Objective To investigate serum levels of eosinophilic neurotoxin(EDN),interleukin(IL)-13 and transforming growth factor(TGF)-β1 in children with recurrent wheezing of mycoplasma pneumoniae(MP)infection and analyze risk factors of recurrent wheezing with MP infection.Methods A total of 80 children with MP infection were divided into the MP infection recurrence wheezing group(45 cases)and the MP infection non-wheezing group(35 cases)according to the previous history of MP infection with wheezing,and 35 children with acute attacks of bronchial asthma were selected as the asthma group.The levels of EDN,IL-13 and TGF-β1 were determined by enzyme-linked immunosorbent assay.Multivariate Logistic regression analysis was performed to analyze risk factors of MP infection recurrence and wheezing.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of EDN,IL-13 and TGF-β1 on MP infection recurrence and wheezing.Results Compared with the non-asthmatic group,levels of EDN,IL-13 and TGF-β1 were higher in the recurrent asthmatic group and the asthmatic group(P＜0.05).There were no significant differences in EDN,IL-13 and TGF-β1 levels between the asthma group and the recurrent asthmatic group.Univariate analysis showed that the birth weight was lower in the recurrent wheezing group than that of the non-wheezing group,and the proportion of atopic constitution,the first and second degree relatives allergy history,smoke exposure and hospital stay≥7 d were higher than those of the non-wheezing group(P＜0.05).Multivariate Logistic regression analysis showed that higher levels of EDN,IL-13,TGF-β1,atopic constitution and smoke exposure were risk factors for recurrent wheezing of MP infection(P＜0.05).ROC curve results showed that the AUC of EDN,IL-13 and TGF-β1 for predicting the recurrence of MP infection and wheeting was 0.688,0.662 and 0.689,respectively,and the AUC of the combined prediction of EDN,IL-13 and TGF-β1 was 0.765,which was the most effective than each single index.Conclusion Serum levels of EDN,IL-13 and TGF-β1 increase in children with recurrent wheezing of MP infection,and their serum levels may predict repeated wheezing in children after MP infection,providing guidance for clinical intervention.

Objective:To explore the effects of magnolol on autophagy in intestinal Cajal cells and intestinal motility in rats with acute necrotizing pancreatitis (ANP).Methods:Forty-five Wistar rats were randomly divided into three groups by a random number table: control group, ANP group and magnolol intervention group, with 15 rats in each group. The ANP model was established by intraperitoneal injection of cerulein. The magnolol intervention group received a tail vein injection of 20 μg/kg magnolol ethanol solution 30 minutes after modeling. After 12 hours, ileal tissues were collected for pathological examination and scoring. Intestinal transit rate was measured using the carbon powder propulsion method, and isolated intestinal muscle strips were prepared to assess amplitude and frequency of spontaneous contraction. Oxidative stress markers in intestinal tissues, including superoxide dismutase (SOD) activity, malondialdehyde (MDA) and nitric oxide (NO) levels, were measured using xanthine oxidase, thiobarbituric acid, and enzymatic reduction assay kits, respectively. Cajal cells were isolated from intestinal smooth muscle tissues, and the expression of autophagy-related proteins (Beclin1, LC3Ⅱ, LC3Ⅰ, p62) and p-Kit was detected by Western blot. Double immunofluorescence staining was used to trace autophagy in Cajal cells.Results:The pathological scores of ileal tissues in the control, ANP, and magnolol intervention groups were (0.33±0.52), (4.83±0.41), and (3.50±0.55), respectively. The score in ANP group was significantly higher than that in the control group, while the score in the magnolol intervention group was lower than that in the ANP group, with statistically significant differences (all P value <0.05). Intestinal transit rate, amplitude and frequency of spontaneous contraction in the ANP group were significantly slower than those in the control group, while these parameters in the magnolol intervention group were significantly improved compared to the ANP group, with statistically significant differences (all P value <0.05). SOD activity in the control, ANP, and magnolol intervention groups were (73.8±8.1), (42.8±7.2), and (71.2±10.4) N/mg prot, respectively; NO levels were (1.72±0.26), (3.19±0.43), and (1.94±0.23) μmol/g prot; and MDA levels were (1.15±0.38), (3.84±0.30), and (1.68±0.33) nmol/mg prot. SOD activity in the ANP group was significantly lower than that in the control group, while NO and MDA contents were significantly higher. In the magnolol intervention group, SOD activity was significantly higher, and NO and MDA contents were significantly lower than those in the ANP group, with