The pharmaceutical manufacturing model is gradually changing from intermittent manufacturing to continuous manufacturing and intelligent manufacturing. This paper briefly reviewed the supervision and research progress in continuous pharmaceutical manufacturing in China and abroad and described the definition and advantages of continuous pharmaceutical manufacturing. The continuous manufacturing of traditional Chinese medicine(TCM) at the current stage was summarized in the following three terms: the enhancement of the continuity of intermittent manufacturing operations, the integration of continuous equipment to improve physical continuity between units, and the application of advanced process control strategies to improve process continuity. To achieve continuous manufacturing of TCM, the corresponding key technologies, such as material property characterization, process modeling and simulation, process analysis technology, and system integration, were analyzed from the process and equipment, respectively. It was proposed that the continuous manufacturing equipment system should have the characteristics of high speed, high response, and high reliability, "three high(H~3)" for short. Considering the characteristics and current situation of TCM manufacturing, based on the two dimensions of product quality control and production efficiency, a maturity assessment model for continuous manufacturing of TCM, consisting of operation continuity, equipment continuity, process continuity, and quality control continuity, was proposed to provide references for the application of continuous manufacturing technology for TCM. The implementation of continuous manufacturing or the application of key continuous manufacturing technologies in TCM can help to systematically integrate advanced pharmaceutical technology elements and promote the uniformity of TCM quality and the improvement of production efficiency.
Medicine, Chinese Traditional ; Reproducibility of Results ; China ; Quality Control ; Pharmaceutical Preparations

AIM: To investigate the effect of orbital decompression on the central macular choroidal thickness(CMCT)in patients with thyroid-associated ophthalmopathy(TAO).METHOD: Prospective clinical studies. A total of 29 TAO patients(42 eyes)treated in our department from January 2021 to January 2022 were analyzed, and they were divided into 20 cases(30 eyes)in the moderate and severe group and 9 cases(12 eyes)in the extremely severe group. Both groups of patients received orbital decompression, and the changes of CMCT, visual acuity, intraocular pressure, exophthalmos, and clinical activity score(CAS)at 3 and 6mo before and after surgery were compared between the two groups.RESULTS: All patients completed follow-up. The CMCT, exophthalmos, intraocular pressure, and CAS of the extremely severe group at 3 and 6mo were 355.13±15.59 and 339.61±13.17μm, 19.33±2.23 and 17.83±1.70mm, 18.86±3.05 and 18.09±1.37mmHg, 3.75±0.87 and 2.42±1.00 points, respectively. The moderate and severe group was 325.00±10.48 and 321.04±11.34μm, 16.07±1.74 and 15.6±1.98mm, 16.65±2.04 and 16.03±2.3mmHg, 1.50±0.51 and 1.43±0.50 points, and there was differences with those before operation(extremely severe group: 396.46±17.61μm, 22.00±2.3mm, 21.85±2.82mmHg, 5.33±1.44 points; moderate and severe group: 335.77±11.60μm, 19.07±1.84mm, 18.89±3.06mmHg, 1.63±0.49 points; all P<0.001). The best corrected visual acuity(LogMAR)before surgery was 0.64±0.22 in the extremely severe group, and 0.43±0.20 and 0.34±0.15 at 3 and 6mo after operation, respectively, which were different from those before surgery(all P<0.001)CONCLUSION: Orbital decompression can effectively reduce CMCT, intraocular pressure and exophthalmos in TAO patients, relieve orbital vein stasis, and effectively improve vision and reduce mobility in patients with extremely severe disease.

