ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

ObjectiveTo characterize the quality differences among different germplasm and introduced varieties of Bupleurum scorzonerifolium roots（BSR）， and explore the underlying molecular mechanisms， providing a basis for high-quality production and quality control. MethodsWild BSR from Yulin（YLW） served as the quality reference， we conducted comparative analysis among YLW， locally domesticated wild germplasm in Yulin（YLC3）， Daqing germplasm introduced and cultivated in Yulin（YLDQC3）， and locally cultivated germplasm in Daqing（DQC3）. A combination of traditional pharmacognostic methods and modern multi-omics analyses was employed， including macroscopic traits（appearance， odor）， microscopic features（proportions of cork， phloem， xylem）， cell wall component contents（hemicellulose， cellulose， lignin）， carbohydrate contents（starch， water-soluble polysaccharides）， marker compound contents（ethanol-soluble extracts， total saponins， liposoluble extracts， and saikosaponins A， B₂， C， D）， metabolomics， and transcriptomics， in order to systematically characterize quality differences and investigate molecular mechanisms among these samples. ResultsMacroscopically， Yulin-produced BSR（YLW， YLC3， YLDQC3） exhibited significantly greater weight， length， and upper and middle diameters than Daqing-produced BSR（DQC3）. Odor-wise， YLW and YLC3 had a a fragrance taste， YLDQC3 had a rancid oil odor， and DQC3 had a sweet and fragrant taste. Microscopically， Yulin germplasm（YLW， YLC3） and Daqing germplasm（YLDQC3， DQC3） shared similar structural features， respectively. However， Yulin germplasm showed significantly higher proportions of cork and phloem， as well as stronger xylem vessel staining intensity compared to Daqing germplasm. Regarding various component contents， Yulin germplasm contained significantly higher levels of ethanol-soluble extracts， total saponins， and saikosaponins A， B₂， C， D， while Daqing germplasm had significantly higher levels of hemicellulose， starch， and liposoluble extracts. After introduction to Yulin， the Daqing germplasm（YLDQC3） showed increased starch， water-soluble polysaccharides and liposoluble extracts contents， decreased cell wall component content， but no significant difference in other component contents. Metabolomics revealed that saponins and terpenes accumulated significantly in Yulin germplasm， while alcohols and aldehydes accumulated predominantly in Daqing germplasm. Transcriptomics indicated similar gene expression patterns within the same germplasm but specificity between different germplasms. Integrative metabolomic-transcriptomic analysis identified 145 potential key genes associated with the saikosaponin biosynthesis pathway， including one acetyl-coenzyme A（CoA） acetyltransferase gene（ACAT）， one 3-hydroxy-3-methylglutaryl-coenzyme A synthase gene（HMGS）， two hydroxymethylglutaryl-CoA（HMG-CoA） reductase genes（HMG）， one phosphomevalonate kinase gene（PMK）， one 1-deoxy-D-xylose-5-phosphate synthase gene（CLA）， one hydroxymethylbuten-1-aldol synthase gene（HDR）， two farnesyl pyrophosphate synthase genes（FPPS）， one squalene synthase gene（SQS）， one β-amyrin synthase gene（BAS）， 102 cytochrome P450（CYP450） gene family members， and 32 uridine diphosphate-glucuronosyltransferase（UGT） gene family members. ConclusionAmong the three cultivated types， YLC3 most closely resembles YLW in appearance， microscopic features， contents of major bioactive constituents， metabolomic and transcriptomic profiles. Yulin germplasm exhibits superior saponin synthesis capability compared to Daqing germplasm， and Yulin region is more suitable for the growth of B. scorzonerifolium. Based on these findings， it is recommended that artificial cultivation in northern Shaanxi and similar regions utilize the local Yulin germplasm source cultivated for at least three years.

As one of the most serious global public health concerns, malaria is highly prevalent in Africa and has severely hindered local social and economic developments. Anti-malaria aid underpinned by artemisinin has emerged as an iconic practice of China’s engagement in global health governance in the context of evolving global health governance, which continuously exerts its distinctive impact. The Artemisinin Anti-Malaria Team at Guangzhou University of Chinese Medicine is dedicated to safeguarding global health, committed to transforming artemisinin, a precious gift of traditional Chinese medicine to the world, into tangible impetus for malaria elimination. At the convergence of the China-Africa Year of People-to-People Exchanges and World Malaria Day, a review of China-Africa health cooperation is of specific significance. Based on the practices of international anti-malaria projects led by the Artemisinin Anti-Malaria Team at Guangzhou University of Chinese Medicine, this paper systematically summarizes the theoretical innovations, practical values and humanistic core of China’s anti-malaria approaches, and analyzes the core challenges in global malaria elimination programmes in the new era.