statistically significant differences (all P value <0.01). The levels of Beclin1, LC3Ⅱ/Ⅰ ratio, and p-Kit in the intestinal Cajal cells of ANP group were significantly higher than those in the intestinal Cajal cells of control group, while the p62 level was significantly lower. In the intestinal Cajal cells of magnolol intervention group, the levels of Beclin1, LC3Ⅱ/Ⅰ ratio, and p-Kit were significantly lower while the p62 level was significantly higher than those in the intestinal Cajal cells of ANP group, with statistically significant differences (all P value <0.01). The numbers of c-Kit/GFP-LC3 double-positive Cajal cells in the control group, ANP group, and magnolol intervention group were (9.59±5.06), (11.27±8.30), and (10.27±6.30), respectively. The ANP group had significantly more double-positive cells than the control group, while the magnolol intervention group had significantly less double-positive cells than the ANP group, with statistically significant differences (all P value <0.05). Conclusions:Excessive oxidative stress and autophagy in Cajal cells are important mechanisms underlying ANP-induced intestinal motility dysfunction. Magnolol can improve intestinal motility in ANP by antagonizing oxidative stress and reducing autophagy in Cajal cells. p-Kit may play a regulatory role in this process.

Objective:To investigate the efficacy and safety of Doxycycline in the treatment of Mycoplasma pneumoniae pneumonia (MPP). Methods:Case series study.A retrospective observational study was conducted on 202 patients diagnosed with MPP in Beijing United Family Hospital from January 2022 to January 2024.The patients were divided into 3 groups according to antibiotics used: Azithromycin group which enrolled 93 cases, 60 cases (Azithromycin alone group) were included after excluding 33 cases with adding steroids; Doxycycline group which enrolled 32 case, 31 cases (Doxycycline alone group) were included after excluding 1 case with adding steroids; Azithromycin switch to Doxycycline when diagnosed Macrolides-unresponsive MPP(MUMPP). Azithromycin switch to Doxycycline group which enrolled 77 cases, 73 cases (switch group) were included after excluding 4 cases with adding steroids.Results used the Mann-Whitney U test, Chi-square test or exact test analyse, comparing the differences in defervescene time, hospitalization day, outcomes and side effects in each group. Results:The fever duration in the Doxycycline alone group was 48(36, 48) h, which was significantly shorter than that in the Azithromycin alone group[120(120, 144) h] ( Z=-7.646, P<0.001). The hospitalization time in the Doxycycline alone group was [3(3, 4) d], which was significantly shorter than that in the Azithromycin alone group [4(3, 5) d] ( Z=-3.368, P=0.002). The medium fever duration in the switch group after Azithromycin was changed to Doxycycline was 48 h, which was not statistically significantly different from that in the Doxycycline alone group ( Z=-0.571, P=0.849). The medium hospitalization time in the switch group after Azithromycin changed to Doxycycline was 4 d, which was significantly longer than that in the Doxycycline alone group (3 d) ( Z=-2.759, P=0.008). Among 93 cases enrolled in the Azithromycin group, 33 cases (35.5%) converted to unresponsive MPP(UMPP), 23 cases (24.7%) progressed to refractory MPP (RMPP), and 33 cases (35.5%) added steroids.Among 32 cases included in the Doxycycline group, 1 case (3.1%) converted to UMPP, no case developed to RMPP, and 1 case (3.1%) added steroids.The above-mentioned 3 proportions were significantly different between the two groups (all P<0.001). Among 93 cases enrolled in the Azithromycin group, 11 cases (11.8%) progressed to severe MPP (SMPP), and 13 cases (14.0%) developed complications.In 32 cases included in the Doxycycline group, 1 case (3.1%) progressed to SMPP, and 3 cases (9.4%) developed complications.The difference in these 2 proportions was not statistically significant between the two groups ( P=0.294, 0.760). In 77 patients included in the Azithromycin switch to Doxycycline group, there were 4 cases converting to UMPP, 4 cases converting to RMPP and 4 cases adding steroids, which were not statistically significantly different from those in the Doxycycline group (all P=0.540). In the Azithromycin switch to Doxycycline group, there were 3 cases progressing to SMPP, and 7 cases developed complications, which were not statistically significantly different from those in the Doxycycline group (all P=1.000). Conclusions:Doxycycline can improve the fever symptom, shorten illness duration and hospitalization time, and reduce steroid usage and the proportions of UMPP and RMPP in pediatric MPP.Switching to Doxycycline is recommended for MUMPP patients as Doxycycline is effective for the treatment of pediatric MPP and no tetracycline pigmentation teeth now.

