The Efficacy and Safety of Shashen-Maidong Decoction Combined with Western Medicine in the Treatment of Omicron Infected Individuals Over 85 Years Old: A Retrospective Study.

Background: During the Omicron variant outbreak of COVID-19 (2022-2023), Chinese healthcare institutions combined traditional Chinese medicine (TCM) with Western medical practices to treat COVID-19 patients, especially the elderly. The efficacy and safety of this approach, especially for individuals aged over 85, need further investigation. Methods: In this retrospective study, a cohort of 62 patients aged over 85 years, diagnosed with COVID-19 infection, was examined. Among them, 34 patients were administered Shashen-Maidong decoction in conjunction with Western medicine (SMD+WM group), while the remaining 28 patients received only Western medicine (WM group). Comparative analysis was conducted between the two groups, encompassing parameters such as the duration for the nucleic acid test to turn negative, length of intensive care unit (ICU) stay, mortality rate, utilization of high-flow nasal cannula oxygen (HFNC), occurrence of endo-tracheal intubation, frequency of recurrent respiratory infections within three months, and various laboratory indicators. Results: There were no significant differences observed between the two groups in terms of the duration for the nucleic acid test to turn negative, the length of ICU stay, mortality rate, utilization of HFNC, performance of endo-tracheal intubation, or the frequency of recurrent respiratory infections within three months (P > 0.05). However, in comparison to the WM group, the SMD+WM group exhibited notably lower growth rates in white blood cell (WBC) and neutrophil (NEUT) values. Additionally, the SMD+WM group demonstrated superior improvement in cardiac troponin I (cTnI) and B-type natriuretic peptide (BNP) values. Conclusion: In contrast to the administration of Western medicine alone, the combined use of Shashen-Maidong decoction with Western medicine significantly suppresses the increase in WBC count, particularly in NEUT levels, in elderly patients diagnosed with COVID-19. Moreover, this combined treatment exhibits a protective effect on cardiac function and demonstrates a relatively safe profile.

Comparison of the safety and efficacy of low fluence Q-switched 1064-nm and conventional Q-Switched 755-nm lasers in the treatment of café-au-lait macules: A prospective self-controlled trial.

BACKGROUND: Conventional high fluence Q-switched (HFQS) Alexandrite 755-nm are widely used in clinical café-au-lait macules (CALMs) treatment. There have been recent concerns regarding the efficacy and safety of low fluence Q-switched (LFQS) Nd: YAG 1064-nm lasers. OBJECTIVE: To evaluate the efficacy and safety of the conventional HFQS and LFQS laser in the treatment of CALMs. METHODS: Within 3 months, 20 patients underwent prospective self-controlled split-lesion treatments with HFQS once or twice depending on the recovery rate, and with LFQS six times biweekly. Then the more effective laser was selected for continued treatments. Efficacy outcomes were evaluated by a visual analog scale (VAS) biweekly during the comparative trail. Recovery process, side effects and recurrence were recorded during the trial and follow-up visit. Patient and physician preferences for laser selection were also recorded. RESULTS: The average VAS scores of areas treated with HFQS and LFQS were 2.92 ± 0.86 and 2.93 ± 1.13, respectively (p > 0.05). The most significant efficacy change of LFQS was after the fourth laser treatment (VAS score: 1.82-2.37, p < 0.001). 11 lesions treated with LFQS and 7 with HFQS achieved an optimal treatment response (3.67 ≤ VAS ≤ 4). Three patients relapsed on one side (one on LFQS, two on HFQS) and five on both sides. Adverse effects included temporary hypopigmentation, hyperpigmentation, uneven pigmentation, and mottled hypopigmentation. Doctors thought 80% of patients were suitable for LFQS. 70% of patients preferred LFQS posttreatment. CONCLUSIONS: The efficacy difference between the LFQS 1064-nm laser and HFQS 755-nm laser in treating CALMs in a 3-month comparative trial was statistically insignificant. LFQS is preferred by doctors and patients and is likely to help more patients achieve treatment efficacy than the HFQS within a short time, with fewer temporary adverse reactions, and a more even pigmentation. But it can cause mottled hypopigmentation. The LFQS had obvious lesion clearance after the fourth treatment.

