OBJECTIVE: Varied acupoint selections represent a potential cause of the uncertainty surrounding the efficacy of acupuncture for knee osteoarthritis (OA). Skin temperature, a guiding factor for acupoint selection, may help to address this issue. This study explored thermal sensitization of acupoints used for the treatment of knee OA. METHODS: This cross-sectional case-control study enrolled cases aged 45-75 years with symptomatic knee OA and age- and gender-matched non-knee OA controls in a 1:1 ratio. All participants underwent infrared thermographic imaging. The primary outcome was the relative skin temperature of acupoint (STA), and the secondary outcome was the absolute STA of 11 acupoints. The Z test was used to compare the relative and absolute STAs between the groups. Principal component analysis was used to extract the common factors (CFs, acupoint cluster) in the STAs. A general linear model was used to identify factors affecting the STA in the knee OA cases. For the group comparisons of relative STA, P < 0.0045 (adjusted for 11 acupoints through Bonferroni correction) was considered to indicate statistical significance. For other analyses, P < 0.05 was used as the threshold for statistical significance. RESULTS: The analysis included 308 participants, consisting of 151 cases (mean age: [64.58 ± 6.67] years; male: 25.83%; mean body mass index: [25.70 ± 3.16] kg/m²) and 157 controls (mean age: [63.37 ± 5.96] years; male: 26.11%; mean body mass index: [24.47 ± 2.84] kg/m²). The relative STAs of ST34 (P = 0.0001), EX-LE2 (P < 0.0001), EX-LE5 (P = 0.0006), SP10 (P < 0.0001), BL40 (P = 0.0012) and GB39 (P = 0.0037) were higher in the knee OA group. No difference was found in the STAs of ST35, ST36, SP9, GB33 and GB34. Four CFs were identified for relative STA in both groups. The acupoints within each CF were consistent between the groups. The mean values of the relative STAs across each CF were higher in the knee OA group. In the knee OA cases, no factors were observed to affect the relative STA, while age and gender were found to affect the absolute STA. CONCLUSION Among patients with knee OA, thermal sensitization occurs in the acupoints of the lower extremity, exhibiting localized and regional thermal consistencies. The thermally sensitized acupoints that we identified in this study, ST34, SP10, EX-LE2, EX-LE5, GB39 and BL40, may be good choices for the acupuncture treatment of knee OA. Please cite this article as: Tu JF, Wang XZ, Yan SY, Wang YR, Yang JW, Shi GX, Zhang WZ, Jing LN, Yang LS, Liu DH, Wang LQ, Mi BH. Thermal sensitization of acupoints in patients with knee osteoarthritis: A cross-sectional case-control study. J Integr Med. 2025; 23(3): 289-296.
Humans ; Osteoarthritis, Knee/physiopathology* ; Male ; Cross-Sectional Studies ; Middle Aged ; Female ; Acupuncture Points ; Case-Control Studies ; Aged ; Skin Temperature ; Acupuncture Therapy

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

This article elaborates on the complex cross-talk and close relationship between muscles and bones involved in this disease,as well as its pathogenesis.It also summarizes that the difficulty of its treatment lies in the need to simultaneously consider both muscles and bones.And elaborated on the key role of the Hedgehog signaling pathway in embryonic development,tissue morphology establishment,and human tissue regeneration and repair.Investigated the remodeling effect of the Hedgehog signaling pathway on skeletal muscle from three aspects:Proliferation and differentiation of muscle stem cells,precursor cell and muscle fiber generation,inhibition of inflammation,and regulation of immunity;this article elucidates the role of the Hedgehog signaling pathway in bone reconstruction from two aspects.