Objective:To characterize the minimal inhibitory concentration (MIC) of macrolides against clinical Mycoplasma pneumoniae (MP) isolates and to investigate the significance of 23S rRNA mutations. Methods:Cross-sectional study.A total of 288 clinical MP strains preserved in the laboratory from 2016 to 2021 were taken for macrolide resistance gene testing and the evaluation of in vitro susceptibility to Azithromycin and Erythromycin.MIC 50 and MIC 90 values were calculated separately for macrolide-susceptible and -resistant strains. Results:All 288 MP strains underwent the test of in vitro susceptibility to Azithromycin, while 86 of them were additionally tested for Erythromycin.Among these strains, 22 strains were Azithromycin-sensitive, and 266 strains were Azithromycin-resistant.A2063G mutations were detected in 260 (97.7%) strains, while A2064G mutations were detected in 6 (2.3%) strains.Azithromycin-resistant strains had an MIC 50 of 128.000 μg/mL and an MIC 90 of 512.000 μg/mL, with the MIC ranging between 16.000 and 512.000 μg/mL.Seven strains were sensitive and 79 strains were resistant to Erythromycin.Among Erythromycin-resistant strains, A2063G mutations were detected in 73 (92.4%) strains, while A2064G mutations were detected in 6 (7.6%) strains.Erythromycin-resistant strains had an MIC 50 of 256.000 μg/mL and an MIC 90 of 512.000 μg/mL, with the MIC ranging between 64.000 and 1 024.000 μg/mL. Conclusions:A2063G and A2064G mutations in the 23S rRNA gene of MP are associated with high-level in vitro resistance to Azithromycin and Erythromycin, significantly limiting the clinical effectiveness of these antibiotics.Early resistance gene testing is recommended for suspected MP patients, which can help optimize the treatment, improve prognosis, and prevent resistance spread.

Objective:To explore the influence of initial high-risk cytogenetic abnormalities on the outcomes of children with acute myeloid leukemia (AML) after post-transplant Cyclophosphamide (PTCy)-based allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A retrospective cohort study.AML children who underwent PTCy-based allo-HSCT after the first complete remission at Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science and Technology between April 2017 and April 2024 were enrolled.Patients were divided into intermediate-risk and high-risk groups based on their initial cytogenetic features.These patients were further divided into complex karyotype, 11q23 rearrangement, and other karyotype groups.Clinical characteristics and survival outcomes were compared among these groups.Measurement and count data were analyzed using Wilcoxon rank-sum/Kruskal-Wallis and χ2 tests, respectively.Survival and risk factor analyses were performed using Kaplan-Meier and Cox proportional hazards methods, respectively. Results:A total of 51 AML children who underwent allo-HSCT were included in this study.The median age at transplantation was 3.2 years and the median follow-up time was 4.6 years.There were 26 cases in the intermediate-risk group and 25 cases in the high-risk group; 8 cases in the complex karyotype group, 14 cases in the 11q23 rearrangement group, and 29 cases in the other karyotype groups.By the end of the follow-up on November 30, 2024, 11 patients relapsed, 8 patients died, and 13 patients developed grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD).The 3-year overall survival (OS), relapse-free survival (RFS), and grades Ⅱ-Ⅳ acute GVHD-free and relapse-free survival (GRFS) were 84.0% (95% CI: 74.4%-94.8%), 74.5% (95% CI: 63.4%-87.5%), and 58.8% (95% CI: 46.7%-74.0%), respectively.The 3-year OS of the high-risk group was significantly lower than that of the intermediate-risk group (71.8% vs.96.2%, P=0.022), while differences in 3-year RFS and GRFS between the 2 groups were not statistically significant (68.0% vs.80.8%, P=0.400; 52.0% vs.65.4%, P=0.420).The 3-year OS, RFS and GRFS of the complex karyotype group were significantly lower than those of 11q23 rearrangement and other karyotype groups (50.0% vs.85.7%, 93.1%, P=0.009; 37.5% vs.85.7%, 79.3%, P=0.022; 25.0% vs.64.3%, 65.5%, P=0.049).Multivariate analysis showed that a complex karyotype was an independent prognostic factor affecting 3-year OS and GRFS [OS: HR=6.79 (95% CI: 1.13-43.80), P=0.044; GRFS: HR=3.72(95% CI: 1.13-12.20), P=0.030]. Conclusions:High-risk cytogenetic features are significant predictors of survival outcomes in pediatric AML patients undergoing PTCy-based allo-HSCT.