Intense Pulsed Light Therapy Improves Acne-Induced Post-inflammatory Erythema and Hyperpigmentation: A Retrospective Study in Chinese Patients.

INTRODUCTION: Post-inflammatory erythema (PIE) and post-inflammatory hyperpigmentation (PIH) are the most common acne-related sequelae with no effective treatments. By combining different cut-off filters, intense pulsed light (IPL) therapy can effectively treat these conditions with few side effects. While the safety and effectiveness of IPL for treating post-burn hyperpigmentation is well known, there is little evidence for its benefits for acne-related PIH. In this article, we evaluate the efficacy and safety of IPL for the treatment of acne-related PIE and PIH. METHODS: This retrospective study evaluated 60 patients with more than 6 months of PIE and PIH treated by the same IPL device and similar protocols. The treatment included three to seven sessions at 4-6-week intervals, and three cut-off filters (640 nm, 590 nm and 560 nm) were used sequentially in each session. Using the Global Aesthetic Improvement Scale (GAIS), Cardiff Acne Disability Index (CADI), and Erythema Assessment Scale (EAS), patients were evaluated on the basis of their facial photographs. The facial brown spots and red areas were visualised and analysed using the VISIA-CR system. Six months after the last treatment, the patients were assessed for acne relapse or any side effects.Please check and confirm that the authors and their respective affiliations have been correctly processed and amend if necessary.Checked and confirmed. No further corrections. RESULTS: On the basis of the GAIS, 49 of 60 patients (81.7%) showed complete or partial clearance of erythema and hyperpigmentation. The CADI and EAS scores showed significant improvement (p < 0.01) after IPL treatment compared with pre-treatment. A significant reduction (p < 0.01) in the facial brown spots and red areas was seen after IPL treatment. While no long-term side effects were reported, seven patients (11.7%) experienced acne relapse at follow-up. CONCLUSION: IPL is an effective and safe treatment for acne-related PIE and PIH.

Imaging and Pathological Characteristics of Port-Wine Stain Patients with Tissue Hypertrophy Before Laser Therapy: Retrospective Data.

Background: Port-wine stain (PWS) patients may simultaneously have accompanied soft tissue hypertrophy. The outcome of laser therapy can be poor. Objective: To study the imaging and histopathological characteristics of PWS patients with facial overgrowth. Materials and methods: We retrospectively assessed the effect of therapy on a subset of PWS patients with facial overgrowth. The degree of hypertrophy and the density of enhanced signals on T1-weighted magnetic resonance imaging (MRI) were independently graded by two radiologists using a quartile scale. Biopsies/resection of tissue deep to the facial muscle was reviewed and compared with flat PWS. Results: Thirty-two PWS patients with facial hypertrophy and 15 patients with flat PWS were included. MRI revealed a statistically significant correlation between the degree of hypertrophy and the density of enhanced signals (3.02 ± 0.92 vs. 2.47 ± 0.69; p < 0.01). Histological features of a subset of patients showed that vascular malformations existed in the dermis and also in the subcutaneous fat and muscle with much larger vessel diameters (fat, 0.048 vs. 0.020; muscle, 0.035 vs. 0.017) and thicker vessel walls (fat, 0.014 vs. 0.006; muscle, 0.010 vs. 0.006) (both p < 0.05). Conclusions: The imaging and pathological findings indicate that capillary malformation in subcutaneous tissue might be a major cause of poor therapeutic effect of laser therapy for PWS. Clinical trial registration no.: ChiCTR1800014278.

Combination Therapy of Pulsed Dye Laser With Intense Pulsed Light in Port-Wine Stain Treatment: A Prospective Side-by-Side Comparison.

BACKGROUND: Pulsed dye laser (PDL) treatment currently represents the mainstream choice for port-wine stain (PWS) treatment in accordance with selective photothermolysis. However, most PWS lesions cannot be removed despite several treatments. Intense pulsed light (IPL) is reportedly an effective alternative to PDL for PWS treatment. No studies have thus far been reported on the combination therapy of PDL with IPL in PWS treatment. OBJECTIVE: This study evaluated the efficacy and safety of PDL with IPL for PWS treatment. METHODS: A total of 33 PWS lesions underwent 3 treatment sessions. Each PWS was divided into IPL + PDL, PDL, and untreated sites. Therapeutic outcomes were evaluated by visual assessment and chromametric assessment 3 months after the final treatment. RESULTS: The overall average blanching rates were 36.2% and 32.6% at the sites treated with IPL + PDL and PDL, respectively (p > .05). No permanent side effects were reported. CONCLUSION: In this laser setting, although IPL + PDL is a safe and effective PWS treatment, no significant improvement in the efficacy was observed using IPL + PDL in contrast to PDL alone.

