We report a case of a 3-year-old girl who suffered from alopecia areata and was successfully treated with rokumigan modified formula. Initially, alopecia areata appeared on her left temporal region at the age of 3. The hair loss range had spread rapidly over the whole head. She visited our Kampo clinic because of insufficient effect of antiallergic drug. We prescribed her yokukansan, shimotsuto and juzentaihoto but the effect was insufficient. Finally, we thought this might be caused by kidney yin deficiency and liver blood deficiency because she had symptoms of pale white complexion, fine pulse, pale tongue with thin fur, and night sweating. Therefore, we administered rokumigan modified formula : rokumigan, tokiinshi and lycium fruit. Her hair began to grow after administering this formulation. There was not the re-hair loss during taking medicine for about 4 months. According to the traditional Chinese medicine, alopecia areata can be classified into 4 types : blood heat type, blood stasis type, dual deficiency type of yin and blood, dual deficiency type of qi and blood. We diagnosed this case as a dual deficiency type of yin and blood and selected rokumigan modified formula. Rokumigan is effective for various symptoms of kidney yin deficiency, and rokumigan modified formula may be useful for the treatment of infant alopecia areata.

Objective: Maternal embryonic leucine zipper kinase (MELK) is receiving an attention as a therapeutic target in various types of cancers. In this study, we aimed to evaluate the prognostic significance of MELK expression in ovarian cancer using clinical samples, and assessed the efficacy of a small molecule MELK inhibitor, OTS167, using patient-derived ovarian cancer cells as well as cell lines. Methods: Expression levels of MELK in 11 ovarian cancer cell lines were confirmed by western blotting. Inhibitory concentration of OTS167 was determined by colorimetric assay.MELK messenger RNA (mRNA) expression was evaluated in 228 ovarian cancer patients by quantitative polymerase chain reaction. Growth inhibition of OTS167 was also evaluated using freshly-isolated primary ovarian cancer cells including spheroid formation condition. Results: MELK mRNA expression was significantly higher in ovarian cancer than in normal ovaries (p<0.001), and high MELK mRNA expression was observed in patients with advanced stage, positive ascites cytology and residual tumor size. Patients with high MELK mRNA expression showed shorter progression-free survival (p=0.001). Expression of MELK was also confirmed in 10 of 11 ovarian cancer cell lines tested, and the half maximal inhibitory concentration of MELK inhibitor, OTS167, ranged from 9.3 to 60 nM. Additionally, OTS167 showed significant growth inhibitory effect against patient-derived ovarian cancer cells, regardless of their tumor locations, histologic subtypes and stages. Conclusions We demonstrated MELK as both a prognostic marker and a therapeutic target for ovarian cancer using clinical ovarian cancer samples. MELK inhibition by OTS167 may be an effective approach to treat ovarian cancer patients.

BACKGROUND: The prognosis of recovery following microneurosurgery for injured lingual nerves varies among individual cases. This study aimed to investigate if recovery ratios of sensory and taste functions are improved by the microneurosurgery within 6 months after lingual nerve injury. METHODS: We retrospectively assessed 70 patients who underwent microneurosurgery at the Wakayama Medical University Hospital for lingual nerve injuries between July 2004 and December 2016. Sensory and taste functions in lingual nerves were preoperatively evaluated using a static two-point discrimination test, an intact superficial pain/tactile sensation test, and a taste discrimination test. They were evaluated again at 12 and at 24 months postoperatively. The abundance ratio of Schwann cells in the excised traumatic neuromas was analyzed with ImageJ software following immunohistochemistry with anti S-100β antibody. RESULTS: In early cases (microneurosurgery within 6 months after the injury), recovery ratios of sensory and taste functions were not significantly different at 24 months after microneurosurgery compared with later cases (microneurosurgery more than 6 months after the injury). Meanwhile, the ratio of patients with taste recovery within 12 months after microneurosurgery was significantly decreased in late cases compared with early cases. The abundance ratio of Schwann cells in traumatic neuroma was also significantly lower in later cases. CONCLUSION Microneurosurgery more than 6 months after lingual nerve injury did not lead to decreased recovery ratio of sensory and taste functions, but it did lead to prolonged recovery of taste. This delay may be associated with a decrease in the abundance ratio of Schwann cells in traumatic neuromas.

