Objective: To compare the efficacy of using “distal acupoints only” vs. “local acupoints mainly combined with distal acupoints” in cases of acute low back pain (ALBP). Methods: A total of 102 eligible patients aged 18–65 years with ALBP lasting less than 6 weeks will be randomized in a 1:1 ratio to the distal acupoints only group (DPOG) and the local acupoints mainly combined with the distal acupoints group (LPMG). During a 4-week treatment period, patients in the DPOG will receive acupuncture at distal acupoints only (Houxi [SI 3] and Yaotongxue [EX-UE 7]) twice a week, while those in the LPMG group will receive acupuncture at local acupoints (mainly Shenshu [BL 23] and Dachangshu [BL 25]) combined with distal points (Weizhong [BL 40]). The patients in both groups will be evaluated at every session of treatment, and the follow-up will be performed for 3 months. The primary outcome measure will be the change in ALBP intensity, assessed using visual analogue scale scores before and after treatment. The secondary outcome measure will be the evaluation of functional disability using the Oswestry Disability Index. Discussion This study compares the DPOG and LPMG to explore the feasibility of the DPOG in the treatment of ALBP.

OBJECTIVE: Functional constipation (FC) is a common intestinal disease worldwide. Despite the presence of criteria such as Roman IV, there is no standardized diagnosis and treatment algorithm in Hong Kong that combines both Western and Chinese medicine approaches. This study integrates current effective and safe diagnosis and treatment methods for FC and provides a clear and scientific pathway for clinical professionals and patients. METHODS: A systematic search of the PubMed, Cochrane Library, and China National Knowledge Infrastructure databases was performed from their inception to June 30th, 2022, collecting the current evidence about the efficacious integrative management for FC. We organized a meeting of professionals in fields relevant to treatment and management of FC to develop a consensus agreement on clinical pathway process. RESULTS: We developed a clinical pathway for the treatment of FC based on the most recent published guidelines and consultation with experts. This pathway includes a hierarchy of recommendations for every step of the clinical process, including clinical intake, diagnostic examination, recommended labs, diagnostic flowchart, and guidance for selection of therapeutic drugs. CONCLUSION This pathway establishes clinical standards for the diagnosis and treatment of FC using Chinese medicine and Western medicine; it will help to provide high-quality medical services in Hong Kong for patients with FC. Please cite this article as: Wei DJ, Li HJ, Lyu ZP, Lyu AP, Bian ZX, Zhong LL. A clinical pathway for integrative medicine in the treatment of functional constipation in Hong Kong, China. J Integr Med. 2023; 21(6): 550-560.
Humans ; Hong Kong ; Integrative Medicine ; Critical Pathways ; China ; Constipation/therapy*

Lingguizhugan Decoction (LGZG) has been investigated in basic studies, with satisfactory effects on insulin resistance in non-alcoholic fatty liver disease (NAFLD). This translational approach aimed to explore the effect and underlying mechanism of LGZG in clinical setting. A randomized, double-blinded, placebo-controlled trial was performed. A total of 243 eligible participants with NAFLD were equally allocated to receive LGZG (two groups: standard dose and low dose) or placebo for 12 weeks on the basis of lifestyle modifications. The primary efficacy variable was homeostasis model assessment of insulin resistance (HOMA-IR). Analyses were performed in two populations in accordance with body mass index (BMI; overweight/obese, BMI ⩾ 24 kg/m²; lean, BMI < 24 kg/m²). For overweight/obese participants, low-dose LGZG significantly decreased their HOMA-IR level compared with placebo (-0.19 (1.47) versus 0.08 (1.99), P = 0.038). For lean subjects, neither dose of LGZG showed a superior effect compared with placebo. Methylated DNA immunoprecipitation sequencing and real-time qPCR found that the DNA N6-methyladenine modification levels of protein phosphatase 1 regulatory subunit 3A (PPP1R3A) and autophagy related 3 (ATG3) significantly increased after LGZG intervention in overweight/obese population. Low-dose LGZG effectively improved insulin resistance in overweight/obese subjects with NAFLD. The underlying mechanism may be related to the regulation of DNA N6-methyladenine modification of PPP1R3A and ATG3. Lean subjects may not be a targeted population for LGZG.
Humans ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Overweight/drug therapy* ; Insulin Resistance ; Obesity/drug therapy* ; China ; DNA/therapeutic use*