Intense pulsed light treatment for Becker's nevus.

BACKGROUND: Becker's Nevus (BN) is a benign hamartoma with an esthetically troublesome condition secondary to hyperpigmentation and hypertrichosis. Many treatment modalities have been utilized with variable outcomes. OBJECTIVES: To evaluate the efficacy and safety of intense pulsed light (IPL) in the treatment of BN. PATIENTS AND METHODS: IPL was used at filter of 590 nm, fluence of 18-22 J/cm2, double-pulse mode (pulse width of 3-10 ms, pulse delay of 20-30 ms) at 3-month intervals. Final evaluations were performed by physician global assessment and patient satisfaction. Side effects were monitored at each treatment session and follow-up visit. RESULTS: Twenty-four patients (9 females, 15 males) with BN (16 hypertrichotic, 8 atrichotic) completed the study. The mean number of treatment sessions was 5 ± 2.17. The improvement in atrichotic BN group (4.87 ± 0.35) was significantly greater than that observed in hypertrichotic BN group (3.63 ± 0.89) (p = .001). Hair density simultaneously decreased with treatment in hypertrichotic BN. The mean satisfaction score was 5.75 ± 2.05 and 8 ± 0.93 in hypertrichotic and atrichotic BN groups respectively (p = .002). No repigmentation was noted during the follow-up period. No permanent side effects were observed. CONCLUSIONS: IPL is an effective and well-tolerated treatment option for patients with hypertrichotic and atrichotic BN.

Comparative Effectiveness of 755-nm Picosecond Laser, 755- and 532-nm Nanosecond Lasers for Treatment of Café-au-Lait Macules (CALMs): A Randomized, Split-Lesion Clinical Trial.

BACKGROUND AND OBJECTIVES: Many types of lasers have been used to treat café-au-lait macules (CALMs) since the introduction of the selective photothermolysis theory. However, the efficacy and safety of picosecond lasers, compared with those of nanosecond lasers, have not been researched. To compare the efficacy and safety of 755 nm picosecond laser (PS-755 nm), Q-switched (QS) Alexandrite 755 nm nanosecond laser (QS-755 nm), and QS Nd:YAG 532 nm nanosecond laser (QS-532 nm) for treating CALMs. STUDY DESIGN/MATERIALS AND METHODS: Forty-one patients received several treatments at 3-month intervals. Lesions were divided into two or three approximately equal parts, which were randomly treated with PS-755 nm, QS-755 nm, and QS-532 nm. The safety and efficacy of three lasers were determined based on blinded visual assessments and self-reports of patients three months after the comparative trial. RESULTS: Visual assessment 3 months after the comparative trial revealed that there was no statistically significant difference among the sites treated by QS-755 nm (2.84 ± 1.11), QS-532 nm (2.63 ± 1.06), and PS-755 nm (2.74 ± 1.05) lasers. Five (26.32%) of 19 patients showed lesion recurrence. Adverse effects included acneiform miliaris, hypopigmentation, and hyperpigmentation, which were resolved within 12 months. Five (26.32%) of 19 patients who showed lesion recurrence 1-5 months after laser treatment had lightened or cleared at least 50% of the lesion. 46.67% of patients were satisfied or very satisfied with the outcome of the overall treatment. CONCLUSIONS: PS-755 nm, QS-755 nm, and QS-532 nm laser treatments were equally effective in treating and improving CALMs. PS-755 nm caused fewer adverse effects. Individuals can react differently to different types of lasers. Patch tests should be conducted before the treatment. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Retrospective study of photodynamic therapy for pulsed dye laser-resistant port-wine stains.