BACKGROUND: Programmed cell death ligand 1 (PD-L1) is an immune checkpoint molecule that attenuates the immune response. PD-L1 contributes to failed antitumor immunity; thereby, blockade of PD-L1 with monoclonal antibody enhances the immune response. Recently, it was reported that PD-L1 was regulated by protein 53 (p53). Besides, cytokeratin 17 (CK17) is thought to be a diagnostic marker of oral squamous cell carcinoma (OSCC). Our aim was to evaluate the correlation between the immunohistochemical expression of PD-L1, p53 and CK17 with clinicopathological characteristics and disease-specific survival in patients with OSCC. METHODS: A total of 48 patients with OSCC were included in this study. Immunohistochemical staining was performed to evaluate the correlation among the expressions of PD-L1, p53 and CK17, and furthermore the correlation among various clinicopathological factors, PD-L1, p53 and CK17. RESULTS: The positive rate of p53, CK17, PD-L1 (tumor cells) and PD-L1 (tumor-infiltrating lymphocytes) was 63.2%, 91.7%, 48.9% and 57.1%. A statistically significant correlation between p53 expression and T stage and TNM stage (p = 0.049, p = 0.03, respectively) was observed. Also, a statistically significant correlation between p53 and PD-L1 (TCs) expression (p = 0.0009) was observed. Five-year disease-specific survival rate was not significantly correlated with gender, TNM stage, p53 expression, PD-L1 expression and CK17 expression. CONCLUSION The expression of p53 and PD-L1 shows significantly positive correlation in oral squamous cell carcinoma in tumor cells. Also, a significant correlation between p53 expression and T stage and TNM stage was observed. No other significant correlation between PD-L1 staining or CK17 and clinical or pathologic characteristics was identified.

BACKGROUND: Through the analysis of clinical data, we attempted to investigate the etiology and determine the risk of severe iatrogenic lingual nerve injuries in the removal of the mandibular third molar. METHODS: A retrospective chart review was performed for patients who had undergone microsurgical repair of lingual nerve injuries. The following data were collected and analyzed: patient sex, age, nerve injury side, type of impaction (Winter's classification, Pell and Gregory's classification). Ratios for the respective lingual nerve injury group data were compared with the ratios of the respective data for the control group, which consisted of data collected from the literature. The data for the control group included previous patients that encountered various complications during the removal of the mandibular third molar. RESULTS: The lingual nerve injury group consisted of 24 males and 58 females. The rate of female patients with iatrogenic lingual nerve injuries was significantly higher than the control groups. Ages ranged from 15 to 67 years, with a mean age of 36.5 years old. Lingual nerve injury was significantly higher in the patient versus the control groups in age. The lingual nerve injury was on the right side in 46 and on the left side in 36 patients. There was no significant difference for the injury side. The distoangular and horizontal ratios were the highest in our lingual nerve injury group. The distoangular impaction rate in our lingual nerve injury group was significantly higher than the rate for the control groups. CONCLUSION Distoangular impaction of the mandibular third molar in female patients in their 30s, 40s, and 50s may be a higher risk factor of severe lingual nerve injury in the removal of mandibular third molars.

A 72-year-old woman was admitted with a sensation of compression and shortness of breath. A mass was detected in the right atrium (RA) by transthoracic echocardiography. Preoperative chest computed tomography showed an RA tumor measuring 30×24 mm in the lateral wall. We performed resection under the cardiopulmonary bypass. Histopathological examination confirmed that this tumor was a lipoma.

