Purpose: Dual anti–human epidermal growth factor receptor 2 (HER2) drugs have become the standard regimen for neoadjuvant systemic treatment (NST) to HER2-positive breast cancer patients. However, the efficacy varies greatly among patients with different HER2 protein expression levels. Materials and Methods: A total of 575 HER2-positive breast cancer patients from multiple centers throughout China from 2013 to 2022 were retrospectively analyzed. We compared clinicopathological features in different HER2 immunohistochemistry classes (HER2 2+/in situ hybridization [ISH] + or HER2 3+), and their difference in response to NST and survival with single or dual anti-HER2 drugs. Drug sensitivity assays were used to evaluate different efficacy of anti-HER2 drugs in vitro. Results: Compared to HER2 3+ subgroup, the HER2 2+/ISH+ group had a higher proportion of hormone receptor–positive status (48.7% vs. 76.1%, p < 0.001), more HER2 protein loss after NST, lower pathological complete response (pCR) rate (46.07% vs. 16.24%, p < 0.001), and tended to have worse disease-free survival (DFS). In HER2 2+/ISH+ patients, treated with pertuzumab and trastuzumab in combination had no significant improvement in pCR (19.12% vs. 12.24%, p=0.287) and DFS (p=0.908) than using alone. Drug sensitivity assay showed poor efficacy with dual anti-HER2 drugs in HER2 2+/ISH+ cell lines; however, fam-trastuzumab deruxtecan drugs had a satisfactory effect. Conclusion Owing to the differences in clinicopathological features and treatment efficacy, we considered the HER2 2+/ISH+ group to be a distinct subtype and defined it as the HER2-moderate–positive subgroup. In this subgroup, dual anti-HER2 drugs did not exert significant improvement in pCR and DFS. Therefore, treatment optimization is warranted, with antibody-drug conjugate drugs as potential options.

ObjectiveTo determine the effects of tuina at "Weizhong （BL 40）" on mechanical pain hypersensitivity in a rat model of chronic dorsal root ganglion （CCD）， and to preliminarily explore the anatomical distribution characteristics of neural afferents associated with "Weizhong （BL 40）" acupoint and their central projections. MethodsThirty SD rats were randomly assigned to a sham operation group， a model group， and a tuina group， with 10 rats in each group. In the model group and the tuina group， a chronic compression of CCD model was established by implanting stainless-steel rods into the right L4/5 and L3/4 intervertebral foramina. Rats in the sham operation group underwent surgical exposure only. From day 4 to day 28 after modeling， rats in the tuina group received daily manipulation at the right "Weizhong （BL 40）" （pressure： 5 N； frequency： 2 Hz； duration： 10 min/session）. Rats in the sham operation group and the model group were subjected only to fixation. Mechanical withdrawal threshold （MWT） was assessed before modeling and on day 3， 7， 14， 21， and 28 after modeling. On day 29 after modeling， pseudorabies virus （PRV）， a retrograde trans-multisynaptic tracer， was injected into the right "Weizhong （BL 40）" acupoint in rats from the model group. After 120 h， rats were perfusion-fixed through the heart， and local tissues surrounding the "Weizhong （BL 40）" acupoint， corresponding lumbar dorsal root ganglia， lumbar spinal cord， and brain tissues were collected for fluorescence imaging of PRV-positive signals. ResultsCompared to the sham operation group， rats in the model group and the tuina group showed significantly reduced MWT on day 3， 7， 14， 21， and 28 after modeling （P＜0.05）. Compared to the model group， rats in the tuina group exhibited significantly increased MWT on day 21 and 28 after modeling （P＜0.05）. Fluorescence imaging revealed PRV-positive signals in the deep fascial layer of local muscle tissue at "Weizhong （BL 40）"， the L4 and L5 dorsal root ganglia， the dorsal horn and central canal region of the spinal cord， as well as the primary somatosensory cortex （S1）， secondary motor cortex （M2）， and anterior cingulate cortex （ACC）. Among the examined cortical regions， M2 contained the largest number of PRV-positive neurons. ConclusionTuina at "Weizhong （BL 40）" alleviates mechanical hyperalgesia in rats with the chronic compression of CCD model. A traceable neuroanatomical connection exists between the linking deep tissues within "Weizhong （BL 40）" region and the corresponding lumbar dorsal root ganglia， the spinal dorsal horn， and specific cortical areas.