Pulsed dye laser-resistant port-wine stains present a therapeutic challenge. The aim of this study was to evaluate the efficacy and safety of photodynamic therapy for treating these lesions. A total of 67 patients with pulsed dye laser-resistant cervicofacial port-wine stains were retrospectively assessed after undergoing photodynamic therapy mediated with a combination of hemoporfin and 532-nm light. For objective evaluation of photodynamic therapy efficacy, first, the colorimetric changes in the port-wine stain lesions were evaluated according to the L*a*b* color coordinate system, then the values of color changes (ΔE) and blanching rate were calculated. For subjective evaluation of improvement, photographs taken before and after photodynamic therapy were evaluated by three independent assessors blindly. Patient satisfaction was also used as a factor in the subjective evaluation. Adverse events were recorded after treatment. The median ΔE decreased significantly from the pretreatment value of 13.42 to 9.90 at the 2-month follow up (P < 0.001). The median blanching rate of port-wine stains was 28.04% after an average of 1.21 sessions of photodynamic therapy. Based on the overall visual assessment, 46.2% patients showed excellent or good levels of improvement (>50% color blanching). Adverse events were minimal, transient and self-limiting. In conclusion, photodynamic therapy serves as an alternative means to treat pulsed dye laser-resistant port-wine stains.

Involvement of MrgprC in Electroacupuncture Analgesia for Attenuating CFA-Induced Thermal Hyperalgesia by Suppressing the TRPV1 Pathway.

Mas-related G-protein-coupled receptor C (MrgprC) plays an important role in modulating chronic inflammatory pain. Electroacupuncture (EA) has a satisfactory analgesic effect on chronic pain. This study aimed to investigate the involvement of MrgprC and its transient receptor potential vanilloid 1 (TRPV1) pathway in EA analgesia in chronic inflammatory pain. Chronic inflammatory pain was induced by subcutaneously injecting complete Freund's adjuvant (CFA) into the left hind paw. EA (2/100 Hz) stimulation was administered. MrgprC siRNAs were intrathecally administered to inhibit MrgprC expression, and bovine adrenal medulla 8-22 (BAM8-22) was used to activate MrgprC. The mechanical allodynia was decreased by EA significantly since day 3. The piled analgesic effect of EA was partially blocked by 6 intrathecal administrations of MrgprC siRNA. Both EA and BAM8-22 could downregulate the expression of TRPV1 and PKC in both the DRG and the SCDH. Both EA and BAM8-22 could also decrease the TRPV1 translocation and p-TRPV1 level in both the DRG and the SCDH. The effects of EA on PKCε, TRPV1 translocation, and p-TRPV1 in both the DRG and the SCDH were reversed by MrgprC siRNA. The results indicated that MrgprC played crucial roles in chronic pain modulation and was involved in EA analgesia partially through the regulation of TRPV1 function at the DRG and SCDH levels.

Double Pass 595 nm Pulsed Dye Laser Does Not Enhance the Efficacy of Port Wine Stains Compared with Single Pass: A Randomized Comparison with Histological Examination.

OBJECTIVE: To compare the efficacy and safety of double-pass pulsed dye laser (DWL) and single-pass PDL (SWL) in treating virgin port wine stain (PWS). BACKGROUND: The increase in the extent of vascular damage attributed to the use of double-pass techniques for PWS remains inconclusive. A prospective, side-by-side comparison with a histological study for virgin PWS is still lacking. MATERIALS AND METHODS: Twenty-one patients (11 flat PWS, 10 hypertrophic PWS) with untreated PWS underwent 3 treatments at 2-month intervals. Each PWS was divided into three treatment sites: SWL, DWL, and untreated control. Chromametric and visual evaluation of the efficacy and evaluation of side effects were conducted 3 months after final treatment. Biopsies were taken at the treated sites immediately posttreatment. RESULTS: Chromametric and visual evaluation suggested that DWL sites showed no significant improvement compared with SWL (p > 0.05) in treating PWS. The mean depth of photothermal damage to the vessels was limited to a maximum of 0.36-0.41 mm in both SWL and DWL sides. Permanent side effects were not observed in any patients. CONCLUSIONS: Double-pass PDL does not enhance PWS clearance. To improve the clearance of PWS lesions, either the depth of laser penetration should be increased or greater photothermal damage to vessels should be generated.

Shorter Treatment Intervals of East Asians with Port-Wine Stain with Pulsed Dye Laser Are Safe and Effective-A Prospective Side-by-Side Comparison.

