• Radiation Oncology Journal
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• v.24 no.3
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• pp.171-178
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• 2006

[ $\underline{Purpose}$ ]: To determine the efficacy and safety of concurrent chemotherapy and radiation therapy with high-dose-rate brachytherapy for cervical cancer. $\underline{Materials\;and\;Methods}$: From January 2001 to December 2002, 30 patients with cervical cancer were treated with concurrent chemotherapy (cisplatin and 5-FU) and definitive radiation therapy. The median age was 58 (range $34{\sim}74$) year old. The pathology of the biopsy sections was squamous cell carcinoma in 29 patients and one was adenocarcinoma. The distribution to FIGO staging system was as follows: stage IB, 7 (23%); IIA, 3 (10%); IIB, 12 (40%); IIIA, 3 (10%); IIIB, 5 (17%). All patients received pelvic external beam irradiation (EBRT) to a total dose of $45{\sim}50.4\;Gy$ (median: 50.4 Gy) over $5{\sim}5.5$ weeks. Ir-192 HDR intracavitary brachytherapy (ICBT) was given after a total dose of 41.4 Gy. HDR-ICBT was performed twice a week, with a fraction point A dose of 4 Gy and median dose to point A was 28 Gy (range: $16{\sim}32\;Gy$) in 7 fractions. The median cumulative biologic effective dose (BED) at point A (EBRT+ICBT) was $88\;Gy_{10}$ (range: $77{\sim}94\;Gy_{10}$). The median cumulative BED at ICRU 38 reference point (EBRT+ICBT) was $131\;Gy_3$ (range: $122{\sim}140\;Gy_3$) at point A, $109\;Gy_3$ (range: $88{\sim}125\;Gy_3$) at the rectum and $111\;Gy_3$ (range: $91{\sim}123\;Gy_3$) at the urinary bladder. Cisplatin ($60\;mg/m^2$) and 5-FU ($1,000\;mg/m^2$) was administered intravenously at 3 weeks interval from the first day of radiation for median 5 (range: $2{\sim}6$) cycles. The assessment was performed at 1 month after completion of radiation therapy by clinical examination and CT scan. The median follow-up time was 36 months (range: $8{\sim}50$ months). $\underline{: The complete response rate after concurrent chemoradiation therapy was 93.3%. The 3-yr actuarial pelvic control rate was 87% and 3-yr actuarial overall survival and disease-free survival rate was 93% and 87%, respectively. The local failure rate was 13% and distant metastatic rate was 3.3%. The crude rate of minor hematologic complications (RTOG grade 1-2) occurred in 3 patients (10%) and one patient had suffered from severe leukopenia (RTOG grade 4) during concurrent treatment. Acute minor enterocolitis (RTOG grade 1-2) occurred in 11 patients (37%) and one patient (3%) was suffered from colon perforation during radiation therapy. Late colitis of RTOG grade 1 occurred in 5 patients (15%). Acute cystitis of RTOG grade 1 occurred in 12 patients (40%) and late cystitis of RTOG grade 2 occurred in one patient (3%). No treatment related death was seen. $\underline{Conclusion}$: The results of this study suggest that the concurrent chemoradiation therapy with HDR brachytherapy could be accepted as an effective and safe treatment for cervical cancer.

• Radiation Oncology Journal
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• v.28 no.4
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• pp.193-204
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• 2010

Purpose: To analyze the treatment outcomes, complications, prognostic factors after a long-term follow-up of patients with nasopharyngeal carcinoma treated with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). Materials and Methods: Between December 1981 and December 2006, 190 eligible patients with non-metastatic nasopharyngeal carcinoma were treated at our department with a curative intent. Of these patients, 103 were treated with RT alone and 87 patients received CCRT. The median age was 49 years (range, 8~78 years). The distributions of clinical stage according to the AJCC 6th edition included I: 7 (3.6%), IIA: 8 (4.2%), IIB: 33 (17.4%), III: 82 (43.2%), IVA: 31 (16.3%), IVB: 29 (15.3%). The accumulated radiation doses to the primary tumor ranged from 66.6~87.0 Gy (median, 72 Gy). Treatment outcomes and prognostic factors were retrospectively analyzed. Acute and late toxicities were assessed using the RTOG criteria. Results: A total of 96.8% (184/190) of patients completed the planned treatment. With a mean follow-up of 73 months (range, 2~278 months; median, 52 months), 93 (48.9%) patients had relapses that were local 44 (23.2%), nodal 13 (6.8%), or distant 49 (25.8%). The 5- and 10-year overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) rates were 55.6% and 44.5%, 54.8% and 51.3%, in addition to 65.3% and 57.4%, respectively. Multivariate analyses revealed that CCRT, age, gender, and stage were significant prognostic factors for OS. The CCRT and gender were independent prognostic factors for both DFS and DSS. There was no grade 4 or 5 acute toxicity, but grade 3 mucositis and hematologic toxicity were present in 42 patients (22.1%) and 18 patients (9.5%), respectively. During follow-up, grade 3 hearing loss in 9 patients and trismus in 6 patients were reported. Conclusion: The results of our study were in accordance with findings of previous studies and we confirmed that CCRT, low stage, female gender, and young age were related to improvement in OS. However, there are limitations in the locoregional control that can be achieved by CCRT with 20 conventional radiation therapy. This observation has led to further studies on clarifying the efficacy of concurrent chemotherapy by intensity modulated radiation therapy.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.311-323
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• 1998

