OBJECTIVE: To observe the effect of electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) on hippocampal neuronal ferritinophagy mediated by the nuclear receptor coactivator 4 (NCOA4)/ferritin heavy chain 1 (FTH1) signaling pathway in vascular dementia (VD) rats, and to explore the potential mechanisms of electroacupuncture for VD. METHODS: A total of 60 male rats of SPF grade were randomly divided into a blank group (12 rats), a sham surgery group (12 rats) and a modeling group (36 rats). In the modeling group, the modified 4-vessel occlusion method was used to establish the VD model. The 24 successfully modeled rats were randomly divided into a model group and an electroacupuncture group, with 12 rats in each group. In the electroacupuncture group, electroacupuncture was applied at left and right "Sishencong" (EX-HN1), and bilateral "Fengchi" (GB20), with continuous wave, in frequency of 2 Hz and current intensity of 1 mA, 30 min a time, once daily for 21 consecutive days. The learning and memory abilities were assessed using the Morris water maze test before modeling, after modeling and after intervention, as well as the novel object recognition test after intervention. After intervention, the neuronal morphology in the hippocampus was observed by Nissl staining; the iron deposition was observed by Prussian blue staining; the reactive oxygen species (ROS) level was detected by dihydroethidium (DHE) fluorescence staining; the levels of iron, malondialdehyde (MDA) and superoxide dismutase (SOD) in the hippocampal tissue were measured by the colorimetric assay, TBA method, and WST-1 method, respectively; the positive expression of NCOA4, FTH1 and glutathione peroxidase 4 (GPX4) was detected by immunohistochemistry; the protein expression of NCOA4, FTH1, GPX4, and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ in the hippocampus were detected by Western blot. RESULTS: Compared with the sham surgery group, in the model group, the escape latency was prolonged, and the number of platform crossings reduced (P<0.01), the recognition index (RI) was decreased (P<0.01); the hippocampal neurons displayed a blurred laminar structure, disorganized cellular arrangement, and the number of Nissl bodies was decreased (P<0.01); the percentage of iron deposition area in the hippocampus was increased (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were increased (P<0.01), the SOD level, and the protein expression of FTH1 and GPX4 were decreased (P<0.01). Compared with the model group, in the electroacupuncture group, the escape latency was shortened and the number of platform crossings was increased (P<0.01), the RI was increased (P<0.01); the hippocampal neurons exhibited more regular morphology, better-organized cellular structure, and the number of Nissl bodies was increased (P<0.05); the percentage of iron deposition area in the hippocampus reduced (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were decreased (P<0.01, P<0.05), the SOD level, and the protein expression of FTH1 and GPX4 were increased (P<0.01). CONCLUSION Electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) can improve learning and memory abilities in VD rats, and its mechanism may be associated with the regulation of the hippocampal NCOA4/FTH1 signaling pathway, inhibition of ferritinophagy, and alleviation of oxidative stress damage.
Animals ; Electroacupuncture ; Dementia, Vascular/genetics* ; Male ; Rats ; Signal Transduction ; Humans ; Memory ; Rats, Sprague-Dawley ; Nuclear Receptor Coactivators/genetics* ; Ferritins/genetics* ; Learning ; Hippocampus/metabolism* ; Acupuncture Points

The Pharmacopeia of the People's Republic of China 2025 Edition(referred to as the Chinese Pharmaco-poeia 2025 Edition,ChP 2025)will be promulgated and implemented.This article introduces the process of devel-opment of ChP 2025 Edition(Volume Ⅱ),including the selection,the revision of general notices,the addition and revision of drug monographs,etc.,and provides some analysis and examples to illustrate,which can facilitate the readers to understand and implement the ChP 2025 Edition(Volume Ⅱ).