OBJECTIVE: To compare the safety and efficacy of pulsed dye laser (PDL) at different intervals for the treatment of East Asians with Port-Wine Stain (PWS). BACKGROUND: The population of East Asians around the world is about 1.6 billion, and they are considered to have more melanin in their skin compared with Caucasians. Nevertheless, no studies about the optimal treatment intervals for East Asians with PWS have been carried out. METHODS: We prospectively investigated 39 East Asian patients with untreated PWS. Half of the PWS lesion was randomly allocated to be treated at 3 weeks and the other half at 6 weeks. Both halves of the PWS were treated three times in total. The efficacy outcome 2 months post final treatment was evaluated by visual and chromameter evaluation. RESULTS: The average blanching rate was 40.27% and 44.17% for PDL treatments at the 3- and 6-week interval sites, respectively (p > 0.05). No patient developed scarring or permanent pigmentation change. LIMITATIONS: There was no age criteria involved in the enrollment of patients in this study. Additionally, there is no comparison with long-term treatments at different intervals. CONCLUSIONS: PDL treatment at 3-week interval proved to be safe for East Asians with PWS. This can reduce the total duration of the course of treatments and had no increase in side effects compared with the standard interval treatments.

In Vivo Investigation of the Safety and Efficacy of Pulsed Dye Laser with Two Spot Sizes in Port-Wine Stain Treatment: A Prospective Side-by-Side Comparison.

OBJECTIVE: Pulsed dye laser (PDL) with 7 and 10 mm spot sizes is widely used on a regular basis for the treatment of port-wine stain (PWS). BACKGROUND DATA: No studies have reported on the differences in efficacy outcomes resulting from the use of different laser spot sizes in the treatment of PWS by PDL. Thus, an in vivo investigation into the differences in safety and efficacy of treatment between two spot sizes (7 vs. 10 mm) of PWS by PDL was conducted. MATERIALS AND METHODS: A total of 35 PWS patients underwent three treatment sessions by using a 595 nm wavelength PDL (Vbeam®, Candela Corp) with two laser settings: (1) 7 mm spot size, radiant exposure of 12 J/cm2 and (2) 10 mm spot size, radiant exposure of 10 J/cm2. Cryogen spray cooling and 1.5 msec pulse duration were applied. Therapeutic outcomes were evaluated by visual and chromametric evaluation 3 months after the final treatment. RESULTS: Average blanching rates were 34.03% and 36.51% at sites treated by PDL with 7 and 10 mm laser spot sizes, respectively (p < 0.05). CONCLUSIONS: On the basis of the laser setting, the therapeutic outcomes of PDL with 7 and 10 mm spot sizes were similar. PDL with a 10 mm laser spot size is more efficacious with lower radiant exposure than PDL with a 7 mm spot size; it can also reduce the treatment time.

Prospective, open-label, rater-blinded and self-controlled pilot study of the treatment of proliferating superficial infantile hemangiomas with 0.5% topical timolol cream versus 595-nm pulsed dye laser.

Topical timolol and 595-nm pulsed dye laser (PDL) are both widely used in the treatment of superficial infantile hemangiomas (IH). However, to date, there is no reliable study comparing the therapeutic outcomes between the two treatment options. We designed the present study to evaluate and compare the efficacy and safety of timolol cream and PDL in the treatment of superficial proliferating IH. Twenty-one patients with superficial IH were included in the study. Each lesion was divided into two regions; one part was treated with 0.5% topical timolol cream four times daily, and the other part was treated monthly with PDL. Both treatments were continued for 2-6 months. Five independent and blinded assessors were asked to judge the results in both the topical timolol-treated and PDL-treated parts by comparing photographs taken before and after treatment. Both treatments resulted in significant clinical improvements after 3.39 sessions in the 2-month follow up. The average visual evaluation showed that PDL had significantly better results than topical timolol (6.55 ± 2.26 to 4.98 ± 2.92, P < 0.01). No patients experienced permanent side-effects during the treatment. Our short-term study revealed that PDL had better results compared with topical timolol cream application in the treatment of superficial proliferating IH. Further studies with longer follow-up time and larger sample size are required to validate our findings.

