Glyceryl phenylbutyrate(GPB)serves as a long-term management medication for Ornithine transcarbamylase deficiency(OTCD),effectively controlling hyperammonemia,but there is a lack of experience in using this medicine in China.This article retrospectively analyzes the case of a child diagnosed with OTCD at Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine,including a review of related literature.After diagnosis,the patient was treated with GPB,followed by efficacy follow-up and pharmacological monitoring.The 6-year and 6-month-old male patient exhibited poor speech development,disobedience,temper tantrums,and aggressive behavior.Blood ammonia levels peaked at 327 μmol/L;urine organic acid analysis indicated elevated uracil levels;cranial MRI showed extensive abnormal signals in both cerebral hemispheres.Genetic testing revealed de novo mutation in the OTC gene(c.241T＞C,p.S81P).Blood ammonia levels were approximately 43,80,and 56 μmol/L at 1,2,and 3 months after starting GPB treatment,respectively.During treatment,blood ammonia was well-controlled without drug-related adverse effects.The patient showed improvement in developmental delays,obedience,temperament,and absence of aggressive behavior.

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans ; Aged ; Treatment Outcome ; Retrospective Studies ; Combined Modality Therapy ; Chemoradiotherapy/methods* ; Urinary Bladder Neoplasms/radiotherapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

With three representative types of gynecological diseases (dysmenorrhea, pelvic inflammation, polycystic ovary syndrome) as examples, the application methods of meridian and acupoint diagnosis for gynecological diseases treated with acupuncture and moxibustion are discussed. During clinical diagnosis and treatment, it is recommended to examine the patient's leg segment along the three yin meridians of foot, aiming to explore the positive reactions of the meridians and acupoints (color, shape, skin temperature, sensory abnormalities, etc.). Acupuncture and moxibustion treatment at this positive reaction place can improve the clinical efficacy. Meridian and acupoint diagnosis could provide basis for meridian syndrome differentiation, thus guiding the selection of acupoint prescriptions; it is also helpful to clarify the deficiency, excess, cold and heat of the disease nature, thus guiding the selection of acupuncture and moxibustion methods. In addition, it is an auxiliary method to estimate the prognosis and outcome of the disease.
Female ; Humans ; Moxibustion ; Meridians ; Acupuncture Points ; Acupuncture Therapy ; Foot ; Genital Diseases, Female/therapy*

This study engineered β-carotene ketolase CrtW and β-carotene hydroxylase CrtZ to improve biosynthesis of astaxanthin in Escherichia coli. Firstly, crtW was randomly mutated to increase CrtW activities on conversion from β-carotene to astaxanthin. A crtW* mutant with A6T, T105A and L239M mutations has improved 5.35-fold astaxanthin production compared with the wild-type control. Secondly, the expression levels of crtW* and crtZ on chromosomal were balanced by simultaneous modulation RBS regions of their genes using RBS library. The strain RBS54 selected from RBS library, directed the pathway exclusively towards the desired product astaxanthin as predominant carotenoid (99%). Lastly, the number of chromosomal copies of the balanced crtW-crtZ cassette from RBS54 was increased using a Cre-loxP based technique, and a strain with 30 copies of the crtW*-crtZ cassette was selected. This final strain DL-A008 had a 9.8-fold increase of astaxanthin production compared with the wild-type control. Fed-batch fermentation showed that DL-A008 produced astaxanthin as predominant carotenoid (99%) with a specific titer of 0.88 g·L without addition of inducer. In conclusion, through constructing crtW mutation, balancing the expression levels between crtW* and crtZ, and increasing the copy number of the balanced crtW*-crtZ cassette, the activities of β-carotene ketolase and β-carotene hydroxylase were improved for conversion of β-carotene to astaxanthin with higher efficiency. The series of conventional and novel metabolic engineering strategies were designed and applied to construct the astaxanthin hetero-producer strain of E. coli, possibly offering a general approach for the construction of stable hetero-producer strains for other natural products.

