This paper systematically reviews the core concepts and lines of theoretical inheritance of major spleen-stomach theories in traditional Chinese medicine （TCM）， including spleen deficiency theory， spleen-stomach damp-heat theory， and liver-spleen disharmony theory. It is found that these theories have all undergone a developmental trajectory characterized by classical foundation， refinement of therapeutic methods， systematization of pathogenesis， and modern innovation. The evolution of spleen-stomach theory has achieved a shift from a singular focus on tonifying the spleen to regulating dynamic middle-jiao （焦） balance， and from localized spleen-stomach regulation to the circular movement of qi involving all five zang organs. In terms of modern disease-syndrome integrative research， spleen deficiency syndrome is shown to be closely associated with impairment of the gastrointestinal mucosal barrier， metabolic disorders， and gene polymorphisms related to Helicobacter pylori-associated gastric diseases. Spleen-stomach damp-heat syndrome is closely linked to hyperactive energy metabolism， inflammatory cytokines， and abnormal expression of aquaporins. Liver-spleen disharmony syndrome is mainly associated with dysregulation of the brain-gut axis and microbiota-related metabolic disorders. It is proposed that future research on spleen-stomach diseases and syndromes should further elucidate their potential multidimensional differential biological characteristics， thereby promoting the modernization of the TCM discipline of spleen-stomach studies.

Objective: To evaluate the intervention effect of school based salt reduction health education, so as to provide a scientific basis for constructing a more effective and sustainable salt reduction intervention model for children. Methods: According to a randomized controlled trial design, in June 2022, probability proportional to size sampling was used to select 501 second grade students (248 in the control group and 253 in the intervention group) from 10 primary schools in Zhenjiang (intervention group) and 10 primary schools in Yangzhou (control group), Jiangsu Province. An one year school based salt reduction health education intervention was implemented. This included 20 online and 8 offline health education sessions, monitoring of salt consumption in the canteen, and the establishment of a salt reduction environment on campus. The control group received no additional salt reduction interventions. A questionnaire survey and 24 hour urinary sodium test were conducted before and after the intervention. The difference in differences method was used to evaluate the intervention effect. Results: After the intervention, the intervention group showed significant net intervention effects in knowledge aspects, including knowing that primary school students consume less salt than adults ( OR=3.55,95%CI =1.69-7.47), daily salt intake of primary school students ( OR=6.64,95%CI =3.71-11.87), long term high salt intake leading to hypertension ( OR=6.83,95%CI =3.93-11.91), low salt intake not causing hair graying ( OR= 1.66 ,95%CI =1.00-2.75), salt content in food labels ( OR=4.56,95%CI =2.63-7.91), and common high salt foods ( OR=3.39,95%CI =1.87-6.14) (all P <0.05). In terms of attitude, the net intervention effect for having a positive attitude toward using less salt in home cooking was significantly increased ( OR=1.88,95%CI =1.13-3.12, P <0.05). There were no statistically significant net intervention effects for salt reduction related behaviors (all P >0.05). There was no statistically significant difference in the changes of 24 hour urinary sodium between the intervention group and the control group before and after intervention ( P >0.05). Conclusions School based salt reduction health education effectively improves students salt reduction knowledge and attitudes but has a limited effect on behavior change. The home-school collaboration should be strengthened, and the dietary environment should be optimized simultaneously.