Objective To propose a novel method based on three-dimensional depthwise separable convolution network(3D DSN)for the separation of PET images with dual tracers of 18F-FDG and 18F-FAPI.Methods A total of 120 pairs of 18F-FDG and 18F-FAPI PET images of the same patient scanned separately at different time points were collected,and the dual-tracer PET image was generated through simulation.After the image registration of PET images of two tracers for ensuring spatial position matching,the registered PET images were forward-projected to generate sinogram data,and the sinogram data of two tracers were accumulated to obtain mixed sinogram data.Subsequently,the dual-tracer PET image was reconstructed using maximum likelihood expectation maximization and input into a 3D DSN based network for image separation,thereby obtaining PET images of two single tracers.Results Compared with 3D CNN method,the proposed method increased the structure similarity index measure(SSIM)of the separated 18F-FDG images to the real 18F-FDG images by 0.87%,increased the peak signal-to-noise ratio(PSNR)by 11.8%,and reduced the normalized root mean square error(NRMSE)by 52%.The SSIM of the separated 18F-FAPI images to the real 18F-FAPI images increased by 1.1%,PSNR increased by 17.0%,and NRMSE decreased by 51%.Conclusion The proposed method can be effectively applied to simultaneous PET imaging with dual PET tracers,reducing the number of scans and costs in time and money,and providing clinical doctors more accurate and abundant diagnostic information.

BACKGROUND:Electromyographic biofeedback therapy has demonstrated unique advantages of non-invasive,real-time feedback,personalized treatment and promotion of neuroplasticity,and can promote the recovery of motor function in patients with spinal cord injury.OBJECTIVE:To review the current application status and therapeutic effects of electromyographic biofeedback combined with exercise therapy,robotic exoskeletons,and virtual reality technology in the recovery of motor function after spinal cord injury.METHODS:Relevant literature was retrieved from CNKI and PubMed databases up to May 2024.The search terms included"spinal cord injury,EMG biofeedback,physical therapy,robotic exoskeleton,VR,motor function,exercise"in both English and Chinese.Finally,71 articles were included for review.RESULTS AND CONCLUSION:Mechanisms by which electromyographic biofeedback therapy promotes spinal cord injury rehabilitation include promoting neural plasticity changes,strengthening neuromuscular connections and improving movement patterns.Electromyographic biofeedback,as an emerging tool for treating spinal cord injury,is often used in conjunction with other therapeutic methods,including exercise therapy,robotic exoskeletons,and VR,to promote the recovery of motor function after spinal cord injury.The effectiveness of combination therapy has been significantly improved.However,there are still some problems and challenges,such as the lack of detailed analysis of the mechanism,the lack of large-scale trials that provide strong evidence for combined efficacy,and the limited adaptability of the technology.Future research can focus on these aspects:to improve the personalization and accuracy of electromyographic biofeedback;to develop new rehabilitation equipment and expand the application areas of electromyographic biofeedback combined with more advanced technologies or engineering equipment;to apply electromyographic biofeedback to gait training systems,respiratory training systems,and limb-linkage rehabilitation systems,so as to improve the accuracy of the feedback and the effect of personalized treatment plans.At the same time,the ease of use and comfort of the equipment will be improved.