OBJECTIVE: To evaluate the safety and efficacy of the seven-step two-lobe holmium laser enucleation of the prostate (HoLEP) technique with low power laser device, and to introduce the detailed operating procedures, key points, short-term outcomes of this modified HoLEP technique. METHODS: From March 2016 to November 2017, 90 patients underwent HoLEP in Peking University Third Hospital. The patients were divided into two groups: high-power group (32 patients) were performed with traditional Gilling's three-lobe enucleation using high power (90 W) laser; Low-power group (58 patients) were performed with seven-step two-lobe enucleation using low power (40 W) laser. The main steps of the low power seven-step two-lobe HoLEP phase included: (1) The identification of the correct plane between adenoma and capsule at 5 and 7 o'clock laterally to the veru montanum; (2) The connection of the bilateral plane by making a adenoma incision at the proximal point of veru montanum; (3) The extension of the dorsal plane under the whole three lobes between adenoma and capsule towards the bladder neck; (4) The separation of the middle lobe from two lateral lobes by making two retrograde incisions separately from apex 5 and 7 o'clock towards the bladder neck; (5) The enucleation of the middle lobe adenoma by extending the dorsal plane through into the bladder; (6) The prevention of the apex mucosa by making a circle incision at the apex of the prostate; (7) The en-bloc enucleation of the two lateral lobe adenomas by extending the lateral and ventral plane between adenoma and capsule from 5 and 7 o'clock to 12 o'clock conjunction and through into the bladder. RESULTS: The mean patient age was (66.25±5.37) years vs. (68.00±5.18) years; The mean body mass indexes were (24.13±4.06) kg/m² vs. (24.57±3.50) kg/m²; The mean prostate specific antigen values were (3.23±2.47) μg/L vs. (6.00±6.09) μg/L; The average prostatic volumes evaluated by ultrasound was (49.03±20.63) mL vs. (67.55±36.97) mL. There was no significant difference between the two groups. Furthermore, there were no significant differences in terms of perioperative and follow up data, including operative time; enucleation efficiencies; hemoglobin decrease; blood sodium and potassiumthe change postoperatively; catheterization duration and hospital stay; the international prostate symptom scores and quality of life scores pre- and post-operatively. There was 1 transurethral resection of the prostate (TURP) conversion in high-power group and 1 transfusion in low-power group during the operations. The follow-up one month after operation showed no severe stress incontinence in both the groups, whereas 3 cases ejaculatory dysfunctions in high-power group versus 1 case in low-power group were observed; Other surgeryrelated complications included: 2 cases postoperative hemorrhage (Clavien II and Clavien IIIb) in high-power group, 2 cases postoperative temperature more than 38 °C (Clavien I) and 1 case dysuria following catheter removal (Clavien I) in low-power group. CONCLUSION Low power laser device can be applied safe and effectively for HoLEP procedure using the seven-step two-lobe HoLEP technique. The outcomes comparable with high power laser HoLEP can be achieved.
Holmium ; Humans ; Laser Therapy ; Lasers, Solid-State ; Male ; Prostatic Hyperplasia/surgery* ; Quality of Life ; Transurethral Resection of Prostate ; Treatment Outcome

Objective To evaluate the survival and prognostic factors of esophageal cancer treated with definitive ( chemo ) radiotherapy by applying novel radiation techniques including three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT). Methods Clinical data of 2762 patients with non-operated esophageal squamous cell carcinoma who underwent definitive ( chemo ) radiotherapy from 2002 to 2016 in 10 hospitals were retrospectively analyzed.The prognostic factors were also identified and analyzed. Results The median follow-up time was 60. 8 months. The 1-, 2-, 3-and 5-year overall survival (OS) of all patients was 71. 4％,48. 9％,39. 3％,and 30. 9％,respectively.The 1-,2-,3-and 5-year progression-free survival (PFS) was 59.5％,41.5％,35.2％,and 30％,respectively.The median survival was 23 months.The median time to progression was 17. 2 months.Multivariate analysis demonstrated that age, primary tumor location, clinical stage, tumor target volume, EQD2 and treatment mode were the independent prognostic factors for OS.Primary tumor location,clinical stage,tumor target volume and EQD2 were the independent prognostic factors for PFS. Conclusions In this first large-scale multi-center retrospective analysis of definitive ( chemo) radiotherapy for esophageal squamous cell carcinoma in China, the 5-year OS of patients with esophageal squamous cell carcinoma is significantly improved by 3DCRT, IMRT combined with chemotherapy drugs. However, the findings remain to be validated by prospective clinical trials with high-level medical evidence.