The Pharmacopeia of the People’s Republic of China 2025 Edition (referred to as the Chinese Pharmacopoeia 2025 Edition, ChP 2025) will be promulgated and implemented. This article introduces the process of development of ChP 2025 Edition (Volume Ⅱ), including the selection, the revision of general notices,the addition and revision of drug monographs, etc., and provides some analysis and examples to illustrate,which can facilitate the readers to understand and implement the ChP 2025 Edition (Volume Ⅱ).

Aim To explore the specific mechanism by which scutellarin(Scu)antagonizes the injury of human aortic endothelial cells(HAEC)induced by 2,2-azobis(2-methylpropylimidate)dihydrochloride(AAPH)by regulating the protein kinase RNA-like endoplasmic reticulum kinase(PERK)-nuclear factor erythroid 2-related factor 2(NRF2)/ac-tivating transcription factor 4(ATF4)-C/EBP homology protein(CHOP)pathway.Methods HAEC were pre-pro-tected by Scu and then injured by AAPH to explore the molecular mechanism of Scu on HAEC injury.The cells were di-vided into control group,AAPH group,AAPH+Scu low,medium and high groups.The contents of superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px)and glutathione S-transferase(GSH-ST)in the cells were measured.The content of reactive oxygen species(ROS)in cells was detected by fluorescent probe,and the apop-tosis rate was detected by Annexin V-FITC/PI method.The mRNA expression of PERK and eIF2α in cells was detected by RT-qPCR.The protein expression of glucose regulated protein 78(GRP78),PERK,p-PERK,eukaryotic initiation factor 2α(eIF2α),p-eIF2α,ATF4,CHOP,Nrf2,Bcl-2,p53 up-regulated modulator of apoptosis(PUMA),Caspase-3 and Caspase-12 in cells was detected by Western blot.In order to further study the molecular mechanism of Scu against HAEC injury,gene silencing technology was used to inhibit the expression of PERK in HAEC.The cells were divided in-to five groups:control group,AAPH+si-con group,AAPH+Scu+si-con group,AAPH+si-PERK group,AAPH+si-PERK+Scu group.The mRNA expression of PERK and eIF2α in cells after si-PERK interference was detected by RT-qPCR.The protein expression of PERK,p-eIF2α,eIF2α,ATF4,CHOP,Nrf2,Bcl-2,PUMA,Caspase-3 and Caspase-12 in cells after si-PERK interference was detected by Western blot.Results The content of ROS and the rate of apoptosis were significantly reduced after Scu intervention(P＜0.01).Scu could down-regulate the mRNA expression of PERK and eIF2α,and down-regulate the protein expression of GRP78,p-PERK,p-eIF2α,ATF4,CHOP,PUMA,Caspase-3,Caspase-12 and up-regulate the protein expression of Nrf2 and Bcl-2(P＜0.01).After interference with si-PERK,there were significant differences in the protein expression of PERK,p-eIF2α,ATF4,CHOP,Nrf2,Bcl-2,PUMA,Caspase-3,Caspase-12,as well as the mRNA expression of PERK and eIF2α in cells compared to before interference(P＜0.01).It is proved that Scu could anti-endoplasmic role in reticulum stress and apoptosis,which is closely associated with the regula-tion of the PERK-Nrf2/ATF4-CHOP pathway.Conclusion Scu can effectively alleviate AAPH-induced injury to HAEC by regulating PERK-Nrf2/ATF4-CHOP pathways to inhibit endoplasmic reticulum stress and cell apoptosis.