Objective:To explore the effects of magnolol on autophagy in intestinal Cajal cells and intestinal motility in rats with acute necrotizing pancreatitis (ANP).Methods:Forty-five Wistar rats were randomly divided into three groups by a random number table: control group, ANP group and magnolol intervention group, with 15 rats in each group. The ANP model was established by intraperitoneal injection of cerulein. The magnolol intervention group received a tail vein injection of 20 μg/kg magnolol ethanol solution 30 minutes after modeling. After 12 hours, ileal tissues were collected for pathological examination and scoring. Intestinal transit rate was measured using the carbon powder propulsion method, and isolated intestinal muscle strips were prepared to assess amplitude and frequency of spontaneous contraction. Oxidative stress markers in intestinal tissues, including superoxide dismutase (SOD) activity, malondialdehyde (MDA) and nitric oxide (NO) levels, were measured using xanthine oxidase, thiobarbituric acid, and enzymatic reduction assay kits, respectively. Cajal cells were isolated from intestinal smooth muscle tissues, and the expression of autophagy-related proteins (Beclin1, LC3Ⅱ, LC3Ⅰ, p62) and p-Kit was detected by Western blot. Double immunofluorescence staining was used to trace autophagy in Cajal cells.Results:The pathological scores of ileal tissues in the control, ANP, and magnolol intervention groups were (0.33±0.52), (4.83±0.41), and (3.50±0.55), respectively. The score in ANP group was significantly higher than that in the control group, while the score in the magnolol intervention group was lower than that in the ANP group, with statistically significant differences (all P value <0.05). Intestinal transit rate, amplitude and frequency of spontaneous contraction in the ANP group were significantly slower than those in the control group, while these parameters in the magnolol intervention group were significantly improved compared to the ANP group, with statistically significant differences (all P value <0.05). SOD activity in the control, ANP, and magnolol intervention groups were (73.8±8.1), (42.8±7.2), and (71.2±10.4) N/mg prot, respectively; NO levels were (1.72±0.26), (3.19±0.43), and (1.94±0.23) μmol/g prot; and MDA levels were (1.15±0.38), (3.84±0.30), and (1.68±0.33) nmol/mg prot. SOD activity in the ANP group was significantly lower than that in the control group, while NO and MDA contents were significantly higher. In the magnolol intervention group, SOD activity was significantly higher, and NO and MDA contents were significantly lower than those in the ANP group, with statistically significant differences (all P value <0.01). The levels of Beclin1, LC3Ⅱ/Ⅰ ratio, and p-Kit in the intestinal Cajal cells of ANP group were significantly higher than those in the intestinal Cajal cells of control group, while the p62 level was significantly lower. In the intestinal Cajal cells of magnolol intervention group, the levels of Beclin1, LC3Ⅱ/Ⅰ ratio, and p-Kit were significantly lower while the p62 level was significantly higher than those in the intestinal Cajal cells of ANP group, with statistically significant differences (all P value <0.01). The numbers of c-Kit/GFP-LC3 double-positive Cajal cells in the control group, ANP group, and magnolol intervention group were (9.59±5.06), (11.27±8.30), and (10.27±6.30), respectively. The ANP group had significantly more double-positive cells than the control group, while the magnolol intervention group had significantly less double-positive cells than the ANP group, with statistically significant differences (all P value <0.05). Conclusions:Excessive oxidative stress and autophagy in Cajal cells are important mechanisms underlying ANP-induced intestinal motility dysfunction. Magnolol can improve intestinal motility in ANP by antagonizing oxidative stress and reducing autophagy in Cajal cells. p-Kit may play a regulatory role in this process.