OBJECTIVE: To explore the potential role of mRNA m7G modification in the pathogenesis of human adenocarcinoma of esophagogastric junction (AEG). METHODS: Pathological tissue specimens from four AEG patients who underwent surgical treatment at the People's Hospital Affiliated to Jiangsu University between 2018 and 2019 were selected. Tumor tissues and adjacent normal tissues were collected from these patients. RNA was extracted from both tissue types and subjected to m7G methylated RNA immunoprecipitation sequencing (m7G-MeRIP-seq) to analyze the patterns of m7G modification, the characteristics of differential m7G modification sites, the differentially expressed mRNA, and the correlation between m7G modification and mRNA expression levels. Differential m7G-modified genes (MSH6, BRCA1, and SOX9) were further validated using methylated RNA immunoprecipitation quantitative PCR (MeRIP-qPCR), while the expression of METTL1 and WDR4 genes was examined by real-time quantitative PCR (RT-qPCR). This study was approved by the Medical Ethics Committee of the People's Hospital Affiliated to Jiangsu University (Ethics No. 20150083). RESULTS: m7G-MeRIP-seq analysis revealed that m7G modifications in both AEG and adjacent normal tissues were predominantly located in the GC-rich region surrounding the internal start codon of mRNA. Differential m7G modification sites between the two groups were closely associated with cancer-related genes. mRNA library analysis showed that differentially expressed mRNA were predominantly upregulated in AEG tissues and downregulated in adjacent normal tissues. Cross-analysis indicated that genes with hypermethylation tended to exhibit upregulated expression, while genes with hypomethylation were typically downregulated in AEG tissues. MeRIP-qPCR validation confirmed that the mRNA expression of MSH6, BRCA1, and SOX9 were significantly upregulated in AEG tissues compared to adjacent normal tissues (AEG vs. normal, P < 0.05). RT-qPCR results demonstrated that the mRNA expression levels of METTL1 and WDR4 were also upregulated in AEG tissues (AEG vs. normal, P < 0.000 5). CONCLUSION These findings suggest that mRNA m7G modification plays a significant role in the development of AEG. Furthermore, proteins as METTL1 and WDR4 may facilitate AEG progression by regulating mRNA m7G modification. These results provide valuable insights into the molecular mechanisms underlying AEG and may inform future therapeutic strategies for this malignancy.
Humans ; RNA, Messenger/metabolism* ; Adenocarcinoma/pathology* ; Esophagogastric Junction/metabolism* ; Esophageal Neoplasms/metabolism* ; Gene Expression Regulation, Neoplastic ; Female ; Male ; Middle Aged ; DNA Methylation ; Methyltransferases/metabolism* ; Stomach Neoplasms/genetics*

OBJECTIVE: To explore the association between single nucleotide polymorphism (SNP) rs2073618 and rs3102735 of the TNFRSF11B gene and the susceptibility to gastric cancer. METHODS: A case-control study was conducted. A total of 577 patients with primary gastric cancer treated at Zhenjiang First People's Hospital from May 2013 to June 2017 were selected as the case group, and 678 healthy individuals who underwent physical examinations at the same hospital during the same period were enrolled as the control group. Blood samples were collected from both groups, and genomic DNA was extracted. The target gene fragments were amplified using PCR, and genotyping was performed using the Snapshot technique. Statistical analysis was conducted using SPSS v2.0 software. This study was approved by the Medical Ethics Committee of the Zhenjiang First People's Hospital (Ethics No. 20150083). RESULTS: The smoking rate was significantly higher in the case group than in the control group (P = 0.006). The T>C polymorphism at the rs3102735 locus of the TNFRSF11B gene was significantly associated with an increased risk of gastric cancer (CC vs. TT: OR = 2.164, 95%CI = 1.063~4.406, P = 0.030). In contrast, the rs2073618 polymorphism did not show a significant association with gastric cancer susceptibility (P > 0.05). Stratified analysis by age, gender, smoking status, and drinking status revealed no significant association between the rs2073618 polymorphism and gastric cancer susceptibility (P > 0.05). However, the rs3102735 polymorphism showed a significant association with gastric cancer risk in individuals over 62 years of age (CC vs. TT: OR = 5.44, 95%CI = 1.54~19.21, P = 0.003). CONCLUSION The rs3102735 polymorphism of the TNFRSF11B gene may be associated with susceptibility to gastric cancer, particularly in older populations. This polymorphism could serve as a potential indicator for identifying high-risk groups for gastric cancer.