Objective:To evaluate the residual risk (RR) of transfusion transmitted HIV (TT-HIV) after the implementation of nucleic acid amplification test (NAT) in blood screening test among blood centers in China.Methods:The data of blood donors and HIV infection markers from 2017 to 2020 were collected from 28 blood centers via the Platform of Comparison of blood establishments Practice in Chinese Mainland. The new infection rate/window period mathematical model was used for two types of blood screening strategies, namely, two rounds ELISA plus individual NAT take turn with pooling NAT (2ELISA+ ID-NAT/MP-NAT) and two ELISA plus one round pooling NAT (2ELISA+ MP-NAT), and the RR of HIV infection was estimated also based on first donors (FDs) and repeated donors (RDs) in different blood donation years. T-test analyses were conducted for comparing TT HIV RR among FDs and RDs in different blood donation years with two blood screening strategies, and the variation trend of RR in HIV test was observed.Results:From 2017 to 2020, the RR of FDs in 2ELISA+ ID-NAT/MP-NAT blood screening strategy was 2.869/10 6 person-year, 3.795/10 6 persons-year, 3.879/10 6 person-year, and 2.890/10 6 person-year respectively. The RR of RDs was 1.797/10 6 person-year, 1.502/10 6 person-year, 1.857/10 6 person-year, and 1.483/10 6 person-year respectively. Significant difference exists between RR of FDs and RDs, with F=9.898 and p<0.05. In 2ELISA+ MP-NAT strategy, the RR of FDs was 3.508/10 6 person-year, 1.868/10 6 person-year, 2.204/10 6 person-year, and 1.765/10 6 person-year respectively. The RR of RDs was 0.948/10 6 person-year, 0.926/10 6 person-year, 0.748/10 6 person-year, and 0.682/10 6 person-year respectively. Statistical difference existed between RR of FDs and RDs, with F=17.126 and P<0.05. There was no significant difference between the RR of FDs in these two strategies with F=3.493 and P>0.05, while there was a difference between the RR of RDs in these two strategies with F=24.516 and P<0.05, and a difference between the RR of total donors (TDs) in these two strategies F=20.216 and P<0.05. Conclusions:The RR of TT HIV significantly decreased after the introduction of NAT into blood test among blood centers in China. There were some differences in the RR of HIV testing among different blood screening strategies. There could be significant differences in the RR of HIV testing among different groups of blood donors. Compared with FDs, RDs is the low risk group for HIV.

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

To investigate the relationship between serum uric acid to creatinine ratio (SUA/Cr) and metabolic syndrome (MS) and other indexes on physical examination population in Nantong area. Using the method of cross-sectional study, 8 148 physical examiners in the physical examination center of the Affiliated Hospital of Nantong University from January 2017 to April 2020 were used as the research objects, and the clinical data and serum biochemical indicators such as smoking and alcohol addiction, physical examination and so on were collected. According to the standard diagnosis of MS of Diabetes Society of Chinese Medical Association, the patients were grouped according to the quartile of SUA/Cr and the clinical data of each group were compared. Pearson correlation analysis and logistic regression analysis were used to explore the correlation between SUA/Cr and clinical indicators and the relationship between SUA/Cr and the risk of MS. The results showed that UA and SUA/Cr were the lowest in normal metabolism group, followed by abnormal metabolism group and the highest in MS group, The difference between the two groups was statistically significant (H=919.21 and 629.34, P<0.001). According to the SUA/Cr quartile, the population was divided into four groups. After adjusting for gender, age, smoking history and drinking history, SUA/Cr in group Q₁ was positively correlated with BMI and TG (r=0.061 and 0.080, P<0.05), but negatively correlated with HDL-C (r=-0.057, P<0.05). Multivariate logistic regression results showed that after adjusting for age, sex, smoking history and drinking history, the risk of MS for BMI, SBP, DBP, FBG, TG, HDL-C and SUA/Cr [OR (95%CI)] were: 1.44 (1.41-1.47), 1.07 (1.06-1.07), 1.10 (1.10-1.11), 1.83 (1.73-1.92), 1.89 (1.79-1.99), 0.08 (0.06-0.10) and 1.54 (1.47-1.62). Compared with SUA/Cr group Q₁, the risk of MS in group Q₂, Q₃ and Q₄ increased by 75%, 162% and 346%, respectively. In conclusion, there was an independent positive correlation between SUA/Cr and MS risk in Nantong area.
Humans ; Metabolic Syndrome/epidemiology* ; Creatinine ; Uric Acid ; Cross-Sectional Studies ; Physical Examination ; Risk Factors

Chronic Disease ; Humans ; Nasal Polyps/complications* ; Rhinitis/complications* ; Rhinitis, Allergic ; Sinusitis/complications* ; Staphylococcal Infections/complications* ; Staphylococcus aureus