Aim To explore the specific mechanism by which scutellarin(Scu)antagonizes the injury of human aortic endothelial cells(HAEC)induced by 2,2-azobis(2-methylpropylimidate)dihydrochloride(AAPH)by regulating the protein kinase RNA-like endoplasmic reticulum kinase(PERK)-nuclear factor erythroid 2-related factor 2(NRF2)/ac-tivating transcription factor 4(ATF4)-C/EBP homology protein(CHOP)pathway.Methods HAEC were pre-pro-tected by Scu and then injured by AAPH to explore the molecular mechanism of Scu on HAEC injury.The cells were di-vided into control group,AAPH group,AAPH+Scu low,medium and high groups.The contents of superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px)and glutathione S-transferase(GSH-ST)in the cells were measured.The content of reactive oxygen species(ROS)in cells was detected by fluorescent probe,and the apop-tosis rate was detected by Annexin V-FITC/PI method.The mRNA expression of PERK and eIF2α in cells was detected by RT-qPCR.The protein expression of glucose regulated protein 78(GRP78),PERK,p-PERK,eukaryotic initiation factor 2α(eIF2α),p-eIF2α,ATF4,CHOP,Nrf2,Bcl-2,p53 up-regulated modulator of apoptosis(PUMA),Caspase-3 and Caspase-12 in cells was detected by Western blot.In order to further study the molecular mechanism of Scu against HAEC injury,gene silencing technology was used to inhibit the expression of PERK in HAEC.The cells were divided in-to five groups:control group,AAPH+si-con group,AAPH+Scu+si-con group,AAPH+si-PERK group,AAPH+si-PERK+Scu group.The mRNA expression of PERK and eIF2α in cells after si-PERK interference was detected by RT-qPCR.The protein expression of PERK,p-eIF2α,eIF2α,ATF4,CHOP,Nrf2,Bcl-2,PUMA,Caspase-3 and Caspase-12 in cells after si-PERK interference was detected by Western blot.Results The content of ROS and the rate of apoptosis were significantly reduced after Scu intervention(P＜0.01).Scu could down-regulate the mRNA expression of PERK and eIF2α,and down-regulate the protein expression of GRP78,p-PERK,p-eIF2α,ATF4,CHOP,PUMA,Caspase-3,Caspase-12 and up-regulate the protein expression of Nrf2 and Bcl-2(P＜0.01).After interference with si-PERK,there were significant differences in the protein expression of PERK,p-eIF2α,ATF4,CHOP,Nrf2,Bcl-2,PUMA,Caspase-3,Caspase-12,as well as the mRNA expression of PERK and eIF2α in cells compared to before interference(P＜0.01).It is proved that Scu could anti-endoplasmic role in reticulum stress and apoptosis,which is closely associated with the regula-tion of the PERK-Nrf2/ATF4-CHOP pathway.Conclusion Scu can effectively alleviate AAPH-induced injury to HAEC by regulating PERK-Nrf2/ATF4-CHOP pathways to inhibit endoplasmic reticulum stress and cell apoptosis.

Objective To investigate the characteristics and rules of tongue image in patients with chronic fatigue syndrome(CFS)with different fatigue degree.Methods Totally 917 patients with severe chronic fatigue syndrome(severe CFS group),351 patients with mild chronic fatigue syndrome(mild CFS group)and 1216 healthy controls(healthy control group)were enrolled in the physical examination center of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine.The tongue image data of subjects in the three groups were collected using TFDA-1 digital tongue and face diagnostic instrument,and the color space indexes of RGB,HSI,Lab and YCrCb were used to analyze the tongue image differences of CFS people with different fatigue degrees and the tongue image features of CFS patients with liver-qi stagnation syndrome,damp-heat stasis syndrome and spleen deficiency syndrome.Results Compared with the healthy control group,the tongue image indexes TB-R,TB-G,TB-B,TB-I,TB-L,TB-Y,TC-H,TC-I,TC-L and TC-Y increased in the severe CFS group;TB-S,TB-a,TC-S,TC-a,TC-Cr decreased(P<0.05).TB-R,TB-G,TB-B,TB-I,TB-L,TB-Y,TC-R,TC-G,TC-B,TC-I,TC-L and TC-Y increased in severe CFS group compared with mild CFS group.TB-H and TB-b increased in mild CFS group compared with healthy control group.The comparison of syndromes in severe CFS group showed that TB-a,TB-Cr,TC-S,TC-a,TC-Cr and TB-S increased in liver-qi stagnation syndrome compared to damp-heat stasis