Objective:To compare the incidence of instrumentation-related complications and health-related quality of life following pelvic fixation using iliac screws (IS) or second sacral alar-iliac (S 2AI) screws in adult spinal deformity (ASD). Methods:A retrospective cohort study was conducted on 108 ASD patients who underwent posterior corrective fusion and fixation extending to the pelvis at Nanjing Drum Tower Hospital between September 2010 and April 2021. According to the type of pelvic fixation, patients were divided into an IS group ( n=34; 12 males, 22 females; mean age 53.7±11.1 years, range 28-73 years) and an S 2AI group ( n=74; 23 males, 51 females; mean age 52.8±8.6 years, range 27-72 years). Pre- and post- operative standing anteroposterior and lateral radiographs were evaluated for Cobb angle, coronal balance distance (CBD), thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). At 2 years postoperatively, health-related quality of life were assessed using the Scoliosis Research Society-22 questionnaire (SRS-22), Oswestry disability index (ODI), and visual analogue scale (VAS) for pain. Instrumentation failure related to pelvic fixation during follow-up was recorded. Results:All patients completed follow-up. Mean follow-up duration was 28.5±3.6 months (range 24-37 months) in the IS group and 28.1±4.3 months (range 24-43 months) in the S 2AI group. Postoperatively, both groups showed significant improvement in Cobb angle, CBD, TK, LL, SVA, PT, and SS compared to baseline ( P<0.05), whereas PI remained unchanged ( t=0.664, P=0.509; t=1.227, P=0.222). Preoperative PT was greater in the IS group than in the S 2AI group (33.6°±8.7° vs. 29.3°±9.6°, t=2.228, P=0.028). No significant intergroup differences were observed in any other pre- or post- operative radiographic parameters ( P>0.05). Pelvic fixation failure occurred in 31 patients (28.7%, 31/108). Patients with fixation failure had a longer fusion segment extension than those without failure (12.0±2.8 vs. 10.8±2.4 segments; t=2.256, P=0.026). In the IS group, complications comprised 3 cases of screw loosening (8.8%), 2 of screw breakage (5.9%), and 4 of rod fracture within the pelvic region (11.8%), including 1 case with concurrent screw and rod failure. In the S 2AI group, there were 21 cases of screw loosening (28.4%) and 2 of screw breakage (2.7%). Screw loosening was less frequent in the IS group than in the S 2AI group (χ 2=5.154, P=0.023), whereas pelvic rod fracture was more common in the IS group (χ 2=9.041, P=0.003). Screw breakage rates did not differ significantly ( P>0.05). Mean VAS, ODI, and SRS-22 scores in the IS group were 3.2±2.4, 24.9%±18.8%, and 3.2±0.8, respectively; corresponding to 2.5±1.8, 18.9%±10.9%, and 3.3±0.6 in the S 2AI group. ODI was significantly higher in the IS group ( t=2.062, P=0.042), whereas VAS and SRS-22 were comparable ( P>0.05). Among S 2AI patients, VAS and ODI scores did not differ significantly between those with and without screw loosening ( P>0.05). Conclusions:The post-operative incidence of pelvic fixation failure following ASD surgery reached 28.7%. The predominant failure mode with S 2AI was screw loosening, whereas IS was more frequently complicated by rod fracture. Early postoperative health-related quality of life was superior with S 2AI screws compared with iliac screws.