ObjectiveTo investigate the analgesic effect of Tuina at the "Weizhong （BL 40）" on neuropathic pain in a rat model of chronic constriction injury （CCI） of the sciatic nerve and its potential central spinal mechanisms. MethodsThirty-two Sprague-Dawley rats were randomly divided into four groups （8 rats in each group）， sham-operated group， model group， Tuina group， and blockade group. The CCI model was established in the model group， Tuina group， and the blockade group by ligating the sciatic nerve with catgut， while the sham-operated group underwent only sciatic nerve exposure without ligation. From postoperative day 4 to day 14， rats in the Tuina group and the blockade group received Tuina manipulation at the "Weizhong （BL 40）" using a dynamic pressure distribution measurement system （5 N pressure， 2 Hz frequency， 10 min per session， once daily）. The blockade group also received intraperitoneal injections of the microglial inhibitor minocycline （10 mg/kg） once daily. The sham-operated and the model group underwent the same handling and fixation as the Tuina group without actual Tuina. Mechanical withdrawal threshold （MWT） and paw withdrawal latency （PWL） were measured before surgery and on day 3， 7， 10， and 14 post-surgery. Transmission electron microscopy was used to evaluate sciatic nerve injury and repair， measuring axon diameter and total myelinated fiber diameter to calculate the g-ratio. Western Blotting was performed to detect the protein levels of ionized calcium-binding adapter molecule 1 （Iba-1）， CD206， CD68， interleukin-10 （IL-10）， and β-endorphin （β-EP） precursor pro-opiomelanocortin （POMC） in the ipsilateral spinal dorsal horn. ResultsCompared with the sham-operated group， the model group showed significantly reduced MWT and PWL on day 3， 7， 10， and 14 （P＜0.01）. Compared with the model group， the Tuina group and the blockade group showed increased MWT and PWL on day 10 and 14 （P＜0.05）. Compared with the Tuina group， the blockade group exhibited higher MWT on day 7， 10， and 14， and higher PWL on day 10 （P＜0.05）. Sciatic nerve pathological morphology revealed intact and well-structured myelin in the sham-operated group， while the model group exhibited myelin collapse， distortion， and myelin ovoid formation. The Tuina group displayed partially irregular myelin with occasional myelin collapse， whereas the blockade group exhibited partial myelin irregularities and phospholipid shedding. Compared with the sham-operated group， the model group showed a decreased g-ratio and increased levels of Iba-1 and CD68 in the spinal dorsal horn （P＜0.05 or P＜0.01）. Compared with the model group， the Tuina group and the blockade group exhibited an increased g-ratio and reduced Iba-1 and CD68 levels. Additionally， the Tuina group showed elevated levels of CD206， IL-10， and POMC， whereas the blockade group had decreased CD206 levels （P＜0.05）. ConclusionTuina at "Weizhong （BL 40）" alleviates neuropathic pain in CCI rats， potentially by regulating microglial activation in the spinal cord， inhibiting M1 polarization while promoting M2 polarization， and activating the IL-10/β-EP pathway to exert analgesic effects.

The pathogenesis of chronic fatigue syndrome(CFS)remains poorly defined,and while the tryptophan metabolic pathway is closely associated with the development of CFS,the underlying mechanisms are not yet fully understood.This review examines the alterations in tryptophan metabolites and related enzymes in both peripheral and central systems of CFS patients,with a particular focus on the involvement of the tryptophan pathway in the gut-brain axis(GBA).Furthermore,it provides a comprehensive analysis of the mechanistic roles of tryptophan metabolites in modulating the progression of CFS,aiming to elucidate the current evidence and potential driving mechanisms linking the tryptophan metabolic pathway to CFS,thereby promoting new insights and advancements in this research domain.