OBJECTIVE: To investigate the mechanism of Tojapride, a Chinese herbal formula extract, on strengthening the barrier function of esophageal epithelium in rats with reflux esophagitis (RE). METHODS: Ten out of 85 SD rats were randomly selected as the sham group (n10), and 75 rats were developed a reflux esophagitis model (RE) by the esophageal and duodenal side-to-side anastomosis. Fifty successful modeling rats were divided into different medicated groups through a random number table including the model, low-, medium-, and high-dose of Tojapride as well as omeprazole groups (n10). Three doses of Tojapride [5.73, 11.46, 22.92 g/(kg•d)] and omeprazole [4.17 mg/(kg•d)] were administrated intragastrically twice daily for 3 weeks. And the rats in the sham and model groups were administered 10 mL/kg distilled water. Gastric fluid was collected and the supernatant was kept to measure for volume, pH value and acidity. Esophageal tissues were isolated to monitor the morphological changes through hematoxylin-eosin (HE) staining, and esophageal epithelial ultrastructure was observed by transmission electron microscopy. The expressions of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-KBp65), κB kinase beta (IKKß), occludin, and zonula occludens-1 (ZO-1) in the esophageal tissues were measured by immunohistochemistry and Western blot, respectively. RESULTS: The gastric pH value in the model group was significantly lower than the sham group (P<0.05). Compared with the model group, gastric pH value in the omeprazole and medium-dose of Tojapride groups were significantly higher (P<0.05). A large area of ulceration was found on the esophageal mucosa from the model rats, while varying degrees of congestion and partially visible erosion was observed in the remaining groups. Remarkable increase in cell gap width and decrease in desmosome count was seen in RE rats and the effect was reversed by Tojapride treatment. Compared with the sham group, the IKKß levels were significantly higher in the model group (P<0.05). However, the IKKß levels were down-regulated after treatment by all doses of Tojapride (P<0.01 or P<0.05). The occluding and ZO-1 levels decreased in the model group compared with the sham group (Ps0.01 or Ps0.05), while both indices were significantly up-regulated in the Tojapride-treated groups (P<0.01 or P<0.05). CONCLUSIONS Tojapride could improve the pathological conditions of esophageal epithelium in RE rats. The underlying mechanisms may involve in down-regulating the IKKß expression and elevating ZO-1 and occludin expression, thereby alleviating the inflammation of the esophagus and strengthening the barrier function of the esophageal epithelium.

BACKGROUND: Zhibai Dihuang pill (ZBDH), a Chinese herbal formula, has been widely used as an adjunctive therapy to help reduce the patient's steroid dose and maintain low disease activity in systemic lupus erythematosus (SLE). OBJECTIVE: This systematic review evaluates the therapeutic effect of modified ZBDH in reducing steroid use in patients with SLE. SEARCH STRATEGY: A systematic literature search was carried out using seven databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chinese VIP Information and Wanfang Database, from their inception to June 1st, 2019. The search terms included "systemic lupus erythematosus," "Chinese medicine" and "clinical trial," and their synonyms. Subject headings matching the above terms were also used. INCLUSION CRITERIA: This meta-analysis included randomized controlled trials that evaluated the reduction of steroid dose in patients with SLE. Traditional Chinese medicine (TCM) formulas in experimental group should be prescribed based on ZBDH and used as adjunctive therapy and the comparator should contain steroids. DATA EXTRACTION AND ANALYSIS: Two authors independently conducted database search, study selection, data extraction and quality assessment. The extracted information contained study design, sample size, recruitment mode, diagnostic criteria, inclusion and exclusion criteria, participant characteristics, TCM patterns, TCM formulas and treatment outcomes. The primary outcome was the change of steroid dose. Secondary outcomes included SLE Disease Activity Index (SLEDAI), biomarkers of disease activity and clinical response rate. STATA 15.0 was used to analyze the pooled effects reported as weighted mean difference (WMD) or odds ratio, with a 95% confidence interval (CI). RESULTS: In total, 20 trials involving 1470 SLE patients were included. The pooled result showed that modified ZBDH taken in combination with standard care led to a larger reduction in steroid dose, compared to standard care alone (WMD: 3.79; 95% CI: 2.58-5.01; P < 0.001). Favorable outcomes were also seen in secondary outcome criteria, such as SLEDAI and complement 3. The modified ZBDH treatments were well tolerated without increasing adverse effects. CONCLUSION The systematic review provided preliminary evidence supporting the use of ZBDH as a co-therapy to aid steroid dose reduction in patients with SLE. However, more rigorous studies should be conducted to validate these findings, and explore the mechanisms of ZBDH's relevant bioactive constituents.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis. METHODS: This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12. RESULTS: A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P < 0.001), and IGA 0/1 (82.3% and 69.7% vs. 2.7%; P < 0.001) at Week 12. Treatment efficacy was maintained until Week 52. There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period. CONCLUSION: Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis. TRIAL REGISTRATION ClinicalTrials.gov, NCT03066609; https://clinicaltrials.gov/ct2/show/record/NCT03066609.
Antibodies, Monoclonal/therapeutic use* ; Antibodies, Monoclonal, Humanized ; China ; Double-Blind Method ; Humans ; Psoriasis/drug therapy* ; Severity of Illness Index ; Treatment Outcome