syndrome;TB-G,TB-B,TB-I,TB-L,TB-Y,TB-b,TB-Cb,TC-G,TC-B,TC-H,TC-I,TC-L,TC-Y and perAll decreased(P<0.05).Compared with spleen deficiency syndrome,TB-a,TB-Cr,TB-CON,TB-ENT,TB-MEAN,TC-a,TC-Cr,TC-CON,TC-ENT,TC-MEAN increased in liver-qi stagnation syndrome;TB-ASM,TC-S and TC-ASM decreased(P<0.05).Compared with spleen deficiency syndrome,TB-a,TB-b,TB-Cr,TB-Cb,TB-CON,TB-ENT,TB-MEAN,TC-G,TC-B,TC-H,TC-I,TC-L,TC-a,TC-Y,TC-Cr,TC-CON,TC-ENT,TC-MEAN,perAll increased;TB-ASM,TC-S and TC-ASM decreased(P<0.05).The comparison of mild CFS syndrome showed that there was no statistical significance between liver-qi stagnation syndrome and spleen deficiency syndrome(P>0.05).TB-Cr,TC-a,TC-Cr and perAll increased and TC-S decreased in damp-heat stasis syndrome compared with spleen deficiency syndrome(P<0.05).TB-S,TB-a,TB-Cr,TC-S,TC-a,TC-Cr increased,and TB-G,TB-B,TB-I,TB-Cb,TB-b,TC-b and TC-Cb decreased(P<0.05)in liver-qi stagnation syndrome compared with damp-heat syndrome.The distribution trend of TC-S was as follows:dampness-heat syndrome

Objective:To conduct a network meta-analysis comparing the efficacy and safety of various drug injections for treating keloids.Methods:The search terms of "triamcinolone acetonide, 5-fluorouracil, verapamil, botulinum toxin, platelet rich plasma, keloid, scar, drug injection" were retrieved in PubMed, Embase, Web of Science, CNKI and Wanfang database to obtain the publicly published randomized controlled trials comparing single or combined drug injection for treating keloid from January 2010 to February 2023. The outcome index was the effective proportion of treatment, incidence proportion of adverse reactions, and recurrence proportion. NoteExpress, RevMan 5.4, and Stata 16.0 statistical software were utilized to perform a network meta-analysis of eligible studies that met the inclusion and exclusion criteria.Results:A total of 1 679 patients were enrolled in 21 studies that evaluated nine treatment modalities: triamcinolone (TAC), 5-fluorouracil (5-FU), botulinum toxin type A (BTA), platelet-rich plasma (PRP), Verapamil, BTA+ 5-FU, TAC+ 5-FU, TAC+ BTA, and TAC+ PRP. The network diagram revealed that there were 36 pairwise comparisons among the 9 treatment measures, with direct comparisons in 13 of them. The funnel plot demonstrated a symmetrical distribution of effect size points, and both Beggs test and Eggers test yielded P values greater than 0.05, indicating a low likelihood of publication bias. Nine treatment measures formed five closed loops with good consistency. The result of the network meta-analysis indicated that BTA+ 5-FU was more effective than TAC, 5-FU, or PRP alone; TAC+ 5-FU was more effective than TAC, 5-FU, or PRP alone; TAC+ BTA was more effective than TAC, 5-FU, BTA, or PRP alone; Verapamil was more effective than 5-FU and BTA was more effective than 5-FU. All result were found to be statistically significant ( P<0.05). A surface under the cumulative ranking area (SUCRA) map was generated, displaying the efficacy ranking and corresponding SUCRA values for each treatment: BTA+ 5-FU (85.6%)>TAC+ 5-FU (84.8%)>BTA+ TAC (76.7%)>Verapamil (48.9%)>BTA (45.0%)>TAC+ PRP (43.8%)>PRP (32.1%)>TAC (24.7%)>5-FU(8.3%). In terms of recurrence rate, the incidence of recurrence was higher with 5-FU compared to BTA or TAC+ 5-FU, and the incidence of recurrence was higher with TAC compared to TAC+ 5-FU; these differences were statistically significant ( P<0.05). A SUCRA map was generated with the ranking and SUCRA value for each treatment as follows: 5-FU (80.4%)>TAC (73.5%)>Verapamil (65.7%)>TAC+ BTA (52.5%)>PRP (34.8%)>BTA+ 5-FU (33.7%)>TAC+ 5-FU (30.2%)>BTA (29.3%). The qualitative analysis revealed a significantly lower incidence of systemic and local adverse reactions following combined drug injection compared to single drug injection. Conclusion:In the treatment of keloids using drug injection, combination therapy utilizing multiple drugs has demonstrated superior efficacy, lower recurrence rates, and fewer adverse reactions in comparison to single-drug therapy. Notably, the utilization of BAT, 5-FU, and TAC in combination may yield the most favorable outcomes.