The pathogenesis of chronic fatigue syndrome(CFS)remains poorly defined,and while the tryptophan metabolic pathway is closely associated with the development of CFS,the underlying mechanisms are not yet fully understood.This review examines the alterations in tryptophan metabolites and related enzymes in both peripheral and central systems of CFS patients,with a particular focus on the involvement of the tryptophan pathway in the gut-brain axis(GBA).Furthermore,it provides a comprehensive analysis of the mechanistic roles of tryptophan metabolites in modulating the progression of CFS,aiming to elucidate the current evidence and potential driving mechanisms linking the tryptophan metabolic pathway to CFS,thereby promoting new insights and advancements in this research domain.

Objective To study the effect of pain on the lumbar and hip joint moments in patients with lumbar disc herniation(LDH)while sitting and standing.Methods Dynamic data from 20 healthy controls and 20 patients with LDH were collected using an AMTI dynamometer.The differences in moments between the lumbar spine and hip joints in the sagittal and coronal planes for the two groups of subjects performing sitting-standing tasks were analyzed using statistical parameter mapping(SPM).Results Compared to the healthy control group,the LDH group showed a significant increase in the maximum lumbar flexion moment and the maximum hip adduction moment from standing to sitting(P＜0.05).SPM analysis showed that during the initial phase of standing(37％-42％),the hip abduction moment of the LDH group was significantly greater than that of the healthy control group(P=0.007).Conclusions Subjects with LDH have an unstable lumbar spine and pelvis during sitting and standing,especially at the stationary stage,which makes it difficult to achieve balance in their body.Therefore,increasing the hip abduction moment is necessary to maintain pelvic stability.During clinical evaluation and treatment,emphasis should be placed on the stable function of the spine and pelvis.

Objective: To analyze the clinical application of manual therapy (MT) to tumor-related adverse reactions via summarizing the research at home and abroad, in order to provide more theoretical evidence for the clinical promotion of MT. Methods: We searched 7 Chinese and English databases, including China National Knowledge Infrastructure (CNKI), Wanfang Academic Journal Full-text Database (Wanfang), Chongqing VIP Database (CQVIP), PubMed, Excerpta Medica Database (EMBASE), Ovid and EBSCO. The publication date was between the establishment date of the database and December 31, 2020. We screened the literature according to the inclusion and exclusion criteria, and then sorted and analyzed the selected information. Results: A total of 46 papers were analyzed. Most studies focused on the adverse reactions in breast cancer patients. MT interventions demonstrated the best efficacy for fatigue, followed by pain, depression and anxiety. In different MT interventions, Tuina (Chinese therapeutic massage) was mainly adopted for fatigue, pain, anxiety, depression, and limb dysfunctions. Acupoint pressing was mainly adopted for gastrointestinal and psychological problems such as abdominal bloating, insomnia, depression and anxiety. The application of reflexotherapy was similar to that of Tuina. Conclusion: MT can alleviate various adverse reactions by effectively relieving patients' somatic symptoms and improving their psychological states and overall functions. It can be popularized as a significant non-drug therapy. Currently, however, the clinical application of MT is neither extensive nor has sufficient basic research. Consequently, we should attach importance to this application.