Objective:To investigate the risk factors for postoperative coronal imbalance in patients with type A degenerative scoliosis and to refine the Qiu classification by reclassifying type A patients.Methods:A retrospective analysis was conducted on the clinical data of patients with type A degenerative scoliosis classified by the Qiu classification who underwent corrective surgery at our hospital from January 2017 to April 2022. A total of 69 patients were enrolled in the study, including 3 males and 66 females, with an age of 60.6±6.8 years (range: 47-71 years). Based on the preoperative CBD, type A patients were further divided into three subtypes: Aa with CBD≤1 cm, Ab with CBD>1 cm with C 7 plumb line deviation toward the concave side, and Ac with CBD>1 cm with C 7 plumb line deviation toward the convex side. The incidence of coronal imbalance was compared among subtypes. During follow-up, patients with CBD ≤3 cm were classified as balanced, and those with CBD>3 cm as imbalanced. Radiographic parameters including coronal Cobb's angle (CA), CBD, L 4 tilt angle, L 5 tilt angle, thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and sagittal vertical axis (SVA) were measured in the standing radiographs preoperatively, 2-weeks postoperatively and 2-years follow-up. Differences in radiographic parameters between balanced and imbalanced groups were compared, and binary logistic regression was used to identify risk factors for postoperative coronal imbalance. Results:In the imbalanced Group (22 patients), there were 6 patients of type Aa (27%), 5 patients of type Ab (23%), and 11 patients of type Ac (50%), and in the balanced Group (47 patients), there were 20 patients of type Aa (43%), 18 patients of type Ab (38%), and 9 patients of type Ae (19%). The difference in subtype distribution between the two groups was significant (χ 2=6.939, P=0.029). The CBD in the imbalanced group was significantly larger than in the balanced group at the 2-years follow-up (4.18±0.86 cm vs. 1.31±0.78 cm, t=-13.813, P<0.001). The preoperative L 4 tilt angle was significantly larger in the imbalanced group compared to the balanced group (23.59°±6.86° vs. 17.64°±8.34°, t=-2.914, P=0.005). And the postoperative and 2-years follow-up L 4 tilt angles were also significantly larger than the balanced group (18.6°±5.5° vs. 11.5°±5.7°, t=-4.904, P<0.001; 18.0°±5.6° vs. 11.1°±5.7°, t=-4.691, P<0.001). Regression analysis identified the Ac type [ OR=3.937, 95% CI(1.07, 14.55), P=0.040] and excessive postoperative L 4 tilt angle [ OR=1.288, 95% CI(1.09, 1.52), P=0.003] as risk factors for postoperative coronal imbalance in type A patients. Conclusions:In the A-type of Qiu classification, patients with preoperative CBD>1 cm and trunk tilting towards the convex side (Ac type), as well as those with a large L 4 tilt angle after surgery, are more likely to experience coronal plane imbalance after surgery.

Objective:To investigate the difference of Roussouly ideal classification in predicting postoperative proximal junctional kyphosis (PJK) between adult degenerative spinal deformity patients with and without pelvic fixation and the potential reasons.Methods:From January 2017 to January 2020, a total of 95 patients (4 males, 91 females; with an average age of 62.03±6.30 years) with degenerative spinal deformities were retrospectively analyzed. There were 35 patients in the non-pelvic group (1 male, 34 females) and 60 patients in the pelvic group (3 males, 57 females). The radiographic parameters included coronal Cobb's angle (CA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), T1 pelvic angle (TPA), and proximal junctional angle (PJA) were measured in the standing radiographs preoperatively, postoperatively at 2 weeks, and 2-year follow-up. Changes in PT and SS were calculated for patients at 2 weeks and the 2-year follow-up. Based on the revised Roussouly classification, 95 patients were classified into different types preoperatively, postoperatively at 2 weeks, and during the 2-year follow-up. Changes in the classification of patients were documented postoperatively at 2 weeks. Roussouly types were determined using preoperative pelvic parameters, and a match was defined when the 2-week postoperative classification aligned with the ideal type. The occurrence of PJK and the relationship with classification matching were recorded in the group. Independent t-tests were used for intergroup comparisons of radiographic parameters, and chi-square tests were employed to assess classification changes and predictive accuracy of the Roussouly classification. Results:Preoperative PT, TPA and SVA in non-pelvic group were significantly smaller than those in pelvic group, and preoperative SS and LL larger than those in pelvic group ( P<0.05). The changes of PT and SS in non-pelvic group were significantly lower than those in pelvic group 2 weeks after surgery ( P<0.05). The proportion of classification changes in the pelvic group was significantly higher than that in the non-pelvic group (60% vs. 34%, χ 2=5.847, P=0.016). Among the 95 patients, a total of 29 experienced PJK during the follow-up, with 3 cases progressing to PJF. The incidence of PJK in mismatched patients was 37% with no significant difference compared with matched patients (19%) (χ 2=3.357, P=0.067). In the sacral spine group of 60 patients, 22 experienced PJK, with 3 cases progressing to PJF. Among them, 19 patients with PJK had a classification mismatch with the ideal classification at 2 weeks postoperatively. The PJK incidence was significantly higher in mismatched patients (45%) compared to matched patients (17%) (χ 2=4.429, P=0.035). In the non-pelvic group, 7 patients developed PJK, with 3 mismatched cases. The PJK incidence in mismatched vs. matched patients was 18% vs. 22%, showing no significant difference (χ 2=0.114, P=0.735). Conclusions:For the patients with degenerative spinal deformity, pelvic fixation leads to a more complete restoration of the ideal Roussouly classification. Restoration of the Roussouly type in patients with pelvic fixation is a reliable predictor of postoperative PJK. However, in patients without pelvic fixation, the alignment with the ideal Roussouly classification does not significantly correlate with PJK development.