Purpose : Prospective, single arm, Phase I/II clinical trial was performed to assess the efficacy and toxicity of the concurrent chemotherapy and definitive radiotherapy (RT) in patients with previously untreated locally advanced carcinoma of the uterine cervix. Methods and Materials : From Mar 1992 to January 1997, a total of 73 patients with advanced cervical carcinoma were entered on the protocol but 5 patients were excluded in analysis because of patients' refusal of treatment. Their ages ranged from 31 to 77 years, median 58 years. The International Federation of Gynecology and Obstetrics (FIGO) stage distribution was as follows: IIB 46, IIIA 2, IIIB 15 and IVA 5. RT consisted of external beam irradiation to 4,140-5,040 cGy/23-28 fractions plus high dose rate intracavitary treatments to deliver a dose of 30-35 Gy to point A in 6-7 fractions. During the intracavitary treatments parametrial boost was delivered for point B dose of 60 Gy in stage IIB and 65 Gy in stage IIIB. Two cycles of concurrent 5-fluorouracil and cisplatin (FP) chemotherapy (5-fluorouracil 1,000 mg/$m^2$/day continuous infusion for 4 days, day 1-4, 29-32 and cisplatin 20 mg/$m^2$/day intravenous bolus for 3 days day 1-3, 29-31) administered starting on day 1 of RT. Results : The median follow-up was 24 months (range 4-68+). Sixty-four patients were evaluable for survival rate in this protocol: The 5-year actuarial and disease-free survival rate were 52$\%$ and 64$\%$, respectively. The 5-rear actuarial survival for stage IIB and III+IVA patients were 58$\%$ and 36$\%$, respectively The 5-year disease-free survival rate for stage IIB and III+IVA patients were 71$\%$ and 40$\%$, respectively. Of the 68 patients evaluated for patterns of failure, overall recurrence rate was 27.9$\%$ (19/68) : local failure in 5.9$\%$ (4/68), distant metastasis in 10.3$\%$ (7/68) and both in 11.8$\%$ (8/68). Of the 64 patients evaluated for response at one month after the completion of treatment the complete response rate was 78$\%$ (50/64). Concurrent chemoradiation appear to be a well-tolerated regimen but there were two treatment-related deaths. Conclusion : Concurrent chemotherapy of FP with high-dose definitive RT in locally advanced carcinoma of the uterine cervix is feasible and effective with acceptable toxicities. This chemoradiation regimen may offer a modest survival benefit for advanced stage. Further follow-up of these patients will evaluate the impact of this regimen on the long-term local control and their survival.

• Tuberculosis and Respiratory Diseases
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• v.54 no.4
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• pp.415-428
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• 2003

Background : This study assessed the efficacy and toxicity of etoposide and carboplatin(EC) combination regimen as a first line therapy for small cell lung cancer(SCLC), and determined the efficacy and toxicity of topotecan for relapsed SCLC. Methods : One hundred and ten patients with previously untreated SCLC received etoposide($100mg/m^2$ i.v., day 1 to 3) and carboplatin($300mg/m^2$ i.v., day 1) combination chemotherapy every 3 weeks. For patients with relapsed SCLC after EC therapy, topotecan($1.5mg/m^2$) was administered for 5 consecutive days every 3 weeks. Response rate, survival and toxicity profiles were assessed. Response was recorded as CR(complete remission), PR(partial remission), SD(stable disease) and PD(progressive disease). Results : One hundred and one patients were assessed for response to EC. Overall response rate to EC was 57.4%(CR 15.8%, PR 41.6%) with a time to progression of 10.3 months(median). The toxicity was tolerable and there was no treatment-related death. Twenty one relapsed SCLC patients were treated with topotecan. Of those who relapsed within 3 months of EC(refractory relapse, RR), 15.4%(2/13) showed PR, while of those who relapsed after 3 months(sensitive relapse, SR), 25%(2/8) exhibited PR. Grade 4 neutropenia was noted in 9.5% and 14.3% showed thrombocytopenia(G4). Conclusion : The EC regimen showed a moderate response rate for SCLC with minimal toxicity. The use of topotecan for relapsed SCLC warrants further investigation.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.391-400
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• 1997