Objective:To evaluate the various wire tension belt ventral compression wiring technologiesfor treating several types of femoral greater trochanter fractures in total hip replacement, according to the different types of greater trochanter of femur fractures.Methods:From March 2013 to June 2019, a total of 1 280 cases of primary total hip arthroplasty were completed in our hospital, 21 patients with greater trochanter fractures were identified in total hip replacement. There were 11 males and 10 females with an average age of 65.81±6.45 years (range 42-76 years). All of them were unilateral. There were 11 cases on the left and 10 cases on the right. There were 11 cases of osteoarthritis secondary to hip dysplasia, 4 cases of hip osteoarthritis, 4 cases of aseptic necrosis of femoral head and 2 cases of femoral neck fracture. Different wire tension belt ventral compression wiring technologies were used for each fracture type. Harris hip function score, Parker activity score, and visual analogue scale (VAS) score of hip pain were evaluated during follow-up. X-ray films were taken to evaluate the fracture healing, prosthesis position, loosening and dislocation.Results:Three new fracture types were proposed: A transverse fracture from the greater trochanter tip to the base (4 cases); B oblique fracture from the greater trochanter tip to the base (according to the fracture line direction, type B was further divided into types B1 (4 cases) and B2 (6 cases); and C fracture line from the greater trochanter to subtrochanteric plane (7 cases). Among the 21 patients, one died at an early stage, two were lost during follow-up, and 18 were followed up for an average of 30.7±7.6 months. In 18 patients, the mean operation time was 110.0±20.0 min, and the mean intraoperative blood loss was 356.9±115.7 ml. The patients' Harris score was 35.26±5.52 at the preoperative, 65.7±6.42 at the 3 months after operation, and 87.75±6.21 at the final follow-up. The difference was statistically significant ( F=377.23, P<0.001). The patients' Parker score was 2.17±0.98 at the preoperative, 5.94±1.11 at the 3 months after operation,and 8.01±0.77 at the final follow-up. The difference was statistically significant ( F=170.96, P<0.001). The patients' VAS score was 6.22±1.11 at the preoperative, 2.61±0.92 at the 3 months after operation, and 1.28±0.67 at the final follow-up. The difference was statistically significant ( F=139.71, P<0.001). Deep vein embolism, heterotopic ossification was noted in one and another patient, respectively. The patient with non-union refused reoperation and had a broken steel wire, lower-limb limp, and no notable pain at the 12-month follow-up examination. Radiographs of 17 patients showed good location of the femoral prosthesis and no chronic pain. Conclusion:Different types of greater trochanter fractures in total hip arthroplasty were proposed, using different wire tension belt ventral compression wiring technologies for the various types of femoral greater trochanter fractures during total hip replacement can improve clinical outcomes.

Objective:To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon α-2b (rIFNα-2b) and the combination of lopinavir/ritonavir plus rIFNα-2b for patients with COVID-19 in Zhejiang province.Methods:A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNα-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data.Results:The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2±4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0±5.0) d] ( t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] ( H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively ( Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8±3.9), (13.5±5.1) and (11.2±4.3) d, respectively( Z=6.722, P<0.05). Conclusions:The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNα-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy; and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.

Objective: Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province. Methods: A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data. Results: The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (t = 6.159, P < 0.01 ). The length of hospital stay [12 (9, 17) d] in the triple combination antiviral drug group was also shorter than that in the dual combination antiviral drug group [15 (10, 18) d] (H = 2.073, P < 0.05). Comparing the antiviral treatment which was started within 48 hours, 3-5 days and > 5 days after the symptom onset of triple combination antiviral drug group, the time from the symptom onset to the negative of viral shedding was 13 (10,16.8), 17 (13,22) and 21 (18-24) days respectively (Z = 32.983, P < 0.01), and the time from antiviral therapy to the negative of viral shedding was (11.8±3.9) , (13.5±5.1) and (11.2±4.3) d. The differences among the three groups were statistically significant (Z=32.983 and 6.722, P<0.01 or<0.05). Conclusions The triple combination antiviral therapy of Abidor, Lopinavir/Litonavir and recombinant interferon α-2b showed shorter viral shedding time and hospitalization time compared with the dual combination antiviral therapy. The earlier the time to initiate triple antiviral treatment, the shorter the time of virus shedding.