Humans ; Stomach Neoplasms/genetics* ; Polymorphism, Single Nucleotide ; Male ; Female ; Genetic Predisposition to Disease ; Middle Aged ; Case-Control Studies ; Osteoprotegerin/genetics* ; Aged ; Adult ; Genotype

Objective:To compare the clinical efficacy and safety of bronchial artery chemoembolization (BACE) combined with anlotinib (BACE+A) versus BACE alone in patients with stage III-IV non-small cell lung cancer (NSCLC).Methods:A total of 94 patients with advanced NSCLC treated at six interventional centers between November 2020 and November 2021 were retrospectively enrolled. Patients were divided into the BACE+A group ( n=46) and the BACE alone group ( n=48) based on treatment regimen. Baseline and perioperative clinical data were collected and compared between the two groups. Treatment response was evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) at 1, 6, and 12 months after the first BACE procedure. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs) were recorded. Kaplan-Meier survival curves were plotted to compare median OS and PFS between groups. Cox proportional hazards regression analysis was used to identify factors influencing OS and PFS. Results:The Kaplan-Meier analysis showed that the median OS was significantly longer in the BACE+A group (18.8 months, 95% CI 16.3-21.3) than in the BACE group (13.4 months, 95% CI 11.6-15.2) ( P=0.001). The median PFS was also significantly longer in the BACE+A group (9.0 months, 95% CI 7.3-10.7) compared to the BACE group (6.1 months, 95% CI 4.9-7.3) ( P=0.001). At 6 and 12 months post-first BACE, the ORR (43.5%, 40.0%) and DCR (89.1%, 83.3%) were significantly higher in the BACE+A group than in the BACE group (ORR: 20.8%, 14.8%; DCR: 66.7%, 59.3%) (all P<0.05). Multivariate Cox regression identified treatment with BACE+A ( HR=0.42, 95% CI 0.27-0.72, P=0.002), tumor stage ( HR=1.80, 95% CI 1.05-3.07, P=0.031), presence of pre-existing complications requiring intervention ( HR=2.72, 95% CI 1.65-4.50, P<0.001), and >2 BACE procedures ( HR=0.32, 95% CI 0.15-0.68, P=0.003) as independent factors influencing OS. Treatment with BACE+A ( HR=0.49, 95% CI 0.32-0.76, P=0.001), tumor stage ( HR=1.72, 95% CI 1.07-2.77, P=0.025), multi-arterial tumor blood supply ( HR=2.76, 95% CI 1.76-4.31, P<0.001), and>2 BACE procedures ( HR=0.40, 95% CI 0.22-0.71, P=0.002) were independent factors influencing PFS. There was no significant difference in BACE-related adverse events between the two groups (all P>0.05). Hypertension, fatigue, hand-foot syndrome, and anorexia were common anlotinib-specific adverse reactions in the combination group, but no grade 4 or higher adverse reactions were observed. Conclusions:BACE combined with anlotinib demonstrates superior efficacy compared to BACE alone in treating advanced NSCLC, significantly prolonging OS and PFS. The safety profile is manageable, with adverse events remaining within tolerable limits.

Objective Based on the general belief that the tongue characteristics of blood stasis constitution is"purple tongue,tortuous sublingual vessels",this study systematically summarized blood stasis tongue characteristics using artificial intelligence image processing combined with expert evaluation.Methods A physical questionnaire survey was conducted on 1275 college students,and 100 cases were randomly selected from the blood stasis constitution group and the mild constitution group.After collecting the tongue images,Unet,OpenCV,YOLOv5 and YOLOv8 algorithms combined with expert evaluation method were used to extract and analyze the tongue features of the two groups.By comparing the differences of tongue image characteristics between the blood stasis constitution group and the mild constitution group,the tongue characteristics of blood stasis constitution were systematically summarized.Results Compared with the mild constitution group,the proportion of light dark tongue and light purple tongue in the blood stasis constitution group was significantly higher(P＜0.05).The I value,L value and a value of the tongue area 1 in the blood stasis constitution group were significantly larger(P＜0.01,P＜0.05).The S value and a value of area 2 and area 3 were significantly larger(P＜0.05),and the I value,L value,a value and b value of area 5 were significantly smaller(P＜0.01,P＜0.05).Compared with the mild constitution group,the proportion of tooth marks tongue in the blood stasis constitution group was significantly higher(P＜0.01),the proportion of cracked tongue in the blood stasis constitution group was significantly larger(P＜0.05),and the number of tooth marks,crack area,relative height of crack and relative width of crack in the blood stasis constitution group were significantly larger(P＜0.01,P＜0.05).Compared with the mild constitution group,the I value,L value,a value and b value of tongue coating area 1 in the blood stasis constitution group were significantly larger(P＜0.01,P＜0.05),the I value,L value,S value,a value and b value of tongue coating area 2 were significantly larger(P＜0.01,P＜0.05),the I value,S value,a value and b value of tongue coating area 3 were significantly larger(P＜0.01,P＜0.05),the b value of tongue coating area 4 was significantly larger(P＜0.05),the S value,a value and b value of tongue coating area 5 were significantly larger(P＜0.01,P＜0.05).The proportion of thick tongue coating and greasy tongue coating in the blood stasis group was significantly higher than that in the gentleness group(P＜0.05).Compared with the mild constitution group,the proportion of tortuous,thickened and nodular sublingual collaterals in the blood stasis constitution group was significantly larger(P＜0.01,P＜0.05).The a value,I value,S value,b value and relative width of sublingual collaterals in the blood stasis constitution group were significantly larger(P＜0.01,P＜0.05).Conclusion On the basis of the general belief that the characteristics of blood stasis constitution tongue are dark purple tongue and dark purple sublingual collaterals/varicose veins/thickening,blood stasis constitution people also have new tongue characteristics,such as redder tips and edges,more teeth marks and fissures,thicker and greasier coatings,and yellow fur.These findings offer new insights for"to identify the constitution of traditional Chinese medicine and prevent diseases by observing the tongue manifestation".