Background : Bronchoscopy is an essential procedure for identifying the bleeding site and evaluating cause of hemoptysis. However, it is controversial regarding to the timing of bronchoscopy in patients with hemoptysis. Early bronchoscopy, which was performed during hemoptysis or with 48hour after cessation of bleeding, was better for identifying the site of bleeding compared with delayed bronchoscopy, which was performed 48 hours after cessation of bleeding. The diagnostic yield of identifying the bleeding site by bronchoscopy was variable in reported literature and the safety of early bronchoscopy was not mentioned in previous literature. Therefore, we evaluated the efficacy and safety of early bronchoscopy in patients with hemoptysis. Method : From October 1994 to August 1996 in Samsung Medical Center, bronchoscopy was performed in patients with hemoptysis. Early bronchoscopy was performed prospectively during hemoptysis or within 48 hours after cessation of bleeding from May 1995 to August 1996. Delayed bronchoscopy group included patients who did not received early bronchoscopy at the same period or in whom bronchoscopy was performed 48 hour after cessation of bleeding from October 1994 to May 1995. Results : Early bronchoscopy group was performed 73 times in 71 patients. Delayed bronchoscopy was performed in 57 times in 55 patients. There was no difference as to amount and underlying cause of hemoptysis between both groups. Indentification of bleeding site by visualizing active bleeding was significantly higher in early bronchoscopy (38.3%) than delayed bronchoscopy group (8.7%)(p < 0.05). Indentification of bleeding site by bleeding after clot removal was 8 in early and 10 in delayed bronchoscopy. Indentification of bleeding site by visualizing active bleeding and bleeding after clot removal was 36 in early and 15 patients in delayed bronchoscopy(p > 0.05). Causes of hemoptysis was found in 18 patients in early and 16 patients in delayed bronchoscopy group. patients who had early bronchoscopy underwent surgery. We diagnosed the site of bleeding in 4 patients preoperatively. In 3 patients we made a treatment plan promptly right after bronchoscopy. Among early bronchoscopy group, bleeding over 100cc during bronchoscopy occurred in 2 patients. In early bronchoscopy group there was no other major complication during bronchoscopy. Conclusion : In patients with hemoptysis, early bronchoscopy which performed within 48 hours after cessation of bleeding was more effective procedure for identifying the bleeding site than delayed bronchoscopy which was performed after 48 hour cessation of bleeding.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.2 no.2
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• pp.169-177
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• 1999

Purpose: To evaluate the efficacy of interferon alpha therapy with or without prednisolone in children with chronic hepatitis B. Methods: Twenty-eight children (22 boys, 6 girls, mean age 130 months) had seropositive results for HBsAg, HBeAg and HBV DNA; 11 had chronic persistent hepatitis and 17 had chronic active hepatitis. The patients were divided into two groups depending upon their inflammatory activity on liver biopsy, pretreatment serum ALT levels and HBV DNA levels. Fourteen children (group 1: chronic active hepatitis, ALT ${\geq}$ 100 IU/L and HBV DNA ${\leq}$ 100 pg/$300\;{\mu}L$) received interferon alpha 2a 5 $MU/m^2$ of body surface three times weekly for 6 months. Fourteen children (group 2: chronic persistent hepatitis or chronic active hepatitis with ALT < 100 IU/L or HBV DNA > 100 pg/$300\;{\mu}L$) received prednisolone in decreasing daily doses of 60 mg/$m^2$, 40 mg/$m^2$, and 20 mg/$m^2$, each for 2 weeks, followed after 2 weeks by interferon alpha 2a on the same schedule. At the end of therapy, 3 end points were analyzed: HBeAg seroconversion, serum ALT normalization rate and clearance of serum HBV DNA. Results: At the end of treatment, HBe antigen-to antibody seroconversion was higher but not more significant in group 1 than group 2 (71.4% vs. 50.0%). Only one patient in group 2 who lost HBeAg, also cleared HBsAg. ALT normalization was similar in both groups (64.3% in group 1 vs. 55.6% in group 2). Clearance of serum HBV DNA was observed in 78.6% of patients in group 1 and 64.3% in group 2, but no significant differences. Complete response was similarly achieved in both groups (57.1% in group 1 vs. 50.0% in group 2). Interferon alpha therapy with prednisolone priming was well tolerated and all children finished therapy. Conclusion: The combined therapy with prednisolone followed by interferon alpha may be safe and effective in inducing a serological and biochemical remission of the disease in approximately 50% of children with chronic hepatitis B and with a high level of viral replication and less active disease. However, a controlled study should be performed to confirm these results.