A 66-year-old female kidney transplant recipient presented to Shanghai Jiao Tong University Affiliated Renji Hospital on May 24th, 2024 due to recurring intermittent diarrhea for over 16 years. The parasites were found through examination of small intestinal fluid. Small intestinal fluid mNGS combined with blood mNGS confirmed Cyclospora cayetanensis infection. The cause of the diarrhea was clarified. Oral compound sulfamethoxazole was used as treatment, and the patient's diarrhea symptoms improved, and no Cyclospora cayetanensis was found in the small intestinal fluid smear three consecutive times. Parasitic infection factors should be excluded in patients with low immune function and chronic diarrhea. Non-invasive small intestinal fluid smear combined with mNGS detection provides a new method to clarify the cause of chronic diarrhea.

Objective To investigate the therapeutic effects of upper limb rehabilitation robot training combined with intermittent theta burst stimulation(iTBS)on upper limb motor and neurological function in stroke patients with hemiplegia.Methods This study retrospectively consecutive enrolled 46 stroke hemiparetic patients from the Department of Rehabilitation Medicine,Nanjing Pukou People's Hospital.The patients were randomly assigned to a control group and an experimental group(23patients in each)using a random number table.Baseline data,including sex,age,disease duration,side of hemiplegia,and stroke type,were collected from patients enrolled.All patients received conventional treatment.The control group received upper limb rehabilitation robot training combined with iTBS sham stimulation(coil placed perpendicular to the skull),while the experimental group received upper limb rehabilitation robot training combined with iTBS real stimulation(coil placed parallel to the skull).Both groups underwent treatment for 3 weeks.Upper limb motor function was assessed using the Fugl-Meyer upper extremity(FMA-UE)scale and Wolf motor function test(WMFT);while neurological function was evaluated using the motor-evoked potentials(MEP)latency,amplitude,and central motor conduction time(CMCT)of the affected thumb abductor muscle.Activities of daily living were assessed using the modified Barthel index(MBI).Results(1)No significant differences in baseline data were found between the two groups(all P＞0.05).(2)Before treatment,the FMA-UE and WMFT scores in the experimental group were 27.48±7.87 and 28.22±3.87,respectively;and in the control group were 26.35±4.78 and 28.35±3.33,respectively;there were no significant differences in both FMA-UE and WMFT scores between the two groups(all P＞0.05).After 3weeks of treatment,the FMA-UE and WMFT scores in the experimental group were 40.35±8.96 and 37.74±4.11,respectively;and in the control group were 32.78±4.50 and 32.57±4.11,respectively;there were significant interaction effects of time and group(Ftime×group values of 19.613 and 31.522,both P＜0.01),main effects of group(Fgroup values of 5.401 and 5.897,both P＜0.05),and main effects of time(Ftime values of 176.516 and 211.478,both P＜0.01).(3)Before treatment,the MEP latency,amplitude,and CMCT in the experimental group were(24.39±3.56)ms,(137.77±42.67)μV,and(10.62±2.76)ms,respectively;and in the control group were(24.64±2.77)ms,(136.74±48.77)μV,and(10.73±1.84)ms,respectively,there were no significant differences between the two groups(all P＞0.05).After 3weeks of treatment,the MEP latency,amplitude,and CMCT in the experimental group were(20.39±1.83)ms,(239.91±43.70)μV,and(6.58±1.23)ms,respectively,and in the control group were(22.53±3.53)ms,(198.54±50.37)μV,and(9.19±1.60)ms,respectively,there were significant interaction effects of time and group(Ftime×group values of 7.270,15.554,and 20.110,all P＜0.05)and main effects of time(Ftime values of 76.540,256.706,and 100.629,all P＜0.01),the main effect of group for CMCT was significant(Fgroup=7.406,P＜0.01),but there were no significant difference in the main effect of group on MEP latency,amplitude between two groups(Fgroup values of 2.145,2.778,both P＞0.05).(4)Before treatment,the MBI score in the experimental group was 42.83±7.36,and in the control group was 43.91±6.56,with no significant difference between two groups(P＞0.05).After 3 weeks of treatments,the MBI score in the experimental group was 67.83±12.69,and in the control group was 54.13±5.57,there were significant interaction effects of time and group(Ftime×group=39.862,P＜0.01),main effects of group(Fgroup=8.083,P=0.007),and main effects of time(Ftime=226.241,P＜0.01).Conclusions Upper limb rehabilitation robot training combined with iTBS can improve upper limb motor function and neurological function and enhance the daily living activity ability of stroke patients.Real iTBS combined with robot training has a more significant effect than sham iTBS.