OBJECTIVE To study the chemical constituents in the root bark of Schisandra sphenanthera and their cytotoxic activ-ities.METHODS The compounds were isolated and purified by silica,Sephadex LH-20 and semi preparative-HPLC and the chem-ical structures were identified by 1 H-NMR,13 C-NMR and MS data analysis.The cytotoxic activities of the compounds were deter-mined by MTT method.RESULTS Twenty lignans were isolated and deduced as:Matairesinol(1),2-Hydroxy-2-(3′,4′-di-hydroxyphenyl)methyl-3-(3″,4″-dimethoxyphenyl)methyl-gamma-butyrolactone(2),(+)-Nortrachelogenin(3),2-Hydroxy-2-(4′-O-β-D-glucopyranosyl-3′-hydroxyphenyl)methyl-3-(3″,4″-dimethoxyphenyl)methyl-γ-butyrolactone(4),Nortracheloside(5),Burselignan(6),(+)-Cycloolivil(7),5-Methoxy-(+)-isolariciresinol(8),(-)-Isolariciresinol 3α-O-β-D-glucopyranoside(9),(+)-9-O-β-D-Glucopyranosyl lyoniresinol(10),(-)-Secoisolariciresinol(11),Licarin A(12),Cedrusin(13),Mataires-inol 4′-O-β-D-glucopyranoside(14),Pregomisin(15),Meso-dihydroguaiaretic acid(16),7S,8R-Erythro-4,9,9′-trihydroxy-3,3′-dimethoxy-8-O-4′-neolignan-7-O-β-D-glucopyranoside(17),Gomisin M2(18),Gomisin M3(19),Pinoresinol(20).Com-pounds 1-3,12,15,16,18 and 19 showed cytotoxic activity against A549,HCT116 and SW620 cell lines with IC50 values ranging from 1.4 to 22.9 μmol·L-1.CONCLUSION Compounds 1-4,6-12,14,17-19 are isolated from the plant for the first time,com-pounds 1-3,12,15,16,18 and 19 exhibit cytotoxic activities.

Trifluridine-tipiracil(TAS-102),as a novel fluorouracil-based chemotherapeutic agent,effectively overcomes fluorouracil resistance in colorectal cancer(CRC)through its unique pharmacological mechanisms,providing a critical treatment option for advanced CRC patients.Probiotics have shown unique value in CRC prevention and adjuvant therapy by regulating intestinal flora homeostasis and modulating host immune response.It is worth noting that the combination of chemotherapeutic drugs and probiotics not only enhances the anti-tumor activity through synergistic effects,but also reduces the adverse effects caused by chemotherapeutic drugs.Based on this,this paper systematically reviews the pharmacological properties of TAS-102 and describes its synergistic effects in combination with other antitumor drugs.It also summarizes the synergistic effect of fluorouracil drugs combined with probiotics to enhance the effectiveness and reduce the toxicity,and discusses the potential value of the combination of TAS-102 and probiotics,which provides a new research direction for optimizing the precision treatment of CRC and a scientific basis for improving the quality of life of patients.