We performed a preliminary study of the reliability of the lymphocyte stimulating test (LST) for Kampo medicine. LST for three kinds of Kampo medicines was performed in both a Kampo-administrated group and a non-administrated group. LST for each of the medicines was negative for seven of eight subjects in the non-administrated group, but was negative for four of 11 subjects in the Kampo-administrated group. The LST-positive participants had no allergic state, and some among them were negative in challenge test. This preliminary study suggests that LST for Kampo medicine is likely to be false-positive.

Chronic hepatitis C has a high incidence of proceeding to liver cirrhosis, and a natural healing from chronic hepatitis C is extremely rare. We observed a case of chronic hepatitis type C, in which the virus was eliminated after Kampo treatment. The patient was a 37-year-old female who underwent a blood transfusion following delivery of her first child in 1982. In January 1983, she became aware of general malaise, and was diagnosed as having chronic hepatitis. She was treated with Stronger Neo Minophagen C, but her symptoms and laboratory data were unchanged. A liver biopsy disclosed chronic active hepatitis in 1988, and she was transferred to our hospital for Kampo treatment in May. Although the symptoms rapidly disappeared after treatment with the Kampo formulas, Hochu-ekki-to and Keishi-bukuryo-gan, her transamilase values did not change. Her transamilase level decreased gradually after the prescription was changed to Saiko-keishi-to-go-Toki-shakuyaku-san-ryo, and returned to normal after her prescription was changed to Kami-shoyo-san-ryo in May 1996.
Concerning HCV-RNA in the serum, in March 1995, when Saiko-keishi-to-go-Toki-shakuyaku-san was administered, the amount of HCV-RNA in the serum was 10⁴ Kcopies/ml. But that was less than the detectable sensitivity in April 1998. We believe this to be a case in which elimination of HCV was achieved by Kampo treatment alone.

We report on two cases of relapsing aspiration pneumonia caused by dysphagia due to cerebrovascular disease. Sei-hai-to (Qing Fei tang) offered useful palliation in both cases. Case 1 was an 83-year-old-woman who was hospitalized for multiple lacunar infarction and lumbago in 1996. She gradually became bedridden within two years of the admission period. She was admitted to a long-term care hospital affiliated with our department in January 1998. Dysphagia and productive cough appeared in May, and enteral tube feeding was started after she developed pneumonia in August. Pneumonia persisted against some antibiotics, and feverish periods ranged from 8 to 18 days a month. CRP values were elevated to more than 5mg/dl. Administration of Sei-hai-to provided negative CRP values and decreased feverish periods to 0-2 days a month. Case 2 was a 93-year-old-man who suffered from cerebral bleeding in the right thalamus in 1984. He developed many attacks of aspiration pneumonia after starting oral feeding. He was admitted to a long-term care hospital affiliated with our department in April 1999. Sputum culture yielded P. aeruginosa and MRSA. Moreover, fluoroscopy showed aspiration into the lower airway. Aspiration pneumonia relapsed continually without antibiotics. Administration of both Sei-hai-to and clarithromycin decreased feverish periods and provided negative CRP values. Pneumonia relapsed easily either with Sei-hai-to therapy alone or Clarithromycin therapy alone.

We investigated the clinical effects of Hochu-ekki-to on symptoms, biological properties, quantities of hepatitis C virus, and fibrotic markers of 25 patients with chronic hepatitis C for six months. Results were analyzed by comparison of sex, age, and Ki-deficiency symptoms. Transaminase levels did not change in total, although decreases in scores of malaise and fatigability were statistically significant. Nevertheless, in patients 60 years old or older, GOT levels were elevated and total cholesterol levels decreased as compared to younger patients. Decreases in transaminases after administration of Hochu-ekki-to were statistically significant only in the 60+ age group. Decreases in transaminases were also statistically significant in patients who suffer from malaise, who are highly susceptible to colds, or who have reduced tension of the radial pulsation and faint red color or edema of tongue. Decreases were not observed in patients without these symptoms. These results suggest that the diagnosis of Ki-deficiency in Kampo medicine is very important in treating hepatitis C with Hochu-ekki-to.