• Progress in Medical Physics
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• v.27 no.2
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• pp.64-71
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• 2016

We develop a manufacture procedure for the production of a patient specific customized bolus (PSCB) using a 3D printer (3DP). The dosimetric accuracy of the 3D-PSCB is evaluated for electron beam therapy. In order to cover the required planning target volume (PTV), we select the proper electron beam energy and the field size through initial dose calculation using a treatment planning system. The PSCB is delineated based on the initial dose distribution. The dose calculation is repeated after applying the PSCB. We iteratively fine-tune the PSCB shape until the plan quality is sufficient to meet the required clinical criteria. Then the contour data of the PSCB is transferred to an in-house conversion software through the DICOMRT protocol. This contour data is converted into the 3DP data format, STereoLithography data format and then printed using a 3DP. Two virtual patients, having concave and convex shapes, were generated with a virtual PTV and an organ at risk (OAR). Then, two corresponding electron treatment plans with and without a PSCB were generated to evaluate the dosimetric effect of the PSCB. The dosimetric characteristics and dose volume histograms for the PTV and OAR are compared in both plans. Film dosimetry is performed to verify the dosimetric accuracy of the 3D-PSCB. The calculated planar dose distribution is compared to that measured using film dosimetry taken from the beam central axis. We compare the percent depth dose curve and gamma analysis (the dose difference is 3%, and the distance to agreement is 3 mm) results. No significant difference in the PTV dose is observed in the plan with the PSCB compared to that without the PSCB. The maximum, minimum, and mean doses of the OAR in the plan with the PSCB were significantly reduced by 9.7%, 36.6%, and 28.3%, respectively, compared to those in the plan without the PSCB. By applying the PSCB, the OAR volumes receiving 90% and 80% of the prescribed dose were reduced from $14.40cm^3$ to $0.1cm^3$ and from $42.6cm^3$ to $3.7cm^3$, respectively, in comparison to that without using the PSCB. The gamma pass rates of the concave and convex plans were 95% and 98%, respectively. A new procedure of the fabrication of a PSCB is developed using a 3DP. We confirm the usefulness and dosimetric accuracy of the 3D-PSCB for the clinical use. Thus, rapidly advancing 3DP technology is able to ease and expand clinical implementation of the PSCB.

• Journal of Soil and Groundwater Environment
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• v.14 no.3
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• pp.40-46
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• 2009

The applicability of a well-type autotrophic sulfur-oxidizing reactive barrier (L $\times$ W $\times$ D = $3m\;{\times}\;4\;m\;{\times}\;2\;m$) as a long-term treatment option for nitrate removal in groundwater was evaluated. Pilot-scale (L $\times$ W $\times$ D = $8m\;{\times}\;4\;m\;{\times}\;2\;m$) flow-tank experiments were conducted to examine remedial efficacy of the well-type reactive barrier. A total of 80 kg sulfur granules as an electron donor and Thiobacillus denitrificans as an active bacterial species were prepared. Thiobacillus denitrificans was successfully colonized on the surface of the sulfur granules and the microflora transformed nitrate with removal efficiency of ~12% (0.07 mM) for 11 days, ~24% (1.3 mM) for 18 days, ~45% (2.4 mM) for 32 days, and ~52% (2.8 mM) for 60 days. Sulfur granules attached to Thiobacillus denitrificans were used to construct the well-type reactive barrier comprising three discrete barriers installed at 1-m interval downstream. Average initial nitrate concentrations were 181 mg/L for the first 28 days and 281 mg/L for the next 14 days. For the 181 mg/L (2.9 mM) plume, nitrate concentrations decreased by ~2% (0.06 mM), ~9% (0.27 mM), and ~15% (0.44 mM) after $1^{st}$, $2^{nd}$, and $3^{rd}$ barriers, respectively. For the 281 mg/L (4.5 mM) plume, nitrate concentrations decreased by ~1% (0.02 mM), ~6% (0.27 mM), and ~8% (0.37 mM) after $1^{st}$, $2^{nd}$, and $3^{rd}$ barriers, respectively. Nitrate plume was flowed through the flow-tank for 49 days by supplying $1.24\;m^3/d$ of nitrate solution. During nitrate treatment, flow velocity (0.44 m/d), pH (6.7 to 8.3), and DO (0.9~2.8 mg/L) showed little variations. Incomplete destruction of nitrate plume was attributed to the lack of retention time, rarely transverse dispersion, and inhibiting the activity of denitrification enzymes caused by relatively high DO concentrations. For field applications, it should be considered increments of retention time, modification of well placements, and intrinsic DO concentration.