ObjectiveTo investigate the significance of different non-treatment thresholds or upper limits of normal （ULN） of alanine aminotransferase （ALT） in evaluating significant liver pathological injury in patients with chronic hepatitis B virus （HBV） infection， and to provide guidance for clinical diagnosis and treatment. MethodsThis study was conducted among 733 patients with chronic HBV infection who were hospitalized in Ningbo No. 2 Hospital from January 2015 to December 2023 and underwent liver biopsy and histopathological examination， and all patients had a persistent ALT level of ≤40 U/L and positive HBV DNA （>30 IU/mL）. According to the treatment threshold or ULN of ALT， the patients were divided into group 1 with 575 patients （≤35 U/L for male patients， ≤25 U/L for female patients）， group 2 with 430 patients （≤30 U/L for male patients， ≤19 U/L for female patients）， group 3 with 443 patients （≤27 U/L for male patients， ≤24 U/L for female patients）， group 4 with 446 patients （≤25 U/L）， group 5 with 158 patients （>35 U/L for male patients， >25 U/L for female patients）， and group 6 with 145 patients （>30 — ≤35 U/L for male patients， >19 — ≤25 U/L for female patients）. Groups 2， 5， and 6 were compared to analyze the severity of liver pathological injury in patients with different ALT levels and the constituent ratio of patients with significant liver pathological injury， and groups 1， 2， 3， and 4 were compared to investigate the value of different ULN or non-treatment thresholds of ALT in determining liver inflammation grade （G）， liver fibrosis stage （S）， and the treatment indication based on liver pathology. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test or the Tambane’s test was used for further comparison between two groups； the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups and further comparison between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； a Ridit analysis was used for comparison of ranked data. A multivariate Logistic regression analysis （forward stepwise） was performed with whether liver pathology met the treatment indication （≥G2 and/or ≥S2） as the dependent variable and related factors with a significant impact on the dependent variable （P <0.05） as the independent variable. The receiver operating characteristic （ROC） curve was plotted， and the area under the ROC curve （AUC）， as well as sensitivity， specificity， positive predictive value， negative predictive value， positive likelihood ratio， and negative likelihood ratio， was used to assess the diagnostic value of different non-treatment thresholds of ALT. ResultsAmong the 733 patients， 259 （35.33%） had ≥G2 liver inflammation， 211 （28.79%） had ≥S2 liver fibrosis， and 306 （41.75%） had treatment indication （≥G2 and/or ≥S2）. There was a significant difference in liver inflammation grade （G0 — G4） between groups 2， 5， and 6 （χ²=22.869， P <0.001）， and there were also significant differences in the constituent ratios of patients with ≥G2 or ≥G3 liver inflammation between the three groups （χ²=21.742 and 14.921， P<0.001 and P=0.001）. There was a significant difference in liver fibrosis stage （S0 — S4） between groups 2， 5， and 6 （χ²=16.565， P<0.001）， and there were also significant differences in the constituent ratios of patients with ≥S2， ≥S3 or S4 liver fibrosis between the three groups （χ²=13.264， 13.050， and 6.260， P=0.001， 0.001， and 0.044）. There were significant differences between groups 2， 5， and 6 in the constituent ratios of patients with or without treatment indication based on liver pathology （χ²=20.728， P<0.001）. There were significant differences between groups 2， 5， and 6 in the constituent ratio of male patients （χ²=24.836， P<0.05）， age （F=5.710， P<0.05）， ALT （F=473.193， P<0.05）， aspartate aminotransferase （AST） （F=107.774， P<0.05）， ALT/AST ratio （F=40.167， P<0.05）， γ-glutamyl transpeptidase （GGT） （H=15.463， P<0.05）， aspartate aminotransferase-to-platelet ratio index （APRI） （H=63.024， P<0.05）， and LIF-5 （5 indicators for liver inflammation and fibrosis） （H=46.397， P<0.05）. In groups 1 — 4， compared with the patients without treatment indication， the patients with