Relevant literature on TCM diagnostic and treatment equipment from January 1994 to May 2023 was collected with three Chinese databases,namely,China National Knowledge Infrastructure,Wanfang and Wipu.CiteSpace software was used for the analyses of the trend of annual publication volume,co-occurrence of publication institutions,co-occurrence of keywords,cluster and burst and the generation of corresponding knowledge graphs.It's pointed out TCM diagnostic and treatment equipment had problems in low publication volume and collaboration between research institutions,hotspots of Chinese medicine diagnosis and treatment,diagnosis and treatment equipment,diagnosis device,Chinese medicine diagnosis,diagnosis and treatment technology and traditional Chinese medicine,and research frontiers of artificial intelligence,medical alliance,curriculum design and innovation and entrepreneurship.References were provided for relevant research in China.[Chinese Medical Equipment Journal,2024,45(3):76-80]

Major depressive disorder(MDD)is a prevalent con-dition associated with substantial impairment and low remission rates.Traditional antidepressants demonstrate delayed effects,low cure rate,and inadequate therapeutic effectiveness for man-aging treatment-resistant depression(TRD).Several studies have shown that ketamine,a non-selective N-methyl-D-aspartate receptor(NMDAR)antagonist,can produce rapid and sustained antidepressant effects.Ketamine has demonstrated efficacy for reducing suicidality in TRD patients.However,the pharmaco-logical mechanism for ketamine's antidepressant effects remains incompletely understood.Previous research suggests that the an-tidepressant effects of ketamine may involve the monoaminergic,glutamatergic and dopaminergic systems.This paper provides an overview of the pharmacological mechanism for ketamine's anti-depressant effects and discuss the potential directions for future research.

Glutamate,norepinephrine,and their receptors com-prise the glutamatergic and norepinephrine systems,which mu-tually affect each other and play essential roles in mediating vari-ous neuropsychiatric diseases.This paper reviews the functions of N-methyl-D-aspartate receptor(NMDA-R)and α2-adrenergic receptor(α2-AR)and their functional crosstalk at the molecular level in brain in common neuropsychiatric diseases,which would benefit our understanding of neuropathophysiology of psychiatric diseases,drug development and optimization of clinical neuro-psychopharmacology.

Protein phosphorylation modification is an important mechanism of physiological regulation that is closely related to protein biological functions. In particular, protein kinases are responsible for catalyzing the phosphorylation process of proteins, and phosphatases are responsible for catalyzing the dephosphorylation process of phosphorylation-modified proteins, which together mediate the achievement of dynamic and reversible phosphorylation modifications of proteins. Abnormal phosphorylation levels of proteins contribute to the development of many diseases, such as cancer, neurodegenerative diseases, and chronic diseases. Therefore, rational design of small molecules to regulate protein phosphorylation is an important approach for disease treatment. Based on the mechanism of protein phosphorylation regulation, small molecule drug design strategies can be classified into three types, protein kinase modulators, phosphatase modulators, and bifunctional molecules with proximity-mediated mechanism. This review emphasizes the above three small molecule design strategies for targeting protein phosphorylation regulation, including molecular design ideas, research progress and current challenges, and provides an outlook on small molecule modulators targeting protein phosphorylation modification.