• Clinical and Experimental Pediatrics
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• v.50 no.11
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• pp.1085-1090
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• 2007

Purpose : Radiofrequency catheter ablation (RFCA) has become an effective therapeutic modality for treating pediatric tachyarrhythmias. Using conventional RFCA catheters, ablation of parahisian accessory pathways may be difficult and have high risk for heart block. We reviewed the efficacy and complications of the RFCA in children and adolescent with arrhythmias including parahisian accessory pathways. Methods : We studied 48 patients (aged 2 years to 20 years) who had undergone RFCA from August 2003 to March 2007. We reviewed clinical findings, electrophysiologic studies, RFCA data, complications, and follow-up results of the patients. Results : Mean age of the patients was 13.1 years. Numbers and types of arrhythmias (age, acute success rate) were as follows: 19 WPW syndrome including 5 parahisian accessory pathways ($13.7{\pm}4.6yr$, 18/19), 11 atrioventricular reentrant tachycardia with concealed bypass tract ($12.3{\pm}5.0yr$, 10/11), 13 atrioventricular nodal reentrant tachycardia ($12.6{\pm}4.4yr$, 13/13), 4 atrial flutter ($13.0{\pm}7.4yr$, 3/4), and 1 ventricular tachycardia (20 yr, 1/1). Associated cardiac structural lesion was not detected in 48 patients. The recurrence rate was 6.5%, and the final success rate was 93.8%. Conclusion : These results suggest that RFCA is a highly effective treatment method in children and adolescent with tachyarrhythmia.

• The Journal of Korean Obstetrics and Gynecology
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• v.30 no.2
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• pp.49-70
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• 2017

Objectives: The present study is to observe the skin-regeneration, anti-wrinkle, whitening and skin moisturizing effects of Cheongsangbangpung-tang (CSBPT) with cytotoxicity. Methods: In the present study, cytotoxicity of CSBPT lyophilized aqueous extracts (yield=18.71%) was experimented against human normal fibroblast cells and B16F10 murine melanoma cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide (MTT) assay, and skin regeneration and anti-wrinkle effects were also showed through the assay of collagen type I synthesis by an enzyme immunoassay (EIA) kit as comparing with transforming growth factor (TGF)-${\beta}1$, hyaluronidase, collagenase and matrix metalloproteinase (MMP)-1 inhibitory assays as comparing with oleanolic acid (OA), and elastase inhibitory effects as comparing with phosphoramidon disodium salt (PP). In addition, whitening effects of CSBPT were observed by tyrosinase inhibitory assay and melanin formation test in B16/F10 melanoma cells as comparing with arbutin, and skin moisturizing effects were measured through mouse skin water contents test, respectively. Results: No CSBPT treatment related cytotoxic effects were demonstrated against human normal fibroblast cells and B16/F10 murine melanoma cells. CSBPT concentration-dependent increased collagen type I synthesis at human normal fibroblast cells. It also effectively suspreessed hyaluronidase, collagenase, elastase and MMP-1 activities, which were enzymes that related to declining of ECM and formation of wrinkle. CSBPT supressed B16/F10 melanoma cells's melanin productions with tyrosinase activity, which was an enzyme connected with melanin formation, and dose-dependent and significant increases of skin water contents were detected in CSBPT treated mouse skin as compared with vehicle control skins. Conclusions: CSBPT showed favorable and enough skin regeneration, anti-wrinkle, whitening and skin moisturizing effects at least in a condition of this experiment. However, more detail mechanism and in vivo skin protective efficacy studies should be conducted in future with the screening of the biological active compounds in individual herbs of Cheongsangbangpung-tang.