OBJECTIVE: To investigate the correlation of procalcitonin (PCT), interleukin-6 (IL-6) and antithrombin III (AT III) with the severity of sepsis, and to compare the predictive value of the above indicators alone or in combination. METHODS: A retrospective cohort study was conducted. Eighty-five patients with sepsis admitted to the department of intensive care medicine of Shandong Provincial Hospital Affiliated to Shandong First Medical University from April 2021 to September 2022 were enrolled. General information, sequential organ failure assessment (SOFA) score and acute physiology and chronic health evaluation II (APACHE II) score within 24 hours of admission, inflammatory indicators [PCT, IL-6, serum amyloid A (SAA), neutrophil to lymphocyte ratio (NLR), and C-reactive protein (CRP)] and coagulation indicators (D-dimer and AT III) levels at admission, and 28-day prognosis were collected. The differences of the above indicators were compared among patients with different prognosis at 28 days and different severity of sepsis. The correlation between PCT, IL-6, AT III and the severity of sepsis was analyzed by Spearman rank correlation method. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of PCT, IL-6 and AT III alone or in combination on the 28-day death of patients with sepsis. RESULTS: Eighty-five patients were enrolled finally, 67 cases survived and 18 cases died at 28 days. The mortality was 21.2%. There were no statistical significant differences in gender, age and other general data between the two groups. The patients in the death group were more serious than those in the survival group, and PCT, IL-6, and CRP levels were significantly higher than those in the survival group [PCT (μg/L): 4.34 (1.99, 14.42) vs. 1.17 (0.31, 3.94), IL-6 (ng/L): 332.40 (50.08, 590.18) vs. 61.95 (31.64, 194.20), CRP (mg/L): 149.28 (75.34, 218.60) vs. 83.23 (48.22, 174.96), all P < 0.05], and AT III activity was significantly lower than that in the survival group [(53.67±28.57)% vs. (80.96±24.18)%, P < 0.01]. However, there were no significant differences in D-dimer, NLR and SAA between the two groups. Among the 85 patients, 36 had sepsis with single organ dysfunction, 29 had sepsis with multiple organ dysfunction, and 20 had septic shock with multiple organ dysfunction. With the increase of the severity of sepsis, PCT and IL-6 levels gradually increased [PCT (μg/L): 0.36 (0.19, 1.10), 3.00 (1.22, 9.94), 4.34 (2.18, 8.86); IL-6 (ng/L): 43.99 (20.73, 111.13), 100.00 (45.37, 273.00), 332.40 (124.4, 693.65)], and the activity of AT III decreased gradually [(89.81±21.42)%, (71.97±24.88)%, and (53.50±25.41)%], all with statistically significant differences (all P < 0.01). Spearman rank correlation analysis showed that PCT and IL-6 levels in sepsis patients were significantly positively correlated with the severity of the disease (r values were 0.562 and 0.517, respectively, both P < 0.01), and AT III activity was significantly negatively correlated with the severity of the disease (r = -0.523, P < 0.01). ROC curve analysis showed that PCT, IL-6, and AT III alone or in combination had some predictive value for the death of sepsis patients at 28 days. The area under the ROC curve (AUC) of the above three indicators in combination was higher than that of the individual tests (0.818 vs. 0.722, 0.725, and 0.770), with a sensitivity of 83.3% and a specificity of 73.1%. CONCLUSIONS PCT, IL-6, and AT III were significantly correlated with the severity of sepsis patients. The combined assay of the above three indicators can effectively improve the prediction of the prognosis of sepsis patients.