Objective: To investigate the clinical characteristics and maternal and fetal prognosis of pregnant women with acute fatty liver of pregnancy (AFLP). Methods: The clinical data of 86 AFLP pregnant women admitted to the Third Affiliated Hospital of Guangzhou Medical University from September 2017 to August 2022 were collected, and their general data, clinical characteristics, laboratory tests and maternal and fetal outcomes were retrospectively analyzed. Results: (1) General information: the age of the 86 pregnant women with AFLP was (30.8±5.4) years, and the body mass index was (21.0±2.5) kg/m². There were 50 primiparas (58.1%, 50/86) and 36 multiparas (41.9%, 36/86). There were 64 singleton pregnancies (74.4%, 64/86) and 22 twin pregnancies (25.6%, 22/86). (2) Clinical characteristics: the main complaints of AFLP pregnant women were gastrointestinal symptoms, including epigastric pain (68.6%, 59/86), nausea (47.7%, 41/86), anorexia (46.5%, 40/86), vomiting (39.5%, 34/86). The main non-gastrointestinal symptoms were jaundice of skin and/or scleral (54.7%, 47/86), edema (38.4%, 33/86), fatigue (19.8%, 17/86), bleeding tendency (16.3%, 14/86), polydipsia or polyuria (14.0%, 12/86), skin itching (8.1%, 7/86), and 17.4% (15/86) AFLP pregnant women had no obvious symptoms. (3) Laboratory tests: the incidence of liver and kidney dysfunction and abnormal coagulation function in AFLP pregnant women was high, and the levels of blood ammonia, lactate dehydrogenase and lactic acid were increased, and the levels of hemoglobin, platelet and albumin decreased. However, only 24 cases (27.9%, 24/86) of AFLP pregnant women showed fatty liver by imageology examination. (4) Pregnancy outcomes: ① AFLP pregnant women had a high incidence of pregnancy complications, mainly including renal insufficiency (95.3%, 82/86), preterm birth (46.5%, 40/86), hypertensive disorders in pregnancy (30.2%, 26/86), gestational diabetes mellitus (36.0%, 31/86), fetal distress (24.4%, 21/86), pulmonary infection (23.3%, 20/86), disseminated intravascular coagulation (16.3%, 14/86), multiple organ dysfunction syndrome (16.3%, 14/86), hepatic encephalopathy (9.3%, 8/86), and intrauterine fetal death (2.3%, 2/86). ② Treatment and outcome of AFLP pregnant women: the intensive care unit transfer rate of AFLP pregnant women was 66.3% (57/86). 82 cases were improved and discharged after treatment, 2 cases were transferred to other hospitals for follow-up treatment, and 2 cases (2.3%, 2/86) died. ③ Neonatal outcomes: except for 2 cases of intrauterine death, a total of 106 neonates were delivered, including 39 cases (36.8%, 39/106) of neonatal asphyxia, 63 cases (59.4%, 63/106) of neonatal intensive care unit admission, and 3 cases (2.8%, 3/106) of neonatal death. Conclusions: AFLP is a severe obstetric complication, which is harmful to mother and fetus. In the process of clinical diagnosis and treatment, attention should be paid to the clinical manifestations and laboratory tests of pregnant women, early diagnosis and active treatment, so as to improve maternal and fetal outcomes.
Pregnancy ; Infant, Newborn ; Female ; Humans ; Adult ; Retrospective Studies ; Premature Birth/epidemiology* ; Pregnancy Complications/diagnosis* ; Fatty Liver/diagnosis* ; Fetal Death ; Stillbirth

OBJECTIVE: To observe the effect of Tiaoqi Jieyu (regulating qi and relieving depression) acupuncture on the clinical symptoms of treatment-resistant depression (TRD), and to explore the relationship between the acupuncture pain sensitivity and symptom's improvement. METHODS: A total of 78 patients with TRD were randomly divided into an observation group (39 cases, 3 cases dropped off) and a control group (39 cases, 4 cases dropped off). The patients in the control group were treated with medications according to the treatment plan of psychiatrists (at least one medication was 5-hydroxytryptamine reuptake inhibitor). On the basis of the control group, the patients in the observation group were treated with Tiaoqi Jieyu acupuncture, and Baihui (GV 20), Yintang (GV 24⁺), Yanglingquan (GB 34), Taichong (LR 3), Hegu (LI 4), Neiguan (PC 6), Yinlingquan (SP 9) and Zusanli (ST 36), etc. were selected. The acupuncture was given three times a week. Both groups were treated for 8 weeks. After 8-week treatment, the response rate of Hamilton depression scale-24 (HAMD-24) score after was evaluated in the two groups. The scores of HAMD-24 and Hamilton anxiety scale (HAMA) were compared between the two groups before treatment, after 4, 8-week treatment and 12 weeks after treatment (follow-up). After the first treatment and 8-week treatment, the visual analogue scale (VAS) score in the observation group was evaluated, and the correlation between VAS score after the first treatment and HAMD-24 score before treatment, between VAS score after the first treatment and the course of disease in the observation group was analyzed, and the correlation between difference of VAS after 8-week treatment and after the first treatment and difference of HAMD-24 score before treatment and after 8-week treatment was analyzed. RESULTS: After 8-week treatment, the response rate of HAMD-24 score in the observation group was 52.8% (19/36), higher than 17.1% (6/35) in the control group (P<0.001). Compared before treatment, the scores of HAMD-24 and HAMA in the two groups were decreased after 4-week treatment, 8-week treatment and in follow-up (P<0.05), and those in the observation group were superior to the control group (P<0.05). After 8-week treatment, the acupuncture pain VAS score in the observation group was (5.28±2.13) points, which was higher than (3.33±1.62) points after the first treatment (P<0.001). There was a negative correlation between VAS score after the first treatment and HAMD-24 score before treatment in the observation group (r =-0.486, P=0.003); there was no correlation between acupuncture pain VAS score after the first treatment and the course of disease in the observation group (P>0.05). After 8-week treatment, there was a positive correlation between the difference of VAS score and the difference of HAMD-24 score in the observation group (r =0.514, P=0.001). CONCLUSION Tiaoqi Jieyu acupuncture could improve the depression and anxiety in patients with TRD, and the symptom's improvement is related to the recovery of acupuncture pain sensitivity.
Humans ; Depression/therapy* ; Treatment Outcome ; Acupuncture Therapy ; Acupuncture Points ; Pain