Hemoporfin Photodynamic Therapy for Port-Wine Stain: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Photodynamic therapy (PDT) has shown potentially beneficial results in treating port-wine stain, but its benefit-risk profile remains undefined. This study aimed to evaluate the efficacy and safety of PDT conducted with hemoporfin and a 532 nm continuous wave laser to treat port-wine stain clinically. PATIENTS AND METHODS: This randomized clinical trial was conducted in eight hospitals in China. Participants were adolescent and adult patients (age range: 14-65 years old) with port-wine stain. During stage 1 (day 1 to week 8) all patients were randomized at a 3:1 ratio to treatment (532 nm laser irradiation (96-120 J/cm2) with hemoporfin (5mg/kg; PDT-hemoporfin, n = 330)) or placebo groups (irradiation with placebo (PDT-placebo, n = 110)); during stage 2 (week 8 to 16) patients in both groups were offered treatment. Clinician-evaluators, who were blind to the study, classified each case on the following four-level scale according to assessment of before and after standardized pictures of the lesion area: no improvement: <20%; some improvement: 20-59%; great improvement: 60-89%; or nearly completely resolved: ≥90%. The primary efficacy endpoint was proportion of patients achieving at least some improvement at week 8. The secondary efficacy endpoints were proportion of patients achieving nearly completely resolved or at least great improvement at week 8, proportion of patients achieving early completely resolved, at least great improvement, or at least some improvement at week 16, and the corresponding satisfaction of the investigators and the patients (designated as 'excellent', 'good', 'moderate', or 'ineffective') at weeks 8 and 16. RESULTS: Compared to the PDT-placebo group, the PDT-hemoporfin group showed a significantly higher proportion of patients that achieved at least some improvement (89.7% [n = 295; 95% CI, 85.9%-92.5%] vs. 24.5% [n = 27; 95% CI, 17.4%-33.3%]) at week 8 (P < 0.0001) and higher improvements for all secondary efficacy endpoints. Treatment reactions occurred in 99.5% (n = 731; 95% CI, 98.7%-99.8%) of the PDT-hemoporfin treatments (n = 735). Hyperpigmentation occurred in 22.9 per 100 patient-treatments (n = 168; 95% CI, 20.0-26.0) in the PDT-hemoporfin treated patients. CONCLUSIONS: Hemoporfin-mediated PDT is an effective and safe treatment option for adolescent and adult patients with port-wine stain. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-08000213.

The role of intestinal microbiota in development of irinotecan toxicity and in toxicity reduction through dietary fibres in rats.

CPT-11 is a drug used as chemotherapy for colorectal cancer. CPT-11 causes toxic side-effects in patients. CPT-11 toxicity has been attributed to the activity of intestinal microbiota, however, intestinal microbiota may also have protective effects in CP!-11 chemotherapy. This study aimed to elucidate mechanisms through which microbiota and dietary fibres could modify host health. Rats bearing a Ward colon carcinoma were treated with a two-cycle CPT-11/5-fluorouracil therapy recapitulating clinical therapy of colorectal cancer. Animals were fed with a semi-purified diet or a semi-purified diet was supplemented with non-digestible carbohydrates (isomalto-oligosaccharides, resistant starch, fructo-oligosaccharides, or inulin) in 3 independent experiments. Changes in intestinal microbiota, bacteria translocating to mesenteric lymphnodes, cecal GUD activity, and cecal SCFA production, and the intestinal concentration of CPT-11 and its metabolites were analysed. Non-digestible carbohydrates significantly influenced feed intake, body weight and other indicators of animal health. The identification of translocating bacteria and their quantification in cecal microbiota indicated that overgrowth of the intestine by opportunistic pathogens was not a major contributor to CPT-11 toxicity. Remarkably, fecal GUD activity positively correlated to body weight and feed intake but negatively correlated to cecal SN-38 concentrations and IL1-ß. The reduction in CPT-11 toxicity by non-digestible carbohydrates did not correlate to stimulation of specific bacterial taxa. However, cecal butyrate concentrations and feed intake were highly correlated. The protective role of intestinal butyrate production was substantiated by a positive correlation of the host expression of MCT1 (monocarboxylate transporter 1) with body weight as well as a positive correlation of the abundance of bacterial butyryl-CoA gene with cecal butyrate concentrations. These correlations support the interpretation that the influence of dietary fibre on CPT-11 toxicity is partially mediated by an increased cecal production of butyrate.