/88) in patients of the AFP response group and 33.33% (39/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=26.030, 25.950, P<0.05). (2) Comparison of patient prognosis. All 205 patients were followed up for 12.4(range, 2.4-34.0)months after treatment. The median progression free survival time and total survival time were 5.5 months and 17.8 months, respectively. The 1-year, 2-year progression free survival rates were 20.8% and 7.2%, and the 1-year, 2-year overall survival rates were 68.7% and 31.5%, respectively. The median progression free survival time, 1-year and 2-year progression free survival rates were 9.7 months, 39.6% and 14.2% in patients of the AFP response group and 3.7 months, 7.8% and 2.0% in patients of the AFP no response group, showing a significant difference in progression free survival between them ( χ2=43.154, P<0.05). The median overall survival time, 1-year and 2-year overall survival rates were not reached, 85.2% and 56.3% in patients of the AFP response group and 14.6 months, 56.3% and 14.5% in patients of the AFP no response group, showing a significant difference in overall survival between them ( χ2=33.899, P<0.05). (3) Analysis of factors affecting patient prognosis. Results of multivariate analysis showed that invasion of large blood vessels, extrahepatic metastasis, combined hepatic artery intervention therapy, and AFP response were independent factors influencing progression free survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio=1.474, 1.584, 0.631, 0.367, 95% confidence interval as 1.069-2.033, 1.159-2.167, 0.446-0.893, 0.261-0.516, P<0.05), and Eastern Cooperative Oncology Group score, invasion of large blood vessels, extrahepatic metastasis, and AFP response were independent factors influencing overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio= 1.347, 1.914, 1.673, 0.312, 95% confidence interval as 1.041-1.742, 1.293-2.833, 1.141-2.454, 0.197-0.492, P<0.05). Conclusions:AFP response at 6-8 weeks after treatment can effectively evaluate anti-tumor efficacy of TKIs in combination with α-PD-1 for intermediate-to-advanced HCC. AFP response is the independent factor influencing progression free survival and overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1.