Humans ; Procalcitonin ; Interleukin-6 ; Antithrombin III ; Retrospective Studies ; Multiple Organ Failure ; ROC Curve ; Sepsis/diagnosis* ; Prognosis ; C-Reactive Protein/analysis* ; Anticoagulants

Objective:To investigate the short-term efficacy of left-sided three-port total laparoscopic distal gastrectomy (TPTLDG).Methods:The prospective randomized controlled study was conducted. The 68 patients undergoing laparoscopic distal gastrectomy in the First Affiliated Hospital of Air Force Medical University from March 2022 to March 2023 were collected. All patients were randomly assigned to the TPTLDG group with a double number, and to the five-port laparoscopic distal gastrectomy (FPLDG) group with a single number, respectively. Observation indicators: (1) grouping situations of the enrolled patients; (2) comparison of perioperative condition; (3) comparison of complications during postoperative 30 days; (4) comparison of pathological examination. Measure-ment data with normal distribution were represented as Mean± SD, and comparison 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 or continuous correction chi-square test. Comparison of ordinal data was analyzed using the non‐parameter rank sum test. Results:(1) Grouping situations of the enrolled patients. A total of 59 patients of gastric cancer were selected for eligibility. There were 40 males and 19 females, aged 59.00(52.00, 67.00)years. The gender (male, female), age, body mass index (BMI), Caprini score (≤2, ≥3), nutritional risk screening 2002 (<3, ≥3), Eastern Coopera-tive Oncology Group performance status (0, 1), preoperative hypersensitive C-reactive protein, preoperative IL-6, preoperative white blood cell count, preoperative albumin were 19, 11, 59.00(51.25,65.25)years, 21.92(20.93,22.73)kg/m 2, 7, 23, 24, 6, 18, 12, 0.78(0.78,1.46)mg/L, 3.07(1.50,10.56)μg/L, 6.07(4.94,7.19)×10 9/L, 44.30(40.83, 46.15) g/L in the 30 patients of TPTLDG group, versus 21, 8, 57.00(51.00, 67.00)years, 21.90(20.95, 23.35)kg/m 2, 11, 18, 24, 5, 17, 12, 1.13(0.78,11.40)mg/L, 5.56(1.88,15.12)μg/L, 5.54(4.71,6.70)×10 9/L, 43.55(40.25,44.88)g/L in the 29 patients of FPLDG group, showing no significant difference in the above indicators between the two groups ( χ2=0.557, Z=-0.444, -0.805, χ2=1.482, 0.074, 0.012, Z=-1.259, -1.262, -0.819, -1.199, P>0.05), confounding bias ensured comparability between the two groups. (2) Comparison of perioperative condition. The length of incision, time to removing drainage tube, IL-6 at postoperative day 3, cost of hospital stay were 6.65(6.48,6.93)cm, 3.00(0,3.00)days, 29.18 (13.67, 43.53)μg/L, 84 164.15(73 084.72, 96 782.14)yuan in the TPTLDG group, versus 8.00(7.50,8.35)cm, 3.00(3.00,4.00)days, 47.56(21.31,85.79)μg/L, 92 120.43(87 069.33, 113 089.74)yuan in the FPLDG group, showing significant differences in the above indicators between the two groups ( Z=-11.065, -2.141, -2.940, -2.220, P<0.05). (3) Comparison of complications during postoperative 30 days. The incidence rate of complications during postoperative 30 days was 30.00%(9/30) and 24.14%(7/29) in the TPTLDG group and FPLDG group, respectively, showing no significant difference between the two groups ( χ2=0.256, P>0.05). (4) Comparison of pathological examination. Cases with pathological N staging as 0 stage, 1 stage, 2 stage, 3 stage were 22, 2, 4, 2 in the TPTLDG group, versus 13, 7, 4, 5 in the FPLDG group, showing a significant difference between the two groups ( Z=-2.021, P<0.05). Conclusion:TPTLDG is safe and feasible for gastric cancer, with a good short-term efficacy.