Objective:To investigate the efficacy and safety of Doxycycline in the treatment of Mycoplasma pneumoniae pneumonia (MPP). Methods:Case series study.A retrospective observational study was conducted on 202 patients diagnosed with MPP in Beijing United Family Hospital from January 2022 to January 2024.The patients were divided into 3 groups according to antibiotics used: Azithromycin group which enrolled 93 cases, 60 cases (Azithromycin alone group) were included after excluding 33 cases with adding steroids; Doxycycline group which enrolled 32 case, 31 cases (Doxycycline alone group) were included after excluding 1 case with adding steroids; Azithromycin switch to Doxycycline when diagnosed Macrolides-unresponsive MPP(MUMPP). Azithromycin switch to Doxycycline group which enrolled 77 cases, 73 cases (switch group) were included after excluding 4 cases with adding steroids.Results used the Mann-Whitney U test, Chi-square test or exact test analyse, comparing the differences in defervescene time, hospitalization day, outcomes and side effects in each group. Results:The fever duration in the Doxycycline alone group was 48(36, 48) h, which was significantly shorter than that in the Azithromycin alone group[120(120, 144) h] ( Z=-7.646, P<0.001). The hospitalization time in the Doxycycline alone group was [3(3, 4) d], which was significantly shorter than that in the Azithromycin alone group [4(3, 5) d] ( Z=-3.368, P=0.002). The medium fever duration in the switch group after Azithromycin was changed to Doxycycline was 48 h, which was not statistically significantly different from that in the Doxycycline alone group ( Z=-0.571, P=0.849). The medium hospitalization time in the switch group after Azithromycin changed to Doxycycline was 4 d, which was significantly longer than that in the Doxycycline alone group (3 d) ( Z=-2.759, P=0.008). Among 93 cases enrolled in the Azithromycin group, 33 cases (35.5%) converted to unresponsive MPP(UMPP), 23 cases (24.7%) progressed to refractory MPP (RMPP), and 33 cases (35.5%) added steroids.Among 32 cases included in the Doxycycline group, 1 case (3.1%) converted to UMPP, no case developed to RMPP, and 1 case (3.1%) added steroids.The above-mentioned 3 proportions were significantly different between the two groups (all P<0.001). Among 93 cases enrolled in the Azithromycin group, 11 cases (11.8%) progressed to severe MPP (SMPP), and 13 cases (14.0%) developed complications.In 32 cases included in the Doxycycline group, 1 case (3.1%) progressed to SMPP, and 3 cases (9.4%) developed complications.The difference in these 2 proportions was not statistically significant between the two groups ( P=0.294, 0.760). In 77 patients included in the Azithromycin switch to Doxycycline group, there were 4 cases converting to UMPP, 4 cases converting to RMPP and 4 cases adding steroids, which were not statistically significantly different from those in the Doxycycline group (all P=0.540). In the Azithromycin switch to Doxycycline group, there were 3 cases progressing to SMPP, and 7 cases developed complications, which were not statistically significantly different from those in the Doxycycline group (all P=1.000). Conclusions:Doxycycline can improve the fever symptom, shorten illness duration and hospitalization time, and reduce steroid usage and the proportions of UMPP and RMPP in pediatric MPP.Switching to Doxycycline is recommended for MUMPP patients as Doxycycline is effective for the treatment of pediatric MPP and no tetracycline pigmentation teeth now.

Objective:To characterize the minimal inhibitory concentration (MIC) of macrolides against clinical Mycoplasma pneumoniae (MP) isolates and to investigate the significance of 23S rRNA mutations. Methods:Cross-sectional study.A total of 288 clinical MP strains preserved in the laboratory from 2016 to 2021 were taken for macrolide resistance gene testing and the evaluation of in vitro susceptibility to Azithromycin and Erythromycin.MIC 50 and MIC 90 values were calculated separately for macrolide-susceptible and -resistant strains. Results:All 288 MP strains underwent the test of in vitro susceptibility to Azithromycin, while 86 of them were additionally tested for Erythromycin.Among these strains, 22 strains were Azithromycin-sensitive, and 266 strains were Azithromycin-resistant.A2063G mutations were detected in 260 (97.7%) strains, while A2064G mutations were detected in 6 (2.3%) strains.Azithromycin-resistant strains had an MIC 50 of 128.000 μg/mL and an MIC 90 of 512.000 μg/mL, with the MIC ranging between 16.000 and 512.000 μg/mL.Seven strains were sensitive and 79 strains were resistant to Erythromycin.Among Erythromycin-resistant strains, A2063G mutations were detected in 73 (92.4%) strains, while A2064G mutations were detected in 6 (7.6%) strains.Erythromycin-resistant strains had an MIC 50 of 256.000 μg/mL and an MIC 90 of 512.000 μg/mL, with the MIC ranging between 64.000 and 1 024.000 μg/mL. Conclusions:A2063G and A2064G mutations in the 23S rRNA gene of MP are associated with high-level in vitro resistance to Azithromycin and Erythromycin, significantly limiting the clinical effectiveness of these antibiotics.Early resistance gene testing is recommended for suspected MP patients, which can help optimize the treatment, improve prognosis, and prevent resistance spread.