Objective: To investigate the surgical indications and perioperative clinical outcomes of pelvic exenteration (PE) for locally advanced, recurrent pelvic malignancies and complex pelvic fistulas. Methods: This was a descriptive study.The indications for performing PE were: (1) locally advanced, recurrent pelvic malignancy or complex pelvic fistula diagnosed preoperatively by imaging and pathological examination of a biopsy; (2)preoperative agreement by a multi-disciplinary team that non-surgical and conventional surgical treatment had failed and PE was required; and (3) findings on intraoperative exploration confirming this conclusion.Contraindications to this surgical procedure comprised cardiac and respiratory dysfunction, poor nutritional status,and mental state too poor to tolerate the procedure.Clinical data of 141 patients who met the above criteria, had undergone PE in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to September 2022, had complete perioperative clinical data, and had given written informed consent to the procedure were collected,and the operation,relevant perioperative variables, postoperative pathological findings (curative resection), and early postoperative complications were analyzed. Results: Of the 141 included patients, 43 (30.5%) had primary malignancies, 61 (43.3%) recurrent malignancies, 28 (19.9%) complex fistulas after radical resection of malignancies,and nine (6.4%)complex fistulas caused by benign disease. There were 79 cases (56.0%) of gastrointestinal tumors, 30 cases (21.3%) of reproductive tumors, 16 cases (11.3%) of urinary tumors, and 7 cases (5.0%) of other tumors such mesenchymal tissue tumors. Among the 104 patients with primary and recurrent malignancies, 15 patients with severe complications of pelvic perineum of advanced tumors were planned to undergo palliative PE surgery for symptom relief after preoperative assessment of multidisciplinary team; the other 89 patients were evaluated for radical PE surgery. All surgeries were successfully completed. Total PE was performed on 73 patients (51.8%),anterior PE on 22 (15.6%),and posterior PE in 46 (32.6%). The median operative time was 576 (453,679) minutes, median intraoperative blood loss 500 (200, 1 200) ml, and median hospital stay 17 (13.0,30.5)days.There were no intraoperative deaths. Of the 89 patients evaluated for radical PE surgery, the radical R0 resection was achieved in 64 (71.9%) of them, R1 resection in 23 (25.8%), and R2 resection in two (2.2%). One or more postoperative complications occurred in 85 cases (60.3%), 32 (22.7%)of which were Clavien-Dindo grade III and above.One patient (0.7%)died during the perioperative period. Conclusion: PE is a valid option for treating locally advanced or recurrent pelvic malignancies and complex pelvic fistulas.
Humans ; Pelvic Exenteration/methods* ; Pelvic Neoplasms/surgery* ; Retrospective Studies ; Neoplasm Recurrence, Local/surgery* ; Postoperative Complications