Traditional Chinese Medicine (TCM) is one of the oldest systems of medicine. More and more attention has been paid to TCM application, but the variable quality of clinical trials with TCM impedes its widespread acceptance. The Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Statement has established guidelines for designing clinical trials to ensure that the trial results are accurate and reliable. However, there are difficulties when applying SPIRIT 2013 Statement to trials with TCM, due to the unique theory and the characteristic of TCM intervention. An Extension to the original SPIRIT was developed to ensure the quality of trial design with TCM. As Chinese herbal formulae, acupuncture and moxibustion are common and representative interventions in TCM practice, the executive working group determined that the SPIRIT-TCM Extension focus on these three interventions. Extension was developed through initiation, 3 rounds of Delphi consensus survey, and finalizing expert meeting. Seven items from the SPIRIT 2013 Statement were modified, namely, "title", "background and rationale", "objectives", "eligibility criteria", "interventions", "outcomes", and "data collection methods". The Extension includes the introduction of the concept of TCM pattern and 3 major TCM interventions, with examples and explanations. The SPIRIT-TCM Extension 2018 provides suggestion for investigators in designing high quality TCM clinical trials. It is expected that wide dissemination and application of this extension ensure continuous improvement of TCM trial quality throughout the world.
Clinical Protocols ; Clinical Trials as Topic ; Humans ; Medicine, Chinese Traditional ; Research Design

BACKGROUND: Syndrome is one of the most important concepts in Chinese medicine (CM) theory. However, it was not well accounted in most of randomized controlled trials (RCTs). OBJECTIVES: To determine whether CM syndrome differentiation affects the treatment results, functional constipation (FC) was selected as a target disease, and MaZiRenWan (, MZRW), a classic CM formula commonly used for constipation with excessive heat syndrome, was selected for study. METHODS: It is an 18-week prospective double-blinded, doubledummy RCT, including 2-week run-in, 8-week treatment and 8-week post treatment follow-up. A total of 120 FC patients diagnosed as excessive heat syndrome will be recruited from the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and the Baokang Affiliated Hospital of Tianjin University of Traditional Chinese Medicine. Patients will be randomly allocated into fixed MZRW (f_MZRW) granule group, modified MZRW (m_MZRW) granule group or bisacodyl group. For m_MZRW group, no more than two herbal granules can be added according to the syndrome differentiation for individual participants. The primary end point is the mean of complete spontaneous bowel movements (CSBMs) per week during the treatment period. Secondary end points include mean of CSBMs per week during follow-up, stool form, global symptom improvement, constipation and constipation-related symptoms assessment, CM syndrome change, and reported adverse events. DISCUSSION This trial is designed to evaluate the effectiveness of these three interventions for FC patients with the CM syndrome of excessive heat, and to determine the change of CM syndrome and the progress of disease during the treatment course. The results are important to explore whether syndrome differentiation is important for the therapeutic effect of a formula on a disease. [Trial registration: Chinese Clinical Trial Registry (Reg No. ChiCTR-TRC-13003742); protocol version: MZRW/NSFC-81173363 (2015.05.04)].
Constipation ; diagnosis ; drug therapy ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Outcome Assessment (Health Care) ; Prospective Studies ; Randomized Controlled Trials as Topic

Stomach pain in Chinese medicine (CM) is a very common disorder in clinical practice and it has been listed as one of the pilot three conditions in Hong Kong to develop evidence-based CM clinical practice guidelines (CM CPGs). The aim of this stomach Pain CPG is to summarize the treatment methods of stomach pain with CM and evaluate reasonably, then to guide local licensed CM practitioners and provide beneficial reference for social medical decision makers and patients. In this manuscript, we defined stomach pain in CM and the category of chronic gastritis in Western medicine. The clinical manifestation, CM pattern classification, and CM intervention including herbal medicine treatment based on pattern differentiation, symptomatic treatment, acupuncture treatment, regulation and nursing were illustrated.

OBJECTIVETo survey the reporting quality of traditional Chinese medicine (TCM) case reports published in recent years and understand the common problems. The assessment results would lay the foundation for the development of recommendations for case report in Chinese medicine.

METHODSThis survey determined the reporting quality of cases with Chinese herbal decoction, Chinese proprietary medicine, acupuncture, moxibustion and other traditional therapies published in 20 core medical journals of China by searching the China Academic Journals Full-text Database from 2006 to 2010. Fifty survey items in 16 domains were used to determine the reporting quality. One point was assigned to each item (Yes=1 point; No=0 point), and total score was 50 points. The domain of treatment was assessed independently, ranging from 2 to 9 items for different TCM interventions.

RESULTSThe total of 1,858 case reports, covering 3,417 cases were included to analyze from 13 out of 20 core medical journals of China. There were 74.8% of them did not identify the nature of study in title, while 73.9% did not comprise an abstract. Incomplete reporting was found in discussions/ comment, and only 38.9% had made recommendations or take-away messages. Figures and tables were infrequently used. Three cases cited the full names of patients, but without declaring that any consent was obtained. Over 90% reported the symptoms and signs of TCM, and characteristics on tongue and pulse, but less than 50% did mention other medical history and diagnostic rationale. More than 90% treatments of the included cases were herbal decoction, with clear reporting on the ingredients and dosages. However, the reporting rate of the dosages of each ingredient was just 48.4%. Almost none reported the quality control of crude herbs, manufacturers and lot numbers of herbal proprietary medicine. Besides, advices and precautions on diet, emotions and living were rare to be illustrated.

CONCLUSIONSystematic reporting recommendations are urged to develop for improving the contents and format of case reports in TCM.