treatment indication had a significantly lower constituent ratio of patients with positive HBeAg， significantly lower levels of platelet count （PLT） and HBV DNA， and significantly higher age， ALT， AST， GGT， APRI， FIB-4， and LIF-5 （all P<0.05）. The Logistic regression analysis showed that age （odds ratio ［OR］=1.044， 95% confidence interval ［CI］： 1.025 — 1.063， P<0.001）， GGT （OR=1.022， 95%CI： 1.007 — 1.038， P=0.003）， and HBV DNA （OR=0.839， 95%CI： 0.765 — 0.919， P<0.001） were influencing factors for treatment indication based on liver pathology in group 1； HBeAg （OR=1.978， 95%CI： 1.269 — 3.082， P=0.003）， age （OR=1.048， 95%CI： 1.025 — 1.071， P<0.001）， GGT （OR=1.016， 95%CI： 1.001 — 1.031， P=0.041）， and PLT （OR=0.995， 95%CI： 0.991 — 1.000， P=0.049） were influencing factors in group 2； age （OR=1.040， 95%CI： 1.014 — 1.066， P=0.002）， ALT （OR=1.047， 95%CI： 1.005 — 1.092， P=0.029）， HBV DNA （OR=0.817， 95%CI： 0.736 — 0.907， P<0.001）， and LIF-5 （OR=7.382， 95%CI： 1.151 — 47.330， P=0.035） were influencing factors in group 3； age （OR=1.054， 95%CI： 1.031 — 1.077， P<0.001）， ALT （OR=1.061， 95%CI： 1.016 — 1.107， P=0.008）， and HBV DNA （OR=0.825， 95%CI： 0.743 — 0.917， P<0.001） were influencing factors in group 4. The diagnostic performance for identifying ≥G2 liver inflammation， ≥S2 liver fibrosis， and treatment indication in groups 1 — 4 had an AUC of >0.7； group 1 showed the lowest sensitivity （28.76%） and the highest specificity， positive predictive value， positive likelihood ratio， and negative likelihood ratio in judging treatment indication； group 2 had the highest sensitivity and negative predictive value and the lowest negative likelihood ratio； groups 3 and 4 had similar diagnostic indicators. ConclusionIn patients with chronic HBV infection and a persistently low ALT level， the severity of liver histopathological injury and the constituent ratio of significant liver histopathological injury decrease with the reduction in ALT level. A higher non-treatment threshold or ULN of ALT can help to identify the patients requiring treatment （with a higher specificity）， while a lower non-treatment threshold or ULN of ALT can help to identify the patients who do not require treatment （with a higher sensitivity）.

Objective:To analyze the genetic characteristics of clinical manifestations in children with KBG syndrome due to microdeletions.Methods:A retrospective case summary was conducted. Four children diagnosed with KBG syndrome due to 16q24.3 microdeletion at Children′s Hospital of Zhengzhou University from July 2021 to April 2024 were enrolled.Their clinical manifestations, biochemical parameters, imaging data, whole-exome sequencing results, treatments and follow-up outcomes were reviewed.Results:The cohort included two males and two females (diagnosed at 81, 18, 26, and 56 months of age, respectively), from four unrelated families. All patients exhibited peculiar facial features (Cupid′s bowed-shaped lips, prominent ears, thick eyebrows), skeletal abnormalities (brachydactyly, abnormal ribs, short stature, etc.), ocular anomalies (astigmatism, strabismus, amblyopia, etc.), intrauterine growth restriction, and developmental retardation. Case 2, 3, 4 had cranial imaging abnormalities, including thin anterior pituitary lobes with pineal cyst, left ventricular cyst, and abnormal pituitary stalk or lateral ventricles with sinusitis, respectively. Two children had intellectual disability, two had congenital heart disease, and one had delayed bone age and hair abnormalities. Whole exome genomic sequencing confirmed 16q24.3 microdeletions encompassing ANKRD11 gene in all four cases. Two children treated with recombinant human growth hormone achieved height increments of 1.5 s and 0.4 s, respectively. Conclusions:Typical features of 16q24.3 microdeletion-induced KBG syndrome include peculiar facial features, macrodontia, skeletal anomalies, neurological abnormalities, and ocular defects. Genetic testing is essential for definitive diagnosis. The treatment of KBG syndrome requires early diagnosis and multidisciplinary collaboration to implement individualized treatment for multisystem symptoms.