OBJECTIVE: To determine the effects of Chinese medicine (CM) involving triple rehabilitation therapy on the progression of knee osteoarthritis (KOA). METHODS: A total of 722 patients recruited from 38 community health service centers located in China from March 2013 to March 2017 were randomly divided into treatment and control groups equally, using a cluster randomization design. Health education combined with CM involving triple rehabilitation therapy for KOA (electro-acupuncture, Chinese medicinal herb fumigating-washing, and traditional exercises) was administered in the treatment group while conventional rehabilitation therapy (physical factor therapy, joint movement training, and muscle strength training) was administered in the control group. Patients with a visual analog scale (VAS) scores ≽4 were treated with dispersible meloxicam tablets (7.5 mg, once daily). The Lequesne index scores, VAS scores, range of motion (ROM), lower limb muscle strength, knee joint circumference, quantitative scores of KOA symptoms, and the short-form 36 item health survey questionnaire (SF-36) scores were measured for each patient at 5 checkpoints (before treatment, at the 2nd week and the 4th week during the 4-week treatment period, at 1 month and 3 months after end of treatment), and adverse reactions were observed also. RESULTS: A total of 696 patients completed the entire process, with 351 in the treatment group and 345 in the control group. At all treatment checkpoints, the treatment group demonstrated better outcomes than the control group with regard to the total Lequesne index scores, effective rate and improvement rate of the total Lequesne index scores, VAS scores, lower limb muscle strength, knee circumference, quantitative scores of KOA symptoms, and SF-36 scores as well (P<0.05 or P<0.01). No adverse reactions were encountered in this study. CONCLUSIONS CM involving triple rehabilitation therapy can alleviate KOA-related pain and swelling, improve lower limb muscle strength, promote flexion and activity of the knee and improve the quality of life in patients undergoing KOA. It is suitable for patients with early or mid-stage KOA. (Registration No. ChiCTR-TRC-12002538).
Humans ; Medicine, Chinese Traditional ; Osteoarthritis, Knee/therapy* ; Outpatients ; Quality of Life ; Treatment Outcome

OBJECTIVE: To investigate the clinical features and outcome of neonatal acute respiratory distress syndrome (ARDS) in southwest Hubei, China. METHODS: According to the Montreux definition of neonatal ARDS, a retrospective clinical epidemiological investigation was performed on the medical data of neonates with ARDS who were admitted to Department of Neonatology/Pediatrics in 17 level 2 or level 3 hospitals in southwest Hubei from January to December, 2017. RESULTS: A total of 7 150 neonates were admitted to the 17 hospitals in southwest Hubei during 2017 and 66 (0.92%) were diagnosed with ARDS. Among the 66 neonates with ARDS, 23 (35%) had mild ARDS, 28 (42%) had moderate ARDS, and 15 (23%) had severe ARDS. The main primary diseases for neonatal ARDS were perinatal asphyxia in 23 neonates (35%), pneumonia in 18 neonates (27%), sepsis in 12 neonates (18%), and meconium aspiration syndrome in 10 neonates (15%). Among the 66 neonates with ARDS, 10 neonates (15%) were born to the mothers with an age of ≥35 years, 30 neonates (45%) suffered from intrauterine distress, 32 neonates (49%) had a 1-minute Apgar score of 0 to 7 points, 24 neonates (36%) had abnormal fetal heart monitoring results, and 21 neonates (32%) experienced meconium staining of amniotic fluid. Intraventricular hemorrhage was the most common comorbidity (12 neonates), followed by neonatal shock (9 neonates) and patent ductus arteriosus (8 neonates). All 66 neonates with ARDS were treated with mechanical ventilation in addition to the treatment for primary diseases. Among the 66 neonates with ARDS, 10 died, with a mortality rate of 15% (10/66), and 56 neonates were improved or cured, with a survival rate of 85% (56/66). CONCLUSIONS Neonatal ARDS in southwest Hubei is mostly mild or moderate. Perinatal asphyxia and infection may be the main causes of neonatal ARDS in this area. Intraventricular hemorrhage is the most common comorbidity. Neonates with ARDS tend to have a high survival rate after multimodality treatment.
China ; Female ; Humans ; Infant, Newborn ; Meconium Aspiration Syndrome ; Pregnancy ; Respiratory Distress Syndrome, Newborn ; Retrospective Studies

BACKGROUND: MAVERIC (Mitral Valve Repair Clinical Trial) validates the safety and efficacy of the ARTO system. We here report the first two successful cases of utilizing the ARTO system in patients with symptomatic heart failure (HF) with functional mitral regurgitation (FMR) in Asia. METHODS: Two patients, aged 70 and 63, had severe HF with FMR. Transesophageal echocardiography confirmed that the left ventricular ejection fractions were less than 50% with severe mitral regurgitation (MR) in both patients. Optimizing drug treatment could not mitigate their symptoms. Therefore, we used the ARTO system to repair the mitral valve for these patients on March 5 and 6, 2019, respectively. RESULTS: Mitral valve repairs using the ARTO system were successfully performed under general anaesthesia for these two patients. MR was decreased immediately after the procedures in both patients. The 30-day and 3-month transthoracic echocardiography (TTE) revealed a moderate to severe MR in both patients, and the New York Heart Association (NYHA) scales were also partially improved. CONCLUSION The first two cases in Asia indicate that the ARTO system is feasible for patients with heart failure with FMR, and the patient selection appears to be crucial.