Objective:To conduct a network meta-analysis comparing the efficacy and safety of various drug injections for treating keloids.Methods:The search terms of "triamcinolone acetonide, 5-fluorouracil, verapamil, botulinum toxin, platelet rich plasma, keloid, scar, drug injection" were retrieved in PubMed, Embase, Web of Science, CNKI and Wanfang database to obtain the publicly published randomized controlled trials comparing single or combined drug injection for treating keloid from January 2010 to February 2023. The outcome index was the effective proportion of treatment, incidence proportion of adverse reactions, and recurrence proportion. NoteExpress, RevMan 5.4, and Stata 16.0 statistical software were utilized to perform a network meta-analysis of eligible studies that met the inclusion and exclusion criteria.Results:A total of 1 679 patients were enrolled in 21 studies that evaluated nine treatment modalities: triamcinolone (TAC), 5-fluorouracil (5-FU), botulinum toxin type A (BTA), platelet-rich plasma (PRP), Verapamil, BTA+ 5-FU, TAC+ 5-FU, TAC+ BTA, and TAC+ PRP. The network diagram revealed that there were 36 pairwise comparisons among the 9 treatment measures, with direct comparisons in 13 of them. The funnel plot demonstrated a symmetrical distribution of effect size points, and both Beggs test and Eggers test yielded P values greater than 0.05, indicating a low likelihood of publication bias. Nine treatment measures formed five closed loops with good consistency. The result of the network meta-analysis indicated that BTA+ 5-FU was more effective than TAC, 5-FU, or PRP alone; TAC+ 5-FU was more effective than TAC, 5-FU, or PRP alone; TAC+ BTA was more effective than TAC, 5-FU, BTA, or PRP alone; Verapamil was more effective than 5-FU and BTA was more effective than 5-FU. All result were found to be statistically significant ( P<0.05). A surface under the cumulative ranking area (SUCRA) map was generated, displaying the efficacy ranking and corresponding SUCRA values for each treatment: BTA+ 5-FU (85.6%)>TAC+ 5-FU (84.8%)>BTA+ TAC (76.7%)>Verapamil (48.9%)>BTA (45.0%)>TAC+ PRP (43.8%)>PRP (32.1%)>TAC (24.7%)>5-FU(8.3%). In terms of recurrence rate, the incidence of recurrence was higher with 5-FU compared to BTA or TAC+ 5-FU, and the incidence of recurrence was higher with TAC compared to TAC+ 5-FU; these differences were statistically significant ( P<0.05). A SUCRA map was generated with the ranking and SUCRA value for each treatment as follows: 5-FU (80.4%)>TAC (73.5%)>Verapamil (65.7%)>TAC+ BTA (52.5%)>PRP (34.8%)>BTA+ 5-FU (33.7%)>TAC+ 5-FU (30.2%)>BTA (29.3%). The qualitative analysis revealed a significantly lower incidence of systemic and local adverse reactions following combined drug injection compared to single drug injection. Conclusion:In the treatment of keloids using drug injection, combination therapy utilizing multiple drugs has demonstrated superior efficacy, lower recurrence rates, and fewer adverse reactions in comparison to single-drug therapy. Notably, the utilization of BAT, 5-FU, and TAC in combination may yield the most favorable outcomes.