Objective:To investigate the effect of preoperative continuous fascia iliaca compartment block (FICB) on perioperative opioids dosage and quality of postoperative recovery in elderly patients with frail.Methods:A prospective study method was used. Sixty elderly frail patients underwent selective unilateral femoral head replacement surgery from November 2022 to October 2024 in Sihui People′s Hospital were selected. The patients were divided into control group and FICB group by random digits table method with 30 cases each. The patients in control group did not receive continuous FICB before surgery, and the patients in FICB group received continuous FICB 1 d before surgery. The perioperative use of opioids and analgesic effect, operative time, intraoperative blood loss, postoperative hospital stay, quality of recovery-40 (QoR-40) score at discharge and postoperative complications were compared between the two groups.Results:A total of 57 patients completed the study, with 29 cases in the FICB group and 28 cases in the control group. There were no statistical differences in operative time, intraoperative blood loss and postoperative hospital stay between the two groups ( P>0.05). The sufentanil dosage of patient-controlled analgesia (PCA), perioperative nalbuphine dosage, frequency of perioperative visual analog score (VAS)>4 scores, rate of preoperative rescue analgesia, rate of postoperative rescue analgesia and pressing frequency of PCA in FICB group were significantly lower than those in control group: (94.1 ± 5.4) μg vs. (102.1 ± 6.1) μg, 0 (0, 0) mg vs. 10.0 (0, 20.0) mg, 3.0 (2.0, 5.0) times vs. 5.0 (4.0, 6.0) times, 3.4% (1/29) vs. 32.1% (9/28), 13.8% (4/29) vs. 39.3% (11/28) and 2.0 (1.0, 3.0) times vs. 4.0 (3.0, 5.0) times, and there were statistical differences ( P<0.01 or <0.05). The total QoR-40 score and physical comfort, pain scores in FICB group were significantly higher than those in control group: 156(153, 161) scores vs. 153 (148, 159) scores, 47 (45, 50) scores vs. 45 (43, 47) scores and 30 (29, 31) scores vs. 28 (25, 30) scores, and there were statistical differences ( P<0.05 or <0.01); there were no statistical differences in emotional state, physical independence and psychological support scores between the two groups ( P>0.05). The incidences of dizziness and nausea vomiting in FICB group were significantly lower than those in control group: 13.8% (4/29) vs. 42.9% (12/28) and 10.3% (3/29) vs. 35.7% (10/28), and there were statistical differences ( P<0.05); there were no statistical difference in the incidences of delirium, pulmonary infection and deep vein thrombosis in the lower extremities between the two groups ( P>0.05). Conclusions:Preoperative continuous FICB can reduce perioperative opioids dosage in elderly patients with frail, and improve early stage postoperative recovery quality.

A 66-year-old female kidney transplant recipient presented to Shanghai Jiao Tong University Affiliated Renji Hospital on May 24th, 2024 due to recurring intermittent diarrhea for over 16 years. The parasites were found through examination of small intestinal fluid. Small intestinal fluid mNGS combined with blood mNGS confirmed Cyclospora cayetanensis infection. The cause of the diarrhea was clarified. Oral compound sulfamethoxazole was used as treatment, and the patient's diarrhea symptoms improved, and no Cyclospora cayetanensis was found in the small intestinal fluid smear three consecutive times. Parasitic infection factors should be excluded in patients with low immune function and chronic diarrhea. Non-invasive small intestinal fluid smear combined with mNGS detection provides a new method to clarify the cause of chronic diarrhea.