Background: Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study. Methods: TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54). Results: Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (-71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning. Conclusions: Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China. Trial Registration ClinicalTrials.gov, NCT00751881; https://clinicaltrials.gov/ct2/show/NCT00751881?term=NCT00751881&rank=1.
China ; Crotonates ; administration & dosage ; adverse effects ; therapeutic use ; Double-Blind Method ; Drug Administration Schedule ; Humans ; Immunosuppressive Agents ; administration & dosage ; adverse effects ; therapeutic use ; Multicenter Studies as Topic ; Multiple Sclerosis ; drug therapy ; metabolism ; Proportional Hazards Models ; Toluidines ; administration & dosage ; adverse effects ; therapeutic use

Objective: To explore the correlation between moxibustion sensation and distance of moxa stick and provide reference for clinical practice. Methods: A total of 16 healthy volunteers aged 18-35 years old in college were recruited and given mild moxibustion at Shousanli (LI 10), Zusanli (ST 36), Shenshu (BL 23) and Tianshu (ST 25) with moxa stick, and the occurrence and frequency of moxibustion sensation were recorded at distances of 5 cm, 4 cm, 3 cm and 2 cm. Mild moxibustion scale was used to count the score. Results: Warm was the main moxibustion sensation, burning pain and soreness decreased with the rise of distance; for the same acupoint, score of mild moxibustion scale increased with the decrease of distance; score ranged between 5.5 and 6.5 at distance 3 cm, which was the most comfortable distance for volunteers. Conclusion: The distance of 3 cm is the most comfortable distance in mild moxibustion.

Objective: To explore the beneficial regulatory effect of mild moxibustion from different distances at Zusanli (ST 36) of healthy population on the functions of temperature-related brain regions. Methods: In 20 recruited healthy subjects, the change of the temperature-related brain regions induced by mild moxibustion from different distances at Zusanli (ST 36) was observed by functional magnetic resonance imaging (fMRI). Results: In comparison of the values in amplitude of low-frequency fluctuation (fALFF) during and before moxibustion, it has been found that in moxibustion of 2 cm distance, fALFF value increased in the brain regions of the left anterior cingulated cortex and lateral surrounding cerebral regions, and fALFF value decreased in the cerebral regions of the peripheral cortex of the calcarine fissure; in moxibustion of 3 cm distance, fALFF value increased in the brain regions of the right and medial side and paracingulated gyrus, and fALFF value decreased in the cerebral zone of the left middle temporal gyrus; in moxibustion of 4 cm distance, fALFF value increased in the brain regions of the right and medial and paracingulated gyrus; and in moxibustion of 5 cm distance, fALFF value increased in the brain regions of the left hippocampus. In comparison of the value of regional homogeneity (ReHo), it has been found that in moxibustion of 2 cm distance, ReHo value increased in the cerebral zone of the posterior lobe of the right cerebellum, and ReHo value decreased in the cerebral zone of the right occipital lobe; in moxibustion of 3 cm distance, ReHo value increased in the brain regions of the left cerebellar posterior lobe and left frontal lobe, and ReHo value decreased in the cerebral zone of the right inferior temporal gyrus; in moxibustion of 4 cm distance, ReHo value increased in the brain regions of the right superior frontal gyrus and ReHo value decreased in the brain regions of the right parietal lobe and angular gyrus; in moxibustion of 5 cm distance, ReHo value increased in the cerebral zone of the right frontal lobe and ReHo value decreased in the cerebral zone of the right brainstem. Conclusion: In moxibustion of 3 cm distance, the changes in the brain regions basically conform to the transmission route of body trunk temperature.

Background: Metastatic colorectal cancer (mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promis-ing anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC. Methods: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), quality-of-life (QoL), and safety. Results: Between July 18, 2012 and Jan 22, 2014, a total of 167 patients were screened, and 154 patients were rand-omized in a 2:1 ratio to receive either famitinib (n = 99) or placebo (n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups (hazard ratio = 0.60, 95% confidence interval = 0.41–0.86, P = 0.004). The DCR was 59.8% and 31.4% (P = 0.002) and the ORR was 2.2% and 0.0% (P = 0.540) in the famitinib and placebo groups, respectively. The most frequent grade 3–4 adverse events were hypertension (11.1%), hand-foot syndrome (10.1%), thrombocytopenia (10.1%), and neutropenia (9.1%). Serious adverse events occurred in 11 (11.1%) patients in the famitinib group and 5 (9.1%) in the placebo group (P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months (P = 0.657). Conclusion: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability. Trial registration This study was registered on ClinicalTrials.gov (NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal Symposium